The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ziv-Gal, Ayelet, E-mail: zivgal1@illinois.edu; Wang, Wei, E-mail: weiwang2@illinois.edu; Zhou, Changqing, E-mail: czhou27@illinois.edu
In utero bisphenol A (BPA) exposure affects reproductive function in the first generation (F1) of mice; however, not many studies have examined the reproductive effects of BPA exposure on subsequent generations. In this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50 μg/kg/day) or diethylstilbestrol (DES; 0.05 μg/kg/day) daily from gestation day 11 until birth. F1 females were used to generate the F2 generation, and F2 females were used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9 months were conducted to evaluate reproductive capacity over time. Further, studiesmore » were conducted to evaluate pubertal onset, litter size, and percentage of dead pups; and to calculate pregnancy rate, and mating, fertility, and gestational indices. The results indicate that BPA exposure (0.5 and 50 μg/kg/day) significantly delayed the age at vaginal opening in the F3 generation compared to vehicle control. Both DES (0.05 μg/kg/day) and BPA (50 μg/kg/day) significantly delayed the age at first estrus in the F3 generation compared to vehicle control. BPA exposure reduced gestational index in the F1 and F2 generations compared to control. Further, BPA exposure (0.5 μg/kg/day) compromised the fertility index in the F3 generation compared to control. Finally, in utero BPA exposure reduced the ability of female mice to maintain pregnancies as they aged. Collectively, these data suggest that BPA exposure affects reproductive function in female mice and that some effects may be transgenerational in nature. - Highlights: • In utero BPA delayed vaginal opening in the F3 generation compared to control. • In utero BPA delayed estrus in the F3 generation compared to control. • In utero BPA reduced the ability of F1 and F2 female mice to maintain pregnancies. • In utero BPA compromised the ability of F3 female mice to become pregnant. • Some effects of in utero BPA may be transgenerational in nature.« less
Two-generation reproduction and teratology studies of feeding aditoprim in Wistar rats.
Wang, Xu; Tan, Ziqiang; Cheng, Guyue; Awais, Ihsan; Huang, Lingli; Chen, Dongmei; Pan, Yuanhu; Liu, Zhenli; Yuan, Zonghui
2015-12-01
Aditoprim, a new bacteriostatic agent that belongs to diaminopyrimidines, has a broad antimicrobial spectrum, good antibacterial activity and excellent pharmacokinetics. To evaluate the reproductive toxicity and teratogenic potential of aditoprim, different concentrations of aditoprim were administered to Wistar rats by feeding diets containing 0, 20, 100 and 1000 mg kg(-1) , respectively. Each group consisting of 18 males and 25 females (F0 ) was treated with different concentrations of aditoprim through a 13-week period before mating and during mating, gestation, parturition and lactation. At weaning, 20 males and 25 females of the F1 generation weanlings per group were selected randomly as parents for the F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At 1000 mg kg(-1) dose group, body weights in F0 and F1 rats, fetal body weight on day 21 (0, 4 and 21) after birth and number of viable fetuses in the F0 and F1 generation significantly decreased. Teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 parents of the reproduction study were mated after weaning of the F2a pups. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. At 1000 mg kg(-1) group, body weights, fetal body lengths, tail lengths, litter weights and number of viable fetuses were significantly decreased. No obvious external, skeletal or visceral malformations in fetuses were noted in any groups in the teratogenic test. The no-observed-adverse-effect level for reproduction/development toxicity of aditoprim was 100 mg kg(-1) diet (about 7.89-9.25 mg kg(-1) body weight day(-1) ). Copyright © 2015 John Wiley & Sons, Ltd.
Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay
2016-09-01
Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes. © The Author(s) 2016.
Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano
2017-05-01
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. Copyright © 2017 Elsevier Inc. All rights reserved.
Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.
2012-01-01
Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PMID:23049995
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pocar, Paola, E-mail: paola.pocar@unimi.it; Fianda
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring.more » In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP reduced oocyte and blastocyst developmental competence up to F3. • DEHP altered expression levels for key genes in ovary and blastocysts up to F4. • DEHP's adverse effects were observed at doses relevant for human exposure.« less
Wang, Mian-Ying; Hurn, Jenae; Peng, Lin; Nowicki, Diane; Anderson, Gary
2011-01-01
The impact of Morinda citrifolia (noni) juice on fertility and offspring health in three generations of ICR mice was evaluated. The authenticity of the source of noni juice in this study was determined by chemical analysis of known marker compounds. Mice were supplied with 5% noni juice at gestation (day 0) until weaning (21 days postpartum). This procedure was followed through three generations of offspring. Three generations of control mice were also evaluated. There were no intergroup differences in gestation and fertility indices or malformation rates. However, litter sizes of the noni group in the first (F1), second (F2), and third (F3) generations were, respectively, 29.3% (P < 0.01), 19.8% (P < 0.01) and 19.6% (P < 0.01) larger than corresponding controls. Despite larger litter sizes, there were no decreases in fetal weight in any generation of the noni group. Further, maternal health and offspring viability in the noni groups were equal to or greater than the controls. The results of this study suggest that authentic noni juice has no adverse effect on fertility and fetal development, consistent with previous two-generation studies of noni fruit from French Polynesia, Indonesia, and Hainan , China. On the contrary, noni juice appears to facilitate pregnancy and fetal development.
Shasa, Desiree R.; Odhiambo, John F.; Long, Nathan M.; Tuersunjiang, Nuermaimaiti; Nathanielsz, Peter W.; Ford, Stephen P.
2014-01-01
Background/Objectives We have reported that maternal overnutrition/obesity (OB) in sheep resulting from feeding 150% of National Research Council (NRC) requirements throughout gestation, leads to maternal hyperglycemia and hyperinsulinemia. Further, newborn lambs born to OB vs. control-fed (CON, 100% of NRC) ewes exhibited greater adiposity, increased blood cortisol, insulin and glucose and the elimination of the postnatal leptin spike seen in lambs born to CON ewes. This early postnatal leptin peak is necessary for development of hypothalamic circuits which program appetite in later life. This study evaluated the multigenerational impact of OB on insulin:glucose dynamics of mature female F1 offspring fed only to requirements throughout gestation, and on their lambs (F2 generation). Design and Methods Adult F1 female offspring born to OB (n=10) or CON (n=7) ewes were utilized. All F1 ewes were subjected to a glucose tolerance test at midgestation and late gestation. Jugular blood was obtained from F2 lambs at birth (day 1) through postnatal day 11, and plasma glucose, insulin, cortisol and leptin concentrations determined. Dual Energy X-ray Absorptiometry (DEXA) was utilized to determine bone mineral density (BMD), bone mineral content (BMC), lean tissue mass, and fat tissue mass. Results Fasted blood glucose and insulin concentrations were greater (P < 0.05) in OBF1 than CONF1 ewes at mid- and late gestation. Further, after glucose infusion, both glucose and insulin concentrations remained higher in OBF1 ewes (P < 0.05) than CONF1 ewes demonstrating greater insulin resistance. Blood concentrations of glucose, insulin, and cortisol, and adiposity were higher (P < 0.01) in OBF2 lambs than CONF2 lambs at birth. Importantly, OBF2 lambs failed to exhibit the early postnatal leptin peak exhibited by CONF2 lambs. Conclusions These data suggest that these OBF2 lambs are predisposed to exhibit the same metabolic alterations as their mothers, suggesting a multi-generational programming effect. PMID:25354845
2013-01-01
Background Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease. Methods Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm. Results The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity. Conclusions Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance. PMID:24228800
Nizhnikov, Michael E.; Popoola, Daniel O.; Cameron, Nicole M.
2018-01-01
Background Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Transgenerationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. Methods Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation–hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. Results EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. Conclusions Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation–hypnosis across 2 generations. PMID:26876534
Rat two-generation reproduction and dominant lethal study of acrylamide in drinking water.
Tyla, R W; Friedman, M A; Losco, P E; Fisher, L C; Johnson, K A; Strother, D E; Wolf, C H
2000-01-01
Fischer 344 (F344) F(0) weanling rats, 30/sex/group, were exposed to acrylamide in drinking water at 0.0, 0.5, 2.0, or 5.0 mg/kg/day for 10 weeks and then mated. Exposure of F(0) females continued through gestation and lactation of F(1) litters. F(0) males, after F(0) mating, were removed from exposure and mated (one male: two untreated females) for the dominant lethal (DL) assay. Thirty F(l) weanlings/sex/group were exposed for 11 weeks to the same dose levels as their parents, and then mated to produce F(2) offspring. F(0) and F(l) parents and F(1) and F(2) weanlings were necropsied. Prebreeding exposure of F(0) and F(l) animals resulted in systemic toxicity at 2.0 to 5.0 mg/kg/day, with head tilt and/or foot splay increased at 0.5 to 5.0 mg/kg/day. F(0) and F(l) reproductive indices and gestational length were unaffected. Implantations and live pups/litter at birth were reduced at 5.0 mg/kg/day. Survival of F(l) and F(2) pups was reduced at 5.0 mg/kg/day for PND 0 through 4 only. In the DL assay, total and live implants were reduced, pre- and postimplantation loss was increased, and the frequency of DL factors (F(L)%) was increased at 5.0 mg/kg/day. At 5.0 mg/kg/day, adult F(l) male peripheral nerves exhibited axonal fragmentation and/or swelling; F(l) female spinal cord sections were unremarkable. The NOEL for prenatal DL was 2.0 mg/kg/day; the NOEL for adult systemic toxicity, including neurotoxicity, was < or = 0.5 mg/kg/day. Therefore, neurotoxicity and DL were differentially affected.
Nohara, Keiko; Okamura, Kazuyuki; Suzuki, Takehiro; Murai, Hikari; Ito, Takaaki; Shinjo, Keiko; Takumi, Shota; Michikawa, Takehiro; Kondo, Yutaka; Hata, Kenichiro
2016-01-01
Gestational exposure can affect the F2 generation through exposure of F1 germline cells. Previous studies reported that arsenite exposure of only F0 females during their pregnancy increases hepatic tumors in the F1 males in C3H mice, whose males are predisposed spontaneously to develop hepatic tumors later in life. The present study addressed the effects of gestational arsenite exposure on tumorigenesis of the F2 males in C3H mice. Expression analysis of several genes in the normal livers at 53 and 80 weeks of age clearly showed significant changes in the F2 males obtained by crossing gestational arsenite-exposed F1 (arsenite-F1) males and females compared to the control F2 males. Some of the changes were shown to occur in a late-onset manner. Then the tumor incidence was assessed at 75-82 weeks of age in the F2 males obtained by reciprocal crossing between the control and arsenite-F1 males and females. The results demonstrated that the F2 males born to arsenite-F1 males developed tumors at a significantly higher rate than the F2 males born to the control F1 males, irrespective of exposure of F1 females. Gene expressions of hepatocellular carcinoma markers β-catenin (CTNNB1) and interleukin-1 receptor antagonist in the tumors were significantly upregulated in the F2 males born to arsenite-F1 males compared to those born to the control F1 males. These results show that arsenite exposure of only F0 pregnant mice causes late-onset changes and augments tumors in the livers of the F2 males by affecting the F1 male offspring. Copyright © 2015 John Wiley & Sons, Ltd.
Zhao, Fei; Li, Rong; Xiao, Shuo; Honglu, Diao; El Zowalaty, Ahmed E.; Ye, Xiaoqin
2014-01-01
This study investigated potential cumulative effects of multiple pregnancy and multigenerational exposure to dietary ZEA (0, 0.8, 4, or 20 ppm) on female puberty and reproduction in C57BL/6J mice. Multiple pregnancies did not significantly affect litter size or offspring puberty. Significant effects were observed in 20 ppm ZEA-treated females: advanced puberty onset in F0, F1, and F2 generations; decreased implantation rate, pregnancy rate, and litter size, and increased pregnancy gap and gestation period in F1 and F2 generations; and reduced fertility index in F2 generation. F3 females from 0 and 20 ppm groups were split into 0 or 20 ppm ZEA diets at weaning, with advanced puberty onset seen in 0-20 and 20-20 groups and decreased implantation rate observed in 20-20 group. In summary, 20 ppm dietary ZEA advanced puberty onset without obvious cumulative effect and impaired fertility with multigenerational cumulative effect, which could be partially alleviated upon exposure cessation. PMID:24972337
Huang, Yan-Hong; Ye, Ting-Ting; Liu, Chong-Xiao; Wang, Lei; Chen, Yuan-Wen; Dong, Yan
2017-01-01
This study aimed to assess the impact of perinatal high-fat (HF) diet in female Sprague-Dawley rats (F0) on glucose metabolism and islet function in their early life of second-generation of offspring (F2). F0 rats were fed with a standard chow (SC) or HF diet for 8 weeks before mating, up to termination of lactation for their first-generation of offspring (F1-SC and F1-HF). F1 females were mated with normal males at the age of week 11, and producing F2 offspring (F2-SC, F2-HF). All the offspring were fed SC diet after weaning for 3 weeks. The glucose level and islet function of F2 offspring were assessed at the age of week 3 and 12. The F2-HF offspring had a high birth weight and maintained a higher body mass at the age of week 3 and 12, along with an impaired glucose tolerance and lower serum insulin levels compared with the F2-SC. β-cell proliferation was also impaired in the islets of F2-HF rats at the age of week 3 and 12. The pancreatic and duodenal homeobox factor-1 (Pdx1) and Neurogenic differentiation 1 (NeuroD1) expressions were decreased in the islet of F2-HF rats at the age of week 12. Maternal HF diet during pre-gestation, gestation, and lactation in rats could result in the increased body weight and glucose intolerance in their early life of F2 offspring due to impaired β-cell function and proliferation.
Karl, Stephan; Li Wai Suen, Connie S N; Unger, Holger W; Ome-Kaius, Maria; Mola, Glen; White, Lisa; Wangnapi, Regina A; Rogerson, Stephen J; Mueller, Ivo
2015-01-01
Knowledge of accurate gestational age is required for comprehensive pregnancy care and is an essential component of research evaluating causes of preterm birth. In industrialised countries gestational age is determined with the help of fetal biometry in early pregnancy. Lack of ultrasound and late presentation to antenatal clinic limits this practice in low-resource settings. Instead, clinical estimators of gestational age are used, but their accuracy remains a matter of debate. In a cohort of 688 singleton pregnancies from rural Papua New Guinea, delivery gestational age was calculated from Ballard score, last menstrual period, symphysis-pubis fundal height at first visit and quickening as well as mid- and late pregnancy fetal biometry. Published models using sequential fundal height measurements and corrected last menstrual period to estimate gestational age were also tested. Novel linear models that combined clinical measurements for gestational age estimation were developed. Predictions were compared with the reference early pregnancy ultrasound (<25 gestational weeks) using correlation, regression and Bland-Altman analyses and ranked for their capability to predict preterm birth using the harmonic mean of recall and precision (F-measure). Average bias between reference ultrasound and clinical methods ranged from 0-11 days (95% confidence levels: 14-42 days). Preterm birth was best predicted by mid-pregnancy ultrasound (F-measure: 0.72), and neuromuscular Ballard score provided the least reliable preterm birth prediction (F-measure: 0.17). The best clinical methods to predict gestational age and preterm birth were last menstrual period and fundal height (F-measures 0.35). A linear model combining both measures improved prediction of preterm birth (F-measure: 0.58). Estimation of gestational age without ultrasound is prone to significant error. In the absence of ultrasound facilities, last menstrual period and fundal height are among the more reliable clinical measures. This study underlines the importance of strengthening ultrasound facilities and developing novel ways to estimate gestational age.
Narotsky, Michael G; Klinefelter, Gary R; Goldman, Jerome M; Best, Deborah S; McDonald, Anthony; Strader, Lillian F; Suarez, Juan D; Murr, Ashley S; Thillainadarajah, Inthirany; Hunter, E Sidney; Richardson, Susan D; Speth, Thomas F; Miltner, Richard J; Pressman, Jonathan G; Teuschler, Linda K; Rice, Glenn E; Moser, Virginia C; Luebke, Robert W; Simmons, Jane Ellen
2013-09-17
Some epidemiological studies report associations between drinking water disinfection byproducts (DBPs) and adverse reproductive/developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. Using a multigenerational rat bioassay, we evaluated an environmentally relevant "whole" mixture of DBPs representative of chlorinated drinking water, including unidentified DBPs as well as realistic proportions of known DBPs at low-toxicity concentrations. Source water from a water utility was concentrated 136-fold, chlorinated, and provided as drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) continued exposures and were bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight and prenatal loss. No adverse effects were observed for pup weight, prenatal loss, pregnancy rate, gestation length, puberty onset in males, growth, estrous cycles, hormone levels, immunological end points, and most neurobehavioral end points. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These results highlight areas for future research, while the largely negative findings, particularly for pup weight and prenatal loss, are notable.
Yu, Zhenyang; Sun, Guohua; Liu, Yanjun; Yin, Daqiang; Zhang, Jing
2017-01-01
Trans-generational effects are increasingly used to indicate long-term influences of environmental pollutants. However, such studies can be complex and yield inconclusive results. In this study, the trans-generational effects of sulfamethoxazole (SMX) on Caenorhabditis elegans on lifespan, reproduction and population growth were tested for 7 consecutive generations, which included gestating generation (F0), embryo-exposed generation (F1), germline-exposed generation (F2), the first non-exposed generation (F3) and the three following generations (F4-F6). Results showed that lifespan was significantly affected by embryo exposure (F1) at 400µm SMX with a value as low as 47% of the control. The reproduction (a total brood size as 49% of the control) and population growth (81% of the control) were significantly affected in germline exposure (F2). Lifespan and reproduction were severely inhibited in non-exposed generations, confirming the real trans-generational effects. Notably, initial reproduction and reproduction duration showed opposite generation-related changes, indicating their interplay in the overall brood size. The population growth rate was well correlated with median lethal time, brood size and initial reproduction, which indicated that the population would increase when the nematodes lived longer and reproduced more offspring within shorter duration. Copyright © 2016 Elsevier Inc. All rights reserved.
Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K
2012-12-01
Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures. Copyright © 2012 Elsevier Inc. All rights reserved.
Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K
2008-05-01
Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.
Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K
2017-01-01
Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1–F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8–E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1–F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1–F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states. PMID:18304984
A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride.
McGough, Doreen; Jardine, Lynne
2017-01-01
A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl 2 ) via inhalation at concentrations of 0 (air-control); 5, 10 and 20μg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20μg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants. Copyright © 2016 Elsevier B.V. All rights reserved.
Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K
2013-04-01
Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. Copyright © 2012 Elsevier Inc. All rights reserved.
Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K.
2012-01-01
Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. PMID:23453003
Two-generation reproductive toxicity study of implanted depleted uranium (DU) in CD rats.
Arfsten, D P; Still, K R; Wilfong, E R; Johnson, E W; McInturf, S M; Eggers, J S; Schaeffer, D J; Bekkedal, M Y-V
2009-01-01
Depleted uranium (DU) munitions and armor plating have been used in several conflicts over the last 17 yr, including the Persian Gulf War and the Iraq War. Because of its effectiveness and availability, DU will continue to be used in military applications into the foreseeable future. There is much controversy over the use of DU in weapons and equipment because of its potential radiological and toxic hazards, and there is concern over the chronic adverse health effects of embedded DU shrapnel in war veterans and bystanders. This study evaluated the effects of long-term implantation of DU on the reproductive success of F0 generation adults and development and survival of subsequent F1 and F2 generations in a two-generation reproductive toxicity study. F0 generation Sprague-Dawley rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm). Inert implant control animals were implanted with 12 or 20 tantallum (Ta) pellets. The F0 generation was then mated at 120 d post DU implantation. In the F0 generation, when measured on postimplantation d 27 and 117, uranium was present in the urine of DU-implanted animals in a dose-dependent manner. F0 reproductive success was similar across treatment groups and the maternal retrieval test revealed no changes in maternal behavior. DU implantation exerted no effect on the survival, health, or well-being of the F0 generation. Necropsy results of F0 animals were negative with the exception of a marked inflammatory response surrounding the implanted DU pellets. For the F1 generation, measures of F1 development through postnatal day (PND) 20 were unremarkable and no gross abnormalities were observed in F1 offspring. No uranium was detected in whole-body homogenates of PND 4 or PND 20 pups. Necropsy findings of F1 PND 20 pups were negative and no instances of ribcage malformation were observed in F1 PND 20 pups. Body weight and body weight gain of F1 rats through PND 120 were similar across treatment groups. Eight of 414 F1 animals observed from PND 20 to 120 died of unknown causes; 7 were from litters of DU-implanted F0 mating pairs. F1 mating success at 10 wk of age was an overall 70% compared with 91% for F0 mating pairs. Mating success was similar between F1 animals derived from DU-implanted F0 adults and those derived from F0 implant control adults suggesting that the comparatively low mating success was not due to F1 DU exposure. The gestational index of F1 animals derived from mid-dose F0 mating pairs was found to be lower compared with F1 controls. The average gestation duration of F1 animals derived from high-dose F0 mating pairs was found to be significantly longer than F1 controls. F1 sperm motility analyses did not differ among experimental groups and no gross abnormalities were identified at necropsy among surviving F1 animals at PND 120. Histopathology of kidneys, spleen, thymus, bone marrow, ovaries, and testes of F1 high-dose animals did not differ from F1 controls. F1 high-dose females had significantly higher mean relative liver and heart weights compared with F1 controls; the biological relevance of this finding could not be determined. For the F2 generation, measures of F2 development through PND 20 were unremarkable and no gross abnormalities were observed in F2 offspring. Necropsy findings of F2 PND 20 pups were negative and no instances of ribcage malformation were observed in F2 PND 20 pups. Body weight and body weight gain of F2 rats through PND 90 were similar across treatment groups. Mean relative heart weights of males derived from high-dose F0 parents were significantly lower compared with F2 controls. Sperm motility and concentration analysis of F2 males at PND 90 were similar across F2 groups. Overall, the consistent absence of positive findings in this study seems to suggest that DU is not a significant reproductive or developmental hazard, particularly when one considers that mid- and high-dose rats were implanted with the equivalent of 0.3 and 0.5 lb of DU in a 70-kg human, respectively. However, the findings that seven of eight F1 adults that died postweaning were from DU-implanted F0 mating pairs, and that mean relative heart weights were elevated in high-dose F1 and F2 pups, suggest conservatism is warranted in characterizing the reproductive and teratogenic hazards of embedded DU until further studies are completed.
Reis-Silva, Thiago M; Cohn, Daniel W H; Sandini, Thaísa M; Udo, Mariana S B; Teodorov, Elizabeth; Bernardi, Maria Martha
2016-03-15
The objective of the present study was to investigate whether prenatal lipopolysaccharide (LPS) administration modifies the expression of depressive and non-depressive-like behavior in male and female mice across two generations. The sexual dimorphism of these mice was also examined in the open-field test. Male and female mice of the parental (F0) generation were selected for depressive- or non-depressive-like behavioral profiles using the tail suspension test (TST). Animals with similar profiles were matched for further mating. On gestation day (GD) 15, pregnant F0 mice received LPS (100μg/kg, i.p.) and were allowed to nurture their offspring freely. Adult male and female of the F1 generation were then selected according to behavioral profiles and observed in the open field. Male and female mice of the two behavioral profiles were then mated to obtain the F2 generation. Adults from the F2 generation were also behaviorally phenotyped, and open field behavior was assessed. Male mice that were selected for depressive- and non-depressive-like behaviors and treated or not with LPS in the parental generation exhibited similar proportions of behavioral profiles in both filial lines, but LPS exposure increased the number of depressive-like behavior. An effect of gender was observed in the F1 and F2 generations, in which male mice were more sensitive to the intergenerational effects of LPS in the TST. These data indicate that prenatal LPS exposure on GD15 in the F0 generation influenced the transmission of depressive- and non-depressive-like behavior across filial lines, with sexual dimorphism between phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.
Schneider, Steffen; Marxfeld, Heike; Gröters, Sibylle; Buesen, Roland; van Ravenzwaay, Bennard
2013-06-01
The goal of this study was to examine the potential transgenerational inheritance of anti-androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats (Crl:WI[Han]). Dams were dosed with Vinclozolin at 0, 4 or 100mg/kg bw/d on gestation days 6-15. Male offspring of F1-F3 generations were bred with untreated females to yield F2-F4 offspring. No evident anti-androgenic effects were observed at 4mg/kg bw/d, but a case of hypospadias as well as delayed sexual maturation in F1 male offspring was observed as a sign of anti-androgenicity at 100mg/kg bw/d. However, F1-F3 males developed normally to sexual maturity and were able to mate and to generate healthy progeny. Sperm count, morphology and motility were not affected in F1-F4 generation male offspring. In conclusion, transgenerational inheritance of Vinclozolin's anti-androgenic effects was not evident in outbred Wistar rats. Copyright © 2013 Elsevier Inc. All rights reserved.
Gestational exposure to hydroxyprogesterone caproate suppresses reproductive potential in male rats
NASA Astrophysics Data System (ADS)
Pushpalatha, T.; Reddy, P. Ramachandra; Reddy, P. Sreenivasula
2005-08-01
Hydroxyprogesterone caproate was administered to pregnant rats at a dose level of 10 and 25 mg/kg body weight on 1st, 7th and 14th gestational day and the male pups (F1 generation) were allowed to grow for 90 days. The effect of gestational exposure to hydroxyprogesterone caproate on fertility was assessed by breeding F1 male rats with control female rats besides analyzing sperm quality and quantity in F1 male rats. The number of implantation sites and viable fetuses was significantly reduced in females mated with F1 males that were exposed to hydroxyprogesterone caproate during embryonic development. The decrease in sperm function was associated with a decrease in sperm motility, sperm viability and sperm count in F1 rats. The study clearly indicates that in utero exposure to hydroxyprogesterone caproate affects fertility in male rats.
Jacob, Sherin; Thangarajan, Sumathi
2017-06-01
Methyl mercury (MeHg) is a developmental neurotoxin that causes irreversible cognitive damage in offspring of gestationally exposed mothers. Currently, no preventive drugs are established against MeHg developmental neurotoxicity. The neuroprotective effect of gestational administration of a flavanoid against in utero toxicity of MeHg is not explored much. Hence, the present study validated the effect of a bioactive flavanoid, fisetin, on MeHg developmental neurotoxicity outcomes in rat offspring at postnatal weaning age. Pregnant Wistar rats were simultaneously given MeHg (1.5 mg/kg b.w.) and two doses of fisetin (10 and 50 mg/kg b.w. in two separate groups) orally from gestational day (GD) 5 till parturition. Accordingly, after parturition, on postnatal day (PND) 24, weaning F 1 generation rats were studied for motor and cognitive behavioural changes. Biochemical and histopathological changes were also studied in the cerebral cortex, cerebellum and hippocampus on PND 25. Administration of fisetin during pregnancy prevented behavioural impairment due to transplacental MeHg exposure in weaning rats. Fisetin decreased the levels of oxidative stress markers, increased enzymatic and non-enzymatic antioxidant levels and increased the activity of membrane-bound ATPases and cholinergic function in F 1 generation rats. In light microscopic studies, fisetin treatment protected the specific offspring brain regions from significant morphological aberrations. Between the two doses of fisetin studied, 10 mg/kg b.w. was found to be more satisfactory and effective than 50 mg/kg b.w. The present study shows that intake of fisetin during pregnancy in rats ameliorated in utero MeHg exposure-induced neurotoxicity outcomes in postnatal weaning F 1 generation rats.
Ben Maamar, Millissia; Sadler-Riggleman, Ingrid; Beck, Daniel; McBirney, Margaux; Nilsson, Eric; Klukovich, Rachel; Xie, Yeming; Tang, Chong; Yan, Wei; Skinner, Michael K
2018-04-01
Epigenetic transgenerational inheritance of disease and phenotypic variation can be induced by several toxicants, such as vinclozolin. This phenomenon can involve DNA methylation, non-coding RNA (ncRNA) and histone retention, and/or modification in the germline (e.g. sperm). These different epigenetic marks are called epimutations and can transmit in part the transgenerational phenotypes. This study was designed to investigate the vinclozolin-induced concurrent alterations of a number of different epigenetic factors, including DNA methylation, ncRNA, and histone retention in rat sperm. Gestating females (F0 generation) were exposed transiently to vinclozolin during fetal gonadal development. The directly exposed F1 generation fetus, the directly exposed germline within the fetus that will generate the F2 generation, and the transgenerational F3 generation sperm were studied. DNA methylation and ncRNA were altered in each generation rat sperm with the direct exposure F1 and F2 generations being distinct from the F3 generation epimutations. Interestingly, an increased number of differential histone retention sites were found in the F3 generation vinclozolin sperm, but not in the F1 or F2 generations. All three different epimutation types were affected in the vinclozolin lineage transgenerational sperm (F3 generation). The direct exposure generations (F1 and F2) epigenetic alterations were distinct from the transgenerational sperm epimutations. The genomic features and gene pathways associated with the epimutations were investigated to help elucidate the integration of these different epigenetic processes. Our results show that the three different types of epimutations are involved and integrated in the mediation of the epigenetic transgenerational inheritance phenomenon.
Anway, Matthew D; Rekow, Stephen S; Skinner, Michael K
2008-10-01
Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8-14 (E8-E14) to 100mg/kg/day vinclozolin or flutamide at either 5mg or 20mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm numbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the low dose (5mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide.
Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.
2017-01-01
Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8–14 (E8–E14) to 100 mg/kg/day vinclozolin or flutamide at either 5mg or 20 mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreasedepididymal spermnumbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the lowdose (5 mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide. PMID:18762243
Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K
2012-12-01
The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.
Guerrero-Bosagna, Carlos; Covert, Trevor R.; Haque, Md. M.; Settles, Matthew; Nilsson, Eric E.; Anway, Matthew D.; Skinner, Michael K.
2012-01-01
The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. PMID:23041264
Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease
Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I.; Skinner, Michael K.
2012-01-01
The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. PMID:22570695
Catanese, Mary C.
2017-01-01
Estrogenic endocrine disrupting chemicals have been shown to disrupt maternal behavior in rodents. We investigated the effects of an emerging xenoestrogen, bisphenol S (BPS), on maternal behavior and brain in CD-1 mice exposed during pregnancy and lactation (F0 generation) and in female offspring exposed during gestation and perinatal development (F1 generation). We observed different effects in F0 and F1 dams for a number of components of maternal behavior, including time on the nest, time spent on nest building, latency to retrieve pups, and latency to retrieve the entire litter. We also characterized expression of estrogen receptor α in the medial preoptic area (MPOA) and quantified tyrosine hydroxylase immunoreactive cells in the ventral tegmental area, 2 brain regions critical for maternal care. BPS-treated females in the F0 generation had a statistically significant increase in estrogen receptor α expression in the caudal subregion of the central MPOA in a dose-dependent manner. In contrast, there were no statistically significant effects of BPS on the MPOA in F1 dams or the ventral tegmental area in either generation. This work demonstrates that BPS affects maternal behavior and brain with outcomes depending on generation, dose, and postpartum period. Many studies examining effects of endocrine disrupting chemicals view the mother as a means by which offspring can be exposed during critical periods of development. Here, we demonstrate that pregnancy and lactation are vulnerable periods for the mother. We also show that developmental BPS exposure alters maternal behavior later in adulthood. Both findings have potential public health implications. PMID:28005399
Cha, Sunyeong; Baek, Jeong Won; Ji, Hye Jin; Choi, Jun Hee; Kim, Chaelim; Lee, Min Young; Hwang, Yeon Jeong; Yang, Eunhyeok; Lee, Sung-Ho; Jung, Hyo-il; Cheon, Yong-Pil
2017-01-01
ABSTRACT 4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both F0 and F1. In females, NP decreased the weight of ovary and uterus in F0 but not in pre-pubertal F1 pubs. Fertility of male and female in F0 or F1 was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both F0 and F1. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in F0, but significantly decreased in NP 50 group of F1. The litter size and sex ratios of offspring in F1 and F2 were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of F0 and F1 but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations. PMID:28785733
Rahman, Md Saidur; Kwon, Woo-Sung; Karmakar, Polash Chandra; Yoon, Sung-Jae; Ryu, Buom-Yong; Pang, Myung-Geol
2017-02-01
Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood. The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice. Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease. BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases. Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238-245; http://dx.doi.org/10.1289/EHP378.
Rahman, Md Saidur; Kwon, Woo-Sung; Karmakar, Polash Chandra; Yoon, Sung-Jae; Ryu, Buom-Yong; Pang, Myung-Geol
2016-01-01
Background: Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood. Objectives: The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice. Methods: Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease. Results: BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases. Conclusions: Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238–245; http://dx.doi.org/10.1289/EHP378 PMID:27384531
Morita, Osamu; Knapp, John F; Tamaki, Yasushi; Nemec, Mark D; Varsho, Bennett J; Stump, Donald G
2008-09-01
Diacylglycerol (DAG) oil is a novel edible oil with similar taste and usability characteristics as conventional edible oils. Recent studies suggest that DAG oil may be helpful in the prevention and management of obesity. The objective of the present two-generation study was to evaluate potential adverse effects of DAG oil on reproductive processes. DAG oil was administered via gavage to rats (30/sex/group) for at least 70 days prior to mating, at dose levels of 0, 1.25, 2.5 or 5.0 ml/kg/day (0, 1160, 2320 and 4630 mg/kg/day). An additional group received a triacylglycerol (TAG) oil with a similar fatty acid composition to DAG oil. The rats were treated throughout the mating, gestation and lactation periods. Administration of DAG or TAG oil did not reveal any toxicologically significant effects on reproductive performance (mating, fertility and copulation/conception indices). DAG oil did not affect mean gestation lengths, the process of parturition, spermatogenic parameters, organ weights, histopathologic findings, mean numbers of pups born, implantation sites and unaccounted sites. F1 and F2 pup viability, live litter sizes, body weights, mean age of attainment of balanopreputial separation and vaginal patency were similar to those in the control group. Based on the results of this study, a dose level of 5.0 ml/kg (4630 mg/kg/day) was considered as the no-observed-adverse-effect level for reproductive and systemic toxicity, and neonatal toxicity.
Catanese, Mary C; Vandenberg, Laura N
2017-03-01
Estrogenic endocrine disrupting chemicals have been shown to disrupt maternal behavior in rodents. We investigated the effects of an emerging xenoestrogen, bisphenol S (BPS), on maternal behavior and brain in CD-1 mice exposed during pregnancy and lactation (F0 generation) and in female offspring exposed during gestation and perinatal development (F1 generation). We observed different effects in F0 and F1 dams for a number of components of maternal behavior, including time on the nest, time spent on nest building, latency to retrieve pups, and latency to retrieve the entire litter. We also characterized expression of estrogen receptor α in the medial preoptic area (MPOA) and quantified tyrosine hydroxylase immunoreactive cells in the ventral tegmental area, 2 brain regions critical for maternal care. BPS-treated females in the F0 generation had a statistically significant increase in estrogen receptor α expression in the caudal subregion of the central MPOA in a dose-dependent manner. In contrast, there were no statistically significant effects of BPS on the MPOA in F1 dams or the ventral tegmental area in either generation. This work demonstrates that BPS affects maternal behavior and brain with outcomes depending on generation, dose, and postpartum period. Many studies examining effects of endocrine disrupting chemicals view the mother as a means by which offspring can be exposed during critical periods of development. Here, we demonstrate that pregnancy and lactation are vulnerable periods for the mother. We also show that developmental BPS exposure alters maternal behavior later in adulthood. Both findings have potential public health implications. Copyright © 2017 by the Endocrine Society.
Kahr, Maike K; Antony, Kathleen M; DelBeccaro, Melanie; Hu, Min; Aagaard, Kjersti M; Suter, Melissa A
2016-04-01
Obesity is associated with alterations in thyroid hormone (TH) levels in obese, pregnant individuals. The maintenance of TH levels throughout gestation is important for proper foetal development. The aim of this study was to measure levels of fT3, fT4 and TSH in maternal and matched cord blood serum from normal weight, overweight and obese gravidae to determine alterations in maternal and neonatal TH levels by virtue of maternal obesity. ELISA was utilized to measure fT3, fT4 and TSH levels from banked, matched maternal and neonatal (cord blood) serum (N = 205 matched pairs). Data were stratified according to prepregnancy or first trimester BMI. Both maternal and neonatal fT3 levels consistently increased with increasing maternal obesity, and maternal and neonatal fT3 were significantly correlated (r = 0·422, P < 0·001). Maternal and neonatal fT3 were also significantly associated with birthweight (β = 0·155, P = 0·027 and β = 0·171, P = 0·018, respectively). Both the maternal and neonatal fT3 to fT4 ratio significantly increased with increasing maternal obesity. We further found that excess gestational weight gain was associated with a decrease in maternal fT4 compared with gravidae who had insufficient gestational weight gain (0·86 ± 0·17 vs 0·95 ± 0·22, P < 0·01). Maternal obesity is not only associated with maternal alterations in TH, but with accompanying neonatal changes. Because both maternal obesity and alterations in TH levels are associated with childhood obesity, based on these findings and our prior analyses in a nonhuman primate model, we propose that changes in fT3 levels in the offspring of obese mothers may be a potential molecular mediator of foetal overgrowth and childhood obesity. © 2015 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.
Shirai, Tomoyuki; Imai, Norio; Wang, Jianqing; Takahashi, Satoru; Kawabe, Mayumi; Wake, Kanako; Kawai, Hiroki; Watanabe, So-Ichi; Furukawa, Fumio; Fujiwara, Osamu
2014-10-01
The present experimental study was carried out with rats to evaluate the effects of whole body exposure to 2.14 GHz band code division multiple access (W-CDMA) signals for 20 h a day, over three generations. The average specific absorption rate (SAR, in unit of W/kg) for dams was designed at three levels: high (<0.24 W/kg), low (<0.08 W/kg), and 0 (sham exposure). Pregnant mothers (4 rats/group) were exposed from gestational day (GD) 7 to weaning and then their offspring (F1 generation, 4 males and 4 females/dam, respectively) were continuously exposed until 6 weeks of age. The F1 females were mated with F1 males at 11 weeks old, and then starting from GD 7, they were exposed continuously to the electromagnetic field (EMF; one half of the F1 offspring was used for mating, that is, two of each sex per dam and 8 males and 8 females/group, except for all offspring for the functional development tests). This protocol was repeated in the same manner on pregnant F2 females and F3 pups; the latter were killed at 10 weeks of age. No abnormalities were observed in the mother rats (F0 , F1 , and F2 ) and in the offspring (F1 , F2 , and F3 ) in any biological parameters, including neurobehavioral function. Thus, it was concluded that under the experimental conditions applied, multigenerational whole body exposure to 2.14 GHz W-CDMA signals for 20 h/day did not cause any adverse effects on the F1 , F2 , and F3 offspring. © 2014 Wiley Periodicals, Inc.
Long, Nathan M.; Shasa, Desiree R.; Ford, Stephen P.; Nathanielsz, Peter W.
2013-01-01
OBJECTIVE Synthetic glucocorticoid administration to women threatening preterm delivery increases neonatal survival. However, mounting evidence shows that fetal exposure to glucocorticoid levels higher than appropriate for current maturation adversely programs offspring development. We examined fetal synthetic glucocorticoid multigenerational metabolic effects on F1 and F2 female offspring. STUDY DESIGN At 0.7 gestation, pregnant F0 ewes received 4 injections of dexamethasone (2 mg, approximately 60 ug.kg−1 day−1 12 hours apart) or saline (control). F1 female offspring were bred to produce F2 female offspring. Postpubertal pancreatic β-cell function was tested in F1 and F2 by intravenous glucose tolerance test. RESULTS F1 and F2 ewe lambs showed reduced birthweight and morphometrics, and similar increased fasting glucose and decreased intravenous glucose tolerance test β-cell response. CONCLUSION This is the first demonstration of multigenerational programming of later life β-cell response by clinically relevant doses of synthetic glucocorticoid indicating the need for study of long-term effects of fetal exposure to synthetic glucocorticoid. PMID:22939726
Lundkvist, U; Kindahl, H; Madej, A
1987-02-01
The urinary levels of estrone sulfate and 11-ketotetranor prostaglandin F metabolite (11-ketotetranor PGF metabolite) during gestation in guinea pigs were measured by radioimmunoassays. Vehicle and Clophen A50 (polychlorinated biphenyls)-treated animals were compared. Gestation was arbitrarily divided into four periods, and the mean hormone levels during each period were compared between the two treatment groups. The Clophen A50 treatment (100 mg total, during Days 16-60), which causes fetal death, was correlated to significantly higher levels of estrone sulfate (p less than 0.05) and 11-ketotetranor PGF metabolite (p less than 0.01) during Days 47-60 (Period IV) of gestation.
Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.
2013-01-01
Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures. PMID:23359474
Naik, Aijaz A.; Patro, Ishan K.; Patro, Nisha
2015-01-01
Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed. PMID:26696810
Zhong, Chunrong; Li, Xiating; Chen, Renjuan; Zhou, Xuezhen; Liu, Chaoqun; Wu, Jiangyue; Xu, Shangzhi; Wang, Weiye; Xiao, Mei; Xiong, Guoping; Wang, Jing; Yang, Xuefeng; Hao, Liping; Yang, Nianhong
2017-12-01
Gestational diabetes mellitus is associated with adverse short- and long-term consequences for both the mother and the offspring. To examine the relationship between the rates of gestational weight gain (RGWG) during early and mid-pregnancy and the risk of gestational diabetes mellitus (GDM). 2090 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed in our study. Gestational weight were measured regularly in every antenatal visit. Gestational diabetes mellitus was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to estimate effect of RGWG on GDM. A total of 8.3% (n = 173) of pregnant women were diagnosed with GDM. Women with elevated rate of gestational weight gain prior to glucose screening test (RGWG-PG) increased the risk of GDM (adjusted p-trend = 0.004; odds ratios (OR) 1.64, 95% confidence intervals (CI) 1.01-2.68 and OR 2.30,95% CI 1.44-3.66 for 0.297-0.384 kg/wk and 0.385 kg/wk or more vs. 0.213 kg/wk or less, respectively). Women with greater rate of gestational weight gain in the first trimester (RGWG-F) increased the risk of GDM (adjusted p-trend = 0.048; OR 1.83, 95% CI 1.14-2.94 and OR 1.76, 95% CI 1.10-2.83 for 0.086-0.200 kg/wk and 0.201 kg/wk or more vs. -0.025 kg/wk or less, respectively). The rate of gestational weight gain in the second trimester (RGWG-S) was significantly associated with GDM only among women with RGWG-F more than 0.086 kg/wk (adjusted p-trend = 0.035; OR 2.04, 95% CI 1.16-3.59 for 0.658 kg/wk or more vs. 0.418 kg/wk or less). Greater early pregnancy weight gain are associated with increased risk of GDM. Elevated weight gain in mid-pregnancy increased the risk of GDM only among pregnant women with greater weight gain in the first trimester. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Nguyen, Nguyen M; de Oliveira Andrade, Fabia; Jin, Lu; Zhang, Xiyuan; Macon, Madisa; Cruz, M Idalia; Benitez, Carlos; Wehrenberg, Bryan; Yin, Chao; Wang, Xiao; Xuan, Jianhua; de Assis, Sonia; Hilakivi-Clarke, Leena
2017-07-03
Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1-F3 generations were fed only the control diet. Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p < 0.016) and F3 generation offspring of HF diet-fed dams (p < 0.040) than in the control offspring. Further, tumor latency was significantly shorter (p < 0.028) and burden higher (p < 0.027) in F1 generation HF offspring, and similar trends were seen in F3 generation HF offspring. RNA sequencing was done on normal mammary glands to identify signaling differences that may predispose to increased breast cancer risk by maternal HF intake. Analysis revealed 1587 and 4423 differentially expressed genes between HF and control offspring in F1 and F3 generations, respectively, of which 48 genes were similarly altered in both generations. Quantitative real-time polymerase chain reaction analysis validated 13 chosen up- and downregulated genes in F3 HF offspring, but only downregulated genes in F1 HF offspring. Ingenuity Pathway Analysis identified upregulation of Notch signaling as a key alteration in HF offspring. Further, knowledge-fused differential dependency network analysis identified ten node genes that in the HF offspring were uniquely connected to genes linked to increased cancer risk (ANKEF1, IGFBP6, SEMA5B), increased resistance to cancer treatments (SLC26A3), poor prognosis (ID4, JAM3, TBX2), and impaired anticancer immunity (EGR3, ZBP1). We conclude that maternal HF diet intake during pregnancy induces a transgenerational increase in offspring mammary cancer risk in mice. The mechanisms of inheritance in the F3 generation may be different from the F1 generation because significantly more changes were seen in the transcriptome.
Transgenerational Effects of Prenatal Bisphenol A on Social Recognition
Wolstenholme, Jennifer T.; Goldsby, Jessica A.; Rissman, Emilie F.
2014-01-01
Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA–containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders. PMID:24100195
Transgenerational effects of prenatal bisphenol A on social recognition.
Wolstenholme, Jennifer T; Goldsby, Jessica A; Rissman, Emilie F
2013-11-01
Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders. © 2013.
Anway, Matthew D; Skinner, Michael K
2008-04-01
The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.
Anway, Matthew D.; Skinner, Michael K.
2018-01-01
PURPOSE The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. METHODS Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. RESULTS Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1–F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). CONCLUSIONS The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease. PMID:18220299
Tracey, Rebecca; Haque, Md. M.; Skinner, Michael K.
2012-01-01
Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1–F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease. PMID:22389676
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ma, Jing; Chen, Xi; Liu, Yanan
2015-12-01
Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8–14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly withmore » hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue. - Highlights: • Ancestral TCDD exposure induces epigenetic transgenerational inheritance. • Ancestral TCDD exposure affects methylation status in ICR and DMR2 region of Igf2. • DNMTs play a role in TCDD induced epigenetic transgenerational changes of Igf2.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pepe, G.J.; Albrecht, E.D.
1984-11-01
We measured uterine extraction (i.e. metabolism) and transuteroplacental interconversion of cortisol (F) and cortisone (E) to determine whether metabolism across the uterus changes during pregnancy and contributes to the MCR of these corticosteroids. On day 100 (n . 4) or 170 (n . 3) of pregnancy (term . day 184), baboons (Papio anubis; 14-18 kg) were sedated with ketamine, and a constant infusion (0.38 ml/min) of 8-12 microCi (/sup 3/H)F and 9-15 microCi (/sup 14/C)E in 80 ml 0.9% NaCl-1% ethanol was initiated (time zero) via a maternal antecubital vein. At 60 min, animals were laparotomized, and at 70, 80,more » and 90 min, blood samples were obtained from right and left uterine veins and from a maternal saphenous vein. At 95 min, a transverse incision was made in the uterus, the fetus was isolated, and blood samples were obtained from the umbilical vein and artery. The cord was then clamped, and the fetus was delivered. Radio-labeled F and E were extracted from serum and purified by sequential paper chromatography, and metabolic parameters were calculated. Endogenous F and E levels were determined by RIA. In the mother, the percent conversions of E to F at midgestation (mean +/- SE; 72 +/- 4) and late gestation (65 +/- 3) were similar and exceeded (P less than 0.01) respective values for oxidation of F to E (51 +/- 7 and 46 +/- 7, respectively), indicating that maternal corticosteroid metabolism favors F formation and is unchanged during the second half of gestation. In contrast, corticosteroid metabolism across the uterus and placenta (transuteroplacental) was altered during pregnancy. At midgestation, transuteroplacental conversion of E to F (37 +/- 9) exceeded (P less than 0.05) the reverse reaction (18 +/- 3), whereas oxidation of F to E at term (28 +/- 4) was 7-fold greater (P less than 0.05) than reduction of E to F (4 +/- 1).« less
Neri, Isabella; Jasonni, Valerio M; Gori, Gian Franco; Blasi, Immacolata; Facchinetti, Fabio
2006-05-01
To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16-45 years, diagnosis of gestational hypertension without proteinuria (patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine (20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a.m. to 10 a.m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08:00, 12:00, 16:00 and 20:00 h. Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo (systolic values F = 8.59, p < 0.005; diastolic values F = 3.36; p < 0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic (F = 5.42, p < 0.005) and diastolic (F = 2.20, p < 0.005) blood pressure values. In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.
Wolstenholme, Jennifer T.; Edwards, Michelle; Shetty, Savera R. J.; Gatewood, Jessica D.; Taylor, Julia A.; Connelly, Jessica J.
2012-01-01
Bisphenol A (BPA) is a plasticizer and an endocrine-disrupting chemical. It is present in a variety of products used daily including food containers, paper, and dental sealants and is now widely detected in human urine and blood. Exposure to BPA during development may affect brain organization and behavior, perhaps as a consequence of its actions as a steroid hormone agonist/antagonist and/or an epigenetic modifier. Here we show that BPA produces transgenerational alterations in genes and behavior. Female mice received phytoestrogen-free chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented dams were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice, whereas in later generations (F2 and F4), the effect of BPA was to increase these social interactions. Brains from embryos (embryonic d 18.5) exposed to BPA had lower gene transcript levels for several estrogen receptors, oxytocin, and vasopressin as compared with controls; decreased vasopressin mRNA persisted into the F4 generation, at which time oxytocin was also reduced but only in males. Thus, exposure to a low dose of BPA, only during gestation, has immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Heritable effects of an endocrine-disrupting chemical have implications for complex neurological diseases and highlight the importance of considering gene-environment interactions in the etiology of complex disease. PMID:22707478
Bagot, C N; Leishman, E; Onyiaodike, C C; Jordan, F; Freeman, D J
2017-09-01
Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n=22). Blood samples were taken just prior to conception and repeated five times during very early pregnancy, up to Day 59 estimated gestation. Mean Endogenous Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI) increased significantly from pre-pregnancy to Day 43 gestation (p=0.024-0.0004). This change persisted to Day 59 gestation. The mean of the percentage change from baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI increased significantly from pre-pregnancy to Day 32 gestation (p=0.0351-<0.0001) with the mean increase from baseline persisting to Day 59 gestation. Thrombin generation increases significantly during the very early stages of normal pregnancy when compared to the pre-pregnancy state. The increased risk of venous thrombosis therefore likely begins very early in a woman's pregnancy, suggesting that women considered clinically to be at high thrombotic risk should start thromboprophylaxis as early as possible after a positive pregnancy test. Copyright © 2017 Elsevier Ltd. All rights reserved.
Jones, A K; Gately, R E; McFadden, K K; Hoffman, M L; Pillai, S M; Zinn, S A; Govoni, K E; Reed, S A
2017-08-01
To determine the effects of poor maternal nutrition and litter size on foetal growth during mid-gestation, pregnant ewes (n = 82) were fed 100%, 60% or 140% of NRC TDN beginning at day 30.2 ± 0.2 of gestation. Transabdominal ultrasound was performed weekly between day 46.0 ± 0.4 and 86.0 ± 0.7 to monitor foetal heart width (HW), umbilical diameter (UMB), rib width (RW) and placentome outer (OD) and inner diameter (ID). Data were analysed with repeated-measures using the mixed procedure for effects of maternal diet, litter size and gestation, and equations predictive of gestational age were generated using the regression procedure. To determine the agreement of ultrasound measurement and actual size, ewes (n = 20-21) were euthanized at day 45 or 90 to obtain corresponding postmortem measurements for Bland-Altman analysis. The HW, UMB and placentome OD and ID increased with gestation (p < .0001) but were unaffected by maternal diet or litter size (p ≥ .12). Ultrasound underestimated postmortem measurements of HW (14.8%), UMB (7.3%), placentome OD (4.5%) and ID (37.3%) at day 90 of gestation. Ultrasound underestimated RW at day 45 (7.7%) but overestimated RW (23.8%) at day 90, indicating inconsistent bias when reporting RW by ultrasound. Combining the HW, UMB, RW and placentome OD generated the strongest equation predictive of gestational age (R 2 = .91). These findings indicate that during mid-gestation, maternal diet or litter size did not affect HW, UMB or placentome diameters and these factors can be used to estimate gestational age. © 2017 Blackwell Verlag GmbH.
Al-Griw, Mohamed A.; Treesh, Soad A.; Alghazeer, Rabia O.; Regeai, Sassia O.
2017-01-01
Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE) on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day). The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide) in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring generations. Hence, linking observed liver abnormality in the offspring to environmental exposure of their parental line. This study also illustrated that oxidative stress and apoptosis appear to be a molecular component of the hepatocyte cell injury. PMID:28884077
Burgess, Wendy; McIntyre, Jordan P. R.; Gunn, Alistair J.; Lear, Christopher A.; Bennet, Laura; Mitchell, Edwin A.; Thompson, John M. D.
2016-01-01
Key points Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position.Fetal state 1F is more likely to occur in maternal supine or right lateral positions.Fetal state 4F is less likely to occur when the woman lies supine or semi‐recumbent.Fetal state change is more likely when the woman is supine or semi‐recumbent.Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi‐recumbent positions. Abstract Fetal behavioural states (FBS) are measures of fetal wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen consuming state with changes in the cardiotocograph and reduced fetal activity. Recent studies of late gestation stillbirth described the importance of sleep position in the risk of intrauterine death. We designed this study to assess the effects of different maternal positions on FBS in healthy late gestation pregnancies under controlled conditions. Twenty‐nine healthy women had continuous fetal ECG recordings under standardized conditions in four randomly allocated positions, left lateral, right lateral, supine and semi‐recumbent. Two blinded observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate variability were calculated from ECG beat to beat data. Compared to state 2F, state 4F was less likely to occur when women were semi‐recumbent [odds ratio (OR) = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95% CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11, 5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State change was more likely when the mother was semi‐recumbent (OR = 2.17, 95% CI 1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant association of maternal position to mean fetal heart rate. The measures of heart rate variability (SDNN and RMSSD) were reduced in both semi‐recumbent and supine positions. In healthy late gestation pregnancy, maternal position affects FBS and heart rate variability. These effects are likely fetal adaptations to positions which may produce a mild hypoxic stress. PMID:27871127
Stone, Peter R; Burgess, Wendy; McIntyre, Jordan P R; Gunn, Alistair J; Lear, Christopher A; Bennet, Laura; Mitchell, Edwin A; Thompson, John M D
2017-02-15
Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position. Fetal state 1F is more likely to occur in maternal supine or right lateral positions. Fetal state 4F is less likely to occur when the woman lies supine or semi-recumbent. Fetal state change is more likely when the woman is supine or semi-recumbent. Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi-recumbent positions. Fetal behavioural states (FBS) are measures of fetal wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen consuming state with changes in the cardiotocograph and reduced fetal activity. Recent studies of late gestation stillbirth described the importance of sleep position in the risk of intrauterine death. We designed this study to assess the effects of different maternal positions on FBS in healthy late gestation pregnancies under controlled conditions. Twenty-nine healthy women had continuous fetal ECG recordings under standardized conditions in four randomly allocated positions, left lateral, right lateral, supine and semi-recumbent. Two blinded observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate variability were calculated from ECG beat to beat data. Compared to state 2F, state 4F was less likely to occur when women were semi-recumbent [odds ratio (OR) = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95% CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11, 5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State change was more likely when the mother was semi-recumbent (OR = 2.17, 95% CI 1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant association of maternal position to mean fetal heart rate. The measures of heart rate variability (SDNN and RMSSD) were reduced in both semi-recumbent and supine positions. In healthy late gestation pregnancy, maternal position affects FBS and heart rate variability. These effects are likely fetal adaptations to positions which may produce a mild hypoxic stress. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population.
Barcelona de Mendoza, Veronica; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa
2016-06-01
Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = -0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = -0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population.
2010-01-01
Background Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. Results All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P < 0.05) with milk protein concentration and calf perinatal mortality. It had a tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was associated (P < 0.05) with reduced milk fat concentration, reduced milk protein concentration, longer gestation length and tended to associate (P < 0.1) with an increase in calving difficulty, calf perinatal mortality and somatic cells in the milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and gestation length. It also tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and length of gestation. The T allele of the Y7F SNP significantly associated with reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There was also a tendency (P < 0.1) for Y7F to associate with increased body condition score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with reduced survival in the herd (P < 0.05). Conclusions Several leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow. PMID:20670403
Suhail, Mohd; Patil, Shridhar; Khan, Salma; Siddiqui, Sana
2010-12-11
Inconsistent reports are available in the literature regarding the oxidative status and antioxidant capacity during the pathogenesis of gestational diabetes. Present study was aimed to evaluate oxidative stress during the development of gestational diabetes and to evaluate antioxidant capability in non-pregnant (control), pregnant and gestational diabetics. The study consisted of non-pregnant, healthy pregnant and patients suffering from gestational diabetes mellitus (GDM). Each group consisted of 23 women. We compared their oxidative and anti-oxidative system in blood. Their blood malondialdehyde (MDA) and antioxidant vitamins (C, E, A) were determined and compared to evaluate the oxidative status and anti-oxidative capacity of these groups. We have also compared the osmotic fragility profiles of the erythrocytes of these groups. Plasma MDA content in pregnant was significantly higher compared to non-pregnant (p < 0.001, 67.5%) and even in gestational diabetics; its value was found significantly further elevated (p = 0.001, 13.8%) compared to healthy pregnant. There was significant decline (p < 0.001, 41.9%) in the level of vitamin C in pregnant as compared to non-pregnant. Although in GDM the decrease was significant (p = 0.025, 20.6%) but comparatively lesser when compared to healthy pregnant. Vitamin E showed the increase of 9.6% during pregnancy, although this alteration was non-significant (p = 0.09), but the level was found to decline significantly (p < 0.001, 25.5%) in GDM compared to pregnant group. Vitamin A contents were also decreased in pregnant (p = 0.002, 17.4%) compared to non-pregnant and in GDM (p = 0.012, 11.2%) compared to pregnant group. Osmotic fragility (O.F.) profiles showed insignificant (p = 0.325) enhanced mean erythrocyte fragility (MEF) in pregnant but this increase was significant (p = 0.003) in case of GDM. The O.F. profiles of pregnant and GDM erythrocytes got shifted to the right side of the control one. Our findings indicate highly enhanced lipid peroxidation and significant depletion in antioxidant capacity during the development of gestational diabetes, and these alterations are not the cause but the consequence of GDM. However, further studies are warranted to examine a wider range of biochemical parameters to evaluate the potential risks of oxidative damage in GDM. Gestational diabetes; Oxidative stress; Anti-oxidants; Vitamins C, E, A; Osmotic fragility; Non-pregnant; Pregnant; GDM.
Narotsky, Michael G; Klinefelter, Gary R; Goldman, Jerome M; DeAngelo, Anthony B; Best, Deborah S; McDonald, Anthony; Strader, Lillian F; Murr, Ashley S; Suarez, Juan D; George, Michael H; Hunter, E Sidney; Simmons, Jane Ellen
2015-06-01
Trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown. We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay. Sprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generation to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500×, 1,000×, or 2,000× of the U.S. Environmental Protection Agency's maximum contaminant levels (MCLs). Maternal water consumption was reduced at ≥ 1,000×; body weights were reduced at 2,000×. Prenatal and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2,000× on PND6 and at ≥ 1,000× on PND21. Postweaning F1 body weights were reduced at 2,000×, and water consumption was reduced at ≥ 500×. Males at 2,000× had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1,000× and 2,000×. F1 estrous cycles and fertility were unaffected, and F2 litters showed no effects on pup weight or survival. Histologically, P0 (parental) dams had nephropathy and adrenal cortical pathology at 2,000×. A mixture of regulated DBPs at up to 2,000× the MCLs had no adverse effects on fertility, pregnancy maintenance, prenatal survival, postnatal survival, or birth weights. Delayed puberty at ≥ 1,000× may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2,000× may have been secondary to reduced body weights.
Beck, Daniel; Sadler-Riggleman, Ingrid; Skinner, Michael K
2017-07-01
Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation has been shown to involve DNA methylation alterations in the germline (e.g. sperm). These differential DNA methylation regions (DMRs) are termed epimutations and in part transmit the transgenerational phenotypes. The agricultural fungicide vinclozolin exposure of a gestating female rat has previously been shown to promote transgenerational disease and epimutations in F3 generation (great-grand-offspring) animals. The current study was designed to investigate the actions of direct fetal exposure on the F1 generation rat sperm DMRs compared to the F3 transgenerational sperm DMRs. A protocol involving methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (Seq) was used in the current study. Bioinformatics analysis of the MeDIP-Seq data was developed and several different variations in the bioinformatic analysis were evaluated. Observations indicate needs to be considered. Interestingly, the F1 generation DMRs were found to be fewer in number and for the most part distinct from the F3 generation epimutations. Observations suggest the direct exposure induced F1 generation sperm DMRs appear to promote in subsequent generations alterations in the germ cell developmental programming that leads to the distinct epimutations in the F3 generation. This may help explain the differences in disease and phenotypes between the direct exposure F1 generation and transgenerational F3 generation. Observations demonstrate a distinction between the direct exposure versus transgenerational epigenetic programming induced by environmental exposures and provide insights into the molecular mechanisms involved in the epigenetic transgenerational inheritance phenomenon.
Randomized Face-to-Face vs. Home Exercise Interventions in Pregnant Women with Gestational Diabetes
DOWNS, Danielle Symons; DINALLO, Jennifer M.; BIRCH, Leann L.; PAUL, Ian M.; ULBRECHT, Jan S.
2017-01-01
Objectives Evaluate effects of a theoretically-based, semi-intensive (Face-to-Face; F2F) exercise intervention and minimum-contact (Home) exercise intervention to the standard care (Control) on exercise, its motivational determinants, blood glucose levels, and insulin use of pregnant women with gestational diabetes mellitus (GDM). Design Randomized control trial with two intervention arms and control (standard care). Method Participants (N=65) were randomized to a Control (standard prenatal care/GDM dietary counseling), Home (standard care + phone education/support + home exercise), or F2F (standard care + on-site education/support + guided exercise with instructor on 2 days/week) group from ~20 weeks gestation to delivery. Assessments of exercise and motivational determinants were obtained at baseline (20-weeks gestation) and follow-up (32-weeks gestation). Blood glucose levels (fasting/postprandial mg/dL) and insulin use were extrapolated from medical records. Results At the 32-week follow-up, the F2F group had significantly higher exercise min, pedometer steps/day, and motivational determinants (attitude, subjective norm, perceived control, intention) than controls (p’s < .05) and significantly higher exercise min and subjective norm than the Home group (p’s < .05); these effect sizes were medium-large (η2 = .11–.23). There was a medium effect (η2 = .13) on postprandial blood glucose at 36-weeks gestation with the F2F group having lower values than controls. Although not significant, the F2F group started insulin later (33 weeks gestation) than the Home (27 weeks) and Control (31 weeks) groups. Conclusion A theoretically-based, F2F exercise intervention has multiple health benefits and may be the necessary approach for promoting exercise motivation and behavior among GDM women. PMID:28428728
Randomized Face-to-Face vs. Home Exercise Interventions in Pregnant Women with Gestational Diabetes.
Downs, Danielle Symons; Dinallo, Jennifer M; Birch, Leann L; Paul, Ian M; Ulbrecht, Jan S
2017-05-01
Evaluate effects of a theoretically-based, semi-intensive (Face-to-Face; F2F) exercise intervention and minimum-contact (Home) exercise intervention to the standard care (Control) on exercise, its motivational determinants, blood glucose levels, and insulin use of pregnant women with gestational diabetes mellitus (GDM). Randomized control trial with two intervention arms and control (standard care). Participants ( N =65) were randomized to a Control (standard prenatal care/GDM dietary counseling), Home (standard care + phone education/support + home exercise), or F2F (standard care + on-site education/support + guided exercise with instructor on 2 days/week) group from ~20 weeks gestation to delivery. Assessments of exercise and motivational determinants were obtained at baseline (20-weeks gestation) and follow-up (32-weeks gestation). Blood glucose levels (fasting/postprandial mg/dL) and insulin use were extrapolated from medical records. At the 32-week follow-up, the F2F group had significantly higher exercise min, pedometer steps/day, and motivational determinants (attitude, subjective norm, perceived control, intention) than controls ( p 's < .05) and significantly higher exercise min and subjective norm than the Home group ( p 's < .05); these effect sizes were medium-large (η 2 = .11-.23). There was a medium effect (η 2 = .13) on postprandial blood glucose at 36-weeks gestation with the F2F group having lower values than controls. Although not significant, the F2F group started insulin later (33 weeks gestation) than the Home (27 weeks) and Control (31 weeks) groups. A theoretically-based, F2F exercise intervention has multiple health benefits and may be the necessary approach for promoting exercise motivation and behavior among GDM women.
An extended one-generation reproductive toxicity test of 1,2,4-Triazol-5-one (NTO) in rats.
Lent, Emily May; Crouse, Lee C B; Jackovitz, Allison M; Carroll, Erica E; Johnson, Mark S
2016-01-01
Nitrotriazolone (1,2,4-triazol-5-one; NTO), an insensitive, energetic material used in explosive formulations, induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests in rats. To evaluate whether NTO produces additional reproductive and developmental effects, a modified extended one-generation reproductive toxicity test was conducted. Rats were provided ad libitum access to NTO in drinking water at 0-, 144-, 720-, or 3600-mg/L NTO. Treatment of the parental generation began 2 (females) and 4 (males) wk premating and continued until weaning of litters. Direct dosing of offspring (F1) occurred from weaning through puberty. Pups were counted and weighed on postnatal day (PND) 0/1. Anogenital distance (AGD) was measured on PND 4 and males were examined for presence of nipples on PND 13. F1 offspring were examined daily for attainment of puberty. NTO did not markedly affect measures of fertility, including mating indices, gestation index, litter size, and sex ratio. Seminiferous tubule degeneration or atrophy was observed in P1 and F1 3600-mg/L NTO males. F1 males in the 3600 mg/L group exhibited reduced reproductive organ mass (testes, epididymides, and accessory sex organs). Nipple retention was increased in NTO exposed F1 males compared to controls. Attainment of puberty was delayed by 2.6 d in the 3600-mg/L NTO-exposed males relative to controls. Comparison of the effects of NTO with those of antiandrogens suggests absence of malformations of the genital tract in NTO-exposed males. This study supports previous findings indicating that NTO is a testicular toxicant with male developmental effects that may be secondary to testicular toxicity.
Biological studies of swine exposed to 60-Hz electric fields. Volume 7. Neurology. Final report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1985-12-01
Neurophysiological responses in three generations of miniature swine chronically exposed to a 30-kV/m, 60-Hz electric field have been assessed in a series of screening experiments. Results are presented from experiments on peripheral nerve function in parental (F/sub 0/) female swine at 100 days of gestation, and from experiments on synaptic transmission in first- and second-generation (F/sub 1/ and F/sub 2/) progeny at 6 weeks of age, all following chronic exposure to a 60-Hz electric field. In the several measures of peripheral nerve function examined, only two showed consistent differences between exposed and sham-exposed animals: C-fiber (but not B-fiber) conduction velocitymore » was decreased in nerve preparations from exposed swine, and recovery, as measured by the increase in amplitude of the compound action potential, was consistently, although not statistically, less in B- and C-fibers from exposed animals when compared to values for the sham-exposed controls. Although changes (increases or decreases) in various parameters of synaptic transmission were observed between exposed and sham-exposed groups, the differences were not consistent across experiments or generations. Only one measure of synaptic function showed a consistent difference throughout the studies: the conduction velocities of B and C components of the postsynaptic compound action potential were increased following electric-field exposure (statistically significant only in B-fibers of the F/sub 2/ generations). 7 refs., 60 figs., 17 tabs.« less
Liu, J; Wang, Y; Su, J; Luo, Y; Quan, F; Zhang, Y
2013-08-01
Total five ear skin fibroblast lines (named F1, F2, F3, F4 and F5) from different newborn Holstein cows have been used as nuclear donor cells for producing cloned cows by somatic cell nuclear transfer (SCNT). The effects of these cell lines on both in vitro and in vivo developmental rates of cloned embryos, post-natal survivability and incidence of large offspring syndrome (LOS) were examined in this study. We found that the different cell lines possessed the same capacity to support pre-implantation development of cloned embryos, the cleavage and blastocyst formation rates ranged from 80.2 ± 0.9 to 84.5 ± 2.5% and 28.5 ± 0.9 to 33.3 ± 1.4%, respectively. However, their capacities to support the in vivo development of SCNT embryos showed significant differences (p < 0.05). The pregnancy rates at 90 and 240 day were significantly lower in groups F2 (4.9% and 3.3%) and F3 (5.4% and 5.4%) compared to groups F1 (23.3% and 16.3%), F4 (25.7% and 18.6%) and F5 (25.9% and 19.8%) (p < 0.05). The cloning efficiency was significantly higher in group F5 than those in group F1, F2, F3 and F4 (9.3% vs 4.1%, 1.2%, 2.0% and 5.0%, respectively, p < 0.05). Moreover, large offspring syndrome (LOS) incidence in group F5 was significantly lower than those in other groups (p < 0.05). All cloned offspring from cell line F1, F2, F3 and F4 showed LOS and gestation length delay, while all cloned offspring from F5 showed normal birthweight and gestation length. We concluded that the nuclear donor cell lines have significant impact on the in vivo development of cloned embryos and the incidence of LOS in cloned calves. © 2013 Blackwell Verlag GmbH.
Fuchs, A R; Rollyson, M K; Meyer, M; Fields, M J; Minix, J M; Randel, R D
1996-03-01
Brahman cows with known breeding dates received i.v. injections of either 10 or 100 IU oxytocin (OT) on Days 50, 150, 250, or 280 of gestation (n = 6 for each stage). Concentrations of the prostaglandin (PG) F2 alpha metabolite, 13,14-dihydro-15-keto-prostaglandin (PGFM), and OT were measured in samples of peripheral plasma collected at 15-min intervals for 1 h before and 1 h after treatment and then at 30-min intervals for 3 h. Plasma progesterone was measured daily for 14 days after OT injections on Days 50 and 250 of gestation. The increase in plasma OT after injection was dose-dependent (p = 0.001) but not affected by stage of gestation. Plasma PGFM increased after OT in a dose- and stage-dependent manner (p = 0.0001). At Day 280, the increase in plasma PGFM after 100 IU OT was sevenfold greater than at Day 50. Plasma progesterone declined significantly during the 7th to 12th days postinjection and returned to normal pregnancy values by the 14th day (4.4 +/- 0.3 ng/ml) except in two cows treated on Day 50 of gestation that later aborted. In these, plasma progesterone was significantly lower, 2.6 +/- 0.1 ng/ml. In a second experiment, the concentration of OT receptors was determined in endometrium collected from purebred Angus or Hereford cows slaughtered on Days 50, 150, 250, and 280 of gestation (n = 3 or 4 at each stage). Endometrial concentrations of OT receptor changed as a function of gestational age, increasing sixfold from Day 50 to Day 280, which was parallel to the increase by OT of plasma PGFM. Thus, endometrial OT receptors are functionally coupled to PGF2 alpha release during pregnancy, and their concentration determines the magnitude of OT-induced PGF2 alpha release during gestation. Consequently, endogenous OT is a factor in the regulation of PGF2 alpha release from the bovine uterus during pregnancy and parturition.
Schneider, Steffen; Kaufmann, Wolfgang; Strauss, Volker; van Ravenzwaay, Bennard
2011-02-01
Feasibility of the ILSI-HESI (ACSA) extended one-generation protocol was tested with vinclozolin (dietary 0, 4, 20, 100mg/kg/day). Parental Wistar rats (n=25/sex/dose) were dosed pre-mating (males 4, females 2 weeks) through F1 offspring weaning (postnatal day PND21); F1 dosing continued through PND70. At PND21, 3 subsets (each 1 pup/sex/litter) were selected for neurotoxicology (functional observational battery, motor activity, neuropathology), clinical pathology (hematology, clinical chemistry, urinalysis, thyroid hormone assay) (subsets 1a, 1b; each n=10/sex/dose), immunotoxicology (IgM) SRBC antibody response and natural killer cell assays (subset 2; n=25/sex/dose), and estrus cycle (subset 3; n=25/dose). Vinclozolin reduced parental and offspring bodyweight and prostate, seminal vesicles and epididymides weight, and increased adrenal weight/induced adrenal cortical hypertrophy at 100mg/kg. Mating, fertility, gestation and lactation were unaffected. At 20 and 100mg/kg, F1 males had reduced anogenital distance and retained areolae; at 100mg/kg only, there was hypospadias, purulent prostatitis and seminal vesicle inflammation with atrophy, and Leydig cell hyperplasia, and in F1 females accelerated vaginal opening. These effects are consistent with vinclozolin's known anti-androgenic developmental effects. Neuro- and immunotoxicology tests were unaffected. F1 Only T4 was reduced at 20 and 100mg/kg. The overall sensitivity of the extended one-generation protocol is comparable to or even greater than the current two-generation study. Thus it reduces animal use while maintaining or enhancing information for risk assessment. Copyright © 2010 Elsevier Inc. All rights reserved.
Zhou, Changqing; Gao, Liying; Flaws, Jodi A
2017-06-01
Phthalates are used in consumer products and are known endocrine-disrupting chemicals. However, limited information is available on the effects of phthalate mixtures on female reproduction. Previously, we developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% di-isononyl phthalate, 8% di-isobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture on reproductive outcomes in first-filial-generation (F1) female mice and found that it impaired reproductive outcomes. However, the impact of this exposure on second-filial-generation (F2) and third-filial-generation (F3) females was unknown. Thus, we hypothesized that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 µg/kg/d, 200 and 500 mg/kg/d) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to generate the F2 generation and adult F2 females born to F1 females were used to generate the F3 generation. F2 and F3 females were subjected to tissue collections and fertility tests. Prenatal phthalate mixture exposure increased uterine weight, anogenital distance, and body weight; induced cystic ovaries; and caused fertility complications in the F2 generation. It also increased uterine weight, decreased anogenital distance, and caused fertility complications in the F3 generation. These data suggest that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Copyright © 2017 Endocrine Society.
Zhou, Changqing; Gao, Liying
2017-01-01
Phthalates are used in consumer products and are known endocrine-disrupting chemicals. However, limited information is available on the effects of phthalate mixtures on female reproduction. Previously, we developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% di-isononyl phthalate, 8% di-isobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture on reproductive outcomes in first-filial-generation (F1) female mice and found that it impaired reproductive outcomes. However, the impact of this exposure on second-filial-generation (F2) and third-filial-generation (F3) females was unknown. Thus, we hypothesized that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 µg/kg/d, 200 and 500 mg/kg/d) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to generate the F2 generation and adult F2 females born to F1 females were used to generate the F3 generation. F2 and F3 females were subjected to tissue collections and fertility tests. Prenatal phthalate mixture exposure increased uterine weight, anogenital distance, and body weight; induced cystic ovaries; and caused fertility complications in the F2 generation. It also increased uterine weight, decreased anogenital distance, and caused fertility complications in the F3 generation. These data suggest that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. PMID:28368545
DOE Office of Scientific and Technical Information (OSTI.GOV)
Inawaka, Kunifumi; Kawabe, Mayumi; DIMS Institute of Medical Science, Inc., Ichinomiya
To verify whether anti-androgens cause transgenerational effects on spermatogenesis and DNA methylation in rats, gravid Crl:CD(SD) female rats (4 or 5/group, gestational day (GD) 0 = day sperm detected) were intraperitoneally treated with anti-androgenic compounds, such as vinclozolin (100 mg/kg/day), procymidone (100 mg/kg/day), or flutamide (10 mg/kg/day), from GD 8 to GD 15. Testes were collected from F1 male pups at postnatal day (PND) 6 for DNA methylation analysis of the region (210 bp including 7 CpG sites) within the lysophospholipase gene by bisulfite DNA sequencing method. F0 and F1 males underwent the sperm analysis (count, motility and morphology), followedmore » by DNA methylation analysis of the sperm. Remaining F1 males were cohabited with untreated-females to obtain F2 male pups for subsequent DNA methylation analysis of the testes at PND 6. These analyses showed no effects on spermatogenesis and fertility in F1 males of any treatment group. DNA methylation status in testes (F1 and F2 pups at PND 6) or sperms (F1 males at 13 weeks old) of the treatment groups were comparable to the control at all observation points, although DNA methylation rates in testes were slightly lower than those in sperm. In F0 males, no abnormalities in the spermatogenesis, fertility and DNA methylation status of sperm were observed. No transgenerational abnormalities of spermatogenesis and DNA methylation status caused by anti-androgenic compounds were observed.« less
Inawaka, Kunifumi; Kawabe, Mayumi; Takahashi, Satoru; Doi, Yuko; Tomigahara, Yoshitaka; Tarui, Hirokazu; Abe, Jun; Kawamura, Satoshi; Shirai, Tomoyuki
2009-06-01
To verify whether anti-androgens cause transgenerational effects on spermatogenesis and DNA methylation in rats, gravid Crl:CD(SD) female rats (4 or 5/group, gestational day (GD) 0=day sperm detected) were intraperitoneally treated with anti-androgenic compounds, such as vinclozolin (100 mg/kg/day), procymidone (100 mg/kg/day), or flutamide (10 mg/kg/day), from GD 8 to GD 15. Testes were collected from F1 male pups at postnatal day (PND) 6 for DNA methylation analysis of the region (210 bp including 7 CpG sites) within the lysophospholipase gene by bisulfite DNA sequencing method. F0 and F1 males underwent the sperm analysis (count, motility and morphology), followed by DNA methylation analysis of the sperm. Remaining F1 males were cohabited with untreated-females to obtain F2 male pups for subsequent DNA methylation analysis of the testes at PND 6. These analyses showed no effects on spermatogenesis and fertility in F1 males of any treatment group. DNA methylation status in testes (F1 and F2 pups at PND 6) or sperms (F1 males at 13 weeks old) of the treatment groups were comparable to the control at all observation points, although DNA methylation rates in testes were slightly lower than those in sperm. In F0 males, no abnormalities in the spermatogenesis, fertility and DNA methylation status of sperm were observed. No transgenerational abnormalities of spermatogenesis and DNA methylation status caused by anti-androgenic compounds were observed.
Skinner, Michael K.; Haque, Carlos Guerrero-Bosagna M.; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R.
2013-01-01
A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. PMID:23869203
Sanderson, J L; Nichols, H J; Marshall, H H; Vitikainen, E I K; Thompson, F J; Walker, S L; Cant, M A; Young, A J
2015-10-01
Dominant females in social species have been hypothesized to reduce the reproductive success of their subordinates by inducing elevated circulating glucocorticoid (GC) concentrations. However, this 'stress-related suppression' hypothesis has received little support in cooperatively breeding species, despite evident reproductive skews among females. We tested this hypothesis in the banded mongoose (Mungos mungo), a cooperative mammal in which multiple females conceive and carry to term in each communal breeding attempt. As predicted, lower ranked females had lower reproductive success, even among females that carried to term. While there were no rank-related differences in faecal glucocorticoid (fGC) concentrations prior to gestation or in the first trimester, lower ranked females had significantly higher fGC concentrations than higher ranked females in the second and third trimesters. Finally, females with higher fGC concentrations during the third trimester lost a greater proportion of their gestated young prior to their emergence from the burrow. Together, our results are consistent with a role for rank-related maternal stress in generating reproductive skew among females in this cooperative breeder. While studies of reproductive skew frequently consider the possibility that rank-related stress reduces the conception rates of subordinates, our findings highlight the possibility of detrimental effects on reproductive outcomes even after pregnancies have become established. © 2015 The Authors.
Valentino, Sarah A; Tarrade, Anne; Aioun, Josiane; Mourier, Eve; Richard, Christophe; Dahirel, Michèle; Rousseau-Ralliard, Delphine; Fournier, Natalie; Aubrière, Marie-Christine; Lallemand, Marie-Sylvie; Camous, Sylvaine; Guinot, Marine; Charlier, Madia; Aujean, Etienne; Al Adhami, Hala; Fokkens, Paul H; Agier, Lydiane; Boere, John A; Cassee, Flemming R; Slama, Rémy; Chavatte-Palmer, Pascale
2016-07-26
Airborne pollution is a rising concern in urban areas. Epidemiological studies in humans and animal experiments using rodent models indicate that gestational exposure to airborne pollution, in particular diesel engine exhaust (DE), reduces birth weight, but effects depend on exposure duration, gestational window and nanoparticle (NP) concentration. Our aim was to evaluate the effects of gestational exposure to diluted DE on feto-placental development in a rabbit model. Pregnant females were exposed to diluted (1 mg/m(3)), filtered DE (NP diameter ≈ 69 nm) or clean air (controls) for 2 h/day, 5 days/week by nose-only exposure (total exposure: 20 days in a 31-day gestation). DE exposure induced early signs of growth retardation at mid gestation with decreased head length (p = 0.04) and umbilical pulse (p = 0.018). Near term, fetal head length (p = 0.029) and plasma insulin and IGF1 concentrations (p = 0.05 and p = 0.019) were reduced. Placental function was also affected, with reduced placental efficiency (fetal/placental weight) (p = 0.049), decreased placental blood flow (p = 0.009) and fetal vessel volume (p = 0.002). Non-aggregated and "fingerprint" NP were observed at various locations, in maternal blood space, in trophoblastic cells and in the fetal blood, demonstrating transplacental transfer. Adult female offspring were bred with control males. Although fetoplacental biometry was not affected near term, second generation fetal metabolism was modified by grand-dam exposure with decreased plasma cholesterol (p = 0.008) and increased triglyceride concentrations (p = 0.015). Repeated daily gestational exposure to DE at levels close to urban pollution can affect feto-placental development in the first and second generation.
Acculturation and gestational weight gain in a predominantly Puerto Rican population.
Tovar, Alison; Chasan-Taber, Lisa; Bermudez, Odilia I; Hyatt, Raymond R; Must, Aviva
2012-11-21
Identifying risk factors that affect excess weight gain during pregnancy is critical, especially among women who are at a higher risk for obesity. The goal of this study was to determine if acculturation, a possible risk factor, was associated with gestational weight gain in a predominantly Puerto Rican population. We utilized data from Proyecto Buena Salud, a prospective cohort study of Hispanic women in Western Massachusetts, United States. Height, weight and gestational age were abstracted from medical records among participants with full-term pregnancies (n=952). Gestational weight gain was calculated as the difference between delivery and prepregnancy weight. Acculturation (measured via a psychological acculturation scale, generation in the US, place of birth and spoken language preference) was assessed in early pregnancy. Adjusting for age, parity, perceived stress, gestational age, and prepregnancy weight, women who had at least one parent born in Puerto Rico/Dominican Republic (PR/DR) and both grandparents born in PR/DR had a significantly higher mean total gestational weight gain (0.9 kg for at least one parent born in PR/DR and 2.2 kg for grandparents born in PR/DR) and rate of weight gain (0.03 kg/wk for at least one parent born in PR/DR and 0.06 kg/wk for grandparents born in PR/DR) vs. women who were of PR/DR born. Similarly, women born in the US had significantly higher mean total gestational weight gain (1.0 kg) and rate of weight gain (0.03 kg/wk) vs. women who were PR/ DR born. Spoken language preference and psychological acculturation were not significantly associated with total or rate of pregnancy weight gain. We found that psychological acculturation was not associated with gestational weight gain while place of birth and higher generation in the US were significantly associated with higher gestational weight gain. We interpret these findings to suggest the potential importance of the US "obesogenic" environment in influencing unhealthy pregnancy weight gains over specific aspects of psychological acculturation.
Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats
Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.
2010-01-01
This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concentrations of 0 (control), 0.15, 1.5, 75, 750, and 2250 ppm daily from gestation day 0 through lactation day 21. F1 offspring were evaluated using the following tests: detailed clinical observations (postnatal days [PNDs] 4, 11, 21, 35, 45, and 60), auditory startle (PNDs 20 and 60), motor activity (PNDs 13, 17, 21, and 61), learning and memory using the Biel water maze (PNDs 22 and 62), and brain and nervous system neuropathology and brain morphometry (PNDs 21 and 72). For F1 offspring, there were no treatment-related neurobehavioral effects, nor was there evidence of neuropathology or effects on brain morphometry. Based on maternal and offspring body weight reductions, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was 75 ppm (5.85 and 13.1 mg/kg/day during gestation and lactation, respectively), with no treatment-related effects at lower doses or nonmonotonic dose responses observed for any parameter. There was no evidence that BPA is a developmental neurotoxicant in rats, and the NOAEL for developmental neurotoxicity was 2250 ppm, the highest dose tested (164 and 410 mg/kg/day during gestation and lactation, respectively). PMID:20164145
First-trimester prediction of birth weight.
Boucoiran, Isabelle; Djemli, Anissa; Taillefer, Catherine; Rypens, Françoise; Delvin, Edgard; Audibert, François
2013-09-01
To determine whether the parameters used in first-trimester screening for aneuploidies contribute significantly to the prediction of birth weight. In this retrospective cohort study (n = 4110), nuchal translucency (NT), free β-chorionic gonadotropin (fβ-hCG), and pregnancy-associated plasma protein-A (PAPP-A) blood concentrations were measured between 11 + 0 and 13 + 6 weeks. Multiple pregnancies, chromosomal anomalies, major fetal defects, and deliveries before 24 weeks were excluded. NT (0.95 versus 0.98 multiples of the expected median [MoM], p < 0.001) and PAPP-A (0.93 versus 1.06 MoM, p = 0.005) were significantly lower in small-for-gestational-age (SGA) newborns (<10th percentile) than the unaffected group, but not fβ-hCG (0.89 versus 0.93 MoM, p = 0.113). NT was significantly higher (1.03 versus 0.98 MoM, p < 0.001) in the large-for-gestational-age (LGA) group (>90th percentile) compared with the unaffected group, and biomarkers did not differ. After controlling for gestational age, maternal weight, smoking status, ethnicity, and fetal sex, first-trimester markers contributed to the prediction of birth weight in a multiple linear model but did not significantly improved the prediction of SGA and LGA compared with maternal characteristics alone. Parameters used in first-trimester screening for aneuploidies contribute to the prediction of birth weight but their clinical utility to detect women at risk of SGA or LGA baby is limited. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Nallagatla, Himaja; Hemalatha, Rajkumar; Kondapalli, Narendra Babu; Mohammed, Shujauddin
2017-06-01
Prebiotics from various regularly consumed cereals and novel substrates are currently being utilised as functional foods. The aim of this study was to determine the effect of synbiotic, formulated with prebiotic extracted from natural resources like green gram (Vigna radiata) along with probiotic Lactobacillus rhamnosus GG (LGG) in modulating immune responses in the offspring when supplemented during gestation and lactation. Synbiotic supplementation was effective in improving cell mediated immunity and humoral immunity among F0 dams. Among F1 pups (F1 Syn + and F1 Syn-), synbiotic supplementation showed significantly heightened (P < 0.05) splenocyte proliferation, increased interleukin-10, interferon gamma and interleukin-17 responses, leucocyte phagocytic ability and increased secretory-immunoglobulin A. However, four-fold increase in IgG titres to Hepatitis-B vaccine was observed only in those mice that were supplemented with synbiotic postweaning (F1 Syn+). Synbiotic supplementation to pregnant dams affected the offspring's cellular and mucosal immunity favorably. However, IgG response to Hepatitis-B vaccine was influenced positively only when the supplementation was extended to the offsprings in the post weaning period. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
Skinner, Michael K; Ben Maamar, Millissia; Sadler-Riggleman, Ingrid; Beck, Daniel; Nilsson, Eric; McBirney, Margaux; Klukovich, Rachel; Xie, Yeming; Tang, Chong; Yan, Wei
2018-02-27
Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm. Gestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated. DNA methylation and ncRNA were altered in each generation sperm with the direct exposure F1 and F2 generations being predominantly distinct from the F3 generation epimutations. The piRNA and small tRNA were the most predominant classes of ncRNA altered. A highly conserved set of histone retention sites were found in the control lineage generations which was not significantly altered between generations, but a large number of new histone retention sites were found only in the transgenerational generation DDT lineage sperm. Therefore, all three different epigenetic processes were concurrently altered as DDT induced the epigenetic transgenerational inheritance of sperm epimutations. The direct exposure generations sperm epigenetic alterations were distinct from the transgenerational sperm epimutations. The genomic features and gene associations with the epimutations were investigated to help elucidate the integration of these different epigenetic processes. Observations demonstrate all three epigenetic processes are involved in transgenerational inheritance. The different epigenetic processes appear to be integrated in mediating the epigenetic transgenerational inheritance phenomenon.
Jin, S S; Jin, Y H; Jang, J C; Hong, J S; Jung, S W; Kim, Y Y
2018-03-01
This experiment was to evaluate the effects of the dietary energy levels on the physiological parameters and reproductive performance during gestation over three parities in sows. A total of 52 F1 gilts (Yorkshire×Landrace) were allotted to one of four dietary treatments using a completely randomized design. The treatments contained 3,100, 3,200, 3,300, or 3,400 kcal of metabolizable energy (ME)/kg diet but feed was provided at 2.0, 2.2, and 2.4 kg/d in the first, second and third parity, respectively. The body weight and body weight gain during gestation increased as the dietary energy level increased (p<0.05, and p<0.01) in the first parity. In the second parity, the body weight of sows was the lowest (p<0.05) when 3,100 kcal of ME/kg treatment diet was provided. The body weight was higher as the dietary energy level increased (p<0.05) during the gestation period in the third parity. During lactation, the voluntary feed intake of lactating sows tended to decrease when gilts were fed higher energy treatment diet (p = 0.08) and the body weight, body weight gain were increased by dietary energy level during gestation (p< 0.05). Backfat thickness was not affected by dietary treatment during the gestation period in three parities, interestingly backfat change from breeding to d 110 of gestation was higher as the dietary energy level increased at the first parity (p<0.05). When gilts were fed 3,400 kcal of ME/kg treatment diet a higher number of weaning piglets was observed in the first parity (p<0.05). The highest culling rate (69%) was seen when gestating sows were fed 3,100 kcal/kg ME treatment diet during three parities. In conclusion, the adequate energy intake of gestating sows should be 6,400 or 6,600 kcal of ME/d, 7,040 or 7,260 kcal of ME/d, and 7,680 or 7,920 kcal of ME/d for parity 1, 2, and 3, respectively.
Neonatal oxidative stress depends on oxygen blood pressure in umbilical artery.
Proietti, F; De Bernardo, G; Longini, M; Sordino, D; Scaramuzzini, G; Tataranno, M L; Belvisi, E; Bazzini, F; Perrone, S; Buonocore, G
2016-01-01
With advancing gestation, partial pressure of oxygen (pO2) and pH fall significantly. Hypoxia is a main factor inducing free radical generation and thereby oxidative stress (OS). Placental and fetal tissue response when oxygen becomes restricted is complex and partially known. We tested the hypothesis that changes in umbilical artery and vein blood gas concentrations modulate OS occurrence in the newborn. Seventy umbilical artery and vein plasma samples were collected from healthy term newborns immediately after delivery. F2 Isoprostanes (F2-Isop) were measured in all samples as reliable markers of lipid peroxidation. Significantly lower pCO2 and higher pO2 and pH were found in umbilical vein than in artery, as expected. A positive correlation was detected between pH and pO2 only in umbilical artery (p=0.019). F2-Isop levels were no different between artery and vein in cord blood. Significant correlations were found between F2-Isop and pCO2 (p=0.025) as well as between F2-Isop and pH in umbilical vein (p=0.027). F2-Isop correlated with pCO2 (p=0.007) as well as with pO2 values (p=0.005) in umbilical artery blood. Oxidative stress (OS) in newborns depends on oxygen concentrations in umbilical artery. OS biomarkers significantly correlate with pO2 and in umbilical artery but not in umbilical vein. In normoxic conditions fetal-maternal gas exchanges occurring in placenta re-establish normal higher oxygen levels in umbilical vein than artery, with a normal production of free radicals without any deleterious effects.
León, Gemma; Murcia, Mario; Rebagliato, Marisa; Álvarez-Pedrerol, Mar; Castilla, Ane M; Basterrechea, Mikel; Iñiguez, Carmen; Fernández-Somoano, Ana; Blarduni, Elizabeth; Foradada, Carles M; Tardón, Adonina; Vioque, Jesús
2015-03-01
Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery. We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4 < 5 th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4 > 95 th percentile and TSH normal), and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery. An inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (β = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes. High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range. © 2015 John Wiley & Sons Ltd.
Schneider, Steffen; Kaufmann, Wolfgang; Buesen, Roland; van Ravenzwaay, Bennard
2008-04-01
The purpose of the study was to investigate a possible transgenerational effect of the fungicide vinclozolin on the male reproductive system following oral exposure since this effect was reported by Anway et al. [Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005;308(5727 (June 3)):1466-9] after intraperitoneal administration. Pregnant Wistar rats were dosed by oral gavage with vinclozolin 0, 4 or 100mg/(kg bw day) on days 6-15 post coitum (p.c.). F1 male offspring was mated with untreated females to produce F2, which were then similarly mated to produce F3 offspring. F0 maternal treatment had no effect on mating and fertility indices or male offspring sexual development, mean sperm parameters, or histopathology of the sexual organs in F1, F2 or F3 males (at age 127-134 days). Apoptotic germ cell counts were statistically significantly lower in F1, F2 and F3 generations, however, control values showed a pronounced variance over time. Also, as anti-androgenic compounds are more likely to induce the opposite effect (increased apoptosis), this observation is not considered to be treatment related. Consequently, spermatogenesis was not affected by vinclozolin exposure in utero. As vinclozolin has been shown to induce clear anti-androgenic effects in offspring following treatment with 100mg/(kg bw day) during entire gestation, the lack of effects in this study indicates that the window of sensitivity for anti-androgenic effects is from days 16-20 p.c. No transgenerational effect on the male reproductive system was found. The NOAEL was >100mg/(kg bw day) for fertility and reproductive performance, for systemic parental and developmental toxicity in F1, F2 and F3 males.
McBirney, Margaux; King, Stephanie E.; Pappalardo, Michelle; Houser, Elizabeth; Unkefer, Margaret; Nilsson, Eric; Sadler-Riggleman, Ingrid; Beck, Daniel; Winchester, Paul
2017-01-01
Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine. Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F1, F2 and F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the control and atrazine lineage sperm. The F1 generation offspring (directly exposed as a fetus) did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease and mammary tumors in males and females, early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations (motor hyperactivity) and a lean phenotype in males and females. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The transgenerational transmission of disease requires germline (egg or sperm) epigenetic alterations. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified in the F1, F2 and F3 generations. Gene associations with the DMRs were identified. For the transgenerational F3 generation sperm, unique sets of DMRs (epimutations) were found to be associated with the lean phenotype or testis disease. These DMRs provide potential biomarkers for transgenerational disease. The etiology of disease appears to be in part due to environmentally induced epigenetic transgenerational inheritance, and epigenetic biomarkers may facilitate the diagnosis of the ancestral exposure and disease susceptibility. Observations indicate that although atrazine does not promote disease in the directly exposed F1 generation, it does have the capacity to promote the epigenetic transgenerational inheritance of disease. PMID:28931070
Martinek, Radek; Kelnar, Michal; Koudelka, Petr; Vanus, Jan; Bilik, Petr; Janku, Petr; Nazeran, Homer; Zidek, Jan
2016-02-01
This paper describes the design, construction, and testing of a multi-channel fetal electrocardiogram (fECG) signal generator based on LabVIEW. Special attention is paid to the fetal heart development in relation to the fetus' anatomy, physiology, and pathology. The non-invasive signal generator enables many parameters to be set, including fetal heart rate (FHR), maternal heart rate (MHR), gestational age (GA), fECG interferences (biological and technical artifacts), as well as other fECG signal characteristics. Furthermore, based on the change in the FHR and in the T wave-to-QRS complex ratio (T/QRS), the generator enables manifestations of hypoxic states (hypoxemia, hypoxia, and asphyxia) to be monitored while complying with clinical recommendations for classifications in cardiotocography (CTG) and fECG ST segment analysis (STAN). The generator can also produce synthetic signals with defined properties for 6 input leads (4 abdominal and 2 thoracic). Such signals are well suited to the testing of new and existing methods of fECG processing and are effective in suppressing maternal ECG while non-invasively monitoring abdominal fECG. They may also contribute to the development of a new diagnostic method, which may be referred to as non-invasive trans-abdominal CTG + STAN. The functional prototype is based on virtual instrumentation using the LabVIEW developmental environment and its associated data acquisition measurement cards (DAQmx). The generator also makes it possible to create synthetic signals and measure actual fetal and maternal ECGs by means of bioelectrodes.
Minamisawa, T; Hirokaga, K
1996-06-01
The open field activity of first generation (F1) hybrid male C57BL/6 x C3H mice irradiated with gamma-rays on the 14th day of gestation was studied at the following ages: 6-7 months, 12-13 months and 19-20 months. Doses were 0.1 Gy or 0.2 Gy. Open field activity was recorded with a camera. The camera output signal was recorded every sec through an A/D converter to a personal computer. The field was divided into 25 units of 8 cm square. All recordings were continuous for 60 min. The time which the 0.2-Gy group recorded at 6-7 months, spent in the 4 squares in the corner fields was high in comparison with the control group at the same age. The walking distance of the 0.1-Gy group recorded at 12-13 months was longer than that for the age matched control group. No effect of radiation was found on any of the behaviors observed and recorded at 19-20 months. The results demonstrate that exposure to low levels of gamma-rays on the 14th day of gestation results in behavioral changes, which occur at 6-7 and 12-13 months but not 19-20 months.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ikeda, Masahiko; Tamura, Masashi; Yamashita, Junko
2005-08-15
The effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male rat offspring (F{sub 1}) and the sex ratio of the subsequent generation (F{sub 2}) were examined. Female Holtzman rats were gavaged with an initial loading dose of 400 ng/kg TCDD prior to mating, followed by weekly maintenance doses of 80 ng/kg during mating, pregnancy, and the lactation period. Maternal exposure to TCDD had no significant effects on fetus/pup (F{sub 1}) mortality, litter size, or sex ratio on gestation day (GD) 20 or postnatal day (PND) 2. The TCDD concentration in maternal livers and adipose tissuemore » on GD20 was 1.21 and 1.81 ng/kg, respectively, and decreased at weaning to 0.72 in the liver and 0.84 in the adipose tissue. In contrast, the TCDD concentration in pup livers was 1.32 ng/kg on PND2 and increased to 1.80 ng/kg at weaning. Ventral prostate weight of male offspring was significantly decreased by TCDD exposure on PND28 and 120 compared with that of controls. Weight of the testes, cauda epididymides, and seminal vesicle, and sperm number in the cauda epididymis were not changed by TCDD exposure at PND120. TCDD- or vehicle-exposed male offspring were mated with unexposed females. The sex ratio (percentage of male pups) of F{sub 2} offspring was significantly reduced in the TCDD-exposed group compared with controls. These results suggest that in utero and lactational TCDD exposures affect the development of male gonads in offspring (F{sub 1}), leading to changes in the sex ratio of the subsequent generation (F{sub 2})« less
Berger, Stefanie; Ronovsky, Marianne; Horvath, Orsolya; Berger, Angelika; Pollak, Daniela D
2018-05-01
Maternal immune activation (MIA) is a well-established model for the investigation of the deleterious effects of gestational infection on offspring mental health later in life. Hence, MIA represents a critical environmental variable determining brain development and the depending neural and behavioral functions in the progeny. Transgenerational transmission of some of the effects of MIA has been recently reported using the Polyinosinic:polycytidylic acid (Poly (I:C)) MIA model in C57BL/6 (C57) inbred mice. However, little is known about the underlying molecular mechanisms and the possible relevance of the specific genetic make-up of the inbred mouse strain used. Here we set out to characterize the effects of gestational Poly (I:C) treatment in C3H/HeNCrl mice (C3H), focusing on maternal care and offspring depression-like behavior and its intergenerational potential. miRNA expression in the offspring hippocampus in the F1 and F2 generations was examined as possible mechanism contributing to the observed behavioral effects. The impact of MIA on maternal care and its transmission to F1 females was previously observed in C57 mice was also found in C3H mice. Depression-like behavior in the adult offspring in C3H F1 and F2 females differed from reports of the C57 strain in the literature, suggesting a potential modulating role of the genetic background in the Poly(I:C) MIA mouse model. As the pattern of expression of selected candidate miRNAs in the F1 and F2 offspring hippocampus was not conserved between the two generations, it is unlikely to be a direct consequence of altered maternal care, or to be an immediate determinant of offspring emotionality. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Sanders, Alison P; Gennings, Chris; Svensson, Katherine; Motta, Valeria; Mercado-Garcia, Adriana; Solano, Maritsa; Baccarelli, Andrea A; Tellez-Rojo, Martha M; Wright, Robert O; Burris, Heather H
2017-01-01
Bacterial vaginosis may lead to preterm birth through epigenetic programming of the inflammatory response, specifically via miRNA expression. We quantified bacterial 16S rRNA, cytokine mRNA and 800 miRNA from cervical swabs obtained from 80 women at 16-19 weeks' gestation. We generated bacterial and cytokine indices using weighted quantile sum regression and examined associations with miRNA and gestational age at delivery. Each decile of the bacterial and cytokine indices was associated with shorter gestations (p < 0.005). The bacterial index was associated with miR-494, 371a, 4286, 185, 320e, 888 and 23a (p < 0.05). miR-494 remained significant after false discovery rate correction (q < 0.1). The cytokine index was associated with 27 miRNAs (p < 0.05; q < 0.01). Future investigation into the role of bacterial vaginosis- and inflammation-associated miRNA and preterm birth is warranted.
Guerrero-Bosagna, Carlos; Savenkova, Marina; Haque, Md. Muksitul; Nilsson, Eric; Skinner, Michael K.
2013-01-01
Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that correlates with adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility. PMID:23555832
Maternal obesity and perinatal oxidative stress: the strength of the association.
Negro, S; Boutsikou, T; Briana, D D; Tataranno, M L; Longini, M; Proietti, F; Bazzini, F; Dani, C; Malamitsi-Puchner, A; Buonocore, G; Perrone, S
2017-01-01
Maternal obesity is a chronic inflammatory state, which has been shown to induce increased levels of free fatty acids, reactive oxygen species and inflammatory cells. Recent evidence reveals increased levels of lipid peroxidation products in the plasma of obese women during pregnancy. The aim of this study was to test the hypothesis that maternal overweight or obesity is associated with increased oxidative stress (OS) in offspring. Two hundred and forty-five pregnant women and their newborns were prospectively enrolled. Mothers were divided in two groups: lean control - LC (n=175, Group I); overweight or obese (n=70, Group II) according to BMI ≥ 25 before pregnancy. Cord blood F2-isoprostanes (F2-IsoPs), as reliable markers of OS, were measured in all newborns. Lower 1 minute APGAR score and higher weight at discharge were found in Group II neonates, compared to those of Group I (p less than 0.05). Small for gestational age (SGA) newborns of both groups showed increased levels of F2-IsoPs than appropriate (AGA) or large (LGA) for gestational age (GA) (p less than 0.01). SGA newborns of Group II had higher F2-IsoPs levels compared to SGA of Group I (p less than 0.01), which were significantly correlated to maternal BMI at the end of pregnancy (r=0.451, p less than 0.01). Multivariate regression analysis corrected for confounding factors, showed that maternal overweight or obesity was significantly associated with high F2-IsoPs levels in SGA offspring (p less than 0.01). Maternal overweight or obesity is associated with increased OS in their SGA newborns. Data suggest the need of antioxidant protection for both mothers during pregnancy and infants soon after birth.
Stephens, Trina V; Payne, Magdalene; Ball, Ronald O; Pencharz, Paul B; Elango, Rajavel
2015-01-01
Adequate maternal dietary protein intake is necessary for healthy pregnancy. However, current protein intake recommendations for healthy pregnant women are based on factorial calculations of nitrogen balance data derived from nonpregnant adults. Thus, an estimate of protein requirements based on pregnancy-specific data is needed. The objective of this study was to determine protein requirements of healthy pregnant women at 11-20 (early) and 31-38 (late) wk of gestation through use of the indicator amino acid oxidation method. Twenty-nine healthy women (24-37 y) each randomly received a different test protein intake (range: 0.22-2.56 g · kg(-1) · d(-1)) during each study day in early (n = 35 observations in 17 women) and late (n = 43 observations in 19 women) gestation; 7 women participated in both early and late gestation studies. The diets were isocaloric and provided energy at 1.7 × resting energy expenditure. Protein was given as a crystalline amino acid mixture based on egg protein composition, except phenylalanine and tyrosine, which were maintained constant across intakes. Protein requirements were determined by measuring the oxidation rate of L-[1-(13)C]phenylalanine to (13)CO2 (F(13)CO2). Breath and urine samples were collected at baseline and isotopic steady state. Linear regression crossover analysis identified a breakpoint (requirement) at minimal F(13)CO2 in response to different protein intakes. The estimated average requirement (EAR) for protein in early and late gestation was determined to be 1.22 (R(2) = 0.60; 95% CI: 0.79, 1.66 g · kg(-1) · d(-1)) and 1.52 g · kg(-1) · d(-1) (R(2) = 0.63; 95% CI: 1.28, 1.77 g · kg(-1) · d(-1)), respectively. These estimates are considerably higher than the EAR of 0.88 g · kg(-1) · d(-1) currently recommended by the Dietary Reference Intakes. To our knowledge, this study is the first to directly estimate gestational stage-specific protein requirements in healthy pregnant women and suggests that current recommendations based on factorial calculations underestimate requirements. This trial was registered at clinicaltrials.gov as NCT01784198. © 2015 American Society for Nutrition.
Peiris, Hassendrini N; Ponnampalam, Anna P; Osepchook, Claire C; Mitchell, Murray D; Green, Mark P
2010-04-01
Maternal undernutrition during gestation is known to be detrimental to fetal development, leading to a propensity for metabolic disorders later in the adult lives of the offspring. Identifying possible mediators and physiological processes involved in modulating nutrient transport within the placenta is essential to prevent and/or develop treatments for the effects of aberrant nutrition, nutrient transfer, and detrimental changes to fetal development. A potential role for myostatin as a mediator of nutrient uptake and transport from the mother to the fetus was shown through the recent finding that myostatin acts within the human placenta to modulate glucose uptake and therefore homeostasis. The mRNA and protein expression of myostatin and its inhibitor, follistatin-like-3 (FSTL3), was studied in the placenta and skeletal muscle of a transgenerational Wistar rat model of gestational maternal undernutrition in which the F2 offspring postweaning consumed a high-fat (HF) diet. Alterations in placental characteristics and offspring phenotype, specifically glucose homeostasis, were evident in the transgenerationally undernourished (UNAD) group. Myostatin and FSTL3 protein expression were also higher (P < 0.05) in the placentae of the UNAD compared with the control group. At maturity, UNAD HF-fed animals had higher (P < 0.05) skeletal muscle expression of FSTL3 than control animals. In summary, maternal undernutrition during gestation results in the aberrant regulation of myostatin and FSTL3 in the placenta and skeletal muscle of subsequent generations. Myostatin, through the disruption of maternal nutrient supply to the fetus, may thus be a potential mediator of offspring phenotype.
Strain-specific programming of prenatal ethanol exposure across generations.
Popoola, Daniel O; Nizhnikov, Michael E; Cameron, Nicole M
2017-05-01
Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17-20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague-Dawley rats. Lastly, we investigated PAE related changes in expression of GABA A receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABA A receptor subunits' expression in the F1 and F2 PAE groups compared to control animals. GABA A receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE did not alter cerebral cortical GABA A receptor subunit expressions in the F1 generation, but it decreased GABA A receptor α4 and δ subunits' expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring. Copyright © 2017 Elsevier Inc. All rights reserved.
STRAIN-SPECIFIC PROGRAMMING OF PRENATAL ETHANOL EXPOSURE ACROSS GENERATIONS
Popoola, Daniel O.; Nizhnikov, Michael E.; Cameron, Nicole M.
2017-01-01
Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanism. This study investigated the intergenerational consequences of prenatal exposure to low ethanol dose (1g/kg) during gestational days 17–20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long Evans and Sprague Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at 3.5g/kg or 4.5g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits’ expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE didn’t alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits’ expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring. PMID:28433421
Stomnaroska, Orhideja; Petkovska, Elizabeta; Ivanovska, Sanja; Jancevska, Snezana; Danilovski, Dragan
2017-09-01
Severe neonatal hypoglycaemia (HG) leads to neurologic damage, mental retardation, epilepsy, impaired cardiac performance and muscle weakness. The aim was to assess the frequency and severity of HG in a population of newborns. We investigated 739 patients with neonatal hypoglycaemia (HG) (M:F=370:369) born at the University Clinic for Gynaecology and Obstetritics in Skopje in the period 2014-2016 and treated at the neonatal intensive care unit (NICU). 1416 babies were treated in the same period in NICU, and HG was observed in 52.18%. The birth weight was dominated by children with low birth weight: very low birth weight (VLBW)(<1500g) 253 children, (34,23%), low birth weight (1500-2500g) 402 (54.39%), appropriate for gestational age (AGA) 78(10.55%), and high birth weight (>4000g) 6 babies (0.81%). The gestational age was also dominated by children with low gestational age: gestational week (GW) 20-25 four children (0.54%), 26-30 GW 133 babies (17.99%), 31-35 GW472 (63.87%), and 36-40 GW130 neonates (17.59 %). 241 mothers (32.61%) have had an infection during pregnancy, 82 preeclampsia or eclampsia (11.09%), 20 diabetes mellitus (2.70%), 78 placental situations (placenta previa, abruption) (10.55%). In this study 47 babies (6.35%) with HG and co-morbidities died. There was a significant positive correlation between HG birth weight (p<0.01), gestational age (p<0.05), and the lowest Apgar score (p<0.01). Neonatal deaths were significantly correlated with GA (р>0,01), co-morbidities of the mothers (р>0,05) but not with the birth weight (р>0,05). In contrast, a significant positive correlation was found between convulsions and body weight (р<0.05). The lowest Apgar score was positively correlated with the gestational age (0.01), but not with the birth weight (0.05). Low birth weight, low gestational age, maternal risk factors, hypoxic-ischemic encephalopathy and neonatal infections are associated with HG and are a significant factor in overall neonatal mortality. Those results indicate that diminishing the frequency of the neonatal HG and the rates of neonatal mortality requires complex interaction of prenatal and postnatal interventions.
Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra; Hougaard, Karin Sørig; Wallin, Håkan; Yauk, Carole L; Vogel, Ulla
2012-06-01
Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR) loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development). Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO(2)) produces a long-lasting inflammatory response in mice, it was chosen for the present study. Pregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO(2) UV-Titan L181 (~42.4 mg UV-Titan/m(3)) or filtered clean air on gestation days (GD) 8-18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring) of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls). ESTR mutation rates of 0.029 (maternal allele) and 0.047 (paternal allele) in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele) and 0.061 (paternal allele). We found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.
Kim, Renita S; Gupta, Simi; Lam-Rachlin, Jennifer; Saltzman, Daniel H; Rebarber, Andrei; Fox, Nathan S
2016-11-01
The objective of this study is to estimate the risk of preterm birth in patients with an ultrasound or physical exam indicated cervical cerclage based on the results of fetal fibronectin (fFN) and cervical length (CL) screening. Retrospective cohort of patients with a singleton pregnancy and an ultrasound or physical exam indicated Shirodkar cerclage placed by one maternal-fetal medicine practice from November 2005 to January 2015. Patients routinely underwent serial CL and fFN testing from 22 to 32 weeks. Based on ROC curve analysis, a short CL was defined as ≤15 mm. All fFN and CL results included are from after the cerclage placement. One hundred and four patients were included. Seventy eight (75%) patients had an ultrasound-indicated cerclage and 26 (25%) patients had a physical exam-indicated cerclage. A positive fFN was associate with preterm birth <32 weeks (15.6% versus 4.2%, p = 0.043), <35 weeks (37.5% versus 11.1%, p = 0.002), <37 weeks (65.6% versus 20.8%, p < 0.001), and earlier gestational ages at delivery (35.2 ± 3.9 versus 37.4 ± 2.9, p = 0.001). A short CL was also associated with preterm birth <35 weeks (50.0% versus 11.9%, p < 0.01), preterm birth <37 weeks (55.0% versus 29.8%, p = 0.033), and earlier gestational ages at delivery (34.8 ± 4.1 versus 37.2 ± 3.0, p = 0.004). The risk of preterm birth <32, <35, and <37 weeks increased significantly with the number of abnormal markers. In patients with an ultrasound or physical exam indicated cerclage, a positive fFN and a short CL are both associated with preterm birth. The risk of preterm birth increases with the number of abnormal biomarkers.
Watanabe, Toshiaki; Ebara, Shuhei; Kimura, Sachiko; Maeda, Kunihiko; Watanabe, Yoshitaka; Watanabe, Hiroshi; Kasai, Shigenobu; Nakano, Yoshihisa
2007-03-01
To evaluate the role of cobalamin (Cbl) on spermatogenesis, the effect of dietary vitamin B(12) deficiency on early spermatogenesis was histologically investigated in male fetuses and newborns in the first filial generation (F(1) males) of rats. There was no difference in the number of gonocytes and supporting cells of Sertoli in the gonad in male fetuses on day 16 of gestation and in the testes in F(1) males at 0 days of age between vitamin B(12)-deficient (VB12-D) and vitamin B(12)-supplemented (VB12-S) groups. However, at 21 days of age, a decreased number of spermatogonia and no spermatocytes were observed in the VB12-D group. Numerous TUNEL positive cells were located among spermatocytes of the spermatogenic epithelium. The ultrastructural features examined using transmission electron microscopy were considered to be indicative of apoptosis. The incidence of seminiferous tubules having apoptotic cells was 51.5% in the VB12-D group. At 60 days of age, aplasia of the spermatids and spermatozoa was detected in the VB12-D group. In the connective tissue between the seminiferous tubules, many interstitial Leydig cells and blood vessels were observed in the VB12-D group, as compared with the VB12-S group. These changes produced by vitamin B(12) deficiency can be reversed by providing a VB12-S diet after weaning at 21 days of age. From these findings, such a vitamin B(12) deficiency during gestation and lactation could affect the germ cells and especially damage spermatocytes in F(1) male rats, which indicates that Cbl may be an essential constituent in the meiosis of spermatogenesis.
Stampalija, T; Casati, D; Monasta, L; Sassi, R; Rivolta, M W; Muggiasca, M L; Bauer, A; Ferrazzi, E
2016-11-01
Phase rectified signal averaging (PRSA) is a new method of fetal heart rate variability (fHRV) analysis that quantifies the average acceleration (AC) and deceleration capacity (DC) of the heart. The aim of this study was to evaluate AC and DC of fHR [recorded by trans-abdominal fetal electrocardiogram (ta-fECG)] in relation to Doppler velocimetry characteristics of intrauterine growth restriction (IUGR). Prospective case-control study. Single third referral centre. IUGR (n = 66) between 25 and 40 gestational weeks and uncomplicated pregnancies (n = 79). In IUGR the nearest ta-fECG monitoring to delivery was used for PRSA analysis and Doppler velocimetry parameters obtained within 48 hours. AC and DC were computed at s = T = 9. The relation was evaluated between either AC or DC and Doppler velocimetry parameters adjusting for gestational age at monitoring, as well as the association between either AC or DC and IUGR with or without brain sparing. In IUGRs there was a significant association between either AC and DC and middle cerebral artery pulsatility index (PI; P = 0.01; P = 0.005), but the same was not true for uterine or umbilical artery PI (P > 0.05). Both IUGR fetuses with and without brain sparing had lower AC and DC than controls, but this association was stronger for IUGRs with brain sparing. Our study observed for the first time that AC and DC at PRSA analysis are associated with middle cerebral artery PI, but not with uterine or umbilical artery PI, and that there is a significant decrease of AC and DC in association with brain sparing in IUGR fetuses from 25 weeks of gestation to term. Brain sparing in IUGR fetuses is associated with decreased acceleration and deceleration capacities of the heart. © 2015 Royal College of Obstetricians and Gynaecologists.
2013-01-01
Background Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze.Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Results Results showed that prenatal and postnatal TRF supplementation increased the brain (4–6 fold increase) and plasma α-tocotrienol (0.8 fold increase) levels in male off-springs. There is also notably better cognitive performance based on the Morris water maze test among these male off-springs. Conclusion Based on these results, it is concluded that prenatal and postnatal TRF supplementation improved cognitive function development in male progeny rats. PMID:23902378
Nagapan, Gowri; Meng Goh, Yong; Shameha Abdul Razak, Intan; Nesaretnam, Kalanithi; Ebrahimi, Mahdi
2013-07-31
Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Results showed that prenatal and postnatal TRF supplementation increased the brain (4-6 fold increase) and plasma α-tocotrienol (0.8 fold increase) levels in male off-springs. There is also notably better cognitive performance based on the Morris water maze test among these male off-springs. Based on these results, it is concluded that prenatal and postnatal TRF supplementation improved cognitive function development in male progeny rats.
Cleal, J K; Thomas, M; Hanson, M A; Paterson-Brown, S; Gardiner, H M; Green, L R
2010-03-01
To investigate whether a noninvasive fetal electrocardiography (fECG) system can identify cardiovascular responses to fetal hypoxaemia and validate the results using standard invasive fECG monitoring techniques. Prospective cohort study. Biological research facilities at The University of Southampton. Late gestation ovine fetuses; n = 5. Five fetal lambs underwent implantation of vascular catheters, umbilical cord occluder and invasive ECG chest electrodes under general anaesthesia (3% halothane/O(2)) at 119 days of gestation (term approximately 147 days of gestation). After 5 days of recovery blood pressure, blood gases, glucose and pH were monitored. At 124 and 125 days of gestation following a 10-minute baseline period a 90-second cord occlusion was applied. Noninvasive fetal ECG was recorded from maternal transabdominal electrodes using advanced signal-processing techniques, concurrently with invasive fECG recordings. Comparison of T:QRS ratios of the ECG waveform from noninvasive and invasive fECG monitoring systems. Our fECG monitoring system is able to demonstrate changes in waveforms during periods of hypoxaemia similar to those obtained invasively, which could indicate fetal distress. These findings may indicate a future use for noninvasive electrocardiography during human fetal monitoring both before and during labour in term and preterm pregnancies.
Essakow, Jenna Lee; Lauterpacht, Aharon; Lilos, Pearl; Kauli, Rivka; Laron, Zvi
2016-09-01
In recent years more and more genetic defects along the GHRH-GH-IGF-I axis have been reported. Mutations of the IGF-I receptor (R) are a rare abnormality of whom only the heterozygote progenies survive. To summarize, from the literature, data on birth length, weight and head circumference of neonates with IGF-I-R mutations, and to correlate the data with that of other types of mutations in the GH/IGF-I axis. Sixty seven neonates from 24 published articles were included and forty seven different mutations of the IGF-I (R) located on chromosome 15 have been identified. Mean (±SD) birth length (BL), available for 26, (10 M, 16F) neonates with a gestational age of 34-41weeks, was 44.2±4cm; one was premature (30cm at 31 weeks). There was a significant correlation between birth length and gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M, 23F) was 2388±743gr. Two premature neonates weighed 650gr and 950gr respectively. The BW correlated significantly with gestational age, (males: r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6 to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16 mothers were short (133 -148cm), m±SD = 150.5±7.3cm. Copyright© of YS Medical Media ltd.
Schumann, K; Guenther, A; Göritz, F; Jewgenow, K
2014-08-01
Fetal growth during pregnancy has previously been studied in the domesticated guinea pig (Cavia aperea f. porcellus) after dissecting pregnant females, but there are no studies describing the fetal growth in their wild progenitor, the wild guinea pig (C aperea). In this study, 50 pregnancies of wild guinea pig sows were investigated using modern ultrasound technique. The two most common fetal growth parameters (biparietal diameter [BPD] and crown-rump-length [CRL]) and uterine position were measured. Data revealed similar fetal growth patterns in the wild guinea pig and domesticated guinea pig in the investigated gestation period, although they differ in reproductive milestones such as gestation length (average duration of pregnancy 68 days), average birth weight, and litter mass. In this study, pregnancy lasted on average 60.2 days with a variance of less than a day (0.96 days). The measured fetal growth parameters are strongly correlated with each (R = 0.91; P < 0.001) other and with gestational age (BPD regression equation y = 0.04x - 0.29; P < 0.001 and CRL regression equation y = 0.17x - 2.21; P < 0.01). Furthermore, fetuses in the most frequent uterine positions did not differ in their growth parameters and were not influenced by the mother ID. Our results imply that ultrasound measurement of a single fetal growth parameter is sufficient to reliably estimate gestational age in the wild guinea pig. Copyright © 2014 Elsevier Inc. All rights reserved.
Cheung, D; Mian, Q; Cheung, P-Y; O'Reilly, M; Aziz, K; van Os, S; Pichler, G; Schmölzer, G M
2015-07-01
If an infant fails to initiate spontaneous breathing after birth, international guidelines recommend a positive pressure ventilation (PPV). However, PPV by face mask is frequently inadequate because of leak between the face and mask. Despite a variety of available face masks, none have been prospectively compared in a randomized fashion. We aimed to evaluate and compare leak between two commercially available round face masks (Fisher & Paykel (F&P) and Laerdal) in preterm infants <33 weeks gestational age in the delivery room. Infants born at the Royal Alexandra Hospital from April to September 2013 at <33 weeks gestational age who received mask PPV in the delivery room routinely had a flow sensor placed between the mask and T-piece resuscitator. Infants were randomly assigned to receive PPV with either a F&P or Laerdal face mask. All resuscitators were trained in the use of both face masks. We compared mask leak, airway pressures, tidal volume and ventilation rate between the two groups. Fifty-six preterm infants (n=28 in each group) were enrolled; mean±s.d. gestational age 28±3 weeks; birth weight 1210±448 g; and 30 (52%) were male. Apgar scores at 1 and 5 min were 5±3 and 7±2, respectively. Infants randomized to the F&P face mask and Laerdal face mask had similar mask leak (30 (25-38) versus 35 (24-46)%, median (interquartile range), respectively, P=0.40) and tidal volume (7.1 (4.9-8.9) versus 6.6 (5.2-8.9) ml kg(-1), P=0.69) during PPV. There were no significant differences in ventilation rate, inflation time or airway pressures between groups. The use of either face mask during PPV in the delivery room yields similar mask leak in preterm infants <33 weeks gestational age.
Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort
Gyllenberg, David; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; McKeague, Ian W.; Brown, Alan S.
2015-01-01
Background Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early to mid-gestation is associated with offspring schizophrenia. Methods The investigation is based on the Finnish Prenatal Study of Schizophrenia (FiPS-S), a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (total N over 1 million). We identified all offspring in the cohort diagnosed with schizophrenia based on the national inpatient and outpatient register and matched them to comparison subjects (1:1) from the cohort on sex, date of birth, and residence in Finland at time of onset of the case. Maternal sera on 1010 case-control pairs were assessed for free thyroxine (fT4) and 948 for thyroid stimulating hormone (TSH). Results Maternal hypothyroxinemia (fT4≤10th percentile, normal TSH) was associated with an increased odds of schizophrenia (OR=1.75, 95% CI=1.22 – 2.50; p=0.002). When adjusted for maternal psychiatric history, province of birth and maternal smoking during pregnancy, the association remained significant (OR=1.70, 95%CI 1.13 – 2.55; p=0.010). Conclusions In a large, national birth cohort, prospectively documented early to mid-gestational hypothyroxinemia was associated with increased odds of schizophrenia in offspring. This can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia. PMID:26194598
Genetic study of kelp ``901'' strain
NASA Astrophysics Data System (ADS)
Xia, Peng; Wang, Xiuliang; Li, Xiaojie; Zhao, Yushan; Yao, Lin; Duan, Delin
2005-06-01
Based on DNA extraction and optimization of random amplified reaction (RAPD) to the gametophytes and sporophytes of Kelp “901” strain, genetic study on variation was conducted to its parents and offsprings of F6, F7, F8, and F9 generation. RAPD results have shown that among 30 selected primers for gametophytes, 297 loci ranging from 200 to 3 000 bp were obtained in the average of 9.9 loci for each primer. This indicated a high polymorphic rate with RAPD detection. UPGMA (unweighted pair-group method arithmetic average) analysis showed that each male and female gametophyte of a generation could be clustered into one pair separately. The genetic distances of the Kelp 901 generation were 0.3212 0.4767, and the maximum was between F7 and F8 (0.4767). Identity analysis showed that F6 generation was more close to the female parent (0.6593), and F7 generation was more close to the male parent (0.578 8). To the sporophytes study in 24 selected primers for RAPD amplification, 191 loci ranging from 230 2800 bp were obtained, in the average to each primer of 8.0 loci. The heterozygosity to six populations were male parent (0.2239), female parent (0.1072), F6 (0.2164), F7(0.2286), F8(0.2296) and F9(0.3172). The nearest genetic distance was 0.083 5(F8, F9). Total heterozygosity (HT) of F6, F7, F8 and F9 generations was 0.3186, the average heterozygosity (HS) for F6, F7, F8 and F9 generations was 0.2480, and deduced coefficient of population differentiation (Gst) was 22.2%. Six sequence characterized amplified regions (SCAR) were preliminary screened through RAPD analysis. It needed to be verified in detail as they are significant for molecular marker assistance in breeding and selecting Laminaria.
Grzesiak, M; Knapczyk-Stwora, K; Slomczynska, M
2017-04-01
Recently, we have indicated that flutamide-induced androgen deficiency diminished progesterone production in the porcine corpus luteum (CL) during late pregnancy and before parturition, as a sign of functional luteolysis. In pigs, the main luteolytic factor is prostaglandin F 2α (PGF 2α ), which acts via specific receptors (PTGFRs), and its biosynthesis is catalyzed by prostaglandin F 2α synthase (PGFS). The present study investigated the impact of flutamide on luteal PGFS and PTGFR expression, as well as intraluteal PGF 2α content during pregnancy in pigs. Flutamide (50 mg/kg BW per day, for 7 d) or corn oil (control groups) were administered subcutaneously into pregnant gilts (n = 3 per group) between 83 and 89 (GD90) or 101-107 (GD108) days of gestation (GD). On GD90 and GD108 ovaries were collected and CLs were obtained. Real-time PCR and Western blot analyses were conducted to quantify PGFS and PTGFR mRNA and protein expression, respectively. In addition, immunohistochemical localization of both proteins was performed and the concentration of PGF 2α was analyzed by enzyme immunoassay method. Flutamide caused upregulation of PGFS mRNA and protein in GD90F (P = 0.008; P = 0.008, respectively) and GD108F (P = 0.041; P = 0.009, respectively) groups. The level of PTGFR mRNA increased only in the GD90F (P = 0.007) group, whereas PTGFR protein expression was greater in both gestational periods (P = 0.035; P = 0.038, respectively). On GD90 PGFS was immunolocalized in the cytoplasm of large luteal cells only, whereas on GD108, sparse small luteal cells also displayed positive staining. PTGFR showed membranous localization within large luteal cells on both days of pregnancy. In luteal tissue, PGF 2α concentration was greater after flutamide exposure on both days (P = 0.041; P = 0.038, respectively), when compared with control groups. Overall, the enhanced luteal PGF 2α content due to increased PGFS expression after flutamide administration might contribute to premature CL regression. Moreover, higher PTGFR protein levels indicate enhanced sensitivity of luteal cells to PGF 2α under androgen deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.
Kwan, Kellie S H; Giele, Carolien M; Combs, Barry; Mak, Donna B
2012-09-01
Antenatal testing for specified sexually transmissible infections (STIs) and blood-borne viruses (BBVs) is recommended by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). In 2007, the Department of Health, Western Australia (DoHWA) issued an operational directive (OD) recommending universal testing for chlamydia and additional testing for women in the STI endemic regions of Western Australia (WA). To assess adherence to these guidelines, seven WA public hospitals were audited. Demographic details and testing information of the last 200 women who gave birth immediately before 30 June 2007 (baseline audit) and 30 June 2010 (follow-up audit) were obtained from each hospital's antenatal records. Data from 2718 women who delivered at ≥36 weeks' gestation were analysed (baselinen=1353; follow-upn=1365). Testing at the first antenatal visit in accordance with the guidelines improved over time (RANZCOG: 68-74%; χ(2)-test = 13.96, d.f.=1, P<0.001; DoHWA OD: 12-40%; χ(2)-test = 279.71, d.f.=1, P<0.001). Retesting at 28-36 weeks' gestation in the STI endemic regions improved for chlamydia (3-10%; χ(2)-test = 17.40, d.f.=1, P<0.001) and gonorrhoea (3-7%; χ(2)-test=6.62, d.f.=1, P<0.05), but not for syphilis or HIV. Chlamydia prevalence was 3% and 8% among nonAboriginal and Aboriginal women, respectively. The proportion of women delivering in WA public hospitals who had antenatal STI and BBV tests improved after publication and promotion of the OD.
Schuster, Andrew; Skinner, Michael K; Yan, Wei
Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.
Cao, Wen-Cheng; Zeng, Qiang; Luo, Yan; Chen, Hai-Xia; Miao, Dong-Yue; Li, Li; Cheng, Ying-Hui; Li, Min; Wang, Fan; You, Ling; Wang, Yi-Xin; Yang, Pan; Lu, Wen-Qing
2015-01-01
Background: Previous studies have suggested that elevated exposure to disinfection by-products (DBPs) in drinking water during gestation may result in adverse birth outcomes. However, the findings of these studies remain inconclusive. Objective: The purpose of our study was to examine the association between blood biomarkers of late pregnancy exposure to trihalomethanes (THMs) in drinking water and fetal growth and gestational age. Methods: We recruited 1,184 pregnant women between 2011 and 2013 in Wuhan and Xiaogan City, Hubei, China. Maternal blood THM concentrations, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM), were measured as exposure biomarkers during late pregnancy. We estimated associations with gestational age and fetal growth indicators [birth weight, birth length, and small for gestational age (SGA)]. Results: Total THMs (TTHMs; sum of TCM, BDCM, DBCM, and TBM) were associated with lower mean birth weight (–60.9 g; 95% CI: –116.2, –5.6 for the highest vs. lowest tertile; p for trend = 0.03), and BDCM and DBCM exposures were associated with smaller birth length (e.g., –0.20 cm; 95% CI: –0.37, –0.04 for the highest vs. lowest tertile of DBCM; p for trend = 0.02). SGA was increased in association with the second and third tertiles of TTHMs (OR = 2.91; 95% CI: 1.32, 6.42 and OR = 2.25; 95% CI: 1.01, 5.03; p for trend = 0.08). Conclusions: Our results suggested that elevated maternal THM exposure may adversely affect fetal growth. Citation: Cao WC, Zeng Q, Luo Y, Chen HX, Miao DY, Li L, Cheng YH, Li M, Wang F, You L, Wang YX, Yang P, Lu WQ. 2016. Blood biomarkers of late pregnancy exposure to trihalomethanes in drinking water and fetal growth measures and gestational age in a Chinese cohort. Environ Health Perspect 124:536–541; http://dx.doi.org/10.1289/ehp.1409234 PMID:26340795
2011-01-01
Background Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. Methods A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG) to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST). Results Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR) 0.55; 95 % confidence interval (CI) 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction in neonatal mortality [RR 0.70; 95 % CI 0.56-0.88] and risk of pre-term birth [RR 0.88, 95 % CI 0.78-0.99]. Recommendations for LiST for reduction in maternal mortality were based on risk reduction in gestational hypertensive related severe morbidity/mortality [RR 0.80; 95% CI 0.70-0.91] and that for neonatal mortality were based on risk reduction in all-cause neonatal mortality [RR 0.70; 95% CI 0.56-0.88]. Conclusion Calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertension, pre-eclampsia neonatal mortality and pre-term birth in developing countries. PMID:21501435
Lifshitz, Y; Levi, L; Eyal, I; Cohen, T; Tessler, S
2015-12-01
The safety of fish phosphatidylserine (PS) conjugated to DHA (InCog™) was examined in a series of toxicology studies as first step to support future use in infants and general population using in vitro genotoxicity tests and in a sub-chronic toxicity study with an in-utero exposure phase. PS is a major lipid in the cell membrane, active in various membrane-mediated processes. PS-DHA, present in human milk, has been suggested to be important for early brain development. Rats were exposed to diets containing 1.5%, 3% or 4.5% InCog or two control diets. Parental (F0) animals were fed throughout mating, gestation and lactation. Subsequently, a subchronic, 13-week study was conducted on the F1 animals followed by 4 weeks of recovery. The genotoxicity tests showed no mutagenicity potential. No significant toxicological findings were found in the F0 rats or the F1 pups. In the 13-weeks study, an increase in the presence of renal minimal-mild multifocal corticomedullary mineralization was noted in nine females of the high-dose group. This change was not associated with any inflammatory or degenerative changes in the kidneys. The no-observed-adverse-effect level (NOAEL) in the present study was placed at 3% in the diet (mid-dose group), equivalent to an overall intake of at least 2.1 g InCog/kg bw/day in the F1 generation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Minamisawa, T; Hirokaga, K
1995-11-01
The open-field activity of first-generation (F1) hybrid male C57BL/6 x C3H mice irradiated with gamma rays on day 14 of gestation was studied at the following ages: 6-7 months (young), 12-13 months (adult) and 19-20 months (old). Doses were 0.5 Gy or 1.0 Gy. Open-field activity was recorded with a camera. The camera output signal was recorded every second through an A/D converter to a personal computer. The field was divided into 25 8-cm2 units. All recordings were continuous for 60 min. The walking speed of the 1.0-Gy group recorded at 19-20 months was higher than that for the comparably aged control group. The time which the irradiated group, recorded at 19-20 months, spent in the corner fields was high in comparison with the control group at the same age. Conversely, the time spent by the irradiated group in the middle fields when recorded at 19-20 months was shorter than in the comparably aged control group. No effect of radiation was shown for any of the behaviors observed and recorded at 6-7 and 12-13 months. The results demonstrate that such exposure to gamma rays on day 14 of gestation results in behavioral changes which occur at 19-20 months but not at 6-7 or 12-13 months.
Li, Wenchun; Huang, Tiezhu; Zeng, Yanjun; Yao, Zhongjun
2006-03-01
The aim of this study was to provide a theoretical basis, using biomechanical properties, for the clinical application of human umbilical vein (HUV) as material for vascular grafting. This was a nonrandomized, non-controlled in vitro study. The experiment was conducted in the Laboratory of Medical Biomechanics, Yunyang Medical College. HUVs of 50 normal fetuses were collected on spontaneous miscarriage or labor with the pregnant women's permission by the Department of Obstetrics and Gynecology, Taihe Hospital, Shiyan, Hubei Province. Gestational aged ranged 24-42 weeks, and parturients were 20-30 years old. The pressure-volume (P-V) relationship of HUV was measured on the biomechanical experiment stand for soft tissues, and then compliance was calculated. The P-V relationship of HUV corresponded to a parabolic curve. The compliance of HUV increased gradually with gestational age [24-27 weeks (2.22+/-0.34) x 10(-4) mL/(kPa * cm), 28-32 weeks (3.65+/-0.46) x 10(-4) mL/(kPa * cm), 33-36 weeks (4.22+/-0.55) x 10(-4) mL/(kPa * cm), 37 weeks (7.63+/-0.48) x 10(-4) mL/(kPa * cm), 38 weeks (8.32+/-0.76) x 10(-4) mL/(kPa * cm)]. However, after 39 weeks of gestation, compliance decreased gradually with gestational age [39 weeks 7.61+/-0.46) x 10(-4) mL/(kPa * cm), 40 weeks (7.53+/-0.72) x 10(-4) mL/(kPa * cm), 41 weeks (4.13+/-0.35) x 10(-4) mL/(kPa * cm), 42 weeks (2.25+/-0.62) x 10(-4) mL/(kPa * cm)]. The compliance of HUVs collected at 37-40 weeks of gestational age was similar. When the HUVs older than 42 weeks or under 28 weeks were compared, there was significant difference in their compliance (F=65.84-86.52, p<0.01). The results of the present study suggest that HUVs collected at 37-40 weeks of gestational age have good compliance, i.e., a good P-V relationship, and therefore may be a suitable material for vascular grafting. HUV is one of several graft materials that may be used when autogenous saphenous vein is absent or inadequate. HUV is very biocompatible and shows promise for use in orthopedic implants.
Eastwood, L; Leterme, P; Beaulieu, A D
2014-12-01
This experiment tested the hypothesis that reducing the omega-6 (n-6) to omega-3 (n-3) fatty acid (FA) ratio in sow diets will improve performance, characterized by increased litter size, decreased preweaning mortality, and improved growth performance. Second, we determined if the FA profile in sow and piglet blood, colostrum, and milk are altered when sows are fed diets with varied n-6:n-3 ratios and if the dietary FA ratio impacts circulating concentrations of IgG, IgA, eicosapentaenoic (EPA), or docosahexaenoic (DHA) acid. Sows (n=150) were assigned to 1 of 5 treatments (each divided into gestation and lactation diets) on d 80 of gestation. Period 1 (P1) is defined as d 80 of gestation to weaning and Period 2 (P2) refers to the subsequent breeding to weaning. Diets were wheat and barley based (5% crude fat) and treatments consisted of a control (tallow), 3 diets with plant oil-based n-6:n-3 ratios (9:1P, 5:1P, and 1:1P), and a 5:1 fish oil diet (5:1F). Litter size was unaffected by treatment during P1 and P2 (P>0.10). In P1, birth weight was unaffected by diet (P>0.10); however, weaning weight (P=0.019) and ADG from birth to weaning (P=0.011) were greatest for piglets born to 9:1P and 5:1P sows. During P2, 5:1F sows consumed 10% less feed during lactation (P=0.036), tended to have reduced piglet birth weights (P=0.052), and piglet weaning weight was reduced by 0.8 kg (P=0.040) relative to the other diets. Colostrum and piglet serum IgA and IgG concentrations were unaffected by diet (P>0.10). Serum n-3 FA were greatest in sows (P<0.01) consuming 1:1P and 5:1F diets and in their offspring (P=0.014). Serum α-linolenic acid (ALA) was greatest in 1:1P sows and EPA and DHA were greatest in 5:1F sows (P<0.01). In pre-suckle piglet serum, ALA did not differ among treatment groups (P>0.10). Relative to piglets of sows consuming the control diet, EPA was 2.5-fold greater in the 1:1P group and 4-fold greater in 5:1F group (P<0.01) before suckling. In post-suckle samples, ALA was greatest in piglets from the 1:1P sows (P<0.01) and EPA and DHA were greatest in piglets from the 5:1F sows (P<0.01). Feeding diets with plant-based n-6:n-3 ratios of 5:1 or 1:1 did not impact performance relative to a control group but improved the conversion of ALA into EPA and increased the transfer of n-3 to piglets through milk. When a fish-based 5:1 ratio diet was fed, pre-weaning mortality was increased, and piglet birth and weaning weights decreased.
NASA Astrophysics Data System (ADS)
Reddy, P. Sreedhar; Pushpalatha, T.; Reddy, P. Sreenivasula
2007-07-01
Sodium fluoride (NaF), a widespread natural pollutant was given to sperm-positive female rats throughout gestation and lactation at a dose of 4.5 and 9.0 ppm via drinking water. The neonates were allowed to grow up to 90 days on tap water, and then sperm parameters, testicular steroidogenic marker enzyme activity levels, and circulatory hormone levels were studied. The sperm count, sperm motility, sperm coiling (hypoosmotic swelling test), and sperm viability were decreased in experimental rats when compared with controls. The activity levels of testicular steroidogenic marker enzymes (3β hydroxysteroid dehydrogenase and 17β hydroxysteroid dehydrogenase) were significantly decreased in experimental animals indicating decreased steroidogenesis. The serum testosterone, follicle stimulating hormone and luteinizing hormone levels were also significantly altered in experimental animals. Our data indicate that exposure to NaF during gestation and lactation affects male reproduction in adult rats by decreasing spermatogenesis and steroidogenesis.
Carlson, D B; Reed, J J; Borowicz, P P; Taylor, J B; Reynolds, L P; Neville, T L; Redmer, D A; Vonnahme, K A; Caton, J S
2009-02-01
The objectives were to examine effects of dietary Se supplementation and nutrient restriction during defined periods of gestation on maternal adaptations to pregnancy in primigravid sheep. Sixty-four pregnant Western Whiteface ewe lambs were assigned to treatments in a 2 x 4 factorial design. Treatments were dietary Se [adequate Se (ASe; 3.05 microg/kg of BW) vs. high Se (HSe; 70.4 microg/kg of BW)] fed as Se-enriched yeast, and plane of nutrition [control (C; 100% of NRC requirements) vs. restricted (R; 60% of NRC requirements]. Selenium treatments were fed throughout gestation. Plane of nutrition treatments were applied during mid (d 50 to 90) and late gestation (d 90 to 130), which resulted in 4 distinct plane of nutrition treatments [treatment: CC (control from d 50 to 130), RC (restricted from d 50 to 90, and control d 90 to 130), CR (control from d 50 to 90, and restricted from d 90 to 130), and RR (restricted from d 50 to 130)]. All of the pregnant ewes were necropsied on d 132 +/- 0.9 of gestation (length of gestation approximately 145 d). Nutrient restriction treatments decreased ewe ADG and G:F, as a result, RC and CR ewes had similar BW and maternal BW (MBW) at necropsy, whereas RR ewes were lighter than RC and CR ewes. From d 90 to 130, the HSe-CC ewes had greater ADG (Se x nutrition; P = 0.05) than did ASe-CC ewes, whereas ADG and G:F (Se x nutrition; P = 0.08) were less for HSe-RR ewes compared with ASe-RR ewes. The CR and RR treatments decreased total gravid uterus weight (P = 0.01) as well as fetal weight (P = 0.02) compared with RC and CC. High Se decreased total (g; P = 0.09) and relative heart mass (g/kg of MBW; P = 0.10), but increased total and relative mass of liver (P < or = 0.05) and perirenal fat (P < or = 0.06) compared with ASe. Total stomach complex mass was decreased (P < 0.01) by all the nutrient restriction treatments, but was reduced to a greater extent in CR and RR compared with RC. Total small intestine mass was similar between RC and CC ewes, but was markedly reduced (P < 0.01) in CR and RR ewes. The mass of the stomach complex and the small and large intestine relative to MBW was greater (P = 0.01) for RC than for CR ewes. Increased Se decreased jejunal DNA concentration (P = 0.07), total jejunal cell number (P = 0.03), and total proliferating jejunal cell number (P = 0.05) compared with ASe. These data indicate that increased dietary Se affected whole-body and organ growth of pregnant ewes, but the results differed depending on the plane of nutrition. In addition, the timing and duration of nutrient restriction relative to stage of pregnancy affected visceral organ mass in a markedly different fashion.
Developmental programming: gestational testosterone treatment alters fetal ovarian gene expression.
Luense, Lacey J; Veiga-Lopez, Almudena; Padmanabhan, Vasantha; Christenson, Lane K
2011-12-01
Prenatal testosterone (T) treatment leads to polycystic ovarian morphology, enhanced follicular recruitment/depletion, and increased estradiol secretion. This study addresses whether expression of key ovarian genes and microRNA are altered by prenatal T excess and whether changes are mediated by androgenic or estrogenic actions of T. Pregnant Suffolk ewes were treated with T or T plus the androgen receptor antagonist, flutamide (T+F) from d 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, and key ovarian regulators were measured by RT-PCR using RNA obtained from fetal ovaries collected on d 65 [n = 4, 5, and 5 for T, T+F, and control groups, respectively] and d 90 (n = 5, 7, 4) of gestation. Additionally, fetal d 90 RNA were hybridized to multispecies microRNA microarrays. Prenatal T decreased (P < 0.05) Cyp11a1 expression (3.7-fold) in d 90 ovaries and increased Cyp19 (3.9-fold) and 5α-reductase (1.8-fold) expression in d 65 ovaries. Flutamide prevented the T-induced decrease in Cyp11a1 mRNA at d 90 but not the Cyp19 and 5α-reductase increase in d 65 ovaries. Cotreatment with T+F increased Cyp11a1 (3.0-fold) expression in d 65 ovaries, relative to control and T-treated ovaries. Prenatal T altered fetal ovarian microRNA expression, including miR-497 and miR-15b, members of the same family that have been implicated in insulin signaling. These studies demonstrate that maternal T treatment alters fetal ovarian steroidogenic gene and microRNA expression and implicate direct actions of estrogens in addition to androgens in the reprogramming of ovarian developmental trajectory leading up to adult reproductive pathologies.
Payne, Magdalene; Stephens, Trina; Lim, Kenneth; Ball, Ronald O; Pencharz, Paul B; Elango, Rajavel
2018-01-01
Lysine is the first limiting amino acid in cereal proteins and is found mainly in animal-derived products. Current Dietary Reference Intake (DRI) recommendations extrapolate lysine requirements during pregnancy from nonpregnant adult data, and may underestimate true requirements. Our objective is to define a quantitative lysine requirement in healthy pregnant women and to determine whether requirements vary between 2 phases of gestation. Fourteen pregnant women in early (12-19 wk) and 19 women in late (33-39 wk) gestation were studied using the indicator amino acid oxidation technique. Individual lysine intakes (6-84 mg · kg-1 · d-1, deficient to excess) were tested on each study day as a crystalline amino acid mixture based on egg protein composition. Isonitrogenous diets maintained protein intake at 1.5 g · kg-1 · d-1 and calorie intake at 1.7 times resting energy expenditure during each study day. Phenylalanine and tyrosine intakes were held constant across all lysine intakes. Breath and urine samples were collected at baseline and isotopic steady state. Lysine requirements were determined by measuring the oxidation of L-[1-13C]-phenylalanine to 13CO2 (F13CO2). Biphase linear regression crossover analysis was used to determine a breakpoint (which represents the estimated average requirement, EAR) in F13CO2. The EAR for lysine during early gestation was determined to be 36.6 mg · kg-1 · d-1 (R2 = 0.484, upper 95% CI = 46.2 mg · kg-1 · d-1), similar to an earlier adult requirement of 36 mg · kg-1 · d-1. The EAR for lysine during late gestation was determined to be 50.3 mg · kg-1 · d-1 (R2 = 0.664, upper 95% CI = 60.4 mg · kg-1 · d-1), 23% higher than the current pregnancy DRI EAR recommendation of 41 mg · kg-1 · d-1. Our results suggest that lysine requirements are higher during late gestation compared to early gestation, and that current dietary lysine recommendations during late stages of pregnancy may be underestimated. The results have implications for populations consuming cereal-based diets as their primary source of protein. This trial was registered at clinicaltrials.gov as NCT01776931. © 2018 American Society for Nutrition. All rights reserved.
Peixoto, Alberto Borges; Caldas, Taciana Mara Rodrigues da Cunha; Martins, Wellington P; Da Silva Costa, Fabricio; Araujo Júnior, Edward
2016-10-01
To establish reference values for the amniotic fluid index (AFI) measurement between 26w0d and 41w6d of gestation in a Brazilian population. We performed a cross-sectional study with 1984 low-risk singleton pregnant women between 26w0d and 41w6d of gestation. AFI was measured according to the technique proposed by Phelan et al. Maternal abdomen was divided into four quadrants using the umbilicus and linea nigra as landmarks. Single vertical pocket in each quadrant was measured and the AFI was generated by the sum of these four values without umbilical cord or fetal parts. All ultrasound exams were performed by only two experienced examiners. AFI was expressed as median, interquartile range, mean and ranges in each gestational age (GA) interval. Polynomial regressions were performed to obtain the best fit with adjustment by the determination coefficient (R(2)). Mean of AFI ranged from 14.0 ± 4.1 cm (range, 9.7-14.0) at 26w0d to 8.3 ± 4.7 cm (range, 1.9-16.5) at 41w6d, respectively. The best polynomial regression fit curve was a first-degree: AFI = 16.29-0.125*GA (R(2) = 0.01). According the scatterplot, AFI values practically did not vary with advancing GA. Reference values for the AFI measurement between 26w0d and 41w6d of gestation in a low-risk Brazilian population were established.
Use of radiotelemetry to assess perinatal cardiac function in the ovine fetus and newborn.
Antolic, A; Wood, C E; Keller-Wood, M
2017-12-01
The late gestation fetal ECG (fECG) has traditionally been difficult to characterize due to the low fECG signal relative to high maternal noise. Although new technologies have improved the feasibility of its acquisition and separation, little is known about its development in late gestation, a period in which the fetal heart undergoes extensive maturational changes. Here, we describe a method for the chronic implantation of radiotelemetry devices into late gestation ovine fetuses to characterize parameters of the fECG following surgery, throughout late gestation, and in the perinatal period. We found no significant changes in mean aortic pressure (MAP), heart rate (HR), or ECG in the 5 days following implantation; however, HR decreased in the first 24 h following the end of surgery, with associated increases in RR, PR, and QRS intervals. Over the last 14 days of fetal life, fetal MAP significantly increased, and HR significantly decreased, as expected. MAP and HR increased as labor progressed. Although there were no significant changes over time in the ECG during late gestation, the duration of the PR interval initially decreased and then increased as birth approached. These results indicate that although critical maturational changes occur in the late gestation fetal myocardium, the mechanisms that control the cardiac conduction are relatively mature in late gestation. The study demonstrates that radiotelemetry can be successfully used to assess fetal cardiac function, in particular conduction, through the process of labor and delivery, and may therefore be a useful tool for study of peripartum cardiac events. Copyright © 2017 the American Physiological Society.
Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Jepsen, Karl J
2018-01-01
Abstract Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals. PMID:29732168
Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Bartolomei, Marisa S; Jepsen, Karl J
2018-04-01
Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals.
Gilbert, Kathleen M; Bai, Shasha; Barnette, Dustyn; Blossom, Sarah J
2017-06-01
Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Timing of umbilical cord clamping among infants born at 22 through 27 weeks' gestation.
Backes, C H; Huang, H; Iams, J D; Bauer, J A; Giannone, P J
2016-01-01
To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation. This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s). Forty mother-infant pairs were randomized. Infants in the ICC and DCC groups had mean gestational ages (GA) of 24.6 and 24.4 weeks, respectively. No differences were observed between the groups across all available safety measures, although infants in the DCC group had higher admission temperatures than infants in the ICC group (97.4 vs. 96.2 °F, P=0.04). During the first 24 h of life, blood pressures were lower in the ICC group than in the DCC group (P<0.05), despite a threefold greater incidence of treatment for hypotension (45% vs. 12%, P<0.01). Infants in the ICC group had increased numbers of red blood transfusions (in first 28 days of life) than infants in DCC group (4.1±3.9 vs. 2.8±2.2, P=0.04). Among infants born at an average GA of 24 weeks', DCC appears safe, logistically feasible, and offers hematological and circulatory advantages compared with ICC. A more comprehensive appraisal of this practice is needed.
Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial.
Dodd, Jodie M; Turnbull, Deborah; McPhee, Andrew J; Deussen, Andrea R; Grivell, Rosalie M; Yelland, Lisa N; Crowther, Caroline A; Wittert, Gary; Owens, Julie A; Robinson, Jeffrey S
2014-02-10
To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women. Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital. Three public maternity hospitals across South Australia. 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks' gestation, and BMI ≥ 25. 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information. Incidence of infants born large for gestational age (birth weight ≥ 90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles. 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups. For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes. Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).
Tura, A; Mari, A; Prikoszovich, T; Pacini, G; Kautzky-Willer, A
2008-08-01
Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.
Schuster, Andrew; Skinner, Michael K.; Yan, Wei
2016-01-01
Abstract Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5′ halves of mature tRNAs (5′ halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5′ halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon. PMID:27390623
Ali, Ehsan; Liao, Xun; Yang, Peng; Mao, Kaikai; Zhang, Xiaolei; Shakeel, Muhammad; Salim, Abdalla M A; Wan, Hu; Li, Jianhong
2017-12-05
In the present study, the effects of sublethal concentrations of buprofezin on life-table traits of S. furcifera were evaluated for two consecutive generations (F0 and F1). Our results exhibited that the fecundity, life span (longevity) and hatchability of the F0 and F1 generations were significantly decreased at LC 30 compared to the control. However, copulation was not significantly affected for the F0 or F1 generations at sublethal concentrations. The female life span was affected negatively at both treatments in F0 and at LC 30 in F1, compared to the control. Furthermore, significant effects of the sublethal concentrations were found on the developmental rate of all instars except the 3 rd instar of F1. However, the pre-adult period, total pre-oviposition period (TPOP) and adult pre-oviposition period (APOP) significantly increased in F1 individuals at LC 30 and LC 10 compared to the control. Our findings revealed that demographic characters (survival rate, intrinsic rate of increase (ri), finite rate of increase (λ), net reproductive rate (R 0 ), and gross reproductive rate (GRR)) of the F1 generation (from F0 parents) significantly decreased compared to the untreated group; however, the generation time (T) increased at LC 10 . Therefore, the results suggested that buprofezin could adversely affect individuals in the successive generation.
Effects of triphenyltin on reproduction in Japanese medaka (Oryzias latipes) across two generations.
Horie, Yoshifumi; Watanabe, Haruna; Takanobu, Hitomi; Shigemoto, Yoshiko; Yamagishi, Takahiro; Iguchi, Taisen; Tatarazako, Norihisa
2017-11-01
Triphenyltin (TPT) is an organotin compound used in marine anti-fouling coatings to prevent the attachment and growth of marine organisms, and it has negative effects on aquatic organisms. TPT is still detected at low concentrations, although its use has been prohibited at least in the European Community and is restricted in Japan as well. Studies using Japanese medaka (Oryzias latipes) indicate that TPT has the potential to inhibit reproduction. Although TPT is detected in many aquatic ecosystems, the multi-generational impact of TPT remains unknown. We investigated the two-generational effects of TPT on Japanese medaka and examined the relationships of several such effects between the F0 and F1 generations. Suppression of fecundity was observed in both generations, and fertility and growth were inhibited in the F1 generation. Moreover, delayed hatching and lower hatchability were observed in F1 embryos. Importantly, the value of the lowest observed effect concentration (LOEC) for these influences in F1 was lower than that in F0: that is, the LOEC values of fecundity and mortality were 3.2μg/L in the F0 generation and 1.0μg/L in the F1 generation. Fertility was not affected by TPT in F0, whereas it was significantly suppressed in the 1.0μg/L-exposure group of the F1 generation. Our results provide the first evidence of the effects of TPT on reproduction in a teleost fish across two generations, highlighting the concern that TPT could affect reproduction and mortality at decreasing concentrations in temporally overlapping generations. Copyright © 2017 Elsevier B.V. All rights reserved.
Parlakgumus, Huriye Ayse; Aytac, Pinar Caglar; Kalaycı, Hakan; Tarim, Ebru
2014-01-01
To investigate if first trimester lipids, sonographic parameters and serum markers are related to small- and large-for-gestational age (SGA, LGA) infants. This study was conducted at Baskent University Adana Research Center between December 2009 and July 2011 and enrolled 433 women. Blood samples were drawn to measure fasting blood glucose, serum triglycerides, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, fβ-hCG and pregnancy associated protein-A (PAPP-A) at the first trimester. Crown rump length and nuchal translucency were measured as suggested by the fetal medicine foundation. LGA group was significantly taller (p = 0.016) and SGA group had significantly greater BMI (0.025). SGA fetuses were born at a significantly earlier gestational age (p = 0.001). Univariate analysis revealed that LGA group had significantly lower cholesterol (p = 0.038) and LDL levels (p = 0.041). PAPP-A was significantly lower in SGA Group compared with LGA Group (0.027). After controlling for age, parity, height, pre-pregnant BMI, weight gain during pregnancy and fasting blood sugar, none of the lipids, serum markers or sonographic parameters was related to LGA. PAPP-A was the only parameter significantly associated with SGA after multivariate analysis (p = 0.008). PAPP-A was significantly associated with SGA after controlling for confounders.
Contreras, Zuelma A; Ritz, Beate; Virk, Jasveer; Cockburn, Myles; Heck, Julia E
2016-10-01
We aimed to examine the influence of pre-pregnancy diabetes, pre-pregnancy body mass index (BMI), gestational diabetes, and gestational weight gain on childhood cancer risk in offspring. We identified cancer cases (n = 11,149) younger than age 6 years at diagnosis from the California Cancer Registry registered between 1988 and 2013. Controls (n = 270,147) were randomly sampled from California birth records, and frequency matched by year of birth to all childhood cancers during the study period. Exposure and covariate information were extracted from birth records. Unconditional logistic regression models were generated to assess the importance of pre-pregnancy diabetes, pre-pregnancy BMI, gestational diabetes, and gestational weight gain on childhood cancer risk. We observed increased risks of acute lymphoblastic leukemia and Wilms' tumor in children of mothers with pre-pregnancy diabetes [odds ratio (OR) 95 % confidence interval (CI) 1.37 (1.11, 1.69); OR (95 % CI) 1.45 (0.97, 2.18), respectively]. When born to mothers who were overweight prior to pregnancy (BMI 25-<30), children were at increased risk of leukemia [OR (95 % CI) 1.27 (1.01, 1.59)]. Insufficient gestational weight gain increased the risk of acute myeloid leukemia [OR (95 % CI) 1.50 (0.92, 2.42)] while excessive gestational weight gain increased the risk of astrocytomas [OR (95 % CI) 1.56 (0.97, 2.50)]. No associations were found between gestational diabetes and childhood cancer risk in offspring. We estimated elevated risks of several childhood cancers in the offspring of mothers who had diabetes and were overweight prior to pregnancy, as well as mothers who gained insufficient or excessive weight. Since few studies have focused on these factors in relation to childhood cancer, replication of our findings in future studies is warranted.
NOTE: Entropy-based automated classification of independent components separated from fMCG
NASA Astrophysics Data System (ADS)
Comani, S.; Srinivasan, V.; Alleva, G.; Romani, G. L.
2007-03-01
Fetal magnetocardiography (fMCG) is a noninvasive technique suitable for the prenatal diagnosis of the fetal heart function. Reliable fetal cardiac signals can be reconstructed from multi-channel fMCG recordings by means of independent component analysis (ICA). However, the identification of the separated components is usually accomplished by visual inspection. This paper discusses a novel automated system based on entropy estimators, namely approximate entropy (ApEn) and sample entropy (SampEn), for the classification of independent components (ICs). The system was validated on 40 fMCG datasets of normal fetuses with the gestational age ranging from 22 to 37 weeks. Both ApEn and SampEn were able to measure the stability and predictability of the physiological signals separated with ICA, and the entropy values of the three categories were significantly different at p <0.01. The system performances were compared with those of a method based on the analysis of the time and frequency content of the components. The outcomes of this study showed a superior performance of the entropy-based system, in particular for early gestation, with an overall ICs detection rate of 98.75% and 97.92% for ApEn and SampEn respectively, as against a value of 94.50% obtained with the time-frequency-based system.
Conde-Agudelo, Agustin; Romero, Roberto
2015-12-01
To determine the accuracy of changes in transvaginal sonographic cervical length over time in predicting preterm birth in women with singleton and twin gestations. PubMed, Embase, Cinahl, Lilacs, and Medion (all from inception to June 30, 2015), bibliographies, Google scholar, and conference proceedings. Cohort or cross-sectional studies reporting on the predictive accuracy for preterm birth of changes in cervical length over time. Two reviewers independently selected studies, assessed the risk of bias, and extracted the data. Summary receiver-operating characteristic curves, pooled sensitivities and specificities, and summary likelihood ratios were generated. Fourteen studies met the inclusion criteria, of which 7 provided data on singleton gestations (3374 women) and 8 on twin gestations (1024 women). Among women with singleton gestations, the shortening of cervical length over time had a low predictive accuracy for preterm birth at <37 and <35 weeks of gestation with pooled sensitivities and specificities, and summary positive and negative likelihood ratios ranging from 49% to 74%, 44% to 85%, 1.3 to 4.1, and 0.3 to 0.7, respectively. In women with twin gestations, the shortening of cervical length over time had a low to moderate predictive accuracy for preterm birth at <34, <32, <30, and <28 weeks of gestation with pooled sensitivities and specificities, and summary positive and negative likelihood ratios ranging from 47% to 73%, 84% to 89%, 3.8 to 5.3, and 0.3 to 0.6, respectively. There were no statistically significant differences between the predictive accuracies for preterm birth of cervical length shortening over time and the single initial and/or final cervical length measurement in 8 of 11 studies that provided data for making these comparisons. In the largest and highest-quality study, a single measurement of cervical length obtained at 24 or 28 weeks of gestation was significantly more predictive of preterm birth than any decrease in cervical length between these gestational ages. Change in transvaginal sonographic cervical length over time is not a clinically useful test to predict preterm birth in women with singleton or twin gestations. A single cervical length measurement obtained between 18 and 24 weeks of gestation appears to be a better test to predict preterm birth than changes in cervical length over time. Published by Elsevier Inc.
Noble, N A; Brewer, G J
1982-03-01
During genetic selection of rats for high and low levels of red cell 2,3-diphosphoglycerate (DPG) the decreased fertility in Low-DPG animals was due to significantly (P less than 0.01) fewer offspring born per litter. The rat lines were intercrossed and animals at the tails of the F2 2,3-diphosphoglycerate distribution were mated. Subsequent matings of F3 offspring were monitored. Low-DPG F3 pregnant females killed at 20 days of gestation showed significantly (P less than 0.05) fewer corpora lutea than High-DPG F3 females. There were also significantly (P less than 0.01) fewer corpora lutea in Low-DPG line rats compared to High-DPG rats. It is concluded that the relationship between 2,3-diphosphoglycerate levels and fertility is not due to inbreeding but to a possible genetic linkage, a shared biochemical determinant or a relationship through the effect of 2,3-diphosphoglycerate levels on oxygen delivery to tissue.
Corrales, Jone; Thornton, Cammi; White, Mallory; Willett, Kristine L.
2014-01-01
In the aquatic environment, adverse outcomes from dietary polycyclic aromatic hydrocarbon (PAH) exposure are poorly understood, and multigenerational developmental effects following exposure to PAHs are in need of exploration. Benzo[a]pyrene (BaP), a model PAH, is a recognized carcinogen and endocrine disruptor. Here adult zebrafish (F0) were fed 0, 10, 114, or 1012 μg BaP/g diet at a feed rate of 1% body weight twice/day for 21 days. Eggs were collected and embryos (F1) were raised to assess mortality and time to hatch at 24, 32, 48, 56, 72, 80, and 96 hours post fertilization (hpf) before scoring developmental deformities at 96 hpf. F1 generation fish were raised to produce the F2 generation followed by the F3 and F4 generations. Mortality significantly increased in the higher dose groups of BaP (2.3 and 20 μg BaP/g fish) in the F1 generation while there were no differences in the F2, F3, or F4 generations. In addition, premature hatching was observed among the surviving fish in the higher dose of the F1 generation, but no differences were found in the F2 and F3 generations. While only the adult F0 generation was BaP-treated, this exposure resulted in multigenerational phenotypic impacts on at least two generations (F1 and F2). Body morphology deformities (shape of body, tail, and pectoral fins) were the most severe abnormality observed, and these were most extreme in the F1 generation but still present in the F2 but not F3 generations. Craniofacial structures (length of brain regions, size of optic and otic vesicles, and jaw deformities), although not significantly affected in the F1 generation, emerged as significant deformities in the F2 generation. Future work will attempt to molecularly anchor the persistent multigenerational phenotypic deformities noted in this study caused by BaP exposure. PMID:24440964
Ferguson, Sherry A; Delclos, K Barry; Newbold, Retha R; Flynn, Katherine M
2009-01-01
Previous work in our laboratory indicated that lifelong dietary exposure to estrogen-like endocrine disrupters increased sodium solution intake in adult male and female rats. Here, we sought to discern the critical periods necessary for this alteration as well as establish the effects of lower dietary concentrations of genistein and nonylphenol. Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-free chow containing 0, 5, 100, or 500 ppm genistein (approximately equal to 0.0, 0.4, 8.0, and 40.0 mg/kg/day) or 0, 25, 200, or 750 ppm nonylphenol (approximately equal to 0.0, 2.0, 16.0, and 60.0 mg/kg/day). Rats were mated within treatment groups and offspring (F1) maintained on the same diets. Mating for the F1, F2, and F3 (genistein only) was within treatment groups. At postnatal day (PND) 21, the F3 generation began to consume unadulterated phytoestrogen-free chow such that genistein exposure occurred only in utero and preweaning. The F4 generation was never directly exposed to genistein. On PNDs 65-68, intake of regular water and a 3.0% sodium chloride solution was measured for F1-F4 generations (genistein portion) or F1-F2 (nonylphenol portion). Although body weights were decreased by the highest dietary concentrations of genistein and nonylphenol, there were only minimal effects of exposure on sodium solution intake. As expected, intake was highest in female rats. With previous data, these results indicate that the dietary concentrations necessary to increase adult sodium solution intake in rats are greater than 500 ppm genistein and 750 ppm nonylphenol and such effects do not appear to increase across generations.
Association of Chiari malformation and vitamin B12 deficit in a family.
Welsch, Melanie; Antes, Sebastian; Kiefer, Michael; Meyer, Sascha; Eymann, Regina
2013-07-01
A clear etiology of Chiari malformation is still lacking. Some associations between this disorder and genetical variations have been reported. Documented cases of familial Chiari malformation in three consecutive generations are rare. Furthermore, an association of Chiari disorder and vitamin B12 deficit has rarely been described in literature. In this study, three generations of a family suffering from Chiari 1 or Chiari 0 malformation have been examined with MRI, clinically and laboratory (hemograms). Chiari malformation could be confirmed in all presented patients: While the F2 generation (children: 1 × ♀, 1 × ♂) and the female F1 generation (mother and sister of mother) suffered from Chiari type 1, the male F0 generation showed Chiari 0 malformation. F0 and F1 generation further presented with syringomyelia (F0: C4-D1; F1: C4-D2). All patients except the grandfather (F0) underwent surgical posterior fossa decompression to relive successfully cerebellar and hydrocephalus associated progressing clinical symptoms. The hemograms of generation 1 and 2 revealed familial vitamin B12 deficit. A hereditary component is discussed in Chiari malformation, yet proved etiology is still lacking. As folic acid plays an important role in the development of the neural tube, vitamin B12 deficit might have some impact on the development of Chiari malformations.
Multigeneration effects of insect growth regulators on the springtail Folsomia candida.
Campiche, Sophie; L'Ambert, Grégory; Tarradellas, Joseph; Becker-van Slooten, Kristin
2007-06-01
Multigeneration tests are very useful for the assessment of long term toxicity of pollutants such as endocrine disruptor compounds. In this study, multigeneration reproduction tests adapted from the ISO standard 11267 were conducted with the Collembola Folsomia candida. Springtails were exposed to artificial soil contaminated with four insect growth regulators (methoprene, fenoxycarb, teflubenzuron, and precocene II) according to two different experimental set-ups. In the first set-up, the parental generation (F(0)) of Collembola was exposed to a pollutant for 28 days. Juveniles from the F(1) generation were transferred to uncontaminated soil for another 28-day period to generate the F(2) generation. In the second set-up, the F(0) generation was exposed to a pollutant for 10 days before being transferred to uncontaminated soil to reproduce. After 18-28 days, juveniles from the F(1) were transferred to clean soil to generate the F(2) generation. An effect on the number of hatched juveniles of the F(2) generation was observed for methoprene after exposure of the F(0) for 28 days and hatching of F(1) in contaminated soil. For methoprene and teflubenzuron, significant effects were even observed on the F(2) generation with the second experimental set-up, when only the F(0) generation was exposed for 10 days. This shows that the impact of these substances is transgenerational, which can have important consequences for the population of these or other organisms. No effect on the F(2) generation was observed with fenoxycarb and precocene II with the 10-day exposure experiment. Our results show that the developed experimental procedures are appropriate to assess the long term effects of endocrine disrupting compounds on the reproduction of the non-target species F. candida. Another important finding is that two substances with the same predicted mode of action (i.e., the two juvenile hormone analogues fenoxycarb and methoprene) do not necessarily affect the same endpoints in F. candida.
Early Childhood Adversity and Pregnancy Outcomes
Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.
2016-01-01
Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511
[Dynamic changes of lung function in infant of different gestational ages].
Qi, Li-feng; Yu, Jia-lin; Liu, Xiao-hong; Wei, Min-chao
2013-06-25
To explore the dynamic changes of lung function in infants born at different gestational ages without respiratory complications. A total of 110 cases of hospitalized neonatal patients were retrospectively recruited and analyzed at Shenzhen Children's Hospital from July 2010 to August 2012. By gestational age they were divided into 3 groups of full term (37-40 weeks, n = 55, 29 males and 26 females) with an average birth weight (3.1 ± 0.3) kg, late preterm group (34- < 37 weeks, n = 30, 18 males and 12 females) with an average birth weight (2.1 ± 0.3) kg and early preterm (<34 weeks, n = 25, 16 males and 9 females )with an average birth weight (1.4 ± 0.3) kg. At Days 1, 14 and 28, lung function parameters of functional residual capacity (FRC) and lung clear index (LCI) were measured by multiple breath washouts with an ultrasonic flow meter and tidal breathing. One-way ANOVA was used for each index. Tidal expiratory flow 75% remaining tidal volume (TEF75), tidal expiratory flow 50% remaining tidal volume (TEF50) and tidal expiratory flow 25% remaining tidal volume (TEF25) gradually increased at Days 1, 14 and 28 in 3 groups. However respiratory rate (RR) gradually decreased. Compared with full term and late preterm, the early preterm infants had lower TEF75, TEF50 and TEF25, lower the ratios of time to peak expiratory flow and expiratory time (TPTEF/TE), lower ratios of volume to peak expiratory flow and expiratory volume (VPEF/VE) ((71 ± 21) and (66 ± 16) vs (55 ± 19)ml/s, (70 ± 20) and (62 ± 17) vs (51 ± 16)ml/s, (54 ± 17) and (51 ± 13) vs (38 ± 10)ml/s, 37% ± 8% and 34% ± 9% vs 29% ± 6%, 38% ± 6% and 33% ± 8% vs 28% ± 7%, F = 5.82, 8.74, 11.30, 7.72, 16.40, all P < 0.01), higher RR and LCI at Day 28((49 ± 6) and (51 ± 8) vs (56 ± 7)/min, 8.6 ± 2.7 and 8.9 ± 2.2 vs 10.8 ± 2.0,F = 10.09, 7.15, both P < 0.05). At a matched post-menstrual age of 40 weeks, compared with full term and late preterm, the early preterm group had lower TEF50, TEF25, TPTEF/TE, VPEF/VE ((65 ± 21) and (62 ± 12) vs (50 ± 17)ml/s,(51 ± 13) and (47 ± 10) vs (39 ± 10)ml/s, 36% ± 8% and 31% ± 7% vs 30% ± 6%, 37% ± 10% and 32% ± 8% vs 29% ± 6%,F = 4.41, 8.23, 9.08, 7.35, all P < 0.05). Lung function improves with the elongation of days. The parameters of lung function in early infants are worse than those in full and late-preterm counterparts. At a corrected gestational age of 40 weeks, early preterm infants fail to achieve catch-up growth in lung function. Dynamic monitoring of lung function in preterm infants of different gestational ages is of vital importance for gauging respiratory maturity and assessing lung development especially for preterm infants.
Factors associated with insomnia in pregnancy: A prospective Cohort Study.
Román-Gálvez, R M; Amezcua-Prieto, C; Salcedo-Bellido, I; Martínez-Galiano, J M; Khan, K S; Bueno-Cavanillas, A
2018-02-01
To quantify insomnia and their components in a longitudinal cohort of pregnant women and factors associated with insomnia. A prospective cohort of 486 healthy singleton pregnancies assembled before the 14th gestational week (February 2013 to March 2016). Insomnia data were collected pre-gestationally, in each trimester and six months post-partum, analysing five different moments. Multiple logistic regression analysis was performed to generate adjusted Odds Ratios (aOR) with 95% confidence intervals (CI) of determinants of insomnia in each trimester, defined using Athens Insomnia Scale (AIS) as score ≥8. Insomnia prevalence was 6.1% (3.9-8.9) pre-gestational, 44.2% (39.3-49.6) in first trimester (T1), 46.3% (41.9-51.3) in second (T2) and 63.7% (57.7-67.8) in third trimester (T3). Post-gestational insomnia was 33.2% (28.2-37.9) (p < 0.001 pre-gestational vs T1, T2 vs T3 and T3 vs after pregnancy). There was worsening mean AIS score, from: 2.34 before pregnancy to 9.87 in T3 because the deterioration of nighttime sleep, in absolute terms, but daytime impact was higher in T1. Previous trimester insomnia was associated with insomnia in T2 (aOR = 4.21, 95% CI 2.78-6.37) and T3 (aOR = 4.43, 95% CI 2.77-7.08). Pre-gestational insomnia was determinant of insomnia in T1 (aOR 12.50, 95% CI 3.58-43.60) and obesity was associated with insomnia in T3 (aOR = 2.30, 95% CI 0.99-5.32). On the contrary, moderate physical activity reduced the odds of insomnia in T3 (aOR 0.65, 95% CI 0.40-1.03). Insomnia prevalence was high from the beginning of pregnancy, associated with pre-gestational insomnia. In late pregnancy, two out of three pregnant women suffering insomnia. Insomnia prevention should be targeted particularly to those with high body mass index and pre-gestational insomnia. Copyright © 2017 Elsevier B.V. All rights reserved.
Morley, S A; Nguyen, K D; Peck, L S; Lai, C-H; Tan, K S
2017-08-01
Thermal acclimation capacity was investigated in adults of three tropical marine invertebrates, the subtidal barnacle Striatobalanus amaryllis, the intertidal gastropod Volegalea cochlidium and the intertidal barnacle Amphibalanus amphitrite. To test the relative importance of transgenerational acclimation, the developmental acclimation capacity of A. amphitrite was investigated in F 1 and F 2 generations reared at a subset of the same incubation temperatures. The increase in CT max (measured through loss of key behavioural metrics) of F 0 adults across the incubation temperature range 25.4-33.4°C was low: 0.00°C (V. cochlidium), 0.05°C (S. amaryllis) and 0.06°C (A. amphitrite) per 1°C increase in incubation temperature (the acclimation response ratio; ARR). Although the effect of generation was not significant, across the incubation temperature range of 29.4-33.4°C, the increase in CT max in the F 1 (0.30°C) and F 2 (0.15°C) generations of A. amphitrite was greater than in the F 0 (0.10°C). These correspond to ARR's of 0.03°C (F 0 ), 0.08°C (F 1 ) and 0.04°C (F 2 ), respectively. The variability in CT max between individuals in each treatment was maintained across generations, despite the high mortality of progeny. Further research is required to investigate the potential for transgenerational acclimation to provide an extra buffer for tropical marine species facing climate warming. Copyright © 2016 Elsevier Ltd. All rights reserved.
Utilizing Infant Cry Acoustics to Determine Gestational Age.
Sahin, Mustafa; Sahin, Suzan; Sari, Fatma N; Tatar, Emel C; Uras, Nurdan; Oguz, Suna S; Korkmaz, Mehmet H
2017-07-01
The date of last menstruation period and ultrasonography are the most commonly used methods to determine gestational age (GA). However, if these data are not clear, some scoring systems performed after birth can be used. New Ballard Score (NBS) is a commonly used method in estimation of GA. Cry sound may reflect the developmental integrity of the infant. The aim of this study was to evaluate the connection between the infants' GA and some acoustic parameters of the infant cry. A prospective single-blind study was carried out. In this prospective study, medically stable infants without any congenital craniofacial anomalies were evaluated. During routine blood sampling, cry sounds were recorded and acoustic analysis was performed. Step-by-step multiple linear regression analysis was performed. The data of 116 infants (57 female, 59 male) with the known GA (34.6 ± 3.8 weeks) were evaluated and with Apgar score of higher than 5. The real GA was significantly and well correlated with the estimated GA according to the NBS, F0, Int, Jitt, and latency parameters. The obtained stepwise linear regression analysis model was formulized as GA=(31.169) - (0.020 × F0)+(0.286 × GA according to NBS) - (0.003 × Latency)+(0.108 × Int) - (0.367 × Jitt). The real GA could be determined with a ratio of 91.7% using this model. We have determined that after addition of F0, Int, Jitt, and latency to NBS, the power of GA estimation would be increased. This simple formula can be used to determine GA in clinical practice but validity of such prediction formulas needs to be further tested. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Meteorological factors and timing of the initiating event of human parturition
NASA Astrophysics Data System (ADS)
Hirsch, Emmet; Lim, Courtney; Dobrez, Deborah; Adams, Marci G.; Noble, William
2011-03-01
The aim of this study was to determine whether meteorological factors are associated with the timing of either onset of labor with intact membranes or rupture of membranes prior to labor—together referred to as `the initiating event' of parturition. All patients delivering at Evanston Hospital after spontaneous labor or rupture of membranes at ≥20 weeks of gestation over a 6-month period were studied. Logistic regression models of the initiating event of parturition using clinical variables (maternal age, gestational age, parity, multiple gestation and intrauterine infection) with and without the addition of meteorological variables (barometric pressure, temperature and humidity) were compared. A total of 1,088 patients met the inclusion criteria. Gestational age, multiple gestation and chorioamnionitis were associated with timing of initiation of parturition ( P < 0.01). The addition of meteorological to clinical variables generated a statistically significant improvement in prediction of the initiating event; however, the magnitude of this improvement was small (less than 2% difference in receiver-operating characteristic score). These observations held regardless of parity, fetal number and gestational age. Meteorological factors are associated with the timing of parturition, but the magnitude of this association is small.
Climate Change and Fetal Health: The Impacts of Exposure to Extreme Temperatures in New York City
NASA Technical Reports Server (NTRS)
Ngo, Nicole S.; Horton, Radley M.
2015-01-01
Background: Climate change is projected to increase the frequency, intensity, and duration of heat waves while reducing cold extremes, yet few studies have examined the relationship between temperature and fetal health. Objectives: We estimate the impacts of extreme temperatures on birth weight and gestational age in Manhattan, a borough in New York City, and explore differences by socioeconomic status (SES). Methods: We combine average daily temperature from 1985 to 2010 with birth certificate data in Manhattan for the same time period. We then generate 33 downscaled climate model time series to project impacts on fetal health. Results: We find exposure to an extra day where average temperature 25 F and 85 F during pregnancy is associated with a 1.8 and 1.7 g (respectively) reduction in birth weight, but the impact varies by SES, particularly for extreme heat, where teen mothers seem most vulnerable. We find no meaningful, significant effect on gestational age. Using projections of temperature from these climate models, we project average net reductions in birth weight in the 2070- 2099 period of 4.6 g in the business-as-usual scenario. Conclusions: Results suggest that increasing heat events from climate change could adversely impact birth weight and vary by SES.
Sexual dimorphism in hybrids rats.
Garcia-Falgueras, Alicia; Pinos, Helena; Fernández, Rosa; Collado, Paloma; Pasaro, Eduardo; Segovia, Santiago; Guillamon, Antonio
2006-12-06
Laboratory rat strains descend from Wistar rats as a consequence of artificial selection. Previously we reported that the medial posterior division of the bed nucleus of the stria terminalis (BSTMP) was sexually dimorphic in Wistar and Long-Evans strains while the medial anterior division (BSTMA) and the locus coeruleus (LC) only showed sex differences in the ancestor Wistar strain. The lateral posterior division (BSTLP) was isomorphic in both strains. The present work studies the number of neurons in the BSTMP, BSTMA, BSTLP and LC of male and female Wistar and Long-Evans rats (F(0)) and their hybrid F(1) and F(2) generations. The BSTMP is sexually dimorphic in the F(0), F(1) and F(2) generations while sex differences in the LC are only seen in F(0) Wistar rats but not in the F(0) Long-Evans or the F(1) and F(2) hybrid generations. Sex differences in the BSTMA are seen in F(0) Wistar but not in F(0) Long-Evans rats and completely disappear in the F(2) generations. The number of neurons in the LC of both males and females decreased in heterozygotic individuals (F(1)) but increased in homozygotic (F(2)). However, the number of neurons in the BSTMP changes significantly over the generations, although the ratio of neurons (female/male) is stable and unaffected in homo- or heterozygosis. Thus, the mechanism that regulates the neuronal female/male ratio would be different from the one that controls the number of neurons. The facts that sex differences in the BSTMP are not affected by homo- or heterozygosis and that they are seen in several mammalian orders suggest the existence of a "fixed" type of brain sex differences in the Mammalia Class.
Generation and Termination of Binary Decision Trees for Nonparametric Multiclass Classification.
1984-10-01
O M coF=F;; UMBER2. GOVT ACCE5SION NO.1 3 . REC,PINS :A7AL:,G NUMBER ( ’eneration and Terminat_,on :)f Binary D-ecision jC j ik; Trees for Nonnararetrc...1-I . v)IAMO 0~I4 EDvt" O F I 00 . 3 15I OR%.OL.ETL - S-S OCTOBER 1984 LIDS-P-1411 GENERATION AND TERMINATION OF BINARY DECISION TREES FOR...minimizes the Bayes risk. Tree generation and termination are based on the training and test samples, respectively. 0 0 0/ 6 0¢ A 3 I. Introduction We state
Impact of aspirin on fetal growth in diabetic pregnancies according to White classification.
Adkins, Katlynn; Allshouse, Amanda A; Metz, Torri D; Heyborne, Kent D
2017-10-01
Current US Preventive Services Task Force and other guidelines recommend low-dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small-for-gestational-age birth. The Maternal-Fetal Medicine Units High-Risk Aspirin trial did not show a reduction in either preeclampsia or small-for-gestational-age birth in diabetic women. Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal-Fetal Medicine Units High-Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z-score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z-score between aspirin and placebo was tested with a 2-sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large-for-gestational-age newborns born to aspirin- vs placebo-treated women was compared between groups using Pearson exact χ 2 analysis, and an adjusted model was estimated by logistic regression. All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z-score (0.283; 95% confidence interval, 0.023-0.544) in the overall cohort (P = .03). In the adjusted model, the association of aspirin with higher birthweight Z-score was confined to neonates of women with nonvascular diabetes (0.341; 95% confidence interval, 0.677-0.006; P = .044). An opposite but nonsignificant effect was observed among neonates from women with vascular diabetes (-0.416; 95% confidence interval, -1.335 to 0.503; P = .6). This difference in the relationship of aspirin and birthweight Z-score by vascular group was significant at P = .046. Aspirin-randomized women with nonvascular diabetes had more large-for-gestational-age births than those treated with placebo (40.2 vs 26.6%; P = .005). Small-for-gestational-age births occurred at the same frequency with aspirin vs placebo randomization in the overall cohort (8% in each group) and in each vascular group. Inconsistent with our hypothesis, aspirin did not reduce small-for-gestational-age births in the overall cohort or either group. The increased incidence of large-for-gestational-age infants in aspirin-treated diabetic gestations is of potential concern given the known increased maternal and neonatal morbidity associated with macrosomia. Copyright © 2017 Elsevier Inc. All rights reserved.
[Fetal growth and activity at 20 to 24 weeks of gestation (preliminary study)].
Conde, Ana; Figueiredo, Bárbara; Tendais, Iva; Pereira, Ana F; Afonso, Elisa; Nogueira, Raúl
2008-01-01
Recent researches show that psychological development begins much before birth and prenatal influences can explain a significant part of the future variability in infants' behaviour and development. The aim of this study was to characterize the fetal development between 20 and 24 weeks of gestation, related to the measures of fetal growth-- iparietal diameter, abdominal circumference, head circumference, femur length and fetal weight-- and fetal activity--fetal heart rate and fetal movements. We also tried to establish if there are any differences in these measures related to the mothers' and fetus' sociodemographic features, obstetrical conditions and exposure to drugs. The sample of this study involved 48 fetus (52.1% female and 47.9% male) with an estimated gestational age (GA) between 20-24 weeks (Mean = 21 weeks and 1 day), whose mothers had appointments at the Obstetric and Gynaecological medical consultation of Júlio Dinis Maternity Hospital (MJD, Oporto). A video tape of the fetal behaviour was made and ultrasound biometry measurements were collected from the morphological ultrasound report. A statistical analysis of fetal data, after gestational age control, showed differences in fetal growth measures related to mothers' occupational status [F(1,41) = 7.28; p = .000], marital status [F(1,41) = 2.61; p = .04], household arrangements [F(1,41) = 2.91; p = .03] and coffee consumption [F(1,40) = 2.55; p = .05]. Differences in fetal activity measures (fetal heart rate) associated to fetus gender [F(1,16) = 5.84; p = .009] were also found. We can conclude about the sensibility of fetal development to prenatal factors related to the mothers' and fetus' sociodemographic features and exposure to drugs.
Laporta, J; Astessiano, A L; López-Mazz, C; Soca, P; Espasandin, A C; Carriquiry, M
2014-07-01
Our objective was to evaluate the metabolic, endocrine and hepatic mRNA profiles through the gestation-lactation cycle in purebred (PU: Angus and Hereford) and crossbred (CR: reciprocal F1 crosses) mutliparous beef cows (n=32), grazing on two herbage allowances of native pastures (2.5 v. 4 kg dry matter/kg BW; LO v. HI) and their associations with cow's productive performance (calf birth weight, milk production and commencement of luteal activity). Cow BW, body condition score (BCS) and blood samples were collected monthly, starting at -165 days relative to calving (days), and every 2 weeks after calving until +60 days of lactation. Liver biopsies were collected at -165, -75, -45, -15±10, and +15 and +60±3 days. Metabolic, endocrine and hepatic gene expression profiles, and calf birth weight, milk yield and postpartum commencement of luteal activity were evaluated. Overall, the most pronounced changes in metabolic, endocrine and hepatic gene expression occurred during winter gestation (-165 to -45 days), when all cows experienced the onset of a negative energy balance (decreased BCS, glucose and insulin, and increased non-esterified fatty acid concentrations, P<0.008). Concentrations of insulin and IGF-I were greater (P<0.037) in HI than in LO cows. However, serum IGF-I concentrations and hepatic growth hormone receptor (GHR) and IGF1 mRNA decreased (P<0.05) during the winter gestation period only in HI cows. Although IGF-I concentrations decreased (P<0.05) during the early postpartum (-15 v.+15 days) for all cows, the typical molecular mechanism that control the uncoupling of the growth hormone-IGF1 axis during the transition period of the dairy cattle (reduced hepatic GHR1A and IGF-I mRNA) was not observed in this study. The hepatic mRNA expression of key transcripts involved in gluconeogenesis and fatty-acid oxidation were upregulated (P<0.05) during winter gestation (from -165 to -45, -15 or +15 days, depending on the cow groups). Particularly, acyl-CoA oxidase-1 mRNA was greater for CR than for PU cows during winter gestation (-75 and -45 days), and fibroblast growth factor-21 mRNA was downregulated (P<0.01) only for HI cows during the transition (-15 v. 15 days) and lactation period (+15 to +60 days, P<0.01). These results, together with the greater BCS, estimated energy intake, increased milk yield and shorter commencement of luteal activity in HI than in LO, and in CR than in PU cows (P<0.018), would indicate that HI and CR cows were able to adapt more efficiently to changes in nutrient and energy supply through the gestation-lactation cycle.
Blum, Jason L.; Chen, Lung-Chi
2017-01-01
Background: Epidemiological studies associate inhalation of fine-sized particulate matter (PM2.5) during pregnancy with preterm birth (PTB) and low birth weight (LBW) but disagree over which time frames are most sensitive, or if effects are cumulative. Objectives: Our objective was to provide experimental plausibility for epidemiological observations by testing the hypothesis that exposure to PM2.5 during discrete periods of pregnancy results in PTB and LBW. Methods: For the first study, timed-pregnant B6C3F1 mice were exposed to concentrated ambient PM2.5 (CAPs) or filtered air (FA) throughout pregnancy [6 h/d from gestational day (GD) 0.5 through GD16.5]. A follow-up study examined the effects of CAPs exposure during discrete gestational periods (1: GD0.5–5.5; 2: GD6.5–14.5; 3: GD14.5–16.5; 4: GD0.5–16.5) aligning to milestones during human development. Results: In the first experiment, exposure to 160 μg CAPs/m3 throughout pregnancy decreased gestational term by 0.5 d (∼1.1 wk decrease for humans) and birth weight by 11.4% compared with FA. The follow-up experiment investigated timing of CAPs exposure (mean concentrations at 178, 193, 171, and 173 μg/m3 for periods 1–4, respectively). Pregnancy was significantly shortened (vs. FA) by ∼0.4d when exposure occurred during gestational periods 2 and 4, and by ∼0.5d if exposure occurred during period 3. Exposure during periods 1, 2, and 4 reduced birth weight by ∼10% compared with FA, and placental weight was reduced (∼8%) on GD17.5 if exposure occurred only during period 3. Conclusions: Adverse PM2.5-induced outcomes such as PTB and LBW are dependent upon the periods of maternal exposure. The results of these experimental studies could contribute significantly to air pollution policy decisions in the future. https://doi.org/10.1289/EHP1029 PMID:28893721
Karouna-Renier, Natalie K.; Chen, Yu; Henry, Paula F.; Maddox, Catherine M.; Sprague, Dan
2017-01-01
We investigated the effects of the androgenic growth promoter 17β-trenbolone (17βTB) on adult Japanese quail (Coturnix japonica) exposed across three generations. The F0 generation was exposed after sexual maturity to 0, 1, 5, 10, 20, and 40 ppm through feed. The F1 generation was exposed in ovo by maternal transfer and through feed at the same doses as their parents. The F2 generation was exposed in ovo only. Levels of plasma sex steroids, gonadal Cytochrome P450 aromatase (CYP19A1) mRNA and select brain neuroendocrine peptide mRNAs were measured. In males, testosterone levels did not differ in any generation from those in controls. Estradiol was significantly elevated in 17βTB treated F0 and F1 males. In F0 and F1 females, testosterone was suppressed by 17βTB, whereas estradiol was significantly higher at 40 ppm in F0 and at 10 ppm in F1 females. CYP19A1 expression in F1 males and females increased suggesting a compensatory response to the androgenic effects of 17βTB. Few significant effects were observed in the F2 birds indicating that in ovo exposure had limited effects on the monitored endpoints. Overall, our results confirmed endocrine disrupting effects of dietary 17βTB in Japanese quail but the response was dependent on sex, developmental stage at initiation of exposure, and dose.
Stapleton, Phoebe A.; Nichols, Cody E.; Yi, Jinghai; McBride, Carroll R.; Minarchick, Valerie C.; Shepherd, Danielle L.; Hollander, John M.; Nurkiewicz, Timothy R.
2016-01-01
Due to the ongoing evolution of nanotechnology, there is a growing need to assess the toxicological outcomes in under-studied populations in order to properly consider the potential of engineered nanomaterials (ENM) and fully enhance their safety. Recently, we and others have explored the vascular consequences associated with gestational nanomaterial exposure, reporting microvascular dysfunction within the uterine circulation of pregnant dams and the tail artery of fetal pups. It has been proposed (via work derived by the Barker Hypothesis) that mitochondrial dysfunction and subsequent oxidative stress mechanisms as a possible link between a hostile gestational environment and adult disease. Therefore, in this study, we exposed pregnant Sprague-Dawley rats to nanosized titanium dioxide aerosols after implantation (gestational day 6). Pups were delivered, and the progeny grew into adulthood. Microvascular reactivity, mitochondrial respiration and hydrogen peroxide production of the coronary and uterine circulations of the female offspring were evaluated. While there were no significant differences within the maternal or litter characteristics, endothelium-dependent dilation and active mechanotransduction in both coronary and uterine arterioles were significantly impaired. In addition, there was a significant reduction in maximal mitochondrial respiration (state 3) in the left ventricle and uterus. These studies demonstrate microvascular dysfunction and coincide with mitochondrial inefficiencies in both the cardiac and uterine tissues, which may represent initial evidence that prenatal ENM exposure produces microvascular impairments that persist throughout multiple developmental stages. PMID:25475392
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lumen, A, E-mail: Annie.Lumen@fda.hhs.gov
The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinkingmore » water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L.« less
Gaillard, Romy; Bakker, Rachel; Steegers, Eric A P; Hofman, Albert; Jaddoe, Vincent W V
2011-09-01
We hypothesized that hemodynamic adaptations related to pregnancy and ageing might be associated with differences in blood pressure levels during pregnancy between younger and older women. This might partly explain the increased risk of gestational hypertensive disorders with advanced maternal age. We examined the associations of maternal age with systolic and diastolic blood pressure in each trimester of pregnancy and the risks of gestational hypertensive disorders. The study was conducted among 8,623 women participating in a population-based prospective cohort study from early pregnancy onwards. Age was assessed at enrolment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical records. In second and third trimester, older maternal age was associated with lower systolic blood pressure (-0.9 mm Hg (95% confidence interval: -1.4, -0.3) and -0.6 mm Hg (95% confidence interval: -1.1, -0.02) per additional 10 maternal years, respectively). Older maternal age was associated with higher third trimester diastolic blood pressure (0.5 mm Hg (95% confidence interval: 0.04, 0.9) per additional 10 maternal years). Maternal age was associated with pregnancy-induced hypertension among overweight and obese women. Older maternal age is associated with lower second and third trimester systolic blood pressure, but higher third trimester diastolic blood pressure. These blood pressure differences seem to be small and within the physiological range. Maternal age is not consistently associated with the risks of gestational hypertensive disorders. Maternal body mass index might influence the association between maternal age and the risk of pregnancy-induced hypertension.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luo, Hanwen; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071; Deng, Zixin
Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats.more » F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced reproductive and developmental toxicities in F1 have hereditary effect. • Caffeine-induced programming of HPA axis in F2 has gender and parental differences.« less
Parisot, Florian; Bourdineaud, Jean-Paul; Plaire, Delphine; Adam-Guillermin, Christelle; Alonzo, Frédéric
2015-06-01
This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h(-1)). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h(-1) increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h(-1) in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h(-1) in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h(-1) in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h(-1) in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h(-1) at hatching to 0.007 mGy h(-1) after ∼21 days) and from F0 to F2 (0.070 mGy h(-1) at hatching to 0.007 mGy h(-1) after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h(-1) and DNA alterations significant at highest dose rates only. The study improved our understanding of long term responses to low doses of radiation at the molecular and organismic levels in a non-human species for a better radioprotection of aquatic ecosystems. Copyright © 2015 Elsevier B.V. All rights reserved.
Zapata, A; Hernandez-Garcia, J M; Grande, C; Martinez, I; Perez, J; de la Fuente, P; Usandizaga, J A
1989-06-01
We evaluated phospholipids, C-peptide and cortisol levels in amniotic fluid of 203 pathologic pregnancies (63, class A, B and C diabetics; 11 class D, F and H diabetics; 44 preclampsia and 85 Rh-isoimmunization); the control group was 82 normal pregnant women. There was an acceleration of fetal pulmonary maturation in women with preclampsia and severe Rh-isoimmunization in class D, F and H diabetics (at 34 weeks gestation the incidence of mature surfactant (lecithin/sphingomyelin greater than or equal to 2.7 and presence of phosphatidyl-glycerol) in these groups was 30%, 50% and 100%, respectively, while it was zero in the control group). At 37 and 38 weeks only 44.4% of the class A, B and C diabetics had mature surfactant and there was a significant difference with respect to the control group (x2 = 4.9; p less than 0.05); C-peptide levels in these diabetics (class A, B and C) were higher than in controls (p less than 0.001); in pregnant women with accelerated fetal lung maturation they were lower. We demonstrated a close relationship between fetal pulmonary maturity and the type of surfactant in amniotic fluid, which was independent of gestational age.
Renaud, Samantha M; Fountain, Stephen B
2016-01-01
This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4days of massed training (20patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a "violation element" of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation. Copyright © 2016 Elsevier Inc. All rights reserved.
Ay, L; Kruithof, C J; Bakker, R; Steegers, E A P; Witteman, J C M; Moll, H A; Hofman, A; Mackenbach, J P; Hokken-Koelega, A C S; Jaddoe, V W V
2009-06-01
We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. Population-based birth cohort study. Data of pregnant women and their children in Rotterdam, the Netherlands. In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.
Fehlert, E; Willmann, K; Fritsche, L; Linder, K; Mat-Husin, H; Schleger, F; Weiss, M; Kiefer-Schmidt, I; Brucker, S; Häring, H-U; Preissl, H; Fritsche, A
2017-11-01
Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT). We measured heart rate variability (HRV) of mothers and fetuses during a three-point OGTT using fetal magnetocardiography (fMCG). Measurements were performed in the fMEG Centre in Tübingen. After exclusion of 23 participants, 13 pregnant women with GDM and 36 pregnant women with normal glucose tolerance were examined. All women underwent the same examination setting with OGTT during which fMCG was recorded three times. Parameters of heart rate variability were measured. Compared with mothers with normal glucose regulation, mothers with GDM showed increased heart rate but no significant differences of maternal HRV. In contrast, HRV in fetuses of mothers with GDM differed from those in the metabolically healthy group regarding standard deviation normal to normal beat (SDNN) (P = 0.012), low-frequency band (P = 0.008) and high-frequency band (P = 0.031). These HRV parameters exhibit a decrease only in GDM fetuses during the second hour of the OGTT. These results show an altered response of the fetal autonomic nervous system to metabolic stress in GDM-complicated pregnancies. Hence, disturbances in maternal glucose metabolism might not only impact on the central nervous system of the fetus but may also affect the fetal autonomic nervous system. Metabolic stress reveals a different response of fetal autonomic nervous system in GDM-complicated pregnancies. © 2016 Royal College of Obstetricians and Gynaecologists.
Parilla, B V; McDermott, T M
1998-01-01
The objective of this article is to prospectively investigate the efficacy of amnioinfusion as a means to reduce febrile morbidity in pregnancies complicated by chorioamnionitis. All laboring patients with a temperature > or =100.1 degrees F were approached for study participation. Exclusion criteria included amnionitis diagnosed at greater than 8 cm dilation, multiple gestation, placental abruption, or a nonreassuring fetal heart rate tracing. Consenting patients were randomized to receive antibiotics (ampicillin or penicillin with gentamicin) and acetaminophen with or without amnioinfusion. All patients received intrauterine pressure catheter placement. For study patients, normal saline at room temperature was infused at 10 mL/min for 60 min, then 3 mL/min until delivery. Postpartum endometritis was defined as a temperature = 100.4 degrees F accompanied by uterine tenderness more than 12 hr after delivery. Statistical analysis was performed using the Student's t-test for continuous data and Chi-square for discrete variables. Thirty-six patients were enrolled, and complete data were available for 34 patients (17 in each group). There were no differences between groups with respect to maternal age, gravidity, race, or gestational age. There were also no differences between groups in duration of rupture of membranes, temperature at randomization, interval from randomization to delivery, cesarean section rate, or umbilical cord arterial pH. The mean temperature at the time of delivery was 99.8+/-0.9 degrees F for the amnioinfusion group versus 100.5+/-1.0 degrees F for the control group (p=0.046). Three of 17 amnioinfusion patients and 3 of 17 control patients had postpartum endometritis. There was 1 neonatal infection in the treatment group and no neonatal infections among the control patients. Prophylactic amnioinfusion was associated with a decline in temperature at the time of delivery. No untoward effects from the amnioinfusion were identified.
POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE
POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE.
J J Diliberto', J T Hamm'.2, F McQuaid', and L S Birnbaum'. 'US EPA, ORD/NHEERL/ETD, RTP, NC; 2Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC.
2,3,7,8-Tetrachlorodibenz...
Philip, Ranjit; Waller, B Rush; Agrawal, Vijaykumar; Wright, Dena; Arevalo, Alejandro; Zurakowski, David; Sathanandam, Shyam
2016-02-01
The aim of this study was to describe and differentiate the morphology of patent ductus arteriosus (PDA) seen in children born prematurely from other PDA types. PDAs are currently classified as types A-E using the Krichenko's classification. Children born prematurely with a PDA morphology that did not fit this classification were described as Type F PDA. A review of 100 consecutive children who underwent transcatheter device closure of PDA was performed. The diameter and length (L) of the PDA and the device diameter (D) were indexed to the descending aorta (DA) diameter. Comparison of 26 Type F PDAs was performed against, 29 Type A, 7 Type C and 32 Type E PDAs. Children with Type F PDAs (median 27.5 weeks gestation) were younger during the device occlusion compared with types A, C, and E (median age: 6 vs. 32, 11, and 42 months; P = 0.002). Type F PDAs were longer and larger, requiring a relatively large device for occlusion than types A, C, and E (Mean L/DA: 1.88 vs. 0.9, 1.21, and 0.89, P ≤ 0.01 and Mean D/DA: 1.04 vs. 0.46, 0.87, and 0.34, P ≤0.01). The Amplatzer vascular plug-II (AVP-II) was preferred for occlusion of Type F PDAs (85%; P <0.001). Children born prematurely have relatively larger and longer PDAs. These "fetal type PDAs" are best classified separately. We propose to classify them as Type F PDAs to add to types A-E currently in use. The AVP-II was effective in occluding Type F PDAs. © 2015 Wiley Periodicals, Inc.
Chen, Leyun; Li, Xiaolin; Hong, Haizheng; Shi, Dalin
2018-01-01
One of the most widely used organic UV filters, 4-methylbenzylidene camphor (4-MBC), is present at high concentrations in offshore waters. The marine copepod Tigriopus japonicus was exposed to different concentrations of 4-MBC (i.e., 0, 0.5, 1, 5 and 10μgL -1 ) for 4 consecutive generations (F0-F3) to evaluate the impact of 4-MBC on marine ecosystems. The results showed that in the F0 generation, 4-MBC caused significant lethal toxicity in T. japonicas at concentrations of 5 and 10μgL -1 and the nauplii were more sensitive to 4-MBC toxicity than the adults. However in the F1-F3 generations, 4-MBC exposure did not affect the survival rate. The hatching rate and the developmental duration from the nauplii to the copepodite (N-C) and from the nauplii to adult (N-A) decreased significantly in the F1-F2 generations and in the F2-F3 generations, respectively, even at the lowest exposure concentration (0.5μgL -1 ). In the subsequent two generations (i.e., the F4-F5 generations) of recovery exposure in clean seawater, the growth rates of the original 4-MBC exposure groups were still faster than the control in both the N-C and N-A stages, suggesting possible transgenerational genetic and/or epigenetic changes upon chronic 4-MBC exposure. The expression of the ecdysone receptor gene was up-regulated by 4-MBC, which was consistent with the decrease of the N-C/N-A duration. In addition, 4-MBC may induce oxidative stress and trigger apoptosis in T. japonicas, resulting in developmental, reproductive and even lethal toxicity. A preliminary risk assessment suggested that under environmentally realistic concentrations, 4-MBC had significant potential to pose a threat to marine crustaceans and marine ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.
Life-cycle toxicity of bis(tributyltin) oxide to the sheepshead minnow (Cyprinodon variegatus).
Manning, C S; Lytle, T F; Walker, W W; Lytle, J S
1999-08-01
The effects of tributyltin (TBT) to the life cycle of the estuarine fish Cyprinodon variegatus were examined in a 180-day flow-through exposure. The study was initiated with embryos less than 24 h postfertilization and monitored through hatch, maturation, growth, and reproduction under continuous exposure to mean measured TBT concentrations of 5.4, 3.2, 1.3, 0.66, and 0.41 microg TBT/L. Progeny isolated at the onset of reproduction by the parental generation (F0) were monitored for survival as embryos, survival as fry/juveniles, and growth 30 days postisolation. TBT, at a concentration of 5.4 microg/L, significantly reduced embryo survival of the F0 generation sheepshead minnows. By day 145 of the exposure, significant effects to the survival of this generation increased and included all test concentrations >/=0.66 microg/L. Survival of 0.66 microg/L was reduced 59% relative to control survival by termination of the F0 generation. Growth of F0 generation organisms as measured by standard length was significantly reduced only on day 90 at 3.2 microg/L, however no significant reductions of wet or dry weight related to treatment concentration were detected. Due to complete mortality of organisms exposed to 5.4 microg/L by study day 7, effects to fecundity and progeny were monitored at measured concentrations of 3.2, 1.3, 0.66, and 0.41 microg TBT/L. Fecundity, as measured by the production of viable eggs produced per female per day, was unaffected by any of the test treatments. All F1 generation embryos isolated from treatment chambers into 3.2 microg/L died. Survival, standard length, wet and dry weight of the F1 generation at the remaining treatment concentrations were unaffected. The results of this study indicate that exposure to TBT reduced survival of the F0 generation sheepshead minnow and establishes the lowest observed effect concentration (LOEC) as 0.66 microg TBT/L, and the no observed effect concentration (NOEC) as 0.41 microg TBT/L for this species.http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p258.html
A Comparative Study on Fetal Heart Rates Estimated from Fetal Phonography and Cardiotocography
Ibrahim, Emad A.; Al Awar, Shamsa; Balayah, Zuhur H.; Hadjileontiadis, Leontios J.; Khandoker, Ahsan H.
2017-01-01
The aim of this study is to investigate that fetal heart rates (fHR) extracted from fetal phonocardiography (fPCG) could convey similar information of fHR from cardiotocography (CTG). Four-channel fPCG sensors made of low cost (<$1) ceramic piezo vibration sensor within 3D-printed casings were used to collect abdominal phonogram signals from 20 pregnant mothers (>34 weeks of gestation). A novel multi-lag covariance matrix-based eigenvalue decomposition technique was used to separate maternal breathing, fetal heart sounds (fHS) and maternal heart sounds (mHS) from abdominal phonogram signals. Prior to the fHR estimation, the fPCG signals were denoised using a multi-resolution wavelet-based filter. The proposed source separation technique was first tested in separating sources from synthetically mixed signals and then on raw abdominal phonogram signals. fHR signals extracted from fPCG signals were validated using simultaneous recorded CTG-based fHR recordings.The experimental results have shown that the fHR derived from the acquired fPCG can be used to detect periods of acceleration and deceleration, which are critical indication of the fetus' well-being. Moreover, a comparative analysis demonstrated that fHRs from CTG and fPCG signals were in good agreement (Bland Altman plot has mean = −0.21 BPM and ±2 SD = ±3) with statistical significance (p < 0.001 and Spearman correlation coefficient ρ = 0.95). The study findings show that fHR estimated from fPCG could be a reliable substitute for fHR from the CTG, opening up the possibility of a low cost monitoring tool for fetal well-being. PMID:29089896
Gallo, Linda A; Tran, Melanie; Moritz, Karen M; Mazzuca, Marc Q; Parry, Laura J; Westcott, Kerryn T; Jefferies, Andrew J; Cullen-McEwen, Luise A; Wlodek, Mary E
2012-02-01
Intrauterine growth restriction caused by uteroplacental insufficiency increases risk of cardiovascular and metabolic disease in offspring. Cardio-renal and metabolic responses to pregnancy are critical determinants of immediate and long-term maternal health. However, no studies to date have investigated the renal and metabolic adaptations in growth restricted offspring when they in turn become pregnant. We hypothesised that the physiological challenge of pregnancy in growth restricted females exacerbates disease outcome and compromises next generation fetal growth. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation in WKY rats and F1 female offspring birth and postnatal body weights were recorded. F1 Control and Restricted females were mated at 4 months and blood pressure, renal and metabolic parameters were measured in late pregnancy and F2 fetal and placental weights recorded. Age-matched non-pregnant Control and Restricted F1 females were also studied. F1 Restricted females were born 10-15% lighter than Controls. Basal insulin secretion and pancreatic β-cell mass were reduced in non-pregnant Restricted females but restored in pregnancy. Pregnant Restricted females, however, showed impaired glucose tolerance and compensatory glomerular hypertrophy, with a nephron deficit but normal renal function and blood pressure. F2 fetuses from Restricted mothers exposed to physiological measures during pregnancy were lighter than Controls highlighting additive adverse effects when mothers born small experience stress during pregnancy. Female rats born small exhibit mostly normal cardio-renal adaptations but altered glucose control during late pregnancy making them vulnerable to lifestyle challenges.
Cheuk, Q Ky; Lo, T K; Wong, S F; Lee, C P
2016-02-01
Several studies have shown that women with pre-existing diabetes mellitus have significantly lower pregnancy-associated plasma protein-A levels than those without. This study aimed to evaluate whether first-trimester pregnancy-associated plasma protein-A multiple of median is associated with gestational diabetes mellitus in Chinese pregnant women. This prospectively collected case series was conducted in a regional hospital in Hong Kong. All consecutive Chinese women with a singleton pregnancy who attended the hospital for their first antenatal visit (before 14 weeks' gestation) from April to July 2014 were included. Pregnancy-associated plasma protein-A multiple of median was compared between the gestational diabetic (especially for early-onset gestational diabetes) and non-diabetic groups. The correlation between pregnancy-associated plasma protein-A level and glycosylated haemoglobin level in women with gestational diabetes was also examined. Of the 520 women recruited, gestational diabetes was diagnosed in 169 (32.5%). Among them, 43 (25.4%) had an early diagnosis, and 167 (98.8%) with the disease were managed by diet alone. The gestational diabetic group did not differ significantly to the non-diabetic group in pregnancy-associated plasma protein-A (0.97 vs 0.99, P=0.40) or free β-human chorionic gonadotrophin multiple of median (1.05 vs 1.02, P=0.29). Compared with the non-gestational diabetic group, women with early diagnosis of gestational diabetes had a non-significant reduction in pregnancy-associated plasma protein-A multiple of median (median, interquartile range: 0.86, 0.57-1.23 vs 0.99, 0.67-1.44; P=0.11). Pregnancy-associated plasma protein-A and glycosylated haemoglobin levels were not correlated in women with gestational diabetes (r=0.027; P=0.74). Chinese women with non-insulin-dependent gestational diabetes did not exhibit significant changes to pregnancy-associated plasma protein-A multiple of median nor a correlation between pregnancy-associated plasma protein-A with glycosylated haemoglobin levels. Pregnancy-associated plasma protein-A multiple of median was not predictive of non-insulin-dependent gestational diabetes or early onset of gestational diabetes. There was a high prevalence of gestational diabetes in the Chinese population.
Epigenetics and Future Generations.
Del Savio, Lorenzo; Loi, Michele; Stupka, Elia
2015-10-01
Recent evidence of intergenerational epigenetic programming of disease risk broadens the scope of public health preventive interventions to future generations, i.e. non existing people. Due to the transmission of epigenetic predispositions, lifestyles such as smoking or unhealthy diet might affect the health of populations across several generations. While public policy for the health of future generations can be justified through impersonal considerations, such as maximizing aggregate well-being, in this article we explore whether there are rights-based obligations supervening on intergenerational epigenetic programming despite the non-identity argument, which challenges this rationale in case of policies that affect the number and identity of future people. We propose that rights based obligations grounded in the interests of non-existing people might fall upon existing people when generations overlap. In particular, if environmental exposure in F0 (i.e. existing people) will affect the health of F2 (i.e. non-existing people) through epigenetic programming, then F1 (i.e. existing and overlapping with both F0 and F2) might face increased costs to address F2's condition in the future: this might generate obligations upon F0 from various distributive principles, such as the principle of equal opportunity for well being. © 2015 John Wiley & Sons Ltd.
Peiró, R; Santacreu, M A; Climent, A; Blasco, A
2007-07-01
The aim of this work is to study early embryo survival and development in 2 lines divergently selected for high and low uterine capacity throughout 10 generations. A total of 162 female rabbits from the high line and 133 from the low line were slaughtered at 25, 48, or 62 h of gestation. There were no differences in ovulation rate and fertilization rate between lines in any of the 3 stages of gestation. Embryo survival, estimated as the number of normal embryos recovered at a constant ovulation rate, was similar in both lines at 25 and 48 h. Embryo survival was greater in the high line [D (posterior mean of the difference between the high and low lines) = 0.57 embryos] at 62 h of gestation. There was no difference in embryonic stage of development at 25 h, but at 48 and 62 h of gestation, the high line, compared with the low line, had a greater percentage of early morulae (83 vs. 72%) and compacted morulae (55 vs. 38%). Divergent selection for uterine capacity appeared to modify embryo development, at least from 48 h of gestation, and embryo survival from 62 h.
Fetal nasal bone length during the second trimester of pregnancy in a Turkish population.
Goynumer, G; Arisoy, R; Yayla, M; Erdogdu, E; Ergin, N
2014-05-01
To determine the distribution of fetal nasal bone length (NBL) according to gestational age during the second trimester of pregnancy in a Turkish population. Fetal NBL and other routine biometric measurements were evaluated retrospectively in 2327 fetuses between 15 and 24 weeks of gestation. The measurements were obtained via transabdominal ultrasound. The distribution of fetal NBL between 15 and 24 weeks of gestation was established, and percentiles were calculated. Relationships between fetal NBL and other parameters were assessed using regression analysis. Mean (±standard deviation) fetal NBL ranged from 2.95±0.52 at 15 weeks of gestation to 6.26±0.77mm at 24 weeks of gestation. The fifth percentile for fetal NBL was 2.1mm at 15 weeks of gestation and 5.0mm at 24 weeks of gestation. A significant positive correlation was noted between fetal NBL and gestational age (NBL=gestational age×0.37-2.55; R(2)=0.59; p<0.01) and between fetal NBL and biparietal diameter (BPD) (NBL=BPD×0.11-0.33; R(2)=0.61; p<0.01). Fetal NBL is less in Turkish subjects compared with non-Turkish subjects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Prenatal exposure to allergen, DNA methylation, and allergy in grandoffspring mice.
Niedzwiecki, M; Zhu, H; Corson, L; Grunig, G; Factor, P H; Chu, S; Jiang, H; Miller, R L
2012-07-01
Prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. We hypothesized that prenatal exposure of mice (F0) to Aspergillus fumigatus (A. fumigatus) would be associated with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in CpG methylation of T-helper genes in third-generation mice (F2). Female BALB/c mice were sensitized to A. fumigatus (62.5, 125, 1250 μg, or saline) and re-exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late) gestation. Grandoffspring were treated with A. fumigatus (62.5 μg) at 9 weeks. IgE, IgG(1) , and IgG(2a) levels and cell counts from bronchoalveolar lavage fluid were determined. Lung DNA was pyrosequenced at multiple sites in the interferon (IFN)-γ and interleukin (IL)-4 promoters. Grandoffspring of mothers dosed with 1250 μg early during pregnancy developed increased airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed late in pregnancy developed lower IgE (P < 0.05) and airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed early had lower methylation at IL-4 CpG(-408) and CpG(-393) compared to late dosed mice (P < 0.005 across all doses). Few correlations were found between methylation levels and airway eosinophilia and IgE. Prenatal exposure to A. fumigatus late during pregnancy, but not early, was associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal exposure to A. fumigatus was associated with changes in CpG methylation in the IFN-γ and IL-4 promoters that did not correlate consistently with indicators of allergic sensitization. © 2012 John Wiley & Sons A/S.
Sell-Kubiak, E; van der Waaij, E H; Bijma, P
2013-08-01
The main focus of this study was to identify sow gestation features that affect growth rate (GR) and feed intake (FI) of their offspring during grower-finishing stage. Because the sow provides a specific environment to her offspring during gestation, certain features (e.g., BW of the sow), feed refusals or gestation group, may affect her ability to deliver and feed a healthy litter. Data on 17,743 grower-finishing pigs, coming from 604 sires and 681 crossbred sows, were obtained from the Institute for Pigs Genetics. Sow gestation features were collected during multiple gestations and divided into 3 clusters describing i) sow body condition (i.e., BW, backfat, and gestation length), ii) sow feed refusals (FR), the difference between offered and eaten feed during 3 periods of gestation: 1 to 28, 25 to 50, 45 to 80 d, and iii) sow group features (i.e., number of sows, and average parity). Sow gestation features were added to the base model 1 at a time to study their effect on GR and FI. Significant gestation features (P < 0.1) were fitted simultaneously in animal model to investigate whether they could explain common litter and permanent sow effects. Gestation length had effect on GR [1.4 (g/d)/d; P = 0.04] and FI [6.8 (g/d)/d; P = 0.007]. Body weights of the sow at insemination [0.07 (g/d)/kg; P = 0.08], at farrowing [0.14 (g/d)/kg; P < 0.0001], and after lactation [0.1 (g/d)/kg; P = 0.003] had effect on GR. Sow parturition-lactation loss in backfat thickness and weight were not significant for GR and FI. Days with FR during 25 to 50 and 45 to 80 d of gestation and average FR during 45 to 80 d of gestation had negative effect on GR and when substantially increased had also a positive effect on FI. Sow FR from 1 to 28 d of gestation were not significant. Number of sows in gestation group had effect on FI [-9 (g/d)/group member; P = 0.04] and day sow entered group had an effect on GR [-0.9 (g/d)/day; P = 0.04]. Sow gestation features explained 1 to 3% of the total variance in grower-finishing pigs. Gestation features did explain phenotypic variance due to permanent sow and part of phenotypic variance due to common litter effects for FI but not for GR.
Gillette, Ross; Miller-Crews, Isaac; Skinner, Michael K; Crews, David
2015-01-01
Exposure to the endocrine disrupting chemical vinclozolin during gestation of an F0 generation and/or chronic restraint stress during adolescence of the F3 descendants affects behavior, physiology, and gene expression in the brain. Genes related to the networks of growth factors, signaling peptides, and receptors, steroid hormone receptors and enzymes, and epigenetic related factors were measured using quantitative polymerase chain reaction via Taqman low density arrays targeting 48 genes in the central amygdaloid nucleus, medial amygdaloid nucleus, medial preoptic area (mPOA), lateral hypothalamus (LH), and the ventromedial nucleus of the hypothalamus. We found that growth factors are particularly vulnerable to ancestral exposure in the central and medial amygdala; restraint stress during adolescence affected neural growth factors in the medial amygdala. Signaling peptides were affected by both ancestral exposure and stress during adolescence primarily in hypothalamic nuclei. Steroid hormone receptors and enzymes were strongly affected by restraint stress in the mPOA. Epigenetic related genes were affected by stress in the ventromedial nucleus and by both ancestral exposure and stress during adolescence independently in the central amygdala. It is noteworthy that the LH showed no effects of either manipulation. Gene expression is discussed in the context of behavioral and physiological measures previously published.
Socio-economic status and risk of gestational diabetes mellitus among Chinese women.
Song, L; Shen, L; Li, H; Liu, B; Zheng, X; Zhang, L; Xu, S; Wang, Y
2017-10-01
The relationship between socio-economic status and gestational diabetes mellitus has received little attention. The purpose of this study was to investigate the association between socio-economic status and risk of gestational diabetes. Data were obtained from the ongoing Healthy Baby Cohort study in Hubei Province, China, in 2012-2014. Information on educational level and household income was collected using standard questionnaires during face-to-face interviews. Gestational diabetes was defined based on the International Association of Diabetes and Pregnancy Study Group's criteria. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for gestational diabetes in relation to socio-economic status. Among 6886 participants, 1005 (14.6%) pregnant women were diagnosed with gestational diabetes. Higher educational level was inversely associated with risk of gestational diabetes (OR, 0.74; 95% CI, 0.58, 0.95 for high school and OR, 0.62; 95% CI, 0.50, 0.76 for college or above). After adjustment for potential confounders, the ORs for gestational diabetes were 0.77 (95% CI, 0.59, 1.00) and 0.65 (95% CI, 0.51, 0.83) for women with high school and college or above education, respectively, compared with women with less than high school education. No significant association between household income and gestational diabetes was observed after adjustment for potential confounders. Subgroup analysis showed that the reduced risk of gestational diabetes with higher educational level was more evident among women with a pre-pregnancy BMI < 24 kg/m 2 (P for interaction = 0.022). Our findings suggested that educational level was a more robust predictor of gestational diabetes than household income among Chinese women. © 2017 Diabetes UK.
Feasibility of noninvasive fetal electrocardiographic monitoring in a clinical setting.
Arya, Bhawna; Govindan, Rathinaswamy; Krishnan, Anita; Duplessis, Adre; Donofrio, Mary T
2015-06-01
Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting. The fECG device has the ability to acquire fECG signals and allow calculation of fetal cardiac time intervals between 16- and 42-week gestational age (GA). We aimed to demonstrate the feasibility of fECG acquisition in a busy fetal cardiology clinic using the Monica fetal heart rate monitor. This is a prospective observational pilot study of fECG acquired from fetuses referred for fetal echocardiography. Recordings were performed for 5-15 min. Maternal signals were attenuated and fECG averaged. fECG and fetal cardiac time intervals (PR, QRS, RR, and QT) were evaluated by two cardiologists independently and inter-observer reliability was assessed using intraclass coefficient (ICC). Sixty fECGs were collected from 50 mothers (mean GA 28.1 ± 6.1). Adequate signal-averaged waveforms were obtained in 20 studies with 259 cardiac cycles. Waveforms could not be obtained between 26 and 30 weeks. Fetal cardiac time intervals were measured and were reproducible for PR (ICC = 0.89; CI 0.77-0.94), QRS (ICC = 0.79; CI 0.51-0.91), and RR (ICC = 0.77; CI 0.53-0.88). QT ICC was poor due to suboptimal T-wave tracings. Acquisition of fECG and measurement of fetal cardiac time intervals is feasible in a clinical setting between 19- and 42-week GA, though tracings are difficult to obtain, especially between 26 and 30 weeks. There was high reliability in fetal cardiac time intervals measurements, except for QT. The device may be useful for assessing atrioventricular/intraventricular conduction in fetuses from 20 to 26 and >30 weeks. Techniques to improve signal acquisition, namely T-wave amplification, are ongoing.
Healthy Pre-Pregnancy Diet and Exercise May Reduce Risk of Gestational Diabetes
... 21, 2014 All NICHD Spotlights Zhang, C., Liu, S., Solomon, C. G., & Hu, F. B. (2006). Dietary fiber ... 2241. PMID: 19940226 Zhang, C., Schulze, M. B., Solomon, C. G., & Hu, F. B. (2006). A prospective ...
Moisés, Elaine Christine Dantas; Duarte, Luciana de Barros; Cavalli, Ricardo de Carvalho; Marques, Maria Paula; Lanchote, Vera Lúcia; Duarte, Geraldo; da Cunha, Sérgio Pereira
2008-12-01
Peridural blockade with lidocaine, bupivacaine, and fentanyl is an anesthetic procedure extensively used in obstetrics, justifying the pharmacokinetic study of these drugs during labor. To investigate the influence of the physiopathological changes of gestational diabetes mellitus (GDM) on the pharmacokinetics of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women subjected to peridural anesthesia. Ten normal pregnant women (group 1) and six pregnant women with GDM (group 2) were studied, all of them at term. The patients received 200 mg 2% lidocaine hydrochloride without a vasoconstrictor by the peridural locoregional route. Maternal blood samples were collected at predetermined times for the analysis of lidocaine and MEGX by chromatography and pharmacokinetic analysis. The median pharmacokinetic parameters of lidocaine for groups 1 and 2 (P = 0.05), respectively, were as follows: for Cmax 879.11 and 1,145.58 ng/ml, AUC(0-infinity) 256.01 and 455.95 mug min(-1) ml(-1), Cl/f/kg 10.61 and 5.64 ml min(-1) kg(-1), and Vd/f/kg 3.26 and 2.19 L/kg. The median pharmacokinetic parameters of MEGX for groups 1 and 2 (P = 0.05), respectively, were as follows: for Cmax 82.71 and 141.38 ng/ml, Tmax 44.71 and 193.14 min, t(1/2)alpha 7.64 and 59.77 min, alpha 0.097 and 0.012/min, and AUC(0-infinity) 29.91 and 108.23 mug min(-1) ml(-1). The present data permit us to conclude that the apparent clearance of lidocaine and MEGX was reduced in diabetic patients compared to normal women, suggesting that GDM inhibits the CYP1A2/CYP3A4 isoforms responsible for the metabolism of this drug and its metabolite.
Martins, Alexandra; Guilhermino, Lúcia
2018-08-01
The environmental contamination by microplastics is a global challenge to ecosystem and human health, and the knowledge on the long-term effects of such particles is limited. Thus, the effects of microplastics and post-exposure recovery were investigated over 4 generations (F 0 , F 1 , F 2 , F 3 ) using Daphnia magna as model. Effect criteria were parental mortality, growth, several reproductive parameters, and population growth rate. Microplastics exposure (0.1mg/l of pristine polymer microspheres 1-5μm diameter) caused parental mortality (10-100%), and significantly (p≤0.05) decreased growth, reproduction, and population growth rate leading to the extinction of the microplastics-exposed model population in the F 1 generation. Females descending from those exposed to microplastics in F 0 and exposed to clean medium presented some recovery but up to the F 3 generation they still had significantly (p≤0.05) reduced growth, reproduction, and population growth rate. Overall, these results indicate that D. magna recovery from chronic exposure to microplastics may take several generations, and that the continuous exposure over generations to microplastics may cause population extinction. These findings have implications to aquatic ecosystem functioning and services, and raise concern on the long-term animal and human exposure to microplastics through diverse routes. Copyright © 2018. Published by Elsevier B.V.
VLF wave generation by beating of two HF waves in the ionosphere
NASA Astrophysics Data System (ADS)
Kuo, Spencer; Snyder, Arnold; Kossey, Paul; Chang, Chia-Lie; Labenski, John
2011-05-01
Theory of a beat-wave mechanism for very low frequency (VLF) wave generation in the ionosphere is presented. The VLF current is produced by beating two high power HF waves of slightly different frequencies through the nonlinearity and inhomogeneity of the ionospheric plasma. Theory also shows that the density irregularities can enhance the beat-wave generation. An experiment was conducted by transmitting two high power HF waves of 3.2 MHz and 3.2 MHz + f, where f = 5, 8, 13, and 2.02 kHz, from the HAARP transmitter. In the experiment, the ionosphere was underdense to the O-mode heater, i.e., the heater frequency f0 > foF2, and overdense or slightly underdense to the X-mode heater, i.e., f0 < fxF2 or f0 ≥ fxF2. The radiation intensity increased with the VLF wave frequency, was much stronger with the X-mode heaters, and was not sensitive to the electrojet. The strongest VLF radiation of 13 kHz was generated when the reflection layer of the X-mode heater was just slightly below the foF2 layer and the spread of the O-mode sounding echoes had the largest enhancement, suggesting an optimal setting for beat-wave generation of VLF waves by the HF heaters.
Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period
Rougé, Carole; Butel, Marie-José; Piloquet, Hugues; Ferraris, Laurent; Legrand, Arnaud; Vodovar, Michel; Voyer, Marcel; de la Cochetière, Marie-France; Darmaun, Dominique; Rozé, Jean-Christophe
2010-01-01
Background Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults. Objective To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut. Methodology F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge. Principal Findings Although median f-calprotectin excretion was 138 µg/g, a wide range of inter- and intra-individual variation in f-calprotectin values (from day 3 to day 78) was observed (86% and 67%, respectively). In multivariate regression analysis, f-calprotectin correlated negatively with ante and per natal antibiotic treatment (p = 0.001), and correlated positively with the volume of enteral feeding (mL/kg/d) (p = 0.009), the need to interrupt enteral feeding (p = 0.001), and prominent gastrointestinal colonization by Clostridium sp (p = 0.019) and Staphylococcus sp (p = 0.047). Conclusion During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment. PMID:20552029
Erdöl, Hidayet; Hacioglu, Dilek; Kola, Mehmet; Türk, Adem; Aslan, Yakup
2017-04-01
To investigate the effect of hemoglobin F (HbF) and hemoglobin A (HbA) levels on development of retinopathy of prematurity (ROP) in premature infants. In this prospective study, blood samples were collected from the side of the heel of 49 premature infants at postnatal months 0, 1, 2, and 3. HbF and HbA levels were measured in all samples and analyzed statistically. Furthermore, correlation analysis was performed regarding development of ROP, blood transfusion, and HbF and HbA levels. A total of 49 infants were included. The mean gestational age of the premature infants was 30.9 ± 2.7 weeks (range, 25-35 weeks); mean birth weight, 1542 ± 582 g (range, 520-3240 g). Of the 49 premature infants, stage 1 ROP or above developed in 26 (53%). Mean HbF levels were lower at postnatal months 1 and 2 in premature infants with ROP compared to those without ROP (P = 0.013 and 0.02, respectively); however, mean HbA levels were higher in the infants with ROP than the others (P = 0.034 and 0.029, respectively). Analysis of covariance that ignored transfusion revealed no difference between the means of Hb variants in the infants with and without ROP (P = 0.572 and 0.486). Blood transfusion significantly altered the levels of HbF and HbA in premature infants, and Hb variants have no direct effect on development of ROP. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Pugh, Sarah J; Albert, Paul S; Kim, Sungduk; Grobman, William; Hinkle, Stefanie N; Newman, Roger B; Wing, Deborah A; Grantz, Katherine L
2017-09-01
Inadequate or excessive total gestational weight gain is associated with increased risks of small- and large-for-gestational-age births, respectively, but evidence is sparse regarding overall and trimester-specific patterns of gestational weight gain in relation to these risks. Characterizing the interrelationship between patterns of gestational weight gain across trimesters can reveal whether the trajectory of gestational weight gain in the first trimester sets the path for gestational weight gain in subsequent trimesters, thereby serving as an early marker for at-risk pregnancies. We sought to describe overall trajectories of gestational weight gain across gestation and assess the risk of adverse birthweight outcomes associated with the overall trajectory and whether the timing of gestational weight gain (first vs second/third trimester) is differentially associated with adverse outcomes. We conducted a secondary analysis of a prospective cohort of 2802 singleton pregnancies from 12 US prenatal centers (2009 through 2013). Small and large for gestational age were calculated using sex-specific birthweight references <5th, <10th, or ≥90th percentiles, respectively. At each of the research visits, women's weight was measured following a standardized anthropometric protocol. Maternal weight at antenatal clinical visits was also abstracted from the prenatal records. Semiparametric, group-based, latent class, trajectory models estimated overall gestational weight gain and separate first- and second-/third-trimester trajectories to assess tracking. Robust Poisson regression was used to estimate the relative risk of small- and large-for-gestational-age outcomes by the probability of trajectory membership. We tested whether relationships were modified by prepregnancy body mass index. There were 2779 women with a mean of 15 (SD 5) weights measured across gestation. Four distinct gestational weight gain trajectories were identified based on the lowest Bayesian information criterion value, classifying 10.0%, 41.8%, 39.2%, and 9.0% of the population from lowest to highest weight gain trajectories, with an inflection at 14 weeks. The average rate in each trajectory group from lowest to highest for 0-<14 weeks was -0.20, 0.04, 0.21, and 0.52 kg/wk and for 14-39 weeks was 0.29, 0.48, 0.63, and 0.79 kg/wk, respectively; the second lowest gaining trajectory resembled the Institute of Medicine recommendations and was designated as the reference with the other trajectories classified as low, moderate-high, or high. Accuracy of assignment was assessed and found to be high (median posterior probability 0.99, interquartile range 0.99-1.00). Compared with the referent trajectory, a low overall trajectory, but not other trajectories, was associated with a 1.55-fold (95% confidence interval, 1.06-2.25) and 1.58-fold (95% confidence interval, 0.88-2.82) increased risk of small-for-gestational-age <10th and <5th, respectively, while a moderate-high and high trajectory were associated with a 1.78-fold (95% confidence interval, 1.31-2.41) and 2.45-fold (95% confidence interval, 1.66-3.61) increased risk of large for gestational age, respectively. In a separate analysis investigating whether early (<14 weeks) gestational weight gain tracked with later (≥14 weeks) gestational weight gain, only 49% (n = 127) of women in the low first-trimester trajectory group continued as low in the second/third trimester, and had a 1.59-fold increased risk of small for gestational age; for the other 51% (n = 129) of women without a subsequently low second-/third-trimester gestational weight gain trajectory, there was no increased risk of small for gestational age (relative risk, 0.75; 95% confidence interval, 0.47-1.38). Prepregnancy body mass index did not modify the association between gestational weight gain trajectory and small for gestational age (P = 0.52) or large for gestational age (P = .69). Our findings are reassuring for women who experience weight loss or excessive weight gain in the first trimester; however, the risk of small or large for gestational age is significantly increased if women gain weight below or above the reference trajectory in the second/third trimester. Published by Elsevier Inc.
Pedersen, H; Santos, A C; Morishima, H O; Finster, M; Plosker, H; Arthur, G R; Covino, B G
1988-03-01
The pharmacokinetics and pharmacodynamics of lidocaine were studied in nine chronically prepared pregnant ewes and their fetuses at a mean ( +/- SE) gestation of 119 +/- 1.0 days, and the results were compared to the data previously published for ten animals at 138 +/- 1.2 days of gestation (term 148 days). Lidocaine was infused intravenously to the mother at a constant rate of 0.1 mg.kg-1.min-1 over a period of 180 min, in order to reach a steady-state maternal plasma lidocaine concentration of approximately 2 micrograms/ml. Maternal and fetal blood samples and maternal urine were collected at intervals throughout the infusion for determination of pH, blood gases, and lidocaine concentrations. Maternal and fetal heart rate, blood pressure, and intraamniotic pressure were continuously recorded. Fetal cardiac output and organ blood flow were determined before and at the end of lidocaine infusion using radionuclide-labeled microspheres. Lidocaine tissue concentrations were determined in several maternal and fetal organs excised at the end of infusion. In both groups, the steady-state plasma concentrations of lidocaine were similar; namely, 2.3 +/- 0.17 and 2.1 +/- 0.21 micrograms/ml in preterm and term ewes, respectively. There were also no significant differences in steady-state plasma drug concentrations in preterm and term fetuses (1.3 +/- 0.11 and 1.2 +/- 0.15 micrograms/ml). The mean fetal maternal concentration ratios (F/M) were the same; namely, 0.6. Maternal urinary excretion of lidocaine correlated with urine pH, being greater in the more acid urine. Tissue uptake of drug tended to be higher in the preterm than term mothers, but only significantly so in the brain and adrenals.(ABSTRACT TRUNCATED AT 250 WORDS)
[Analysis of pregnancy outcomes of polycystic ovary syndrome patients after frozen embryo transfer].
Lyu, X D; Qiao, J
2018-01-25
Objective: To investigate pregnancy outcomes of the patients with polycystic ovary syndrome (PCOS) after frozen embryo transfer (FET) . Methods: Data of 2 367 PCOS patients received in vitro fertilization-embryo transfer [including fresh embryo transfer (fET) and FET] from January 2009 to December 2015 in Peking University Third Hospital were evaluated retrospectively. The basal characteristics, pregnancy complications and outcomes were analyzed, then identified the relative factors followed. Results: Totally 2 367 patients received in vitro fertilization-embryo transfer: 1 106 were treated with fET, and the rest 1 261 cases were treated with FET. The incidence of gestational diabetes mellitus (GDM) was lower in FET group [4.04%(51/1 261) versus 6.15%(68/1 106)], the difference was statistically significant ( P< 0.05). Singletons born after FET had higher birth weight than fET [(3 406±548) versus (3 360±533) g], the difference was statistically significant ( P< 0.05). There was no difference of other pregnancy complications between the two groups (all P> 0.05). fET was an independent risk factor for GDM (adjusted OR= 1.570, 95% CI: 1.075-2.294). Conclusion: Compared with fET, FET could decrease the risk of GDM and receive better neonatal outcomes in patients with PCOS.
Tokutomi, Tomoharu; Fukushima, Akimune; Yamamoto, Kayono; Bansho, Yasushi; Hachiya, Tsuyoshi; Shimizu, Atsushi
2017-07-14
The Tohoku Medical Megabank project aims to create a next-generation personalized healthcare system by conducting large-scale genome-cohort studies involving three generations of local residents in the areas affected by the Great East Japan Earthquake. We collected medical and genomic information for developing a biobank to be used for this healthcare system. We designed a questionnaire-based pedigree-creation software program named "f-treeGC," which enables even less experienced medical practitioners to accurately and rapidly collect family health history and create pedigree charts. f-treeGC may be run on Adobe AIR. Pedigree charts are created in the following manner: 1) At system startup, the client is prompted to provide required information on the presence or absence of children; f-treeGC is capable of creating a pedigree up to three generations. 2) An interviewer fills out a multiple-choice questionnaire on genealogical information. 3) The information requested includes name, age, gender, general status, infertility status, pregnancy status, fetal status, and physical features or health conditions of individuals over three generations. In addition, information regarding the client and the proband, and birth order information, including multiple gestation, custody, multiple individuals, donor or surrogate, adoption, and consanguinity may be included. 4) f-treeGC shows only marriages between first cousins via the overlay function. 5) f-treeGC automatically creates a pedigree chart, and the chart-creation process is visible for inspection on the screen in real time. 6) The genealogical data may be saved as a file in the original format. The created/modified date and time may be changed as required, and the file may be password-protected and/or saved in read-only format. To enable sorting or searching from the database, the file name automatically contains the terms typed into the entry fields, including physical features or health conditions, by default. 7) Alternatively, family histories are collected using a completed foldable interview paper sheet named "f-sheet", which is identical to the questionnaire in f-treeGC. We developed a questionnaire-based family tree-creation software, named f-treeGC, which is fully compliant with international recommendations for standardized human pedigree nomenclature. The present software simplifies the process of collecting family histories and pedigrees, and has a variety of uses, from genome cohort studies or primary care to genetic counseling.
Maternal exposure to benzo[b]fluoranthene disturbs reproductive performance in male offspring mice.
Kim, Ahyoung; Park, Mira; Yoon, Tae Ki; Lee, Woo Sik; Ko, Jeong-Jae; Lee, Kangseok; Bae, Jeehyeon
2011-05-30
Polycyclic aromatic hydrocarbons (PAHs) are a large family of environmentally prevalent toxic compounds generated from the combustion of organic materials and diesel exhaust. Humans and wild animals are exposed to PAHs mostly through dietary intake of contaminated food. Benzo[b]fluoranthene (B[b]F) is a common constituent of PAH complexes present in diverse types of food. B[b]F has been found in human milk, raising the demand for the need for risk assessment of offspring after maternal exposure to B[b]F. In the present study, pregnant mice were orally exposed to low doses (2-2000μg/kg body weight) of B[b]F during gestational and lactational periods, and their male offspring were assessed. Maternal B[b]F exposure disturbed normal sperm function in F1 offspring. To understand the molecular and cellular mechanisms by which the perinatal exposure to B[b]F decreased sperm quality, the testes of young adult F1 mice were examined for changes in expression of steroidogenesis-related and testicular apoptosis mediators and found that aryl hydrocarbon receptor, estrogen receptor α, and a set of proapoptotic proteins including Bax, Noxa, Bad, and Bim were significantly upregulated. Therefore, the current transgenerational animal study implies that consumption of PAH-contaminated diets by mothers may possibly influence their offspring to cause dysfunctional male reproductive function in humans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Jones, Nia W; Raine-Fenning, Nick J; Mousa, Hatem A; Bradley, Eileen; Bugg, George J
2011-03-01
Three-dimensional (3-D) power Doppler angiography (3-D-PDA) allows visualisation of Doppler signals within the placenta and their quantification is possible by the generation of vascular indices by the 4-D View software programme. This study aimed to investigate intra- and interobserver reproducibility of 3-D-PDA analysis of stored datasets at varying gestations with the ultimate goal being to develop a tool for predicting placental dysfunction. Women with an uncomplicated, viable singleton pregnancy were scanned at 12, 16 or 20 weeks gestational age groups. 3-D-PDA datasets acquired of the whole placenta were analysed using the VOCAL software processing tool. Each volume was analysed by three observers twice in the A plane. Intra- and interobserver reliability was assessed by intraclass correlation coefficients (ICCs) and Bland Altman plots. At each gestational age group, 20 low risk women were scanned resulting in 60 datasets in total. The ICC demonstrated a high level of measurement reliability at each gestation with intraobserver values >0.90 and interobserver values of >0.6 for the vascular indices. Bland Altman plots also showed high levels of agreement. Systematic bias was seen at 20 weeks in the vascular indices obtained by different observers. This study demonstrates that 3-D-PDA data can be measured reliably by different observers from stored datasets up to 18 weeks gestation. Measurements become less reliable as gestation advances with bias between observers evident at 20 weeks. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Mesbah, H A; El-Sayed, Nagda A; El-Kady, Magda B; Tayeb, E H; Mourad, A K; Kordy, A M; Henaidy, Zeinab M
2014-01-01
The present study is initiated to determine the toxic and delayed effects of four botanical oils on the greasy cutworm A. ipsilon, aiming to attain an alternative environmentally safe and effective phytochemicals against the insect-pest. Four botanical oils (camphor, red basil, menthol and rose oil) were added at rates of 0.5 and 1.0% (v/w). The tested oils were added alone, and/or admixed at proportional rate of 1:1 in the prepared baits against the exposed 4th instar till the 6th instar larvae of the insect. The study was run under the laboratory higrothermic conditions of 25±2°C and 65±5% R.H. The results showed that the tested baits of camphor, red basil and menthol oils at concentration rates of 0.5 and 1.0% (v/w) adversely affected the inspected parameters of fitness components of the treated individuals of parent (p) generation. They gave more or less fewer numbers of weak unviable adult-moths, which were either sterile or they laid few numbers of infertile eggs and died before the induction of (F1) progeny. That failure could be elucidated by the rapid occurrence of drastic effects on the biological performance of both the influenced sexes of adult-moths along the period of parent's development. Finally it ended by the inhibited induction of (F1) progeny. A delayed effect of the prepared baits of rose oil at 0.5 and 1.0% (v/w), was assessed on the following raised F1, F2, F3 and F4 generations after parent's treatment. The delayed effect was detected as less efficient latent effect on each of these consequently raised generations; characterized by the gradual decrease of the number of alive immatures and adult-moths. The effect was recorded as gradual increase of dead and malformed individuals and adult-moths. In addition to the gradual decrease of deposited and/or hatched eggs up to the 4th generation, which ended by the complete failure of the development. That failure could be also attributed to the cumulated effects of the induced recessive lethal genes in both the influenced sexes during the periods of raised F1, F2 and F3 generations. The recessive lethal genes caused drastic unprofitable effects that appeared at the beginning of the 4th generation that failed. Also, the tested baits (0.5 and 1.0%, v/w) of each of admixed camphor, red basil and menthol oil with rose oil (1:1), greatly affected the developmental parameters of the treated insects. The highest efficient toxicity and an adverse biological performance of the admixed camphor and/or red basil oils with rose oil at 0.5 and 1.0 (v/w), and menthol/rose oil at 0.5% (v/w) on the treated parent generation were detected. The previous treatment gave unviable sterile adults, which died before the induction of (F1) progeny. That recorded failure of (F1) proves the fastest toxic efficiency and a drastic biological performance which were entirely unable to induce (F1) progeny. The tested bait of mixed menthol/rose oils (1.0%, v/w), showed significant reduction in all studied parameters of F1 and F2 fitness components. The tested bait raised sterile unviable adult-moths of (F2) generation which furtherly ended by the distinct failure of (F2) development. This effect may be caused by the cumulative effects of the induced recessive lethal genes in both of the affected sexes through the developmental period of (F1) generation after (P) one treatment, inducing apparent drastic effects, which were revealed at the beginning of (F2) generation. Remarkably, the inspected faster or slower occurred toxicity and drastic biological performance of these admixed botanical oils, may be referred to the synergistic action for most of the evaluated mixtures or/and the additive one for menthol/rose oil (1.0%), which needs further investigation.
Ren, P; Yang, X J; Kim, J S; Menon, D; Pangeni, D; Manu, H; Tekeste, A; Baidoo, S K
2017-12-01
Sows are usually restricted fed during pregnancy to maximize their reproductive efficiency, which may predispose sows to a state of hunger. However, an objective measurement of hunger status has not been established. In the present study, we examined the correlation of plasma hormones and NEFA and selected the best predictors for hunger status using pregnant gilts. Three different levels of feed intake (0.5, 1.0 and 2.0 × maintenance energy intake [0.5M, 1.0M and 2.0M, respectively]) were imposed from Day 28 to 34 of gestation to create different hunger statuses in pregnant gilts. Plasma hormones related to energy homeostasis and NEFA were analyzed to quantify their response to different levels of feed intake. A total of 18 gilts (197.53 ± 6.41 kg) were allotted to 1 of 3 dietary treatments using a completely randomized design. Results showed that BW change, ADG, and G:F from Day 28 to 34 of gestation were higher ( < 0.01) for gilts on the 2.0M feeding level than for gilts on the 0.5M feeding level. Plasma acyl ghrelin concentrations showed a relatively flat pattern during the 24-h period. Plasma acyl ghrelin and NEFA concentrations and areas under the curve (AUC) were greater ( < 0.05) in gilts on the 0.5M level of feed intake than in those on the 2.0M level of feed intake. No differences were observed among the 3 feeding levels in terms of plasma glucagon-like peptide 1 and leptin concentrations. Additionally, consumption time for 1.82 kg feed on Day 35 of gestation was longer ( < 0.01) in gilts fed the 2.0M level of feed intake from Day 28 to 34 of gestation than in those on the 0.5M level of feed intake. Simple linear regression results showed that the AUC of acyl ghrelin was the best predictor for consumption time ( = 0.82), whereas the AUC of NEFA was the best predictor for BW ( = 0.55) or backfat change ( = 0.42) from Day 28 to 34 of gestation. In conclusion, our data suggested that a relative flat pattern existed in pregnant gilts in terms of the diurnal plasma profile of acyl ghrelin and that the level of feed intake of pregnant gilts was negatively correlated with plasma concentrations of acyl ghrelin and NEFA, which, in turn, were negatively associated with feed consumption time. The AUC of acyl ghrelin and NEFA seemed to be the best predictors for hunger status of pregnant gilts.
Li, Hong; Zhang, Chenyun; Ni, Feng; Guo, Suhua; Wang, Wenxiang; Liu, Jing; Lu, Xiaoli; Huang, Huiling; Zhang, Wenchang
2015-12-15
Research has revealed that n-hexane can disrupt adult female endocrine functions; however, few reports have focused on endocrine changes in adult F1 females after maternal exposure during gestation. In this study, female Wistar rats inhaled 100, 500, 2500, or 12,500 ppm n-hexane for 4 h daily during their initial 20 gestational days. The F1 female offspring exhibited abnormal oestrus cycles. Compared with the controls, the in vitro-cultured ovarian granulosa cells of the 12,500 ppm group showed significantly reduced in vitro progesterone and oestradiol secretion. Elevated progesterone secretion was observed in the 500 ppm group, and decreased and significantly upregulated mRNA expression of the Star, Cyp11a1, Cyp17a1, and Hsd3b genes was observed in the 12,500 ppm and 500 ppm groups, respectively. The protein expression levels were consistent with the mRNA expression levels. Methylation screening of the promoter regions of these genes was performed using MeDIP-chip and confirmed by methylation-sensitive high-resolution melting (MS-HRM), and the observed methylation state changes of the promoter regions were correlated with the gene expression levels. The results suggest that the hormone levels in the female offspring after gestational n-hexane inhalation correspond to the expression levels and DNA methylation states of the hormone production genes. Copyright © 2015. Published by Elsevier Ireland Ltd.
Zheng, J; Wang, H; Ren, M
2017-10-01
Exercise intervention might be a promising approach to prevent gestational diabetes mellitus. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the effect of exercise intervention on gestational diabetes mellitus. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of exercise intervention on gestational diabetes mellitus were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was the incidence of gestational diabetes mellitus, preterm birth, and gestational age at birth. Meta-analysis was performed using random-effect model. Five RCTs involving 1872 patients were included in the meta-analysis. Overall, compared with control intervention, exercise intervention was found to significantly reduce the risk of gestational diabetes mellitus (std. mean difference 0.62; 95% CI 0.43-0.89; P = 0.01), but demonstrated no influence on preterm birth (OR 0.93; 95% CI 0.44-1.99; P = 0.86), gestational age at birth (std. mean difference -0.03; 95% CI -0.12 to 0.07; P = 0.60), glucose 2-h post-OGTT (std. mean difference -1.02; 95% CI -2.75 to 0.71; P = 0.25), birth weight (std. mean difference -0.10; 95% CI -0.25 to 0.04; P = 0.16), Apgar score less than 7 (OR 0.78; 95% CI 0.21-2.91; P = 0.71), and preeclampsia (OR 1.05; 95% CI 0.53-2.07; P = 0.88). Compared to control intervention, exercise intervention was found to significantly reduce the incidence of gestational diabetes mellitus, but had no significant influence on preterm birth, gestational age at birth, glucose 2-h post-OGTT, birth weight, Apgar score less than 7, and preeclampsia.
Medaka extended one-generation reproduction test evaluating 4-nonylphenol.
Watanabe, Haruna; Horie, Yoshifumi; Takanobu, Hitomi; Koshio, Masaaki; Flynn, Kevin; Iguchi, Taisen; Tatarazako, Norihisa
2017-12-01
The medaka extended one-generation test (MEOGRT) was developed as a multigenerational toxicity test for chemicals, particularly endocrine-disrupting chemicals. Briefly, 3 generations of Japanese medaka (Oryzias latipes) are exposed to a chemical over a 20-wk period: 3 wk in the parental generation (F0), 15 wk in the first generation (F1), and 2 wk in the second generation (F2). The present study reports the first MEOGRT results concerning branched isomer mixtures of 4-nonylphenol (NP). Adult F0 medaka exposed to NP at 5 actual concentrations (1.27, 2.95, 9.81, 27.8, 89.4 µg/L) were unaffected in terms of reproduction, although vitellogenin in the male liver was increased dose-dependently at concentration of 2.95 µg/L and higher. In F1, in contrast, total egg (fecundity), fertile egg, and fertility decreased as NP increased; lowest-observed-effect concentrations (LOECs) for total egg, fertile egg, and fertility were 1.27, 1.27, 27.8 µg/L, respectively. In F1, but not in F0, secondary sex characteristics (i.e., anal fin papillae in males) were suppressed at 27.8 µg/L NP. Vitellogenin induction in adult male fish was slightly weaker in F1 than it was in F0, however. Gonadal sex abnormality and sex reversal occurred at 27.8 and 89.4 µg/L NP in F1 subadults. At 89.4 µg/L NP, all genotypic F1 males in breeding pairs had female phenotype, and some even demonstrated spawning. Concentrations of NP lower than 89.4 µg/L did not affect F2 survival or hatching. The highest detected NP level in environmental freshwater in Japan was approximately a half of the LOEC (1.27 µg/L for F1 fecundity); in other countries, however, environmental concentrations above the LOEC are reported, suggesting that NP may be affecting fish populations. Environ Toxicol Chem 2017;36:3254-3266. © 2017 SETAC. © 2017 SETAC.
[Effects of aromatase inhibitor on sexual differentiation of SDN-POA in rats].
Ohe, E
1994-03-01
The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats is larger than that of females, the difference being caused by the perinatal effect of estrogen converted from androgen. To investigate the role of estrogen formation in the SDN-POA during the critical period of this sexual differentiation, CGS16949A (0.5 mg/kg, sc) was injected into the mothers in the late gestational age(F) or into neonates for 14 days from birth(N). Animals were sacrificed on the 20th. day of gestation and 7 days after birth, and fetal and neonatal brain aromatase activities (AA) as well as serum levels of testosterone(T) and corticosterone(B) were measured. On the 30th day after birth, the offspring of treated mothers and neonatally treated rats were sacrificed and the cross-sectional areas of the SDN-POA were evaluated by image processor NEXUS 6800. In group F, CGS16949A markedly suppressed brain AA in vitro (fetal hypothalamus: IC50 1.4nM) and in vivo in both the hypothalamus and amygdala. However, the levels of T and B did not show any significant change in group F. The same depression of AA was also observed in group N on the 7th day after birth. In CGS-treated males in groups F and N, the SDN-POA area markedly decreased to that of control females. The area in males in group F was not significantly different from that in females. These results suggest that estrogen converted from androgen plays a dominant role in the development of sexual dimorphism of the SDN-POA, and that the brain AA in the pre- and postnatal period is important in this process.
Inclusion of extremes of prematurity in ventricular index centile charts.
Boyle, M; Shim, R; Gnanasekaran, R; Tarrant, A; Ryan, S; Foran, A; McCallion, N
2015-06-01
To assess the relationship between ventricular index (VI) measurements and postmenstrual age in preterm infants and to generate centile charts and normal ranges for frontal horn ratio (FHR) for a large contemporary cohort of preterm infants. A retrospective cohort study of 253 infants with birth gestation less than 32 weeks admitted between January 2009 and December 2011 to a tertiary NICU in Ireland. A total of 816 cranial ultrasounds were reviewed. Data collected were grouped according to postmenstrual age at the time of scan from 23 weeks to 45 weeks. Median values for VI show a general trend to increase with gestation. FHR did not significantly change with postmenstrual age at scan with a median value of 0.31. There is a slight increase in VI as gestation at the time of scans increases. These results provide the basis for updated centile charts which we propose for current practice.
Yang, Ruiqi; Wang, Fei; Zhang, Jialing; Zhu, Chonglei; Fan, Limei
2015-05-19
To establish the reference values of thalamus, caudate nucleus and lenticular nucleus diameters through fetal thalamic transverse section. A total of 265 fetuses at our hospital were randomly selected from November 2012 to August 2014. And the transverse and length diameters of thalamus, caudate nucleus and lenticular nucleus were measured. SPSS 19.0 statistical software was used to calculate the regression curve of fetal diameter changes and gestational weeks of pregnancy. P < 0.05 was considered as having statistical significance. The linear regression equation of fetal thalamic length diameter and gestational week was: Y = 0.051X+0.201, R = 0.876, linear regression equation of thalamic transverse diameter and fetal gestational week was: Y = 0.031X+0.229, R = 0.817, linear regression equation of fetal head of caudate nucleus length diameter and gestational age was: Y = 0.033X+0.101, R = 0.722, linear regression equation of fetal head of caudate nucleus transverse diameter and gestational week was: R = 0.025 - 0.046, R = 0.711, linear regression equation of fetal lentiform nucleus length diameter and gestational week was: Y = 0.046+0.229, R = 0.765, linear regression equation of fetal lentiform nucleus diameter and gestational week was: Y = 0.025 - 0.05, R = 0.772. Ultrasonic measurement of diameter of fetal thalamus caudate nucleus, and lenticular nucleus through thalamic transverse section is simple and convenient. And measurements increase with fetal gestational weeks and there is linear regression relationship between them.
Pan, Jiajia; Pan, Qiangwei; Chen, Yumei; Zhang, Hongping; Zheng, Xiaodong
2017-09-19
Probiotic supplement might be beneficial for gestational diabetes mellitus. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of probiotic supplement in gestational diabetes mellitus. PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of probiotic supplement in gestational diabetes mellitus were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome were fasting serum insulin and fasting plasma glucose. Meta-analysis was performed using the fixed-effect or random-effect model. Six RCTs involving 830 patients were included in the meta-analysis. Overall, compared with control intervention in gestational diabetes mellitus, probiotic supplementation intervention was found to significantly reduce fasting serum insulin (Std. mean difference = -0.95; 95% CI = -1.73 to -0.17; p < .00001) and HOMA-IR (Std. mean difference = -1.12; 95% CI = -2.05 to -0.18; p = .02), but showed no substantial impact on fasting plasma glucose (Std. mean difference = -0.49; 95% CI = -1.05-0.08; p = .09), gestational age (Std. mean difference = 0.07; 95% CI = -0.20-0.34; p = .63), and gestational weight (Std. mean difference = -0.11; 95% CI = -0.38-0.16; p = .43). Compared with control intervention in gestational diabetes mellitus, probiotic supplementation was found to significantly reduce insulin resistance (HOMA-IR) and fasting serum insulin, but had no substantial influence on fasting plasma glucose, gestational age and gestational weight.
Manuck, Tracy A; Stoddard, Gregory J; Fry, Rebecca C; Esplin, M Sean; Varner, Michael W
2016-11-01
Spontaneous preterm birth remains a leading cause of neonatal morbidity and mortality among nonanomalous neonates in the United States. Spontaneous preterm birth tends to recur at similar gestational ages. Intramuscular 17-alpha hydroxyprogesterone caproate reduces the risk of recurrent spontaneous preterm birth. Unfortunately, one-third of high-risk women will have a recurrent spontaneous preterm birth despite 17-alpha hydroxyprogesterone caproate therapy; the reasons for this variability in response are unknown. We hypothesized that clinical factors among women treated with 17-alpha hydroxyprogesterone caproate who suffer recurrent spontaneous preterm birth at a similar gestational age differ from women who deliver later, and that these associations could be used to generate a clinical scoring system to predict 17-alpha hydroxyprogesterone caproate response. Secondary analysis of a prospective, multicenter, randomized controlled trial enrolling women with ≥1 previous singleton spontaneous preterm birth <37 weeks' gestation. Participants received daily omega-3 supplementation or placebo for the prevention of recurrent preterm birth; all were provided 17-alpha hydroxyprogesterone caproate. Women were classified as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest previous spontaneous preterm birth. Responders were women with pregnancy extending ≥3 weeks later compared with the delivery gestational age of their earliest previous preterm birth; nonresponders delivered earlier or within 3 weeks of the gestational age of their earliest previous preterm birth. A risk score for nonresponse to 17-alpha hydroxyprogesterone caproate was generated from regression models via the use of clinical predictors and was validated in an independent population. Data were analyzed with multivariable logistic regression. A total of 754 women met inclusion criteria; 159 (21%) were nonresponders. Responders delivered later on average (37.7±2.5 weeks) than nonresponders (31.5±5.3 weeks), P<.001. Among responders, 27% had a recurrent spontaneous preterm birth (vs 100% of nonresponders). Demographic characteristics were similar between responders and nonresponders. In a multivariable logistic regression model, independent risk factors for nonresponse to 17-alpha hydroxyprogesterone caproate were each additional week of gestation of the earliest previous preterm birth (odds ratio, 1.23; 95% confidence interval, 1.17-1.30, P<.001), placental abruption or significant vaginal bleeding (odds ratio, 5.60; 95% confidence interval, 2.46-12.71, P<.001), gonorrhea and/or chlamydia in the current pregnancy (odds ratio, 3.59; 95% confidence interval, 1.36-9.48, P=.010), carriage of a male fetus (odds ratio, 1.51; 95% confidence interval, 1.02-2.24, P=.040), and a penultimate preterm birth (odds ratio, 2.10; 95% confidence interval, 1.03-4.25, P=.041). These clinical factors were used to generate a risk score for nonresponse to 17-alpha hydroxyprogesterone caproate as follows: black +1, male fetus +1, penultimate preterm birth +2, gonorrhea/chlamydia +4, placental abruption +5, earliest previous preterm birth was 32-36 weeks +5. A total risk score >6 was 78% sensitive and 60% specific for predicting nonresponse to 17-alpha hydroxyprogesterone caproate (area under the curve=0.69). This scoring system was validated in an independent population of 287 women; in the validation set, a total risk score >6 performed similarly with a 65% sensitivity, 67% specificity and area under the curve of 0.66. Several clinical characteristics define women at risk for recurrent preterm birth at a similar gestational age despite 17-alpha hydroxyprogesterone caproate therapy and can be used to generate a clinical risk predictor score. These data should be refined and confirmed in other cohorts, and women at high risk for nonresponse should be targets for novel therapeutic intervention studies. Copyright © 2016 Elsevier Inc. All rights reserved.
Barquiel, Beatriz; Herranz, Lucrecia; Hillman, Natalia; Burgos, Ma Ángeles; Grande, Cristina; Tukia, Keleni M; Bartha, José Luis; Pallardo, Luis Felipe
2016-06-01
Maternal glucose and weight gain are related to neonatal outcome in women with gestational diabetes mellitus (GDM). The aim of this study was to explore the influence of average third-trimester HbA1c and excess gestational weight gain on GDM neonatal complications. This observational study included 2037 Spanish singleton pregnant women with GDM followed in our Diabetes and Pregnancy Unit. The maternal HbA1c level was measured monthly from GDM diagnosis to delivery. Women were compared by average HbA1c level and weight gain categorized into ≤ or > the current Institute of Medicine (IOM) recommendations for body mass index. The differential effects of these factors on large-for-gestational-age birth weight and a composite of neonatal complications were assessed. Women with an average third-trimester HbA1c ≥5.0% (n = 1319) gave birth to 7.3% versus 3.8% (p = 0.005) of large-for-gestational-age neonates and 22.0% versus 16.0% (p = 0.006) of neonates with complications. Women with excess gestational weight gain (n = 299) delivered 12.5% versus 5.2% (p < 0.001) of large-for-gestational-age neonates and 24.7% versus 19.0% (p = 0.022) of neonates with complications. In an adjusted multiple logistic regression analysis among mothers exposed to the respective risk factors, ∼47% and 52% of large-for-gestational-age neonates and 32% and 37% of neonatal complications were potentially preventable by attaining an average third-trimester HbA1c level <5.0% and optimizing gestational weight gain. Average third-trimester HbA1c level ≥5% and gestational weight gain above the IOM recommendation are relevant risk factors for neonatal complications in mothers with gestational diabetes.
Nomaguchi, T A; Sakurai, Y
1993-04-01
Inbreeding of 8 groups in molossinus mouse began in (Miura female x Urawa male) F1 (MU) from the stock captured in the Kanto district of Japan and were accomplished by each primiparous littermates. The animals were kept under a clean conventional condition at 23.5 +/- 2.5 degrees C and 50 +/- 5% in relative humidity. Pellet feed, CRF-1, and tap water were provided ad libitum. The respective number of inbreeding generations of MUA, MUF and MUG now exceeds F21, F20 and F22, respectively. Inbreeding of MUD and MUE have reached to F18 up to now, but the other 3 groups became extinct at F10. Time required for inbreeding from F0 to F20 was 2,280 days for MUA, 2,454 days for MUF and 2,143 days for MUG. Generation time was 114.0 +/- 47.2 days for MUA, 122.7 +/- 54.6 days for MUF and 107.2 +/- 48.5 days for MUG. Though the generation time varied from a minimum of 60 days to a maximum of 258 days from F0 to F10 in the inbreeding process (mean: 150.2 +/- 41.7 days), which were shortened from F10 and the mean was 79.0 +/- 29.1 days. In the breeding of the molossinus mouse, primiparous age was 124.5 +/- 29.7 days from F0 to F9 and 77.8 +/- 9.3 days from F10 to F19. The litter size was 5.1 +/- 1.3 for MUA and 5.0 +/- 1.3 for MUG in offspring, 5.0 +/- 1.2 and 4.9 +/- 1.2 in weanling, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Anevska, Kristina; Cheong, Jean N; Wark, John D; Wlodek, Mary E; Romano, Tania
2018-02-01
Females born growth restricted have poor adult bone health. Stress exposure during pregnancy increases risk of pregnancy complications. We determined whether maternal stress exposure in growth-restricted females exacerbates long-term maternal and offspring bone phenotypes. On gestational day 18, bilateral uterine vessel ligation (restricted) or sham (control) surgery was performed on Wistar-Kyoto rats. At 4 mo, control and restricted females were mated and allocated to unstressed or stressed pregnancies. Stressed pregnancies had physiological measurements performed; unstressed females were not handled. After birth, mothers were aged to 13 mo. Second-generation (F2) offspring generated four experimental groups: control unstressed, restricted unstressed, control stressed and restricted stressed. F2 offspring were studied at postnatal day 35 (PN35), 6, 12, and 16 mo. Peripheral quantitative computed tomography was performed on maternal and F2 offspring femurs. Restricted females, irrespective of stress during pregnancy, had decreased endosteal circumference, bending strength, and increased osteocalcin concentrations after pregnancy at 13 mo. F2 offspring of stressed mothers were born lighter. F2 male offspring from stressed pregnancies had decreased trabecular content at 6 mo and decreased endosteal circumference at 16 mo. F2 female offspring from growth-restricted mothers had reduced cortical thickness at PN35 and reduced endosteal circumference at 6 mo. At 12 mo, females from unstressed restricted and stressed control mothers had decreased trabecular content. Low birth weight females had long-term bone changes, highlighting programming effects on bone health. Stress during pregnancy did not exacerbate these programmed effects. Male and female offspring responded differently to maternal growth restriction and stress, indicating gender-specific programming effects.
Reyes-López, Ruth; Pérez-Luque, Elva; Malacara, Juan Manuel
2014-11-01
Variation in TCF7L2 gene is associated with type 2 diabetes and with gestational diabetes mellitus in several populations, but there are no data in Mexican women with gestational diabetes mellitus. In this study, we examined metabolic and hormonal measurements as well as TCF7L2 genetic variants. We selected 108 pregnant women with normal glucose tolerance and 90 with gestational diabetes mellitus according to 2010 American Diabetes Association criteria matched for gestational week. We collected data on blood pressure, body mass index (BMI) and concentrations of blood glucose, HbA1c , lipids profile, insulin and glucagon-like peptide-1 (GLP-1). The genotyping of rs7903146 and rs12255372 polymorphisms were made with polymerase chain reaction-restriction fragment length polymorphism. Actual and pre-gestational BMI, fasting glucose and HbA1c were higher (p < 0.001), and high-density lipoprotein cholesterol was lower (p < 0.02) in gestational diabetes mellitus women than euglycemic women. No significant differences were found for lipids, insulin and homeostasis model assessment-insulin resistance. Gestational diabetes mellitus women had high GLP-1 levels (32 vs 24, p < 0.004) and decreased β-cell function (266 vs 438, p < 0.001). The frequency of rs12255372 risk allele in gestational diabetes women was significantly higher than that in euglycemic women (χ² = 8.96; p < 0.003) and confers a risk for gestational diabetes mellitus (OR = 9.1, 95% CI 2.8-29, p < 0.0002; and OR = 4.3, 95% CI 1.6-11.4, p < 0.003 based on dominant and co-dominant model, respectively). The generalized linear model showed that low beta function, high pre-gestational BMI and rs12255372 risk allele are independently associated with gestational diabetes. The elevated GLP-1 levels in gestational diabetes women suggested some abnormality in insulin secretion. The low β-cell function, high pre-gestational BMI and rs12255372 risk allele are risk factors independently associated with the development of gestational diabetes. Copyright © 2014 John Wiley & Sons, Ltd.
Xu, Xiaojuan; Weber, Daniel; Burge, Rebekah; VanAmberg, Kelsey
2016-01-01
The zebrafish has become a useful animal model for studying the effects of environmental contaminants on neurobehavioral development due to its ease of breeding, high number of eggs per female, short generation times, and a well-established avoidance conditioning paradigm. Using avoidance conditioning as the behavioral paradigm, the present study investigated the effects of embryonic exposure to lead (Pb) on learning in adult zebrafish and the third (F3) generation of those fish. In Experiment 1, adult zebrafish that were developmentally exposed to 0.0, 0.1, 1.0 or 10.0μM Pb (2-24h post fertilization) as embryos were trained and tested for avoidance responses. The results showed that adult zebrafish hatched from embryos exposed to 0.0 or 0.1μM Pb learned avoidance responses during training and displayed significantly increased avoidance responses during testing, while those hatched from embryos exposed to 1.0 or 10.0μM Pb displayed no significant increases in avoidance responses from training to testing. In Experiment 2, the F3 generation of zebrafish that were developmentally exposed to an identical exposure regimen as in Experiment 1 were trained and tested for avoidance responses. The results showed that the F3 generation of zebrafish developmentally exposed as embryos to 0.0 or 0.1μM Pb learned avoidance responses during training and displayed significantly increased avoidance responses during testing, while the F3 generation of zebrafish developmentally exposed as embryos to 1.0 or 10.0μM Pb displayed no significant changes in avoidance responses from training to testing. Thus, developmental Pb exposure produced learning impairments that persisted for at least three generations, demonstrating trans-generational effects of embryonic exposure to Pb. Copyright © 2015. Published by Elsevier B.V.
Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study
Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail
2018-01-01
Abstract Objective To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. Design One and two sample mendelian randomisation analyses. Setting Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). Participants 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Exposures Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Main outcome measures Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. Results In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. Conclusions No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. PMID:29925546
2013-01-01
Background Fetal ultrasound scanning is considered vital for routine antenatal care with first trimester scans recommended for accurate estimation of gestational age (GA). A reliable estimate of gestational age is key information underpinning clinical care and allows estimation of expected date of delivery. Fetal crown-rump length (CRL) is recommended over last menstrual period for estimating GA when measured in early pregnancy i.e. 9+0-13+6 weeks. Methods The INTERGROWTH-21st Project is the largest prospective study to collect data on CRL in geographically diverse populations and with a high level of quality control measures in place. We aim to develop a new gestational age estimation equation based on the crown-rump length (CRL) from women recruited between 9+0-13+6 weeks. The main statistical challenge is modelling data when the outcome variable (GA) is truncated at both ends, i.e. at 9 and 14 weeks. We explored three alternative statistical approaches to overcome the truncation of GA. To evaluate these strategies we generated a data set with no truncation of GA that was similar to the INTERGROWTH-21st Project CRL data, which we used to explore the performance of different methods of analysis of these data when we imposed truncation at 9 and 14 weeks of gestation. These 3 methods were first tested in a simulation based study using a previously published dating equation by Verburg et al. and evaluated how well each of them performed in relation to the model from which the data were generated. After evaluating the 3 approaches using simulated data based on the Verburg equations, the best approach will be applied to the INTERGROWTH-21st Project data to estimate GA from CRL. Results Results of these rather “ad hoc” statistical methods correspond very closely to the “real data” for Verburg, a data set that is similar to the INTERGROWTH-21st project CRL data set. Conclusions We are confident that we can use these approaches to get reliable estimates based on INTERGROWTH-21st Project CRL data. These approaches may be a solution to other truncation problems involving similar data though their application to other settings would need to be evaluated. PMID:24314232
Verdon, Megan; Zegarra, Natalia; Achayra, Rutu; Hemsworth, Paul H
2018-06-05
This research studied whether floor feeding group-housed sows their daily allocation over multiple feed drops per day provides more equitable feeding opportunities in later drops. Over four time replicates, 275 sows were mixed into groups of 10 for both their first and second gestations (200 sows/gestation, 126 sows observed in both gestations). The feeding behavior of individual sows was recorded for 10 min following each of four feed drops per day (0730, 0900, 1100, 1500 h) on days 2, 9 and 51 post-mixing. The location of feeding sows (i.e., feeding in areas associated with high, reduced or little/no food availability) was also recorded. Sow aggressive behavior on day 2 was used to classify sows as dominant (D), subdominant (SD), or submissive (SM). Dominant sows spent the most time feeding in areas of high-food availability (gestation 1, p < 0.001; gestation 2, p = 0.023); SD sows fed more frequently than D sows from areas of reduced food availability (gestation 1, p = 0.001; gestation 2, p = 0.025); and SM sows performed more feeding behavior in areas of little/no food availability (gestation 1, p < 0.001; gestation 2, p < 0.001). These relationships did not change over feed drops or days in either gestation ( p > 0.05). Further research on the management and design of floor feeding systems is required, with a particular emphasis on increasing accessibility to sows that avoid the feeding area.
Gazibara, Tatjana; Elbert, Niels J; den Dekker, Herman T; de Jongste, Johan C; Reiss, Irwin; McGrath, John J; Eyles, Darryl W; Burne, Thomas H; Tiemeier, Henning; Jaddoe, Vincent W V; Pasmans, Suzanne G M A; Duijts, Liesbeth
2016-05-01
Exposure to low levels of vitamin D in fetal life might affect the developing immune system, and subsequently the risk of childhood eczema. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with the risk of eczema until the age of 4 years. In a population-based prospective cohort study of 3019 mothers and their children, maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels (severely deficient <25.0 nmol/l, deficient 25.0-49.9 nmol/l, sufficient 50.0-74.9 nmol/l, optimal ≥75.0 nmol/l). Eczema was prospectively assessed by annual questionnaires until the age of 4 years. Eczema patterns included never, early (age ≤1 year only), late (age >1 year only), and persistent eczema (age ≤ and >1 year). Data were assessed using the generalized estimating equations and multinomial regression models. Compared with the optimal 25-hydroxyvitamin D group, sufficient, deficient, and severely deficient groups of 25-hydroxyvitamin D level in mid-gestation were not associated with the risk of overall eczema (odds ratios [95% confidence interval]: 1.09 [0.82, 1.43], 1.04 [0.87, 1.25], and 0.94 [0.81, 1.10], p-values for trend >0.05), nor with eczema per year or eczema patterns in children up to the age of 4 years. Similarly, we observed no associations of 25-hydroxyvitamin D groups at birth with any eczema outcome. Our results suggest that levels of 25-hydroxyvitamin D in mid-gestation and at birth are not associated with the risk of overall eczema, eczema per year, or eczema patterns among children until the age of 4 years. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Is gestational hypertension protective against perinatal mortality in twin pregnancies?
Luo, Qi-Guang; Zhang, Ji-Yan; Cheng, Wei-Wei; Audibert, Francois; Luo, Zhong-Cheng
2014-01-01
Pregnancy-induced or gestational hypertension is a common pregnancy complication. Paradoxically, gestational hypertension has been associated with a protective effect against perinatal mortality in twin pregnancies in analytic models (logistic regression) without accounting for survival time. Whether this effect is real remains uncertain. This study aimed to validate the impact of gestational hypertension on perinatal mortality in twin pregnancies using a survival analysis approach. This was a retrospective cohort study of 278,821 twin pregnancies, using the U.S. 1995-2000 matched multiple birth dataset (the largest dataset available for multiple births). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death (stillbirth and neonatal death) comparing gestational hypertensive vs. non-hypertensive pregnancies controlling for maternal characteristics and twin cluster-level dependence. Comparing births in gestational hypertensive vs. non-hypertensive twin pregnancies, perinatal mortality rates were significantly lower (1.20% vs. 3.38%), so were neonatal mortality (0.72% vs. 2.30%) and stillbirth (0.48% vs. 1.10%) rates. The aHRs (95% confidence intervals) were 0.34 (0.31-0.38) for perinatal death, 0.31 (0.27-0.34) for neonatal death, and 0.45 (0.38-0.53) for stillbirth, respectively. The protective effect of gestational hypertension against perinatal death became weaker over advancing gestational age; the aHRs in very preterm (<32 weeks), mild preterm (32-36 weeks) and term (37+ weeks) births were 0.29, 0.48 and 0.76, respectively. The largest risk reductions in neonatal mortality were observed for infections and immaturity-related conditions. Gestational hypertension appears to be beneficial for fetal survival in twin pregnancies, especially in those ending more prematurely or for deaths due to infections and immaturity-related conditions. Prospective studies are required to rule out the possibility of unmeasured confounders.
Does grandparents' diet affect weight and risk of hypogonadism in subsequent generations?
Chambers, Thomas; Drake, Amanda; Sharpe, Richard
2015-02-26
Worldwide, obesity has doubled since 1980. WHO declares obesity as preventable and attributes the increase in prevalence to high consumption of energy-rich foods and decreased physical activity. Epidemiological and experimental studies suggest that parents' and grandparents' diet could also have a role. We established a model of grandparents' high-fat diet (HFD) to explore potential mechanisms. Sprague-Dawley rats were fed a HFD (45% fat) or a matched control diet (10% fat) from weaning for 14 weeks. After metabolic testing, founders (F0) were bred with controls to establish an F1 generation. F1 rats were maintained on the control diet for 14 weeks after weaning and then underwent metabolic testing followed by mating with control rats to generate F2 offspring. We analysed F0 data with ANOVA and the F1 and F2 data using mixed models, with group and sex as a fixed factor and litter as a random factor. F0 male rats (n=11-13) and female rats (n=6-12) were, respectively, 9·7% (p=0·017) and 14·7% (p=0·001) heavier after 14 weeks' HFD, with a 33·3% increase in visceral adiposity (p=0·014). F1 male and female offspring (n=6) of HFD mothers were heavier (p=0·034 and 0·01, respectively) than controls. F1 daughters of HFD fathers were also heavier (p=0·01). F2 male offspring (n=4-7) derived from HFD maternal grandfathers were 7·7% heavier (p=0·029), exhibited a 31% increase in visceral adiposity (p=0·032), a 97% increase in plasma leptin (p=0·027), a trend for lower testosterone (p=0·057), and an increase in the luteinising hormone to testosterone ratio (p=0·017). F2 male and female rats whose maternal grandfather consumed a HFD had reduced insulin sensitivity (p<0·0005). Our results show that founder diet affects the metabolic and reproductive health of two subsequent generations of rats in a grandparent-specific, parent-specific, and sex-specific manner. The causal mechanisms remain to be further explored. The present human obesity epidemic might thus have a wider aetiology than currently accepted. UK Medical Research Council. Copyright © 2015 Elsevier Ltd. All rights reserved.
Chrupcala, Kimberly A; Edwards, Taryn M; Spatz, Diane L
2015-01-01
To increase the number of neonates who were fed according to cues prior to discharge and potentially decrease length of stay. Continuous quality improvement. Eighty-five bed level IV neonatal intensive care unit. Surgical and nonsurgical neonates of all gestational ages. Neonates younger than 32 weeks gestation, who required intubation, continuous positive airway pressure (CPAP), high flow nasal cannula (HFNC), or did not have suck or gag reflexes were excluded as potential candidates for infant-driven feeding. The project was conducted over a 13-month period using the following methods: (a) baseline data collection, (b) designation of Infant Driven Feeding (IDF) Champions, (c) creation of a multidisciplinary team, (d) creation of electronic health record documentation, (e) initial staff education, (f) monthly team meetings, (g) reeducation throughout the duration of the project, and (h) patient-family education. Baseline data were collected on 20 neonates with a mean gestational age of 36 0/7(th) weeks and a mean total length of stay (LOS) of 43 days. Postimplementation data were collected on 150 neonates with a mean gestational age of 36 1/7(th) weeks and a mean total LOS of 36.4 days. A potential decrease in the mean total LOS of stay by 6.63 days was achieved during this continuous quality improvement (CQI) project. Neonates who are fed according to cues can become successful oral feeders and can be safely discharged home regardless of gestational age or diagnosis. © 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.
Knapczyk-Stwora, Katarzyna; Ciereszko, Renata E.; Golas, Aniela; Wieciech, Iwona; Slomczynska, Maria
2014-01-01
We determined whether androgen deficiency induced by flutamide treatment during mid- and late pregnancy affects the functions of the porcine corpus luteum (CL). Pregnant gilts were injected with flutamide between days 43 and 49 (gestation day [GD] 50F), days 83 and 89 (GD90F), or days 101 and 107 (GD108F) of gestation. Antiandrogen treatment increased the luteal progesterone concentration in the GD50F group and decreased progesterone content in the GD90F and GD108F groups. Luteal levels of side-chain cleavage cytochrome P450 (CYP11A1) mRNA and protein were significantly downregulated in the GD90F and GD108F groups as compared with the respective controls. The 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (HSD3B) mRNA and protein expression were significantly reduced only in the GD108F group as compared with the control. Decreased luteal 20α-hydroxysteroid dehydrogenase (AKR1C1) mRNA and protein levels were observed in the GD50F group. Thus, androgen deficiency during pregnancy in pigs led to CL dysfunction that is marked by decreased progesterone production. Furthermore, exposure to flutamide during late pregnancy downregulated steroidogenic enzymes (CYP11A1 and HSD3B) in pigs. We conclude that androgens are important regulators of CL function during pregnancy. PMID:24429677
Grzesiak, Malgorzata; Knapczyk-Stwora, Katarzyna; Ciereszko, Renata E; Golas, Aniela; Wieciech, Iwona; Slomczynska, Maria
2014-06-01
We determined whether androgen deficiency induced by flutamide treatment during mid- and late pregnancy affects the functions of the porcine corpus luteum (CL). Pregnant gilts were injected with flutamide between days 43 and 49 (gestation day [GD] 50F), days 83 and 89 (GD90F), or days 101 and 107 (GD108F) of gestation. Antiandrogen treatment increased the luteal progesterone concentration in the GD50F group and decreased progesterone content in the GD90F and GD108F groups. Luteal levels of side-chain cleavage cytochrome P450 (CYP11A1) mRNA and protein were significantly downregulated in the GD90F and GD108F groups as compared with the respective controls. The 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (HSD3B) mRNA and protein expression were significantly reduced only in the GD108F group as compared with the control. Decreased luteal 20α-hydroxysteroid dehydrogenase (AKR1C1) mRNA and protein levels were observed in the GD50F group. Thus, androgen deficiency during pregnancy in pigs led to CL dysfunction that is marked by decreased progesterone production. Furthermore, exposure to flutamide during late pregnancy downregulated steroidogenic enzymes (CYP11A1 and HSD3B) in pigs. We conclude that androgens are important regulators of CL function during pregnancy.
Wang, Tiange; Liu, Huikun; Wang, Leishen; Huang, Tao; Li, Weiqin; Zheng, Yan; Heianza, Yoriko; Sun, Dianjianyi; Leng, Junhong; Zhang, Shuang; Li, Nan; Hu, Gang; Qi, Lu
2016-12-01
Zinc transporter 8 genetic variant SLC30A8 has been associated with postpartum risk of type 2 diabetes among women with gestational diabetes mellitus (GDM). Gestational weight gain is one of the strongest risk factors for postpartum hyperglycemia. We assessed the interaction between type 2 diabetes-associated SLC30A8 rs13266634 and gestational weight gain on 1-5 years of postpartum glycemic changes in 1,071 women with prior GDM in a longitudinal study. Compared with gestation of 26-30 weeks, postpartum levels of fasting glucose, oral glucose tolerance test 2-h glucose, and hemoglobin A 1c (HbA 1c ) increased across rs13266634 TT, CT, and CC genotypes in women with excessive gestational weight gain, whereas opposite genetic associations were found in women with inadequate or adequate gestational weight gain. Postpartum changes in fasting glucose per additional copy of the C allele were -0.18, -0.04, and 0.12 mmol/L in women with inadequate, adequate, and excessive gestational weight gain, respectively (P for interaction = 0.002). We also found similar interactions for changes in 2-h glucose and HbA 1c (P for interaction = 0.003 and 0.005, respectively). Our data indicate that gestational weight gain may modify SLC30A8 variant on long-term glycemic changes, highlighting the importance of gestational weight control in the prevention of postpartum hyperglycemia in women with GDM. © 2016 by the American Diabetes Association.
Garcia, Rebecca; Ali, Nasreen; Guppy, Andy; Griffiths, Malcolm; Randhawa, Gurch
2017-08-11
To compare mean birth weights and gestational age at delivery of infants born to Indian, Pakistani, Bangladeshi and white British mothers in Luton, UK. Retrospective analysis using routinely recorded secondary data in Ciconia Maternity information System, between 2008 and 2013. Luton, UK. Mothers whose ethnicity was recorded as white British, Bangladeshi, Pakistani or Indian and living in Luton, aged over 16, who had a live singleton birth over 24 weeks of gestation were included in the analysis (n=14 871). Primary outcome measures were mean birth weight and gestational age at delivery. After controlling for maternal age, smoking, diabetes, gestation age, parity and maternal height and body mass index at booking, a significant difference in infants' mean birth weight was found between white British and Indian, Pakistani and Bangladeshi infants, F(3, 12 287)=300.32, p<0.0001. The partial Eta-squared for maternal ethnicity was η 2 =0.067. The adjusted mean birth weight for white British infants was found to be 3377.89 g (95% CI 3365.34 to 3390.44); Indian infants, 3033.09 g (95% CI 3038.63 to 3103.55); Pakistani infants, 3129.49 g (95% CI 3114.5 to 3144.48); and Bangladeshi infants, 3064.21 g (95% CI 3041.36 to 3087.06). There was a significant association in preterm delivery found in primipara Indian mothers, compared with Indian mothers (Wald=8.192, df 1, p<0.005). Results show important differences in adjusted mean birth weight between Indian, Pakistani, Bangladeshi and white British women. Moreover, an association was found between primipara Indian mothers and preterm delivery, when compared with Pakistani, Bangladeshi and white British women. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Yu, Ying; Xie, Rongrong; Shen, Cainuo; Shu, Lianting
2018-06-01
Exercise showed some potential in preventing gestational diabetes mellitus. However, the results remained controversial. We conducted a systematic review and meta-analysis to evaluate the impact of exercise during pregnancy on gestational diabetes mellitus. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the influence of exercise during pregnancy on gestational diabetes mellitus were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was the incidence of gestational diabetes mellitus. Meta-analysis was performed using random-effect model. Six RCTs involving 2164 patients were included in the meta-analysis. Compared with control intervention, exercise intervention was associated with significantly decreased incidence of gestational diabetes mellitus (Std. mean difference = 0.59; 95%CI = 0.39-.88; p = .01), but had no effect on gestational age at birth (Std. mean difference = -0.03; 95%CI = -0.12 to 0.07; p = .60), the number of preterm birth (OR = 0.85; 95%CI = 0.43-1.66; p = .63), glucose 2-h post-OGTT (Std. mean difference = -1.02; 95%CI = -2.75 to 0.71; p = .25), birth weight (Std. mean difference = -0.13; 95%CI = -0.26 to 0.01; p = .06), and Apgar score less than 7 (OR = .78; 95%CI = 0.21-2.91; p = .71). Compared to control intervention, exercise intervention could significantly decrease the risk of gestational diabetes mellitus, but showed no impact on gestational age at birth, preterm birth, glucose 2-h post-OGTT, birth weight, and Apgar score less than 7.
Kioumourtzoglou, Marianthi-Anna; Coull, Brent A; O'Reilly, Éilis J; Ascherio, Alberto; Weisskopf, Marc G
2018-05-21
Animal evidence suggests that endocrine disruptors affect germline cells and neurodevelopment. However, to date, the third-generation neurodevelopmental outcomes in humans have not been examined. To explore the potential consequences of exposure to diethylstilbestrol or DES across generations-specifically, third-generation neurodevelopment. This cohort study uses self-reported health information, such as exposure to diethylstilbestrol during pregnancy and attention-deficit/hyperactivity disorder (ADHD) diagnosis, from 47 540 participants enrolled in the ongoing Nurses' Health Study II. The 3 generations analyzed in this study were the participants (F1 generation), their mothers (F0 generation), and their live-born children (F2 generation). Participant- and mother-reported exposure to diethylstilbestrol during pregnancy and physician-diagnosed child ADHD. The total number of women included in this study was 47 540. Of the 47 540 F0 mothers, 861 (1.8%) used diethylstilbestrol and 46 679 (98.2%) did not while pregnant with the F1 participants. Use of diethylstylbestrol by F0 mothers was associated with an increased risk of ADHD among the F2 generation: 7.7% vs 5.2%, adjusted odds ratio (OR), 1.36 (95% CI, 1.10-1.67) and an OR of 1.63 (95% CI, 1.18-2.25) if diethylstilbestrol was taken during the first trimester of pregnancy. No effect modification was observed by the F2 children's sex. This study provides evidence that diethylstilbestrol exposure is associated with multigenerational neurodevelopmental deficits. The doses and potency level of environmental endocrine disruptors to which humans are exposed are lower than those of diethylstilbestrol, but the prevalence of such exposure and the possibility of cumulative action are potentially high and thus warrant consideration.
Adverse effects of small for gestational age differ by gestational week among very preterm infants.
Jensen, Erik A; Foglia, Elizabeth E; Dysart, Kevin C; Simmons, Rebecca A; Aghai, Zubair H; Cook, Alison; Greenspan, Jay S; DeMauro, Sara B
2018-05-05
To characterise the excess risk for death, grade 3-4 intraventricular haemorrhage (IVH), bronchopulmonary dysplasia (BPD) and stage 3-5 retinopathy of prematurity independently associated with birth small for gestational age (SGA) among very preterm infants, stratified by completed weeks of gestation. Retrospective cohort study using the Optum Neonatal Database. Study infants were born <32 weeks gestation without severe congenital anomalies. SGA was defined as a birth weight <10th percentile. The excess outcome risk independently associated with SGA birth among SGA babies was assessed using adjusted risk differences (aRDs). Of 6708 infants sampled from 717 US hospitals, 743 (11.1%) were SGA. SGA compared with non-SGA infants experienced higher unadjusted rates of each study outcome except grade 3-4 IVH among survivors. The excess risk independently associated with SGA birth varied by outcome and gestational age. The highest aRD for death (0.27; 95% CI 0.13 to 0.40) occurred among infants born at 24 weeks gestation and declined as gestational age increased. In contrast, the peak aRDs for BPD among survivors (0.32; 95% CI 0.20 to 0.44) and the composites of death or BPD (0.35; 95% CI 0.24 to 0.46) and death or major morbidity (0.35; 95% CI 0.24 to 0.45) occurred at 27 weeks gestation. The risk-adjusted probability of dying or developing one or more of the evaluated morbidities among SGA infants was similar to that of non-SGA infants born approximately 2-3 weeks less mature. The excess risk for neonatal morbidity and mortality associated with being born SGA varies by adverse outcome and gestational age. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Association of Gestational Weight Gain With Maternal and Infant Outcomes
Goldstein, Rebecca F.; Abell, Sally K.; Ranasinha, Sanjeeva; Misso, Marie; Boyle, Jacqueline A.; Black, Mary Helen; Li, Nan; Hu, Gang; Corrado, Francesco; Rode, Line; Kim, Young Ju; Haugen, Margaretha; Song, Won O.; Kim, Min Hyoung; Bogaerts, Annick; Devlieger, Roland; Chung, Judith H.
2017-01-01
Importance Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear. Objective To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI <18.5]; 11.5-16 kg for normal-weight women [BMI 18.5-24.9]; 7-11 kg for overweight women [BMI 25-29.9]; and 5-9 kg for obese women [BMI ≥30]) and maternal and infant outcomes. Data Sources and Study Selection Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain. Data Extraction and Synthesis Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data. Main Outcomes and Measures Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus. Results Of 5354 identified studies, 23 (n = 1 309 136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, −2% [−10% to −6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, −2% [−3% to −1%]); cesarean delivery showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [−2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, −3%; [−4% to −2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, −2% [−2% to −1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data. Conclusions and Relevance In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes. PMID:28586887
Goldstein, Rebecca F; Abell, Sally K; Ranasinha, Sanjeeva; Misso, Marie; Boyle, Jacqueline A; Black, Mary Helen; Li, Nan; Hu, Gang; Corrado, Francesco; Rode, Line; Kim, Young Ju; Haugen, Margaretha; Song, Won O; Kim, Min Hyoung; Bogaerts, Annick; Devlieger, Roland; Chung, Judith H; Teede, Helena J
2017-06-06
Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear. To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI <18.5]; 11.5-16 kg for normal-weight women [BMI 18.5-24.9]; 7-11 kg for overweight women [BMI 25-29.9]; and 5-9 kg for obese women [BMI ≥30]) and maternal and infant outcomes. Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain. Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data. Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus. Of 5354 identified studies, 23 (n = 1 309 136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, -2% [-10% to -6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, -2% [-3% to -1%]); cesarean delivery showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [-2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, -3%; [-4% to -2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, -2% [-2% to -1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data. In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.
Melamed, Nir; Ray, Joel G; Geary, Michael; Bedard, Daniel; Yang, Cathy; Sprague, Ann; Murray-Davis, Beth; Barrett, Jon; Berger, Howard
2016-03-01
In women with gestational diabetes mellitus, it is not clear whether routine induction of labor at <40 weeks of gestation is beneficial to mother and newborn infant. The purpose of this study was to compare outcomes among women with gestational diabetes mellitus who had induction of labor at either 38 or 39 weeks with those whose pregnancy was managed expectantly. We included all women in Ontario, Canada, with diagnosed gestational diabetes mellitus who had a singleton hospital birth at ≥38 + 0 weeks of gestation between April 2012 and March 2014. Data were obtained from the Better Outcomes Registry & Network Ontario, which is a province-wide registry of all births in Ontario, Canada. Women who underwent induction of labor at 38 + 0 to 38 + 6 weeks of gestation (38-IOL; n = 1188) were compared with those who remained undelivered until 39 + 0 weeks of gestation (38-Expectant; n = 5229). Separately, those women who underwent induction of labor at 39 + 0 to 39 + 6 weeks of gestation (39-IOL; n = 1036) were compared with women who remained undelivered until 40 + 0 weeks of gestation (39-Expectant; n = 2162). Odds ratios and 95% confidence intervals were adjusted for maternal age, parity, insulin treatment, and prepregnancy body mass index. Of 281,480 women who gave birth during the study period, 14,600 women (5.2%) had gestational diabetes mellitus; of these, 8392 women (57.5%) met all inclusion criteria. Compared with the 38-Expectant group, those women in the 38-IOL group had lower odds for cesarean delivery (adjusted odds ratio, 0.73; 95% confidence interval, 0.52-0.90), higher odds for neonatal intensive care unit admission (adjusted odds ratio, 1.36; 95% confidence interval, 1.09-1.69), and no difference in other maternal-newborn infant outcomes. Compared with the 39-Expectant group, women in the 39-IOL group likewise had lower odds for cesarean delivery (adjusted odds ratio, 0.73; 95% confidence interval, 0.58-0.93) but no difference in neonatal intensive care unit admission (adjusted odds ratio, 0.83; 95% confidence interval, 0.61-1.11). In women with gestational diabetes mellitus, the routine induction of labor at 38 or 39 weeks is associated with a lower risk of cesarean delivery compared with expectant management but may increase the risk of neonatal intensive care unit admission when done at <39 weeks of gestation. Copyright © 2016 Elsevier Inc. All rights reserved.
Deputy, Nicholas P; Nguyen, Phuong H; Pham, Hoa; Nguyen, Son; Neufeld, Lynnette; Martorell, Reynaldo; Ramakrishnan, Usha
2017-01-11
Accurate estimation of gestational age is important for both clinical and public health purposes. Estimates of gestational age using fetal ultrasound measurements are considered most accurate but are frequently unavailable in low- and middle-income countries. The objective of this study was to assess the validity of last menstrual period and Farr neonatal examination estimates of gestational age, compared to ultrasound estimates, in a large cohort of women in Vietnam. Data for this analysis come from a randomized, placebo-controlled micronutrient supplementation trial in Vietnam. We analyzed 912 women with ultrasound and prospectively-collected last menstrual period estimates of gestational age and 685 women with ultrasound and Farr estimates of gestational age. We used the Wilcoxon signed rank sum test to assess differences in gestational age estimated by last menstrual period or Farr examination compared to ultrasound and computed the intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) to quantify agreement between methods. We computed the Kappa coefficient (κ) to quantify agreement in preterm, term and post-term classification. The median gestational age estimated by ultrasound was 273.9 days. Gestational age was slightly overestimated by last menstrual period (median 276.0 days, P < 0.001) and more greatly overestimated by Farr examination (median 286.7 days, P < 0.001). Gestational age estimates by last menstrual period and ultrasound were moderately correlated (ICC = 0.78) and concordant (CCC = 0.63), whereas gestational age estimates by Farr examination and ultrasound were weakly correlated (ICC = 0.26) and concordant (CCC = 0.05). Last menstrual period and ultrasound estimates of gestational age were within ± 14 days for 88.4% of women; Farr and ultrasound estimates were within ± 14 days for 55.8% of women. Last menstrual period and ultrasound estimates of gestational age had higher agreement in term classification (κ = 0.41) than Farr and ultrasound (κ = 0.05). In this study of women in Vietnam, we found last menstrual period provided a more accurate estimate of gestational age than the Farr examination when compared to ultrasound. These findings provide useful information about the utility and accuracy of different methods to estimate gestational age and suggest last menstrual period may be preferred over Farr examination in settings where ultrasound is unavailable. The trial was registered at ClinicalTrials.Gov as NCT01665378 on August 13, 2012.
Muegge, C R; Brennan, K M; Schoonmaker, J P
2017-03-01
Angus × Simmental cows ( = 48, BW = 594 kg, BCS = 5.26, age = 2.7) pregnant with male fetuses were used to determine the effect of selenium source during the last 80 d of gestation and first 108 d of lactation on progeny feedlot performance. At 203 d of gestation, cows were blocked by BW, breed composition, and calf sire and randomly allotted to 1 of 3 treatments: no supplemental Se, 3 mg/d inorganic Se (sodium selenite), and 3 mg/d organic Se (Sel-plex). Maternal diets were formulated to contain 10.4% CP and 0.90 Mcal/kg NE during gestation and 12.1% CP and 1.01 Mcal/kg NE during lactation. Basal diets contained 0.07 and 0.11 mg/kg Se for gestation and lactation diets, respectively. Diets were fed daily as a total mixed ration, and no additional Se, 3 mg/d Se as sodium selenite, or 3 mg/d Se as Sel-Plex were top-dressed daily. Treatment diets were fed through 108 d postpartum (DPP). At 108 DPP cow-calf pairs were commingled until weaning at 210 DPP. At 28 d postweaning, steers ( = 47, BW = 301 kg) were placed in individual pens and fed a diet formulated to provide 13.9% CP and 1.24 Mcal/kg NE. No supplemental Se was fed; however, basal Se concentration was 0.10 mg/kg. The diet was delivered as a total mixed ration once daily. Steers were slaughtered at a target BW of 625 kg. Steers from cows supplemented with organic Se tended to enter the feedlot heavier ( = 0.06) than steers from cows supplemented with inorganic Se. There was no difference in ADG among treatments ( ≥ 0.73), but steers from organic Se cows tended to spend fewer days on feed compared to steers from inorganic Se cows ( = 0.09). Steers from organic Se cows had a greater overall DMI compared to steers from inorganic Se cows ( = 0.04), but there was no difference in overall G:F ( = 0.49). Dressing percentage was greater for steers from cows fed no Se compared with steers from cows fed either inorganic or organic Se ( = 0.03). Maternal Se source had no effect on HCW, back fat, percentage KPH, LM area, yield grade, marbling score, or quality grade distribution ( ≥ 0.17) of progeny. In conclusion, maternal supplementation with organic Se appears to have a long-term benefit on intake of steer progeny and may result in improvements in growth that could decrease days on feed.
Magro-Malosso, Elena R; Saccone, Gabriele; Di Tommaso, Mariarosaria; Roman, Amanda; Berghella, Vincenzo
2017-08-01
Gestational hypertensive disorders, including gestational hypertension and preeclampsia, are one of the leading causes of maternal morbidity and mortality. The aim of our study was to evaluate the effect of exercise during pregnancy on the risk of gestational hypertensive disorders. Electronic databases were searched from their inception to February 2017. Selection criteria included only randomized controlled trials of uncomplicated pregnant women assigned before 23 weeks to an aerobic exercise regimen or not. The summary measures were reported as relative risk with 95% confidence intervals. The primary outcome was the incidence of gestational hypertensive disorders, defined as either gestational hypertension or preeclampsia. Seventeen trials, including 5075 pregnant women, were analyzed. Of them, seven contributed data to quantitative meta-analysis for the primary outcome. Women who were randomized in early pregnancy to aerobic exercise for about 30-60 min two to seven times per week had a significant lower incidence of gestational hypertensive disorders (5.9% vs. 8.5%; relative risk 0.70, 95% confidence interval 0.53-0.83; seven studies, 2517 participants), specifically a lower incidence of gestational hypertension (2.5% vs. 4.6%; relative risk 0.54, 95% confidence interval 0.40-0.74; 16 studies, 4641 participants) compared with controls. The incidence of preeclampsia (2.3% vs. 2.8%; relative risk 0.79, 95% confidence interval 0.45-1.38; six studies, 2230 participants) was similar in both groups. The incidence of cesarean delivery was decreased by 16% in the exercise group. Aerobic exercise for about 30-60 min two to seven times per week during pregnancy, as compared with being more sedentary, is associated with a significantly reduced risk of gestational hypertensive disorders overall, gestational hypertension, and cesarean delivery. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.
Mao, Yuanyuan; Hu, Wenbin; Liu, Qin; Liu, Li; Li, Yuanming; Shen, Yueping
2015-08-01
To examine the dose-response relationship between gestational weight gain rate and the neonate birth weight. A total of 18 868 women with singleton gestations who delivered between January 2006 and December 2013 were included in this study. Maternal and neonate details of these women were drawn from the Perinatal Monitoring System database. Gestational weight gain rate was defined as the total weight gain during the last and first prenatal care visits divided by the interval weeks. Both Multiple logistic regression analysis and restricted cubic spline methods were performed. Confounding factors included maternal age, education, pre-pregnancy body mass index (BMI), state of residence, parity, gestational weeks of prenatal care entry, and sex of the neonate. The adjusted odds ratio for macrosomia was associated with gestational weight gain rate in lower pre-pregnancy BMI (OR = 3.15, 95% CI: 1.40-7.07), normal (OR = 3.64, 95% CI: 2.84-4.66) or overweight (OR = 2.37, 95% CI: 1.71-3.27). The odds ratios of low birth weight appeared a decrease in those women with lower pre-pregnancy BMI (OR = 0.28, 95% CI: 0.13-0.61) while the normal weight (OR = 0.37, 95% CI: 0.22-0.64) group with gestational weight gain, the rate showed an increase. Association of gestational weight gain rate for macrosomia was found a S-curve in those term delivery women (non-linearity test P < 0.000 1). However, L-curve was observed for low birth weight and gestational weight gain rate in term births (non-linearity test P < 0.000 1). A S-curve was seen between gestational weight gain rate and term delivered macrosomia while L-curve was observed among term delivered low birth weight neonates.
Meems, M; Truijens, Sem; Spek, V; Visser, L H; Pop, V J M
2015-07-01
To investigate the prevalence, severity and relation to fluid retention of self-reported pregnancy-related carpal tunnel syndrome (CTS) symptoms in a large sample of pregnant women. A prospective longitudinal cohort study. Dutch women who became pregnant between January 2013 and January 2014 in the southeast of The Netherlands. A total of 639 Dutch pregnant women. Baseline characteristics were assessed at 12 weeks' gestation. CTS symptoms were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ) at 32 weeks and during the first postpartum week regarding the last weeks of pregnancy. Fluid retention, sleeping problems and depressive symptoms (using the Edinburgh Depression Scale) were assessed at several time points during pregnancy. BCTQ scores, fluid retention and sleeping problems. Of the 639 women, 219 (34%) reported CTS symptoms during pregnancy. Total mean scores on the BCTQ were significantly higher after 32 weeks' than up to 32 weeks' gestation. Most women experienced mild to moderate symptoms. Pregnant women with CTS symptoms reported significantly higher levels of fluid retention during gestation compared with pregnant women without CTS symptoms [F = 60.6, df (1598), P < 0.001], adjusted for body mass index (BMI), age, parity, and depression scores. Higher scores on fluid retention throughout the pregnancy were significantly related to CTS (OR = 1.8, 95%CI 1.5, 2.1, P < 0.001). Finally, the occurrence of CTS was independently related to sleeping problems. Although the severity of symptoms and functional impairment of CTS were relatively mild, health care professionals should be aware of the high prevalence. The occurrence of CTS symptoms is significantly higher in women who report fluid retention during gestation and it can contribute to sleeping problems. © 2015 Royal College of Obstetricians and Gynaecologists.
Chan, Priscilla Y L; Tang, Shu-Min; Au, Sunny C L; Rong, Shi-Song; Lau, Henry H W; Ko, Simon T C; Ng, Danny S C; Chen, Li Jia; Yam, Jason C S
2016-08-05
The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.
Liu, Zhong; Hu, Zhe; Pan, Xinghua; Li, Minshu; Togun, Taiwo A.; Tuck, David; Pelizzola, Mattia; Huang, Junjiu; Ye, Xiaoying; Yin, Yu; Liu, Mengyuan; Li, Chao; Chen, Zhisheng; Wang, Fang; Zhou, Lingjun; Chen, Lingyi; Keefe, David L.; Liu, Lin
2011-01-01
Parthenogenetic embryonic stem cells (pESCs) have been generated in several mammalian species from parthenogenetic embryos that would otherwise die around mid-gestation. However, previous reports suggest that pESCs derived from in vivo ovulated (IVO) mature oocytes show limited pluripotency, as evidenced by low chimera production, high tissue preference and especially deficiency in germline competence, a critical test for genetic integrity and pluripotency of ESCs. Here, we report efficient generation of germline-competent pESC lines (named as IVM pESCs) from parthenogenetic embryos developed from immature oocytes of adult mouse ovaries following in vitro maturation (IVM) and artificial activation. In contrast, pESCs derived from IVO oocytes show defective germline competence, consistent with previous reports. Further, IVM pESCs resemble more ESCs from fertilized embryos (fESCs) than do IVO pESCs on genome-wide DNA methylation and global protein profiles. In addition, IVM pESCs express higher levels of Blimp1, Lin28 and Stella, relative to fESCs, and in their embryoid bodies following differentiation. This may indicate differences in differentiation potentially to the germline. The mechanisms for acquisition of pluripotency and germline competency of IVM pESCs from immature oocytes remain to be determined. PMID:21239471
Grace, M R; Vladutiu, C J; Nethery, R C; Siega-Riz, A M; Manuck, T A; Herring, A H; Savitz, D; Thorp, J T
2018-06-01
To estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery. Prospective cohort study. The study was conducted in the USA at the University of North Carolina. We assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005. Fasting blood was collected at two time points (<20 and 24-29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates. Gestational age at delivery, preterm birth (<37 weeks of gestation), and spontaneous preterm birth. At <20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDL NMR (HR 0.78, 95% CI 0.64-0.96), total VLDL NMR (HR 0.77, 95% CI 0.61-0.98), and small VLDL NMR (HR 0.78, 95% CI 0.62-0.98], whereas large VLDL NMR (HR 1.19, 95% CI 1.01-1.41) was associated with a greater hazard of earlier delivery. At 24-28 weeks of gestation, average VLDL NMR (HR 1.25, 95% CI 1.03-1.51) and a detectable level of medium HDL NMR (HR 1.90, 95% CI 1.19-3.02) were associated with earlier gestational ages at delivery. In this sample of pregnant women, particle concentrations of VLDL NMR , LDL NMR , IDL NMR , and HDL NMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries <37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth. Nuclear magnetic resonance spectroscopy may identify lipoprotein particles associated with preterm delivery. © 2017 Royal College of Obstetricians and Gynaecologists.
Jeong, Tae-Yong; Kim, Tae-Hun; Kim, Sang Don
2016-09-01
Multigenerational bioaccumulation and biotransformation activity and short-term kinetics (e.g., uptake and depuration) of propranolol in Daphnia magna were investigated at environmental concentration. The body burden and the major metabolite, desisopropyl propranolol (DIP), of propranolol were quantified using LC-MS/MS at the end of each generation after exposure for 11 generations. The accumulation of propranolol in D. magna at an environmental concentration of 0.2 μg/L was not much different between the parent (F0) and the eleventh filial (F10) generation. However, at 28 μg/L, its accumulation was 1.6 times higher-up to 18.9 μg/g-in the F10 generation relative to the F0. In contrast to propranolol, DIP intensity gradually increased from F0 to F10 at 0.2 μg/L, reflecting an increase in detoxification load and biotransformation performance; no increasing trend was observed at 28 μg/L. The bioaccumulation factor (BAF) showed higher values with a lower concentration and longer period of exposure. The average values of the BAF for 21 days of long-term exposure in successive 11 generations were 440.4 ± 119.7 and 1026.5 ± 208.6 L/kg for 28 μg/L and 0.2 μg/L, respectively. These are comparable to the BAF of 192 for the short-term 72-h exposure at 28 μg/L in the parent generation. It is also recommended that future studies for pharmaceutical ingredients be conducted on drug-drug interaction and structural characteristics on the prediction of biotransformation activity and bioaccumulation rate. Copyright © 2016 Elsevier Ltd. All rights reserved.
McCreary, J Keiko; Truica, L Sorina; Friesen, Becky; Yao, Youli; Olson, David M; Kovalchuk, Igor; Cross, Albert R; Metz, Gerlinde A S
2016-08-25
Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioral and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal stress than males. Here, we examined if repeated stress across generations may diminish stress resiliency and cumulatively enhance the susceptibility for adverse health outcomes in females. Pregnant female rats of three successive generations were exposed to stress from gestational days 12-18 to generate multigenerational prenatal stress (MPS) in the maternal lineage. Stress response was measured by plasma corticosterone levels and open-field exploration in each generation. Neuromorphological consequences of MPS were investigated in the F3 generation using in vivo manganese-enhanced magnetic resonance imaging (MEMRI), T2-relaxometry, and cytoarchitectonics in relation to candidate gene expression involved in brain plasticity and mental health. Each additional generation of prenatal stress incrementally elevated hypothalamic-pituitary-adrenal axis activation, anxiety-like and aversive behaviors in adult female offspring. Elevated stress responses in the MPS F3 generation were accompanied by reduced neural density in prefrontal cortex, hippocampus and whole brain along with altered brain activation patterns in in vivo MEMRI. MPS increased ephrin receptor A5 (Epha5), neuronal growth regulator (Negr1) and synaptosomal-associated protein 25 (Snap25) gene expression and reduced fibroblast growth factor 12 (Fgf12) in prefrontal cortex. These genes regulate neuronal maturation, arborization and synaptic plasticity and may explain altered brain cytoarchitectonics and connectivity. These findings emphasize that recurrent stress across generations may cumulatively increase stress vulnerability and the risk of adverse health outcomes through perinatal programing in females. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Parellada, C B; Asbjörnsdóttir, B; Ringholm, L; Damm, P; Mathiesen, E R
2014-12-01
To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI < 25, 25-29.9, ≥ 30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations). Excessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9-32) vs. 7.0 (-5-16) kg (P < 0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs. 3258 g; P = 0.001), birth weight z-score (1.14 vs. -0.01, P = 0.001) and prevalence of large-for-gestational-age infants (48 vs. 20%; P < 0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [β=0.1 (95% CI 0.06-0.14), P < 0.001]. Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain. © 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
Parellada, C B; Ásbjörnsdóttir, B; Ringholm, L; Damm, P; Mathiesen, E R
2014-01-01
Aims To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. Methods A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI < 25, 25–29.9, ≥ 30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations). Results Excessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9–32) vs 7.0 (−5–16) kg (P < 0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs 3258 g; P = 0.001), birth weight z-score (1.14 vs -0.01, P = 0.001) and prevalence of large-for-gestational-age infants (48 vs 20%; P < 0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [β=0.1 (95% CI 0.06–0.14), P < 0.001]. Conclusions Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain. PMID:25081349
Castrillio, Stephanie M; Rankin, Kristin M; David, Richard J; Collins, James W
2014-12-01
Small for gestational age (weight for gestational age <10th percentile, SGA) and preterm birth (<37 weeks, PTB) are the major determinants of infant mortality rates and racial disparities therein. To determine the generational inheritance patterns of SGA and PTB among non-Hispanic Whites and African-Americans. Stratified and multivariable binominal regression analyses were performed on an Illinois transgenerational dataset of White and African-American infants (1989-1991) and their mothers (1956-1976) with appended US census income information. Former SGA White mothers (N = 8,993) had a twofold greater infant SGA frequency than former non-SGA White mothers (N = 101,312); 14.4 versus 6.9 %, RR = 2.1 (2.0-2.2). Former SGA African American (N = 4,861) mothers had a SGA birth frequency of 25.7 % compared to 16.1 % for former non-SGA mothers (N = 28,090); RR = 1.5 (1.5-1.6). The adjusted (controlling for maternal age, education, marital status, parity, prenatal care usage, cigarette smoking, and hypertension) RR (95 % CI) of infant SGA for former SGA (compared to non-SGA) White and African-American mothers equaled 2.0 (1.9-2.1 and 1.5 (1.5-1.6), respectively. The adjusted RR (95 % CI) of infant preterm birth for former preterm (compared to term) White and African-American mothers were 1.1 (1.0-1.2). The findings were minimally changed among mothers with a lifelong residence in impoverished or affluent neighborhoods. In both races, approximately 8 % of SGA births were attributable to maternal SGA. There is a transgenerational association of SGA but not preterm birth among non-Hispanic Whites and African-Americans. In both races, a similar proportion of SGA births are attributable to maternal SGA.
Boghossian, Nansi S.; McDonald, Scott A.; Bell, Edward F.; Carlo, Waldemar A.; Brumbaugh, Jane E.; Stoll, Barbara J.; Laptook, Abbot R.; Shankaran, Seetha; Walsh, Michele C.; Das, Abhik; Higgins, Rosemary D.
2017-01-01
Importance Little is known about the benefits of antenatal corticosteroids on extremely preterm multiples. Objective To examine in extremely preterm multiples if use of antenatal corticosteroids is associated with improvement in major outcomes. Design, Setting, and Participants Infants with gestational age 22–28 weeks born at an NICHD Neonatal Research Network center (1998–2013) were studied. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables. Main Outcome Measures In-hospital mortality, the composite outcome of neurodevelopmental impairment at 18–22 months’ corrected age or death before assessment. Results Of 6925 multiple-birth infants, 6094 (88%) were born to women who received antenatal corticosteroids. In-hospital mortality was lower among infants with exposure to antenatal corticosteroids vs no exposure (aRR=0.87, 95% CI 0.78–0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to antenatal corticosteroids vs no exposure (aRR=0.93, 95% CI 0.84–1.03). Other adverse outcomes that occurred less frequently among infants of women receiving antenatal corticosteroids included severe intraventricular hemorrhage (aRR=0.68, 95% CI 0.58–0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to antenatal corticosteroids was associated with a lower risk of mortality and the composite of neurodevelopmental impairment or mortality among non-small for gestational age multiples (aRR=0.82, 95% CI 0.74–0.92 and aRR=0.89, 95% CI 0.80–0.98, respectively) and a higher risk among small for gestational age multiples (aRR=1.40, 95% CI 1.02–1.93 and aRR=1.62, 95% CI 1.22–2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR=1.55, 95% CI 1.00–2.38) but not among infants of mothers without diabetes (aRR=0.91, 95% CI 0.83–1.01). Conclusion In extremely preterm multiples, exposure to antenatal corticosteroids compared with no exposure was associated with a lower risk of mortality with no significant differences for the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples. PMID:27088897
Keller, Roberta L; Feng, Rui; DeMauro, Sara B; Ferkol, Thomas; Hardie, William; Rogers, Elizabeth E; Stevens, Timothy P; Voynow, Judith A; Bellamy, Scarlett L; Shaw, Pamela A; Moore, Paul E
2017-08-01
To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs). We enrolled ELGANs (<29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy. Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907. Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year. ClinicalTrials.gov: NCT01435187. Copyright © 2017 Elsevier Inc. All rights reserved.
The FL/AC ratio for prediction of shoulder dystocia in women with gestational diabetes.
Duryea, Elaine L; Casey, Brian M; McIntire, Donald D; Twickler, Diane M
2017-10-01
To determine if sonographic variables, including fetal femur length to abdominal circumference (FL/AC) ratio, are associated with shoulder dystocia in women with gestational diabetes. This was a retrospective cohort study of women with gestational diabetes who delivered singleton infants at Parkland Hospital from 1997 to 2015. Diagnosis and treatment of gestational diabetes were uniform including sonography at 32-36 weeks. Biometric calculations were evaluated for correlation with shoulder dystocia. During the study period, 6952 women with gestational diabetes underwent a sonogram at a mean gestation of 34.8 ± 1.8 weeks. Of 4183 vaginal deliveries, 66 experienced shoulder dystocia (16/1000). The FL/AC was associated with shoulder dystocia (p < 0.001) with an AUC of 0.70 (95% CI: 0.64-0.77). This was similar to age-adjusted AC and head circumference to AC ratio (HC/AC) (both with an AUC of 0.72). All other measurements, including estimated fetal weight, were inferior. When examining the 257 women with multiple sonograms after 32 weeks' gestation, FL/AC was stable with advancing gestational age (p = 0.54) whereas age-adjusted AC and HC/AC were not (p < 0.001). The FL/AC is associated with shoulder dystocia in women with gestational diabetes. Additionally, it is a simple ratio that is independent of the reference used and remains stable, unlike age-adjusted AC and HC/AC ratio.
Ananth, Cande V; Goldenberg, Robert L; Friedman, Alexander M; Vintzileos, Anthony M
2018-05-14
Whether the changing gestational age distribution in the United States since 2005 has affected perinatal mortality remains unknown. To examine changes in gestational age distribution and gestational age-specific perinatal mortality. This retrospective cohort study examined trends in US perinatal mortality by linking live birth and infant death data among more than 35 million singleton births from January 1, 2007, through December 31, 2015. Year of birth and changes in gestational age distribution. Changes in the proportion of births at gestational ages 20 to 27, 28 to 31, 32 to 33, 34 to 36, 37 to 38, 39 to 40, 41, and 42 to 44 weeks; changes in perinatal mortality (stillbirth at ≥20 weeks, and neonatal deaths at <28 days) rates; and contribution of gestational age changes to perinatal mortality. Trends were estimated from log-linear regression models adjusted for confounders. Among the 34 236 577 singleton live births during the study period, the proportion of births at all gestational ages declined, except at 39 to 40 weeks, which increased (54.5% in 2007 to 60.2% in 2015). Overall perinatal mortality declined from 9.0 to 8.6 per 1000 births (P < .001). Stillbirths declined from 5.7 to 5.6 per 1000 births (P < .001), and neonatal mortality declined from 3.3 to 3.0 per 1000 births (P < .001). Although the proportion of births at gestational ages 34 to 36, 37 to 38, and 42 to 44 weeks declined, perinatal mortality rates at these gestational ages showed annual adjusted relative increases of 1.0% (95% CI, 0.6%-1.4%), 2.3% (95% CI, 1.9%-2.8%), and 4.2% (95% CI, 1.5%-7.0%), respectively. Neonatal mortality rates at gestational ages 34 to 36 and 37 to 38 weeks showed a relative adjusted annual increase of 0.9% (95% CI, 0.2%-1.6%) and 3.1% (95% CI, 2.1%-4.1%), respectively. Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality showed an annual relative adjusted decline of -1.3% (95% CI, -1.8% to -0.9%). The decline in neonatal mortality rate was largely attributable to changes in the gestational age distribution than to gestational age-specific mortality. Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality at this gestational age declined. This finding may be owing to pregnancies delivered at 39 to 40 weeks that previously would have been unnecessarily delivered earlier, leaving fetuses at higher risk for mortality at other gestational ages.
Xia, Brian; de Belle, Steven
2016-01-01
Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies. PMID:27025190
Zhu, Min; Cai, Jing; Liu, Shujuan; Huang, Mingwei; Chen, Yao; Lai, Xiaolan; Chen, Yuyu; Zhao, Zhongwen; Wu, Fangzhen; Wu, Dongmei; Miu, Haiyan; Lai, Shenghan; Chen, Gang
2014-09-01
Little is known about the optimal cut-off point of fasting plasma glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese women. This study investigates the relationship between gestational fasting plasma glucose and several variables: neonatal birth weight, prenatal blood pressure and dystocia rate of pregnant women. In this study, we hoped to provide a useful tool to screen gestational diabetes mellitus in pregnant Chinese women. For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22-30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as well as dystocia conditions, were examined. We analysed the correlations between the following: gestational fasting plasma glucose and neonatal birth weight; prenatal blood pressure and gestational fasting plasma glucose as well as dystocia rate and gestational fasting plasma glucose group. A modest correlation was observed between gestational fasting plasma glucose and neonatal birth weight (r = 0.093, p = 0.003). The macrosomia rate was smallest when the gestational fasting plasma glucose was in the range 3.51-5.5 mmol/L. Prenatal blood pressure increased linearly with increasing gestational fasting plasma glucose (p = 0.000). There was a significant difference between the dystocia rates in different fasting plasma glucose groups (chi-squared = 13.015, p = 0.043). The results showed that the dystocia rate significantly increased when gestational fasting plasma glucose was >4.9 mmol/L; p = 0.03, OR = 2.156 (95% CI, 1.077-4.318). We suggest that the optimal range of gestational fasting plasma glucose for pregnant Chinese women is in the range 3.5-4.9 mmol/L. Copyright © 2014 John Wiley & Sons, Ltd.
Heatley, Emer; Middleton, Philippa; Hague, William; Crowther, Caroline
2013-04-12
Postpartum follow up of women who have been found to have gestational diabetes during pregnancy is essential because of the strong association of gestational diabetes with subsequent type 2 diabetes. Postal reminders have been shown to increase significantly attendance for oral glucose tolerance testing postpartum. It is possible that a short message service (text) reminder system may also be effective. This trial aims to assess whether a text message reminder system for women who have experienced gestational diabetes in their index pregnancy will increase attendance for oral glucose tolerance testing within six months after birth. Single centre (Women's and Children's Hospital, South Australia), parallel group randomised controlled trial. Women diagnosed with gestational diabetes in their index pregnancy (oral glucose tolerance test with fasting glucose ≥ 5.5 mmol/L and/or two hour glucose ≥ 7.8 mmol/L), with access to a mobile phone, whose capillary blood glucose profile measurements prior to postnatal discharge are all normal (fasting glucose < 6.0 mmol/L, postprandial glucoses < 8.0 mmol/L). Pregestational diabetes mellitus, triplet/higher order multiple birth or stillbirth in the index pregnancy, requirement for interpreter.Trial entry and randomisation: Allocation to intervention will be undertaken using a telephone randomisation service (computer-generated random number sequence generation, with balanced variable blocks, and stratification by insulin requirement).Study groups: Women in the intervention group will receive a text reminder to attend for an oral glucose tolerance test at 6 weeks postpartum, with further reminders at 3 months and 6 months if they do not respond to indicate test completion. Women in the control group will receive a single text message reminder at 6 months postpartum.Blinding: Baseline data collection will be undertaken blinded. Blinding of participants and blinded collection of primary outcome data will not be possible for this study.Primary study outcome: Attendance for the oral glucose tolerance test within 6 months postpartum. 276 subjects will be required to show an 18% absolute increase in the rate of attendance (α=0.05 two tailed, β=80%, 5% loss to follow up) from 37% to 55% in the intervention group. Given the heightened risk of impaired glucose tolerance and type 2 diabetes in women who have had gestational diabetes, ensuring the highest possible rate of attendance for postpartum glucose tolerance testing, so that early diagnosis and intervention can occur, is important. A text message reminder system may prove to be an effective method for achieving improved attendance for such testing. This randomised controlled trial will assess whether such a system will increase rates of attendance for postpartum oral glucose tolerance testing in women who have experienced gestational diabetes. Australian New Zealand Clinical Trials Registry - ACTRN12612000621819.
Effects of tartrazine on exploratory behavior in a three-generation toxicity study in mice.
Tanaka, Toyohito; Takahashi, Osamu; Oishi, Shinshi; Ogata, Akio
2008-10-01
Tartrazine was given to mice in the diet at levels of 0 (control), 0.05%, 0.15%, and 0.45% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(2) generation, and selected reproductive and neurobehavioral parameters were measured. In the F(1) generation, the development of swimming direction at postnatal day (PND) 7 was accelerated significantly in male offspring in a dose-related manner. Surface righting at PND 7 was affected significantly in female offspring in dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age. In the F(2) generation, the development of swimming direction at PND 7 was accelerated significantly in the high-dosed group in male offspring. Time taken of olfactory orientation at PND 14 was accelerated significantly in male offspring in a dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age, and in males at 8 weeks of age. The dose levels of tartrazine in the present study produced a few adverse effects on neurobehavioral parameters throughout generations in mice.
Ajayi; Lale
2000-01-15
Ten local cultivars of bambara groundnut, Vigna subterranea (L.) Verdcourt obtained directly from farmers in Potiskum, Nigeria and from the Institute for Agricultural Research, Samaru, Nigeria were compared with three improved varieties developed at the International Institute of Tropical Agriculture, Ibadan, Nigeria for their susceptibility to infestation by Callosobruchus maculatus (F.). Three cultivars (Maifarinhaneh, Angale and Bunmonu) with a susceptibility index (SI) of 3.06-3.71 were identified as slightly susceptible to C. maculatus; four cultivars (Bagantere, Bakingangala, Ole and Bakiyawa 1) and one improved variety (TVSU 1061) with an SI of 4.39-4.93 as moderately susceptible; and three cultivars (Bidi, Uzu and Dadinkowa 1) and two improved varieties (TVSU 702 and TVSU 751) with an SI of 5.00-5.34 as susceptible. Five of the cultivars were used to examine the ability of beetle populations to overcome varietal resistance over six successive generations. Development time was significantly longer but percentage of adults that emerged and susceptibility of bambara groundnuts were significantly lower in F(4), F(5) or F(6) generations than in the F(1) or F(2) generation. The efficacy of combining insecticidal essential oils obtained from clove, Syzgium aromaticum, West African black pepper (WABP), Piper guineense, and ginger, Zingiber officinale applied at the rate of 2 mg/20 g seed and six of the local bambara groundnut cultivars (Angale, Maifarinhaneh, Bakingangala, Bagantere, Bunmonu and Bidi) with differing susceptibilities to C. maculatus (F.) was also assessed during a 3-month storage period. The three essential oils significantly reduced the percentage of C. maculatus adults that emerged from the bambara groundnut cultivars in the F(1) generation and the number of adult offspring that developed in the cultivars during the 3-month storage period. The mean number of progeny that developed in untreated seeds and seeds treated with clove, WABP and ginger oils during the study period were 73.0, 0.0, 0.1 and 0.2, respectively. No adult C. maculatus, however, developed in slightly and moderately susceptible cultivars treated with essential oils. Treatment of seeds of Bidi (a susceptible cultivar) with the essential oils reduced the percentage of adults that emerged in the F(1) generation from 26.8% in untreated seeds to 0.0, 0.1 and 0.4% in seeds treated with clove, WABP and ginger oils, respectively; and reduced loss in seed weight after three months' storage from 34% to 0.0, 0.01 and 0.1%, respectively.
Foster, Paul M D
2014-12-01
The National Toxicology Program (NTP) has developed a new flexible study design, termed the modified one generation (MOG) reproduction study. The MOG study will encompass measurements of developmental and reproductive toxicity parameters as well as enable the setting of appropriate dose levels for a cancer bioassay through evaluation of target organ toxicity that is based on test article exposure that starts during gestation. This study design is compared and contrasted with the new Organization for Economic Co-operation and Development (OECD) 443 test guideline, the extended one generation reproduction study. The MOG study has a number of advantages, with a focus on F 1 animals, the generation of adequately powered, robust data sets that include both pre and postnatal developmental toxicity information, and the measurement of effects on reproductive structure and function in the same animals. This new study design does not employ the use of internal triggers in the design structure for the use of animals already on test and is also consistent with the principles of the 3R's. © 2014 by The Author(s).
Is Gestational Hypertension Protective against Perinatal Mortality in Twin Pregnancies?
Luo, Qi-Guang; Zhang, Ji-Yan; Cheng, Wei-Wei; Audibert, Francois; Luo, Zhong-Cheng
2014-01-01
Background Pregnancy-induced or gestational hypertension is a common pregnancy complication. Paradoxically, gestational hypertension has been associated with a protective effect against perinatal mortality in twin pregnancies in analytic models (logistic regression) without accounting for survival time. Whether this effect is real remains uncertain. This study aimed to validate the impact of gestational hypertension on perinatal mortality in twin pregnancies using a survival analysis approach. Methods This was a retrospective cohort study of 278,821 twin pregnancies, using the U.S. 1995–2000 matched multiple birth dataset (the largest dataset available for multiple births). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death (stillbirth and neonatal death) comparing gestational hypertensive vs. non-hypertensive pregnancies controlling for maternal characteristics and twin cluster-level dependence. Results Comparing births in gestational hypertensive vs. non-hypertensive twin pregnancies, perinatal mortality rates were significantly lower (1.20% vs. 3.38%), so were neonatal mortality (0.72% vs. 2.30%) and stillbirth (0.48% vs. 1.10%) rates. The aHRs (95% confidence intervals) were 0.34 (0.31–0.38) for perinatal death, 0.31 (0.27–0.34) for neonatal death, and 0.45 (0.38–0.53) for stillbirth, respectively. The protective effect of gestational hypertension against perinatal death became weaker over advancing gestational age; the aHRs in very preterm (<32 weeks), mild preterm (32–36 weeks) and term (37+ weeks) births were 0.29, 0.48 and 0.76, respectively. The largest risk reductions in neonatal mortality were observed for infections and immaturity-related conditions. Conclusions Gestational hypertension appears to be beneficial for fetal survival in twin pregnancies, especially in those ending more prematurely or for deaths due to infections and immaturity-related conditions. Prospective studies are required to rule out the possibility of unmeasured confounders. PMID:24733364
Carlo, Waldemar A.; McDonald, Scott A.; Fanaroff, Avroy A.; Vohr, Betty R.; Stoll, Barbara J.; Ehrenkranz, Richard A.; Andrews, William W.; Wallace, Dennis; Das, Abhik; Bell, Edward F.; Walsh, Michele C.; Laptook, Abbot R.; Shankaran, Seetha; Poindexter, Brenda B.; Hale, Ellen C.; Newman, Nancy S.; Davis, Alexis S.; Schibler, Kurt; Kennedy, Kathleen A.; Sanchez, Pablo J.; Van Meurs, Krisa P.; Goldberg, Ronald N.; Watterberg, Kristi L.; Faix, Roger G.; Frantz, Ivan D.; Higgins, Rosemary D.
2013-01-01
Context Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24–34 weeks gestational age, but not before 24 weeks because of lack of data. However, many infants born before 24 weeks are provided intensive care now. Objective To determine if antenatal corticosteroids are associated with improvement in major outcomes in infants born at 22 and 23 weeks. Design, Setting, Participants Data for this cohort study were collected prospectively on 401–1000 gram inborn infants (N=10,541) of 22–25 weeks gestation born between 1993–2009 at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4,924 (86.5%) of the infants born in 1993–2008 who survived to 18–22 months. Logistic regression models generated adjusted odds ratios, controlling for maternal and neonatal variables. Main Outcome Measures Mortality and neurodevelopmental impairment at 18–22 months corrected age RESULTS Death or neurodevelopmental impairment at 18–22 months was lower for infants whose mothers received antenatal corticosteroids born at 23 weeks (antenatal corticosteroids, 83.4% vs no antenatal corticosteroids, 90.5%; adjusted odds ratio 0.58; 95% CI, 0.42–0.80), at 24 weeks (antenatal corticosteroids, 68.4% vs no antenatal corticosteroids, 80.3%; adjusted odds ratio 0.62; 95% CI, 0.49–0.78), and at 25 weeks (antenatal corticosteroids, 52.7% vs no antenatal corticosteroids, 67.9%; adjusted odds ratio 0.61; 95% CI, 0.50–0.74) but not at 22 weeks (antenatal corticosteroids, 90.2% vs no antenatal corticosteroids, 93.1%; adjusted odds ratio 0.80; 95% CI, 0.29–12.21). Death by 18–22 months, hospital death, death/intraventricular hemorrhage/periventricular leukomalacia, and death/necrotizing enterocolitis were significantly lower for infants born at 23, 24, and 25 weeks gestational age if the mothers had received antenatal corticosteroids but the only outcome significantly lower at 22 weeks was death/necrotizing enterocolitis (antenatal corticosteroids, 73.5% vs no antenatal corticosteroids, 84.5%; adjusted odds ratio 0.54; 95% CI, 0.30–0.97). CONCLUSIONS Among infants born at 23–25 weeks gestation, use of antenatal corticosteroids compared to non-use was associated with a lower rate of death or neurodevelopmental impairment at 18–22 months. PMID:22147379
Gigante, Denise P; Horta, Bernardo L; Matijasevich, Alicia; Mola, Christian Loret de; Barros, Aluisio J D; Santos, Ina S; Barros, Fernando C; Victora, Cesar G
2015-10-01
We examined the associations between socioeconomic trajectories from birth to adulthood and gestational age and birth size in the next generation, using linked data from two population-based birth cohorts carried out in a Brazilian city. By comparing socioeconomic trajectories of mothers and fathers, we attempted to identify-specific effects of maternal and paternal socioeconomic trajectory on offspring birth weight, birth length, head circumference and gestational age at birth. 2 population-based birth cohort studies were carried out in 1982 and 2004 in Pelotas (Brazil); 156 mothers and 110 fathers from the earlier cohort had children in 2004. Gestational age and birth length, weight and head circumference were measured. Analyses were carried out separately for mothers and fathers. Mediation analyses assessed the role of birth weight and adult body mass index (BMI). Among mothers, but not for fathers, childhood poverty was strongly associated with smaller size in the next generation (about 400 g in weight and 1.5 cm in height) and shorter gestations (about 2 weeks). Adult poverty did not play a role. For mothers, the associations with gestational age, birth length and weight-but not with head circumference-persisted after adjusting for maternal birth weight and for the height and weight of the grandmother. Maternal birth weight did not mediate the observed associations, but high maternal BMI in adulthood was partly responsible for the association with gestational age. Strong effects of early poverty on gestational age and birth size in the next generation were observed among mothers, but not among fathers. These findings suggest a specific maternal effect of socioeconomic trajectory, and in particular of early poverty on offspring size and duration of pregnancy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Sámano, Reyna; Martínez-Rojano, Hugo; Chico-Barba, Gabriela; Godínez-Martínez, Estela; Sánchez-Jiménez, Bernarda; Montiel-Ojeda, Diana; Tolentino, Maricruz
2017-09-27
Introduction : Gestational weight gain is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Leptin is normally correlated with adiposity and is also known to increase throughout pregnancy, as the placenta becomes a source of leptin synthesis. Several studies have reported positive correlations between cord blood leptin level and either birthweight or size for gestational age, as well as body mass index (BMI). Objective : To determine the correlation of prenatal leptin concentration in pregnant adolescents with their gestational weight gain, postpartum weight retention, and weight/length of their newborn. Methods : A cohort study was conducted on pregnant Mexican adolescents from Gestational Week 26-28 to three months postpartum ( n = 168 mother-child dyads). An anthropometric assessment was made of each pregnant adolescent, and the serum level of leptin and the intake of energy were determined. The newborn was evaluated each month during postpartum. Clinical records were reviewed to obtain sociodemographic data. Bivariate correlations, tests for repeating measurements and logistic regression models were performed. Results : Leptin concentration gradually increased during the third trimester of pregnancy. At Gestation Week 36, leptin level correlated with gestational weight gain. When comparing adolescents that had the lowest and highest concentration of leptin, the former presented a mean of 6 kg less in gestational weight gain (inter-subject leptin concentration, p = 0.001; inter-subject energy intake, p = 0.497). Leptin concentration and gestational weight gain exerted an effect on the weight of the newborn (inter-subject leptin concentration for Week 32, p = 0.024; inter-subject gestational weight gain, p = 0.011). Newborn length was associated with leptin concentration at Week 28 (leptin effect, p = 0.003; effect of gestational weight gain, p = 0.722). Conclusions : Pregnant adolescents with leptin concentration over 20 ng/mL showed a greater gestational weight gain. Leptin concentration correlated with length and weight of the newborn.
Sámano, Reyna; Martínez-Rojano, Hugo; Godínez-Martínez, Estela; Sánchez-Jiménez, Bernarda; Montiel-Ojeda, Diana; Tolentino, Maricruz
2017-01-01
Introduction: Gestational weight gain is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Leptin is normally correlated with adiposity and is also known to increase throughout pregnancy, as the placenta becomes a source of leptin synthesis. Several studies have reported positive correlations between cord blood leptin level and either birthweight or size for gestational age, as well as body mass index (BMI). Objective: To determine the correlation of prenatal leptin concentration in pregnant adolescents with their gestational weight gain, postpartum weight retention, and weight/length of their newborn. Methods: A cohort study was conducted on pregnant Mexican adolescents from Gestational Week 26–28 to three months postpartum (n = 168 mother–child dyads). An anthropometric assessment was made of each pregnant adolescent, and the serum level of leptin and the intake of energy were determined. The newborn was evaluated each month during postpartum. Clinical records were reviewed to obtain sociodemographic data. Bivariate correlations, tests for repeating measurements and logistic regression models were performed. Results: Leptin concentration gradually increased during the third trimester of pregnancy. At Gestation Week 36, leptin level correlated with gestational weight gain. When comparing adolescents that had the lowest and highest concentration of leptin, the former presented a mean of 6 kg less in gestational weight gain (inter-subject leptin concentration, p = 0.001; inter-subject energy intake, p = 0.497). Leptin concentration and gestational weight gain exerted an effect on the weight of the newborn (inter-subject leptin concentration for Week 32, p = 0.024; inter-subject gestational weight gain, p = 0.011). Newborn length was associated with leptin concentration at Week 28 (leptin effect, p = 0.003; effect of gestational weight gain, p = 0.722). Conclusions: Pregnant adolescents with leptin concentration over 20 ng/mL showed a greater gestational weight gain. Leptin concentration correlated with length and weight of the newborn. PMID:28953229
Yang, Ying-Fei; Chen, Pei-Jen; Liao, Vivian Hsiu-Chuan
2016-05-01
Nanoscale zerovalent iron (nZVI) is widely used with large scale for environmental remediation for in situ or ex situ applications. The potential impact of nZVI on biota at environmentally relevant concentrations needs to be elucidated. In this study, the reproductive toxicities of three irons species: carboxymethyl cellulose (CMC)-stabilized nZVI, nanoscale iron oxide (nFe3O4), and ferrous ion (Fe(II)aq) in the soil-dwelling nematode Caenorhabditis elegans were examined. In addition, the generational transfer of reproductive toxicity of CMC-nZVI on C. elegans was investigated. The results showed that CMC-nZVI, nFe3O4, and Fe(II)aq did not cause significant mortality after 24 h exposure at the examined concentrations. Reproductive toxicity assays revealed that CMC-nZVI, nFe3O4, and Fe(II)aq significantly decreased offsprings in parental generation (F0) in accompany with the increased intracellular reactive oxygen species (ROS). Furthermore, the reproductive toxicity of CMC-nZVI at environmentally relevant concentrations was transferrable from the F0 to the F1 and F2 generations, but then recovered in the F3 and F4 generations. Further evidence showed that total irons were accumulated in the F0 and F1 generations of C. elegans after CMC-nZVI parental exposure. This study demonstrated that environmentally relevant concentrations of CMC-nZVI induced multigenerational reproductive toxicity which can be ascribed to its high production of ROS in F0 generation, toxicity of Fe(II)aq, and iron accumulation in C. elegans. Since nZVI is widely used for environmental remediation, considering the multigenerational toxicity, this study thus implicates a potential environmental risk of nZVI-induced nanotoxicity in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.
Bruijn, Mmc; Vis, J Y; Wilms, F F; Oudijk, M A; Kwee, A; Porath, M M; Oei, G; Scheepers, Hcj; Spaanderman, Mea; Bloemenkamp, Kwm; Haak, M C; Bolte, A C; Vandenbussche, Fpha; Woiski, M D; Bax, C J; Cornette, Jmj; Duvekot, J J; Nij Bijvanck, Bwa; van Eyck, J; Franssen, Mtm; Sollie, K M; van der Post, Jam; Bossuyt, Pmm; Opmeer, B C; Kok, M; Mol, Bwj; van Baaren, G-J
2016-11-01
To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. Post hoc analysis of frozen fFN samples of a nationwide cohort study. Ten perinatal centres in the Netherlands. Symptomatic women between 24 and 34 weeks of gestation. The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. Spontaneous delivery within 7 days after study entry. We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD. © 2015 Royal College of Obstetricians and Gynaecologists.
Jousse, Céline; Muranishi, Yuki; Parry, Laurent; Montaurier, Christophe; Even, Patrick; Launay, Jean-Marie; Carraro, Valérie; Maurin, Anne-Catherine; Averous, Julien; Chaveroux, Cédric; Bruhat, Alain; Mallet, Jacques; Morio, Béatrice; Fafournoux, Pierre
2014-01-01
Epidemiological findings indicate that transient environmental influences during perinatal life, especially nutrition, may have deleterious heritable health effects lasting for the entire life. Indeed, the fetal organism develops specific adaptations that permanently change its physiology/metabolism and that persist even in the absence of the stimulus that initiated them. This process is termed "nutritional programming". We previously demonstrated that mothers fed a Low-Protein-Diet (LPD) during gestation and lactation give birth to F1-LPD animals presenting metabolic consequences that are different from those observed when the nutritional stress is applied during gestation only. Compared to control mice, adult F1-LPD animals have a lower body weight and exhibit a higher food intake suggesting that maternal protein under-nutrition during gestation and lactation affects the energy metabolism of F1-LPD offspring. In this study, we investigated the origin of this apparent energy wasting process in F1-LPD and demonstrated that minimal energy expenditure is increased, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat-diet-induced obesity. Clearly, different paradigms of exposure to malnutrition may be associated with differences in energy expenditure, food intake, weight and different susceptibilities to various symptoms associated with metabolic syndrome. Taken together these results demonstrate that intra-uterine environment is a major contributor to the future of individuals and disturbance at a critical period of development may compromise their health. Consequently, understanding the molecular mechanisms may give access to useful knowledge regarding the onset of metabolic diseases.
Pei, Minjuan; Matsuda, Ken-Ichi; Sakamoto, Hirotaka; Kawata, Mitsuhiro
2006-03-01
Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.
van Baaren, Gert-Jan; Hermes, Wietske; Franx, Arie; van Pampus, Maria G; Bloemenkamp, Kitty W M; van der Post, Joris A; Porath, Martina; Ponjee, Gabrielle A E; Tamsma, Jouke T; Mol, Ben Willem J; Opmeer, Brent C; de Groot, Christianne J M
2014-10-01
To assess the cost-effectiveness of post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term. Two separate Markov models evaluated the cost-effectiveness analysis of hypertension (HT) screening and screening on metabolic syndrome (MetS), respectively, as compared to current practice in women with a history of term hypertensive pregnancy disorders. Analyses were performed from the Dutch health care perspective, using a lifetime horizon. One-way sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results. Both screening on HT and MetS in women with a history of gestational hypertension or pre-eclampsia resulted in increase in life expectancy (HT screening 0.23year (95% CI -0.06 to 0.54); MetS screening 0.14years (95% CI -0.16 to 0.45)). The gain in QALYs was limited, with HT screening and MetS screening generating 0.04 QALYs (95% CI -0.12 to 0.20) and 0.03 QALYs (95% CI -0.14 to 0.19), resulting in costs to gain one QALY of €4228 and €28,148, respectively. Analyses for uncertainty showed a chance of 74% and 75%, respectively, that post-partum screening is cost-effective at a threshold of €60,000/QALY. According to the available knowledge post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term is likely to be cost-effective. Copyright © 2014 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study.
Zhang, Cuilin; Tobias, Deirdre K; Chavarro, Jorge E; Bao, Wei; Wang, Dong; Ley, Sylvia H; Hu, Frank B
2014-09-30
To quantify the association between a combination of healthy lifestyle factors before pregnancy (healthy body weight, healthy diet, regular exercise, and not smoking) and the risk of gestational diabetes. Prospective cohort study. Nurses' Health Study II, United States. 20,136 singleton live births in 14,437 women without chronic disease. Self reported incident gestational diabetes diagnosed by a physician, validated by medical records in a previous study. Incident first time gestational diabetes was reported in 823 pregnancies. Each lifestyle factor measured was independently and significantly associated with risk of gestational diabetes. The combination of three low risk factors (non-smoker, ≥ 150 minutes a week of moderate to vigorous physical activity, and healthy eating (top two fifths of Alternate Healthy Eating Index-2010 adherence score)) was associated with a 41% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.59, 95% confidence interval 0.48 to 0.71). Addition of body mass index (BMI) <25 before pregnancy (giving a combination of four low risk factors) was associated with a 52% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.48, 0.38 to 0.61). Compared with pregnancies in women who did not meet any of the low risk lifestyle factors, those meeting all four criteria had an 83% lower risk of gestational diabetes (relative risk 0.17, 0.12 to 0.25). The population attributable risk percentage of the four risk factors in combination (smoking, inactivity, overweight, and poor diet) was 47.5% (95% confidence interval 35.6% to 56.6%). A similar population attributable risk percentage (49.2%) was observed when the distributions of the four low risk factors from the US National Health and Nutrition Examination Survey (2007-10) data were applied to the calculation. Adherence to a low risk lifestyle before pregnancy is associated with a low risk of gestational diabetes and could be an effective strategy for the prevention of gestational diabetes. © Zhang et al 2014.
NASA Astrophysics Data System (ADS)
Huang, Ying; Zhu, Liyan; Liu, Guangxing
2006-08-01
In order to study the biological effects by bis(tributyltin) oxide (TBTO) exposure, chronic toxicity tests were conducted on the calanoid copepod Pseudodiaptomus marinus over two generations. The results indicated that nauplii were more sensitive than copepodites. F1 copepods were more vulnerable than F0 copepods and a drastic increase in mortality was observed as the TBTO concentration became higher. Exposure of copepods to 60 ng l -1 TBTO concentration reduced the fecundity and resulted in some females being infecund (in the F0 generation). The time to the first egg sac for females in the F1 generation exposed to 6 ng l -1 TBTO concentration was significantly reduced, and the fecundity of this generation was increased. The female-to-male ratio in the F1 generation exposed to 20 ng l -1 TBTO concentration was significantly reduced. These results show that the current ambient TBT concentration may influence populations of copepods in the coastal environment.
Oriquat, Ghaleb A.; Abu-Samak, Mahmoud; Al Hanbali, Othman A.; Salim, Maher D.
2016-01-01
Background. Our aim was to evaluate the protective effect of lipoic acid (LA) on fetal outcome of diabetic mothers. Methods. Diabetes was induced in female rats using streptozotocin and rats were made pregnant. Pregnant control (group 1; n = 9; and group 2; n = 7) or pregnant diabetic (group 3; n = 10; and group 4; n = 8) rats were treated daily with either LA (groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the fetuses, placentas, and membranes were dissected, examined morphologically, and then homogenized, to measure cyclooxygenase (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2 α (PGFM) levels. The level of total glutathione was measured in the maternal liver and plasma and in all fetuses. Results. Supplementation of diabetic rats with LA was found to significantly (p < 0.05) reduce resorption rates in diabetic rats and led to a significant (p < 0.05) increase in liver, plasma, and fetuses total glutathione from LA-TD rats as compared to those from V-TD. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas, and membranes were characteristic of experimental diabetic gestation associated with malformation. The levels of PGEM in malformed fetuses from LA-TD mothers was significantly (p < 0.05) higher than those in malformed fetuses from V-TD rats. Conclusions. LA treatment did not completely prevent the occurrence of malformations. Thus, other factors may be involved in the pathogenesis of the diabetes-induced congenital malformations. PMID:28042582
Ziadi, C; Mocé, M L; Laborda, P; Blasco, A; Santacreu, M A
2013-07-01
The aim of this work was to estimate direct and correlated responses in survival rates in an experiment of selection for ovulation rate (OR) and litter size (LS) in a line of rabbits (OR_LS). From generation 0 to 6 (first selection period), females were selected only for second gestation OR estimated by laparoscopy. From generation 7 to 13 (second selection period), a 2-stage selection for OR and LS was performed. In stage 1, females having the greatest OR at second gestation were selected. In stage 2, selection was for the greatest average LS of the first 2 parities of the females selected in stage 1. Total selection pressure in females was about 30%. The line had approximately 17 males and 75 females per generation. Traits recorded were OR estimated as the number of corpora lutea in both ovaries, number of implanted embryos (IE) estimated as the number of implantation sites, LS estimated as total number of rabbits born recorded at each parity, embryo survival (ES) estimated as IE/OR, fetal survival (FS) estimated as LS/IE, and prenatal survival (PS) estimated as LS/OR. Data were analyzed using Bayesian methodology. The estimated heritabilities of LS, OR, IE, ES, FS, and PS were 0.07, 0.21, 0.10, 0.07, 0.12, and 0.16, respectively. Direct and correlated responses from this study were estimated in each period of selection as the difference between the average genetic values of last and first generation. In the first selection period, OR increased 1.36 ova, but no correlated response was observed in LS due to a decrease on FS. Correlated responses for IE, ES, FS, and PS in the first selection period were 1.11, 0.00, -0.04, and -0.01, respectively. After 7 generations of 2-stage selection for OR and LS, OR increased 1.0 ova and response in LS was 0.9 kits. Correlated responses for IE, ES, FS, and PS in the second selection period were 1.14, 0.02, 0.02, and 0.07, respectively. Two-stage selection for OR and LS can be a promising procedure to improve LS in rabbits.
Effects of season and stage of gestation on luteinizing hormone release in gilts.
Smith, C A; Almond, G W
1991-01-01
This study was designed to examine the effects of two seasons and stage of gestation on luteinizing hormone (LH) release in the gilt. Eleven Yorkshire-Landrace crossbred gilts were each fitted with an indwelling vena caval cannula. Blood samples were collected at 6 h intervals for six days during early (day 39 to 44) or mid-gestation (day 69 to 74). Serum progesterone, estradiol-17 beta and LH concentrations were determined in samples collected at 6 h intervals. Early and mid-gestation occurred during August and September in group 1 (n = 6) and during January and February in group 2 gilts (n = 5). To characterize pulsatile LH release, samples were collected at 15 min intervals for 8 h on day 40, 43, 70 and 73 of gestation. Following each 8 h sampling period, gilts were treated intravenously with 0.5 micrograms gonadotropin-releasing hormone (GnRH)/kg body weight and blood collected at 10 min intervals for 3 h. Progesterone concentrations decreased (p less than 0.01) from 22.1 +/- 0.4 ng/mL during early gestation to 18.2 +/- 0.4 ng/mL during mid-gestation. Estradiol-17 beta concentrations increased (p less than 0.01) from early to mid-gestation (13.5 +/- 0.8 versus 28.4 +/- 0.7 pg/mL). Frequency of LH pulses and LH pulse amplitude were higher (p less than 0.05) in pregnant gilts during January and February compared to August and September.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1889040
Santos, S; Severo, M; Gaillard, R; Santos, A C; Barros, H; Oliveira, A
2016-11-01
It remains unknown whether the effects of prenatal exposures on child's adiposity reflect entirely intrauterine programming. We aimed to assess the effects of maternal gestational weight gain, diabetes and smoking on the child's body fat patterns, disentangling the direct (through intrauterine programming) and indirect (through birthweight) effects. We included 4747 singleton 7-year-old children from the Generation XXI birth cohort (Porto, Portugal). At birth, maternal and newborn's characteristics were obtained. Anthropometrics were measured at age 7 years and body fat patterns were identified by principal component analysis. Path analysis was used to quantify direct, indirect and total effects of gestational weight gain, diabetes and smoking on body fat patterns. Pattern 1 was characterized by strong factor loadings with body mass index, fat mass index and waist-to-height ratio (fat quantity) and pattern 2 with waist-to-hip ratio, waist-to-thigh ratio, and waist-to-weight ratio (fat distribution). The positive total effect of maternal gestational weight gain and diabetes on the child's fat quantity was mainly through a direct pathway, responsible for 91.7% and 83.7% of total effects, respectively (β = 0.022; 95% Confidence Interval (CI): 0.017, 0.027; β = 0.041; 95% CI: -0.011, 0.093). No effects on fat distribution were found. Maternal prenatal smoking had a positive direct effect on patterns 1 and 2, explaining 94.9% and 76.1% of total effects, respectively. The effects of maternal gestational weight gain, diabetes and smoking on a child's fat quantity seem to be mainly through intrauterine programming. Maternal smoking also showed a positive direct effect on child's fat distribution. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Susiarjo, Martha; Xin, Frances; Stefaniak, Martha; Mesaros, Clementina; Simmons, Rebecca A; Bartolomei, Marisa S
2017-08-01
Increasing evidence has demonstrated that exposure to endocrine-disrupting chemicals impacts maternal and fetal health, but the underlying mechanisms are still unclear. We previously showed that dietary exposure to 10 µg/kg body weight (bw)/d and 10 mg/kg bw/d of bisphenol A (BPA) during pregnancy induced metabolic abnormalities in F1 male offspring and gestational glucose intolerance in F0 pregnant mice. The aim of this study was to elucidate the underlying etiologies of BPA exposure-induced metabolic disease by analyzing the male fetal liver metabolome. Using the Metabolon Discover HD4 Platform, our laboratory identified metabolic pathways that were altered by BPA exposure, including biochemicals in lipid and amino acid metabolism. Specifically, primary and secondary bile acids were increased in liver from BPA-exposed embryonic day 18.5 male fetuses. We subsequently showed that increased bile acid was associated with a defective farnesoid X receptor-dependent negative feedback mechanism in BPA-exposed fetuses. In addition, through metabolomics, we observed that BPA-exposed fetuses had elevated tryptophan levels. Independent liquid chromatography and mass spectrometry measurement revealed that BPA-exposed dams also had increased tryptophan levels relative to those of controls. Because several key enzymes in tryptophan catabolism are vitamin B6 dependent and vitamin B6 deficiencies have been linked to gestational diabetes, we tested the impact of vitamin B6 supplementation and showed that it rescued gestational glucose intolerance in BPA-exposed pregnant mice. Our study has therefore identified two pathways (bile acid and tryptophan metabolism) that potentially underlie BPA-induced maternal and fetal metabolic disease. Copyright © 2017 Endocrine Society.
Metabolic syndrome and selenium during gestation and lactation.
Nogales, Fátima; Ojeda, M Luisa; Del Valle, Paulina Muñoz; Serrano, Alejandra; Murillo, M Luisa; Carreras Sánchez, Olimpia
2017-03-01
Selenium (Se) has a dual role in metabolic syndrome (MS) development as it has an antioxidant action against both "good" and "bad" reactive oxygen species. This study evaluates Se body profile in dams which present MS during gestation and lactation, in order to elucidate a normal dietary Se's implication in this pathology. Rats were randomized into control (C) and fructose (F) groups. The rich fructose diet (65 %) during gestation and lactation periods induced MS in dams. Se body distribution was determined by atomic absorption spectrophotometry, and the hepatic activity of the four antioxidant enzymes and the bimolecular oxidation were determined by spectrophotometry. The cardiac activity was monitored using the indirect tail occlusion method. Lipid and glucidic profile was also analyzed. Despite the fact that the diet supplied has 0.1 ppm of Se, the minimal dietary requirement for rats, F dams ate less amount of food, and therefore, they had lower Se retention. However, they had normal levels of Se in serum and milk. Dams with MS had Se depletion in heart and muscle joint to hypertension and a lower heart rate, and Se repletion in liver and kidney. Despite the increase in hepatic glutathione peroxidase (GPx) and catalase activity found, lipid oxidation occurred-probably because superoxide dismutase activity was diminished. In heart, the activity and expression of the selenoprotein GPx1 were decreased. With these results, it is not possible to elucidate whether a dietary Se supplementation or a Se-restricted diet are good for MS; because despite the fact that GPx activity is increased in liver, it is also found, for the first time, that heart Se deposits are significantly decreased during MS.
Metabolomic and oxidative effects of quantum dots-indolicidin on three generations of Daphnia magna.
Falanga, Annarita; Mercurio, Flavia A; Siciliano, Antonietta; Lombardi, Lucia; Galdiero, Stefania; Guida, Marco; Libralato, Giovanni; Leone, Marilisa; Galdiero, Emilia
2018-05-01
This study evaluated the effect of QDs functionalized with the antimicrobial peptide indolicidin on oxidative stress and metabolomics profiles of Daphnia magna across three generations (F0, F1, and F2). Exposing D. magna to sub-lethal concentrations of the complex QDs-indolicidin, a normal survival of daphnids was observed from F0 to F2, but a delay of first brood, fewer broods per female, a decrease of length of about 50% compared to control. In addition, QDs-indolicidin induced a significantly higher production of reactive oxygen species (ROS) gradually in each generation and an impairment of enzymes response to oxidative stress such as superoxide dismutase (SOD), catalase (CAT) and glutathione transferase (GST). Effects were confirmed by metabolomics profiles that pointed out a gradual decrease of metabolomics content over the three generations and a toxic effect of QDs-indolicidin likely related to the higher accumulation of ROS and decreased antioxidant capacity in F1 and F2 generations. Results highlighted the capability of metabolomics to reveal an early metabolic response to stress induced by environmental QDs-indolicidin complex. Copyright © 2018 Elsevier B.V. All rights reserved.
Hunnam, J C; Parkinson, T J; Lopez-Villalobos, N; McDougall, S
2009-09-01
To determine bovine fetal characteristics significantly associated with increasing gestational age as measured via transcutaneous ultrasonography over the right flank. The length of gestation at date of pregnancy diagnosis via transcutaneous and transrectal ultrasonography was determined for 224 dairy cattle by estimation from subsequent calving dates. A separate dataset was created for each measurable fetal characteristic (i.e. thoracic diameter, abdominal diameter, umbilical diameter, placentome length and placentome height) and risk factors significantly associated with gestational age at pregnancy diagnosis within each dataset, including the fetal characteristic, were identified. Abdominal diameter was the most frequently observed fetal characteristic and thoracic diameter was the least. Gestational age at pregnancy diagnosis (d) was significantly associated with fetal thoracic diameter (P < 0.01), abdominal diameter (P < 0.01) and umbilical diameter (P = 0.02) when measured via transcutaneous ultrasound. Within each model, sire breed, dam breed, dam age and/or calf sex were also significantly associated with gestational age. Gestational age at pregnancy diagnosis was not significantly associated with either placentome height or length (P > 0.05). Fetal thoracic diameter, abdominal diameter and umbilical diameter were found to be significantly associated with gestational age between approximate days 73 to 190 of gestation. Transcutaneous ultrasonography may prove a useful method of estimating gestational age in the absence of accurate breeding records.
Lisonkova, S; Sabr, Y; Butler, B; Joseph, K S
2012-12-01
To examine international rates of preterm birth and potential associations with stillbirths and neonatal deaths at late preterm and term gestation. Ecological study. Canada, USA and 26 countries in Europe. All deliveries in 2004. Information on preterm birth (<37, 32-36, 28-31 and 24-27 weeks of gestation) and perinatal deaths was obtained for 28 countries. Data sources included files and publications from Statistics Canada, the EURO-PERISTAT project and the National Center for Health Statistics. Pearson correlation coefficients and random-intercept Poisson regression were used to examine the association between preterm birth rates and gestational age-specific stillbirth and neonatal death rates. Rate ratios with 95% confidence intervals were estimated after adjustment for maternal age, parity and multiple births. Stillbirths and neonatal deaths ≥ 32 and ≥ 37 weeks of gestation. International rates of preterm birth (<37 weeks) ranged between 5.3 and 11.4 per 100 live births. Preterm birth rates at 32-36 weeks were inversely associated with stillbirths at ≥ 32 weeks (adjusted rate ratio 0.94, 95% CI 0.92-0.96) and ≥ 37 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) of gestation and inversely associated with neonatal deaths at ≥ 32 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) and ≥ 37 weeks (adjusted rate ratio 0.82, 95% CI 0.78-0.86) of gestation. Countries with high rates of preterm birth at 32-36 weeks of gestation have lower stillbirth and neonatal death rates at and beyond 32 weeks of gestation. Contemporary rates of preterm birth are indicators of both perinatal health and obstetric care services. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.
Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.
Magnus, Maria C; Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; Magnus, Per; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail
2018-06-20
To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. One and two sample mendelian randomisation analyses. Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Preeclampsia and retinopathy of prematurity in preterm births.
Yu, Xiao Dan; Branch, D Ware; Karumanchi, S Ananth; Zhang, Jun
2012-07-01
The relationship between gestational hypertension, preeclampsia, and the risk of retinopathy of prematurity (ROP) remains unclear. Thus, we used a large cohort database to study the influence of maternal gestational hypertension and preeclampsia on the occurrence of ROP in preterm infants. We used data from a previous retrospective cohort study that includes 25,473 eligible preterm neonates. We examined the association between gestational hypertension, preeclampsia, and ROP while controlling for potential confounders by multiple logistic regression analysis. Of the 8758 early preterm infants (gestational age <34 weeks), 1024 (11.69%) had ROP, while of the 16,715 late preterm infants, only 29 (0.17%) had ROP. After adjusting for confounders, preeclampsia was associated with a significantly reduced risk of ROP (adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI], 0.49-0.86 for early preterm birth; aOR, 0.10; 95% CI, 0.01-0.93 for late preterm birth; aOR, 0.66; 95% CI, 0.50-0.87 for all preterm births). Gestational hypertension was not significantly associated with ROP at early or late preterm births. Preeclampsia, but not gestational hypertension, was associated with a reduced risk of ROP in preterm births.
Gq/11-Dependent Changes in the Murine Ovarian Transcriptome at the End of Gestation1
Waite, Courtney; Mejia, Rachel; Ascoli, Mario
2016-01-01
Parturition in rodents is highly dependent on the engagement of the luteal prostaglandin F2 alpha receptor, which, through activation of the Gq/11 family of G proteins, increases the expression of Akr1c18, leading to an increase in progesterone catabolism. To further understand the involvement of Gq/11 on luteolysis and parturition, we used microarray analysis to compare the ovarian transcriptome of mice with a granulosa/luteal cell-specific deletion of Galphaq/11 with their control littermates on Day 18 of pregnancy, when mice from both genotypes are pregnant, and on Day 22, when mice with a granulosa/luteal cell-specific deletion of Galphaq/11 are still pregnant but their control littermates are 1–2 days postpartum. Ovarian genes up-regulated at the end of gestation in a Galphaq/11 -dependent fashion include genes involved in focal adhesion and extracellular matrix interactions. Genes down-regulated at the end of gestation in a Galphaq/11-dependent manner include Serpina6 (which encodes corticosteroid-binding globulin); Enpp2 (which encodes autotaxin, the enzyme responsible for the synthesis of lysophosphatidic acid); genes involved in protein processing and export; reproductive genes, such as Lhcgr; the three genes needed to convert progesterone to estradiol (Cyp17a1, Hsd17b7, and Cyp19a1); and Inha. Activation of ovarian Gq/11 by engagement of the prostaglandin F2 alpha receptor on Day 18 of pregnancy recapitulated the regulation of many but not all of these genes. Thus, although the ovarian transcriptome at the end of gestation is highly dependent on the activation of Gq/11, not all of these changes are dependent on the actions of prostaglandin F2 alpha. PMID:26843449
Autonomic regulation in fetuses with Congenital Heart Disease
Siddiqui, Saira; Wilpers, Abigail; Myers, Michael; Nugent, J. David; Fifer, William P.; Williams, Ismée A.
2015-01-01
Background Exposure to antenatal stressors affects autonomic regulation in fetuses. Whether the presence of congenital heart disease (CHD) alters the developmental trajectory of autonomic regulation is not known. Aims/Study Design This prospective observational cohort study aimed to further characterize autonomic regulation in fetuses with CHD; specifically hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF). Subjects From 11/2010 – 11/2012, 92 fetuses were enrolled: 41 controls and 51 with CHD consisting of 19 with HLHS, 12 with TGA, and 20 with TOF. Maternal abdominal fetal electrocardiogram (ECG) recordings were obtained at 3 gestational ages: 19-27 weeks (F1), 28-33 weeks (F2), and 34-38 weeks (F3). Outcome measures Fetal ECG was analyzed for mean heart rate along with 3 measures of autonomic variability of the fetal heart rate: interquartile range, standard deviation, and root mean square of the standard deviation of the heart rate (RMSSD), a measure of parasympathetic activity. Results During F1 and F2 periods, HLHS fetuses demonstrated significantly lower mean HR than controls (p<0.05). Heart rate variability at F3, as measured by standard deviation, interquartile range, and RMSSD was lower in HLHS than controls (p<0.05). Other CHD subgroups showed a similar, though non-significant trend towards lower variability. Conclusions Autonomic regulation in CHD fetuses differs from controls with HLHS fetuses most markedly affected. PMID:25662702
Autonomic regulation in fetuses with congenital heart disease.
Siddiqui, Saira; Wilpers, Abigail; Myers, Michael; Nugent, J David; Fifer, William P; Williams, Ismée A
2015-03-01
Exposure to antenatal stressors affects autonomic regulation in fetuses. Whether the presence of congenital heart disease (CHD) alters the developmental trajectory of autonomic regulation is not known. This prospective observational cohort study aimed to further characterize autonomic regulation in fetuses with CHD; specifically hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF). From 11/2010 to 11/2012, 92 fetuses were enrolled: 41 controls and 51 with CHD consisting of 19 with HLHS, 12 with TGA, and 20 with TOF. Maternal abdominal fetal electrocardiogram (ECG) recordings were obtained at 3 gestational ages: 19-27 weeks (F1), 28-33 weeks (F2), and 34-38 weeks (F3). Fetal ECG was analyzed for mean heart rate along with 3 measures of autonomic variability of the fetal heart rate: interquartile range, standard deviation, and root mean square of the standard deviation of the heart rate (RMSSD), a measure of parasympathetic activity. During F1 and F2 periods, HLHS fetuses demonstrated significantly lower mean HR than controls (p<0.05). Heart rate variability at F3, as measured by standard deviation, interquartile range, and RMSSD was lower in HLHS than controls (p<0.05). Other CHD subgroups showed a similar, though non-significant trend towards lower variability. Autonomic regulation in CHD fetuses differs from controls, with HLHS fetuses most markedly affected. Copyright © 2015 Elsevier Ltd. All rights reserved.
Impact of obesity on perinatal outcomes among asthmatic women
Thuot, Meggie; Coursol, Marc-André; Nguyen, Sonia; Lacasse-Guay, Vanessa; Beauchesne, Marie-France; Fillion, Anne; Forget, Amélie; Kettani, Fatima-Zohra; Blais, Lucie
2013-01-01
BACKGROUND: Only one study has investigated the combined effect of maternal asthma and obesity on perinatal outcomes; however, it did not consider small-for-gestational age and large-for-gestational age infants. OBJECTIVES: To examine the impact of obesity on perinatal outcomes among asthmatic women. METHODS: A cohort of 1386 pregnancies from asthmatic women was reconstructed using three of Quebec’s administrative databases and a questionnaire. Women were categorized using their prepregnancy body mass index. Underweight, overweight and obese women were compared with normal weight women. The primary outcome was the birth of a small-for-gestational-age infant, defined as a birth weight below the 10th percentile for gestational age and sex. Secondary outcomes were large-for-gestational-age infants (birth weight >90th percentile for gestational age) and preterm birth (<37 weeks’ gestation). Logistic regression models were used to obtain the ORs of having small-for-gestational-age infants, large-for-gestational-age infants and preterm birth as a function of body mass index. RESULTS: The proportions of underweight, normal weight, overweight and obese women were 10.8%, 53.3%, 19.7% and 16.2%, respectively. Obese asthmatic women were not found to be significantly more at risk for giving birth to small-for-gestational-age infants (OR 0.6 [95% CI 0.4 to 1.1]), large-for-gestational-age infants (OR 1.2 [95% CI 0.7 to 2.2]) or having a preterm delivery (OR 0.7 [95% CI 0.4 to 1.3]) than normal-weight asthmatic women. CONCLUSIONS: No significant negative interaction between maternal asthma and obesity on adverse perinatal outcomes was observed. PMID:23951559
Outcomes for Gestational Carriers Versus Traditional Surrogates in the United States.
Fuchs, Erika L; Berenson, Abbey B
2018-05-01
Little is known about the obstetric and procedural outcomes of traditional surrogates and gestational carriers. Participants included 222 women living in the United States who completed a brief online survey between November 2015 and February 2016. Differences between gestational carriers (n = 204) and traditional surrogates (n = 18) in demographic characteristics, pregnancy outcomes, and procedural outcomes were examined using chi-squared tests, Fisher's exact tests, and t-tests. Out of 248 eligible respondents, 222 surveys were complete, for a response rate of 89.5%. Overall, obstetric outcomes were similar among gestational carriers and traditional surrogates. Traditional surrogates were more likely than gestational carriers to have a Center for Epidemiologic Studies Depression Scale Revised score of 16 or higher (37.5% vs. 4.0%). Gestational carriers reported higher mean compensation ($27,162.80 vs. $17,070.07) and were more likely to travel over 400 miles (46.0% vs. 0.0%) than traditional surrogates. Procedural differences, but not differences in obstetric outcomes, emerged between gestational carriers and traditional surrogates. To ensure that both traditional surrogates and gestational carriers receive optimal medical care, it may be necessary to extend practice guidelines to ensure that traditional surrogates are offered the same level of care offered to gestational carriers.
Shearrer, G E; Whaley, S E; Miller, S J; House, B T; Held, T; Davis, J N
2015-06-01
The goal of this study was to examine if breastfeeding duration by gestational diabetes mellitus status impacted the prevalence of obesity in offspring. Data were obtained from a 2011 phone survey with caregivers of low-income children (2-4 years) participating in the Women, Infants and Children programme in Los Angeles County. The final sample included 2295 children, 84% Hispanic and 48% female. Chi-square and binary logistic regression were used to assess gestational diabetes status and breastfeeding duration on the prevalence of obesity, with the following a priori covariates: child's ethnicity, birth weight, age in months and sex. Breastfeeding and gestational diabetes were significantly associated with obesity prevalence (P < 0.01). Using gestational diabetes mellitus and no breastfeeding as the referent category, gestational diabetes mellitus offspring who were breastfed ≥12 months had a 72% decrease in obesity prevalence (adjusted odds ratio = 0.28, confidence interval 0.89-0.03, P = 0.05). These findings suggest that > 12 months of breastfeeding duration in the gestational diabetes mellitus group and any duration of breastfeeding in the non-gestational diabetes mellitus mothers is needed to reduce obesity levels in a primarily Hispanic population. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.
Relationship between hypothyroidism and the incidence of gestational diabetes: A meta-analysis.
Gong, Li-Li; Liu, He; Liu, Li-Hong
2016-04-01
Hypothyroidism disorders and gestational diabetes are among the most common endocrinopathies during pregnancy. We conducted a meta-analysis to investigate whether hypothyroidism in pregnancy is associated with gestational diabetes risk. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. Seven articles described the relationship between hypothyroidism and risk of gestational diabetes. This meta-analysis revealed that overt hypothyroidism was associated with an increased risk of gestational diabetes (OR 1.892, 95% CI 1.679-2.132, p < 0.001). The relative risk of gestational diabetes was also increased in subclinical hypothyroidism, with the OR of 1.558 (95% CI 1.292-1.877, p < 0.001). There was no evidence of significant association between hypothyroxinemia and risk of gestational diabetes (OR 1.394, 95% CI 0.753-2.580, p = 0.291). The OR for all of the hypothyroidism was 1.749 (95% CI 1.586-1.928, p < 0.001), and an association was found. Results of this meta-analysis indicate that hypothyroidism may be a risk factor for gestational diabetes. Copyright © 2016. Published by Elsevier B.V.
Wright, E C; Boehmer, B H; Cooper-Prado, M J; Bailey, C L; Wettemann, R P
2014-10-01
Fall-calving Angus cows were used to evaluate the effect of ambient temperature on duration of gestation. In Exp. 1, cows were AI and calved in August (n = 14) or October (n = 10). Cows grazed native prairie pasture in Oklahoma and had a BCS of 6.0 ± 0.5 (1 = emaciated, and 9 = obese) at parturition. Commencing 2 wk before the expected calving date, blood samples were taken from the coccygeal vein every 2 to 3 d until calving. Cows that calved in August tended to have shorter gestations (P = 0.07) compared with cows that calved in October. Maximum daily ambient temperature during the last 14 d of gestation was greater for August-calving cows (P < 0.001) compared with October cows. Concentrations of cortisol in plasma during the last 4 d of gestation were greater in cows that calved in August (P < 0.04) compared with cows that calved in October. In Exp. 2, cows were AI and calved in either mid-August (n = 7), late-August (n = 6), September (n = 6), or October (n = 8) to evaluate the effects of elevated ambient temperature on duration of gestation, ruminal temperature at parturition, and plasma cortisol, progesterone, and estradiol. Temperature boluses (SmartStock, LLC, Pawnee, OK) programmed to transmit temperature every hour were place in the rumen at 255 d of gestation. Cows grazed native prairie pasture in Oklahoma and had a BCS of 6.5 ± 0.4 at calving. Maximum ambient temperatures during d 263 to 273 of gestation were influenced by month of calving × day (P < 0.001). Duration of gestation was shorter for mid-August cows (P < 0.05) compared with October cows, but did not differ compared with late-August (P = 0.29) and September (P = 0.50) cows. Ruminal temperature during the 4 d before calving was not influenced by month of calving (P = 0.76). Ruminal temperature was decreased during the 24 h before parturition for cows in all months (P < 0.01) compared with 2 to 4 d before parturition. Concentrations of cortisol in plasma during d 271 to 276 of gestation were less (P < 0.05) for late-August compared with cows that calved during the other months. Concentrations of progesterone were greater during 7 d before parturition in October compared with cows that calved in September. Estradiol in plasma of cows during late gestation was not affected by month of calving (P = 0.76). Exposure of beef cows to elevated ambient temperature resulted in shorter gestations. Ruminal temperature in cows decreased ≥ 0.3°C the day before parturition.
Tavaniello, S; Maiorano, G; Siwek, M; Knaga, S; Witkowski, A; Di Memmo, D; Bednarczyk, M
2014-08-01
The current research was conducted to compare growth, carcass traits, pH, intramuscular collagen (IMC) properties, and genetic bases of IMC and carcasses (breast-muscle weight) of different lines and generations of adult males and females of Japanese quail (Coturnix japonica). Forty-four quails (generation F0), 22 Pharaoh (F-33) meat-type males and 22 Standard (S-22) laying-type females, were crossed to produce the F1 hybrids generation. The F2 generation was created by mating one F1 male with one F1 female, full siblings. The birds, randomly chosen from F0 (22 males and 22 females), F1 (22 males and 22 females), and F2 (84 males and 152 females) were raised to 20 wk of age in collective cages. Quails were fed ad libitum commercial diets. At slaughter, all birds were individually weighed (after a fasting period of 12 h) and dressing yield (without giblets) was calculated. The carcasses were then dissected. Genomic DNA was extracted from all of the blood, and 30 microsatellite markers located on 2 quail chromosomes were genotyped. The F -: 33 quails had higher in vivo and postmortem performances and a higher abdominal fat percentage than those of the egg line. Meat from S -: 22 quails had a slower collagen maturation (hydroxylysylpyridinoline crosslink/collagen) and a higher ultimate pH. The F1 and F2 generations showed an evident sexual dimorphism, and an additional effect could be due to hybrid heterosis evident in F2. Meat from quails of F1 and F2 generations had a lower IMC amount with a higher degree of collagen maturation compared with parental lines. Two statistically significant QTL have been detected on quail chromosome 2 (CJA02): a QTL with an additive effect (0.50) for IMC in the marker bracket GUJ0037 and GUJ0093; a second QTL with additive (1.32) and dominant (1.91) effects for breast-muscle weight in the marker bracket GUJ0084 and GUJ0073. To our knowledge, this is the first report of a QTL associated with breast-muscle weight and IMC in quail and poultry species, respectively. © Poultry Science Association Inc.
Yousefzadeh, Gholamreza; Hojat, Hashem; Enhesari, Ahmad; Shokoohi, Mostafa; Eftekhari, Nahid; Sheikhvatan, Mehrdad
2012-11-01
Pregnant women with previous gestational diabetes mellitus are at increased risk of progressive carotid artery disorders. The current study evaluated carotid intima-media thickness (IMT) in pregnant women with gestational diabetes at two time points of mid-term and full-term pregnancy to determine whether gestational diabetes mellitus causes increased IMT. This cross-sectional study carried out at Afzalipour Hospital (Kerman, Iran) between 2009 and 2010, recruited 50 women who were at high risk of gestational diabetes during pregnancy and had an oral glucose challenge test (OGCT) as screening for gestational diabetes. B-mode ultrasound scans were performed at baseline and at two time points of mid-term pregnancy (20 to 24 weeks) and full-term pregnancy (36 to 38 weeks) on all the participants. The mean IMT of common carotids and internal carotid arteries from two walls (near and far walls) at four different angles was assessed. An overall comparison between the impaired OGCT test group and the control group revealed significant differences in carotid IMT in the mid-term (0.65 ± 0.07 vs. 0.59 ± 0.06 mm; p value = 0.002) and full-term (0.65 ± 0.05 vs. 0.59 ± 0.04 mm; p value < 0.001) pregnancy; however, the trend of the changes in carotid IMT during mid to full-term pregnancy was insignificant in each group (p value > 0.05). Carotid IMT was significantly higher in the women with gestational diabetes than that in the normoglycemic group in different trimesters. This finding denotes that atherosclerosis might start years before the diagnosis of gestational diabetes in vulnerable women.
Liu, Gongshu; Li, Nan; Sun, Shurong; Wen, Jing; Lyu, Fengjun; Gao, Wen; Li, Lili; Chen, Fang; Baccarelli, Andrea A.; Hou, Lifang
2014-01-01
Aims. We aim to evaluate the association of maternal gestational oral glucose tolerance test (OGTT) glucose concentrations with anthropometry in the offspring from birth to 12 months in Tianjin, China. Methods. A total of 27,157 pregnant women underwent OGTT during 26–30 weeks gestation, and their children had body weight/length measured from birth to 12 months old. Results. Maternal OGTT glucose concentrations at 26–30 gestational weeks were positively associated with Z-scores for birth length-for-gestational age and birth weight-for-length. Compared with infants born to mothers with normal glucose tolerance, infants born to mothers with gestational diabetes mellitus (impaired glucose tolerance/new diabetes) had higher mean values of Z-scores for birth length-for-gestational age (0.07/0.23; normal group −0.08) and birth weight-for-length (0.27/0.57; normal group −0.001), smaller changes in mean values of Z-scores for length-for-age (0.75/0.62; normal group 0.94) and weight-for-length (0.18/−0.17; normal group 0.37) from birth to month 3, and bigger changes in mean values in Z-scores for weight-for-length (0.07/0.12; normal group 0.02) from month 9 to 12. Conclusions. Abnormal maternal glucose tolerance during pregnancy was associated with higher birth weight and birth length, less weight and length gain in the first 3 months of life, and more weight gain in the months 9–12 of life. PMID:24689042
Ozdemir, Ozdemir; Tunay, Zuhal Ozen; Acar, Damla Erginturk; Erol, Muhammet Kazım; Sener, Ender; Acar, Ugur
2015-01-01
To analyze ocular biometry parameters and evaluate their relationship with gestational age, birth weight, and postmenstrual age in prematurely born infants. The right eyes of 361 premature infants born before the 36th gestational week were evaluated. Birth weight, gestational week, and gender were recorded. An A-scan Biometer was used for obtaining axial measurements, including anterior chamber depth, lens thickness, vitreous length, and total axial length. Gestational age and birth weight values ranged from 23 to 36 weeks and from 560 to 2,670 g, respectively. The mean gestational age and birth weight were 30.8 ± 2.8 weeks and 1,497.9 ± 483.6 g, respectively. During the first examination (4-5 weeks of postnatal age), birth weight and gestational age of the infants correlated significantly and positively with lens thickness, vitreous length, and axial length (r>0.5, p<0.001), but not with anterior chamber depth (r<0.5). Increased vitreous and axial lengths correlated significantly with increasing postmenstrual age of the infants (r=0.669, p<0.001; r=0.845, p<0.001, respectively). Lens thickness, vitreous length, and axial length, but not anterior chamber depth, were significantly correlated with birth weight and gestational age. All four parameters increased with increasing postmenstrual age, with higher correlations for vitreous and axial lengths than for anterior chamber depth and lens thickness. It was concluded that axial elongation resulted primarily from increasing posterior chamber length.
Matsuura, Ikuo; Saitoh, Tetsuji; Ashina, Michiko; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru
2005-12-01
A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using vinclozolin by dietary administration at 0, 40, 200, and 1000 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed changes due to vinclozolin in the AGD, nipple development, sexual maturation, sex organ weights, and blood sex hormone concentrations in males of both parental animals and offspring, even at the lowest dose of 40 ppm, confirmed by results for the classical endpoints of histopathological examination at 200 ppm and mating at 1000 ppm. The effects on parental males included increased pituitary and testis weights, and decreased epididymis weights at 1000 ppm in both generations, and decreased prostate and epididymis weights at 200 and 1000 ppm and seminal vesicle weights at 1000 ppm in F1 males. Histopathological examination revealed hypertrophy of the basophilic cells in the pituitary at these two doses, and diffuse hyperplasia of the testicular interstitial cells and atrophy of the seminal vesicle mucosa at 1000 ppm in F0 and F1 males. In addition, F1 males demonstrated decrease in prostate fluid at 200 and 1000 ppm. Blood hormone analysis revealed increases in LH, FSH, testosterone, and DHT in F0 and F1 males at 1000 ppm. General toxicological effects included suppressed body weight gain in F0 and F1 females and in F1 males, and reduced food consumption in F0 and F1 females at 1000 ppm. Histopathological examination revealed centrilobular hepatocellular hypertrophy in males at 200 and 1000 ppm and in females at 1000 ppm, increased lipid droplets in the adrenal zona fasciculata and zona glomerulosa in males at 200 and 1000 ppm and in females at 40 ppm and above, and hyperplasia of ovarian interstitial cells and vacuolation of lutein cells in females at 1000 ppm in both generations. Almost all the tissue changes were accompanied by changes in weights. Decreases in T3 and/or T4 were observed in both sexes and generations at 1000 ppm and in F0 females at 200 ppm. However, these were presumed to be secondary to induction of hepatic drug-metabolizing enzymes, activities being increased for a range of enzymes in both sexes and generations at 1000 ppm. Rise in BROD activity was the most prominent, suggesting that vinclozolin mainly induces CYP2B. As for effects on reproductive function, a marked decrease in the fertility index caused by male infertility was observed in F1 animals at 1000 ppm. However, no effects on spermatogenesis were seen in either F0 or F1 males. Since cleft prepuce and penile hypoplasia were observed in infertile males, it is probable that the cause of infertility in F1 males was related to morphological abnormalities in the external genitalia. Vinclozolin did not affect the estrous cycle, mating, fertility, pregnancy, parturition, or nursing behavior in either F0 or F1 females. In offspring, in addition to suppressed body weight gain in F1 males and females at 1000 ppm, neonatal toxicity caused by antiandrogen activity of vinclozolin was observed in F1 and F2 males. Effects included shortened AGD in F1 males at 1000 ppm and in F2 males at 200 and 1000 ppm, and nipple/areola remnants in F1 males at 200 and 1000 ppm and in F2 males at 40 ppm and above. In addition, decreased epididymis weights at weaning and morphological abnormalities of the external genitalia, including cleft prepuce, penile hypoplasia, and vaginal pouch, were seen in F1 and F2 males at 1000 ppm.
Transfer entropy analysis of maternal and fetal heart rate coupling.
Marzbanrad, Faezeh; Kimura, Yoshitaka; Endo, Miyuki; Palaniswami, Marimuthu; Khandoker, Ahsan H
2015-01-01
Although evidence of the short term relationship between maternal and fetal heart rates has been found in previous model-based studies, knowledge about the mechanism and patterns of the coupling during gestation is still limited. In this study, a model-free method based on Transfer Entropy (TE) was applied to quantify the maternal-fetal heart rate couplings in both directions. Furthermore, analysis of the lag at which TE was maximum and its changes throughout gestation, provided more information about the mechanism of coupling and its latency. Experimental results based on fetal electrocardiograms (fECGs) and maternal ECG showed the evidence of coupling for 62 out of 65 healthy mothers and fetuses in each direction, by statistically validating against the surrogate pairs. The fetuses were divided into three gestational age groups: early (16-25 weeks), mid (26-31 weeks) and late (32-41 weeks) gestation. The maximum TE from maternal to fetal heart rate significantly increased from early to mid gestation, while the coupling delay on both directions decreased significantly from mid to late gestation. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. In conclusion, the application of TE with delays revealed detailed information about the changes in fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.
Grzesiak, Malgorzata; Knapczyk-Stwora, Katarzyna; Ciereszko, Renata E; Wieciech, Iwona; Slomczynska, Maria
2014-09-15
Recently, we have found that flutamide-induced androgen deficiency altered progesterone production in the porcine corpus luteum (CL) during mid- and late pregnancy. Herein, we tested whether flutamide administration subsequently influences androgen and estrogen metabolism in the CL of pregnancy. Pregnant gilts were treated with flutamide between Days 43 and 49 (GD50F), 83 and 89 (GD90F), or 101 and 107 (GD108F) of gestation. Corpora lutea (CLs) were collected from treated and nontreated (control) pigs. The concentrations of androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) together with the levels of expression of mRNAs and proteins for cytochrome P450 17α-hydroxylase/c17-20 lyase (CYP17A1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), cytochrome P450 aromatase (CYP19A1), and 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) were measured in the CL of control and flutamide-treated animals. Steroidogenic enzymes were also immunolocalized in luteal tissues. The luteal concentrations of A4 and T were higher in the GD50F (P = 0.006, P = 0.03) and GD108F (P = 0.005, P = 0.035) groups, but lower in the GD90F (P = 0.004, P = 0.014) group. The E1 level was greater only in the GD90F (P = 0.03) and GD108F (P = 0.035) groups, whereas E2 concentration was not affected by flutamide treatment. Increased luteal CYP17A1 mRNA and protein expression was found in the GD50F (P = 0.002, P = 0.03) and GD108F (P = 0.0026, P = 0.03) groups, but reduced in the GD90F (P = 0.002, P = 0.03) group. mRNA of 17β-HSD1 was upregulated in the GD50F (P = 0.0005) group, but downregulated in the GD90F (P = 0.002) and GD108F (P = 0.0005) groups. In contrast, 17β-HSD1 protein expression was higher in the GD50F and GD108F (P = 0.03) groups, but lower in the GD90F (P = 0.03) group. Both CYP19A1 mRNA and protein levels were greater in the GD90F (P = 0.001, P = 0.028) and GD108F (P = 0.005, P = 0.03) groups. Neither 17β-HSD7 mRNA nor protein level were affected by flutamide exposure. Both CYP17A1 and 17β-HSD1 were immunolocalized exclusively in small luteal cells, whereas CYP19A1 and 17β-HSD7 were found in large luteal cells of control and flutamide-treated CLs. Overall, flutamide administration led to the alterations in A4, T, and E1, but not in E2, production in the CL of pregnancy in pigs, probably because of disrupted steroidogenic enzymes expression. These changes suggest that androgens are important modulators of luteal function during pregnancy in pigs. Copyright © 2014 Elsevier Inc. All rights reserved.
á Rogvi, Rasmus; Forman, Julie Lyng; Damm, Peter; Greisen, Gorm
2012-01-01
Introduction Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain. Methods Through nation-wide registries we identified all Danish mothers in the years 1989–2007. Two separate cohorts consisting mothers born 1974–1977 (n = 84219) and 1978–1981 (n = 32376) were studied, due to different methods of registering birthweight and gestational age in the two periods. Data was linked with information on GDM, pre-eclampsia and education. Results In a multivariate logistic regression model the odds of developing GDM was increased by 5–7% for each week the mother was born before term (p = 0.018 for 1974–1977, p = 0.048 for 1978–1981), while the odds were increased by 13–17% for each standard deviation (SD) reduction in birthweight for gestational age for those who were small or normal for gestational age (p<0.0001 and p = 0.035) and increased by 118–122% for each SD increase above the normal range (p<0.0001 and p = 0.024). The odds of pre-eclampsia was increased by 3–5% for each week the mother was born before term (p = 0.064 and p = 0.04), while the odds were increased 11–12% for each SD reduction in birthweight for gestational age (p<0.0001 and p = 0.0002). Conclusion In this cohort of young Danish mothers, being born premature or with increasingly low birthweight for gestational age was associated with an increased risk of GDM and pre-eclampsia in adulthood, while increasingly high birthweight for gestational age was associated with an increased risk of GDM and a decreased risk of pre-eclampsia. Inappropriate weight for gestational age was a more important risk factor than prematurity. PMID:22479500
Quraishi, B M; Zhang, H; Everson, T M; Ray, M; Lockett, G A; Holloway, J W; Tetali, S R; Arshad, S H; Kaushal, A; Rezwan, F I; Karmaus, W
2015-01-01
The prevalence of eczema is increasing in industrialized nations. Limited evidence has shown the association of DNA methylation (DNA-M) with eczema. We explored this association at the epigenome-scale to better understand the role of DNA-M. Data from the first generation (F1) of the Isle of Wight (IoW) birth cohort participants and the second generation (F2) were examined in our study. Epigenome-scale DNA methylation of F1 at age 18 years and F2 in cord blood was measured using the Illumina Infinium HumanMethylation450 Beadchip. A total of 307,357 cytosine-phosphate-guanine sites (CpGs) in the F1 generation were screened via recursive random forest (RF) for their potential association with eczema at age 18. Functional enrichment and pathway analysis of resulting genes were carried out using DAVID gene functional classification tool. Log-linear models were performed in F1 to corroborate the identified CpGs. Findings in F1 were further replicated in F2. The recursive RF yielded 140 CpGs, 88 of which showed statistically significant associations with eczema at age 18, corroborated by log-linear models after controlling for false discovery rate (FDR) of 0.05. These CpGs were enriched among many biological pathways, including pathways related to creating transcriptional variety and pathways mechanistically linked to eczema such as cadherins, cell adhesion, gap junctions, tight junctions, melanogenesis, and apoptosis. In the F2 generation, about half of the 83 CpGs identified in F1 showed the same direction of association with eczema risk as in F1, of which two CpGs were significantly associated with eczema risk, cg04850479 of the PROZ gene (risk ratio (RR) = 15.1 in F1, 95 % confidence interval (CI) 1.71, 79.5; RR = 6.82 in F2, 95 % CI 1.52, 30.62) and cg01427769 of the NEU1 gene (RR = 0.13 in F1, 95 % CI 0.03, 0.46; RR = 0.09 in F2, 95 % CI 0.03, 0.36). Via epigenome-scaled analyses using recursive RF followed by log-linear models, we identified 88 CpGs associated with eczema in F1, of which 41 were replicated in F2. Several identified CpGs are located within genes in biological pathways relating to skin barrier integrity, which is central to the pathogenesis of eczema. Novel genes associated with eczema risk were identified (e.g., the PROZ and NEU1 genes).
Steinberg, Rebecca M.; Walker, Deena M.; Juenger, Thomas E.; Woller, Michael J.; Gore, Andrea C.
2009-01-01
Perinatal exposures to endocrine-disrupting chemicals such as polychlorinated biphenyls (PCBs) can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally-exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture Aroclor (A) 1221 (0, 0.1, 1 or 10 mg/kg) on embryonic days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed towards females. In the F1 generation, additional effects were found including a significant alteration of serum luteinizing hormone (LH) in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been perinatally exposed to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared to F2 decendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant consequences on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans. PMID:18305224
Postmenstrual age correlates to indices of protein metabolism in very low birth weight infants.
Boehm, G; Räihä, N C
1993-04-01
In 14 infants who were normal in weight for gestational age and 14 infants who were small for gestational age, the plasma essential amino acid profiles and serum urea concentrations were studied between the 30th and 46th weeks of postmenstrual age. All infants were of very low birth weight (< 1,500 g) and were fed with fresh human milk fortified with 6 g freeze-dried human milk per 100 ml (mean protein intake 3.1 g/kg/day, mean energy intake 130 kcal/kg/day). With the exception of threonine, all measured plasma essential amino acid concentrations increased significantly with increasing postmenstrual age (appropriate for gestational age infants: r = 0.861, p < 0.01; small for gestational age infants: r = 0.772, p < 0.001). No differences in this increase could be found between the infants who were small or appropriate for gestational age. The serum urea concentrations also increased with increasing postmenstrual age without differences between the study groups (appropriate for gestational age infants: r = 0.658, p < 0.01; small for gestational age infants: r = 0.604, p < 0.05). The results indicate that very low birth weight infants of similar weights may have very different protein requirements, depending on their postmenstrual ages. Thus, postmenstrual age is of greater importance than birth weight when protein nutrition is planned for very low birth weight infants.
Szczesniak, Rhonda D; Li, Dan; Duan, Leo L; Altaye, Mekibib; Miodovnik, Menachem; Khoury, Jane C
2016-11-01
Objective To identify phenotypes of type 1 diabetes control and associations with maternal/neonatal characteristics based on blood pressure (BP), glucose, and insulin curves during gestation, using a novel functional data analysis approach that accounts for sparse longitudinal patterns of medical monitoring during pregnancy. Methods We performed a retrospective longitudinal cohort study of women with type 1 diabetes whose BP, glucose, and insulin requirements were monitored throughout gestation as part of a program-project grant. Scores from sparse functional principal component analysis (fPCA) were used to classify gestational profiles according to the degree of control for each monitored measure. Phenotypes created using fPCA were compared with respect to maternal and neonatal characteristics and outcome. Results Most of the gestational profile variation in the monitored measures was explained by the first principal component (82-94%). Profiles clustered into three subgroups of high, moderate, or low heterogeneity, relative to the overall mean response. Phenotypes were associated with baseline characteristics, longitudinal changes in glycohemoglobin A1 and weight, and to pregnancy-related outcomes. Conclusion Three distinct longitudinal patterns of glucose, insulin, and BP control were found. By identifying these phenotypes, interventions can be targeted for subgroups at highest risk for compromised outcome, to optimize diabetes management during pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Prenatal stress and ethanol exposure produces inversion of sexual partner preference in mice.
Popova, Nina K; Morozova, Maryana V; Amstislavskaya, Tamara G
2011-02-01
The presence of a sexually receptive female behind perforated transparent partition induced sexual arousal and specific behavior in male mice so they spent more time near partition in an attempt to make their way to the female. Three-chambered free-choice model was used to evaluate sexual partner preference. The main pattern of sexual preference was the time spent by a male mouse at the partition dividing female (F-partition time) versus a partition dividing male (M-partition time). Pregnant mice were given ethanol (11vol.%) for 1-21 gestational days, and were exposed to restraint stress (2h daily for 15-21 day of the gestation). Control pregnant mice had free access to water and food and were not stressed. Adult male offspring of ethanol and stress exposed dams (E+S) showed decreased F-partition time and increased M-partition time. Whereas F-partition time in all control mice prevailed over M-partition time, 78% E+S mice demonstrated prevailed M-partition time. E+S mice were more active in social interaction with juvenile male. No significant differences between E+S and control mice in the open field and novelty tests were revealed. Therefore, E+S exposure during dam gestation inverted sexual partner preference in male offspring, suggesting that stress and alcohol in pregnancy produces predisposition to homosexuality. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Liu, Chaoqun; Zhong, Chunrong; Zhou, Xuezhen; Chen, Renjuan; Wu, Jiangyue; Wang, Weiye; Li, Xiating; Ding, Huisi; Guo, Yanfang; Gao, Qin; Hu, Xingwen; Xiong, Guoping; Yang, Xuefeng; Hao, Liping; Xiao, Mei; Yang, Nianhong
2017-01-01
Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.
Blomberg, Marie
2011-05-01
To estimate whether weight loss or low gestational weight gain in class I-III obese women is associated with adverse maternal and neonatal outcomes compared with gestational weight gain within the new Institute of Medicine recommendations. This was a population-based cohort study, which included 32,991 obesity class I, 10,068 obesity class II, and 3,536 obesity class III women who were divided into four gestational weight gain categories. Women with low (0-4.9 kg) or no gestational weight gain were compared with women gaining the recommended 5-9 kg concerning obstetric and neonatal outcome after suitable adjustments. Women in obesity class III who lost weight during pregnancy had a decreased risk of cesarean delivery (24.4%; odds ratio [OR] 0.77, 95% confidence interval [CI] 0.60-0.99), large-for-gestational-age births (11.2%, OR 0.64, 95% CI 0.46-0.90), and no significantly increased risk for pre-eclampsia, excessive bleeding during delivery, instrumental delivery, low Apgar score, or fetal distress compared with obese (class III) women gaining within the Institute of Medicine recommendations. There was an increased risk for small for gestational age, 3.7% (OR 2.34, 95% CI 1.15-4.76) among women in obesity class III losing weight, but there was no significantly increased risk of small for gestational age in the same group with low weight gain. Obese women (class II and III) who lose weight during pregnancy seem to have a decreased or unaffected risk for cesarean delivery, large for gestational age, pre-eclampsia, excessive postpartum bleeding, instrumental delivery, low Apgar score, and fetal distress. The twofold increased risk of small for gestational age in obesity class III and weight loss (3.7%) is slightly above the overall prevalence of small-for-gestational-age births in Sweden (3.6%).
Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants.
Wei, J C; Catalano, R; Profit, J; Gould, J B; Lee, H C
2016-05-01
To determine the association between antenatal steroids administration and intraventricular hemorrhage rates. We used cross-sectional data from the California Perinatal Quality Care Collaborative during 2007 to 2013 for infants ⩽32 weeks gestational age. Using multivariable logistic regression, we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by gestational age. In 25 979 very-low-birth weight infants, antenatal steroid use was associated with a reduction in incidence of any grade of intraventricular hemorrhage (odds ratio=0.68, 95% confidence interval: 0.62, 0.75) and a reduction in incidence of severe intraventricular hemorrhage (odds ratio=0.51, 95% confidence interval: 0.45, 0.58). This association was seen across gestational ages ranging from 22 to 29 weeks. Although current guidelines recommend coverage for preterm birth at 24 to 34 weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even before 24 weeks of gestational age.
Fish full life-cycle testing for androgen methyltestosterone on medaka (Oryzias latipes).
Seki, Masanori; Yokota, Hirofumi; Matsubara, Haruki; Maeda, Masanobu; Tadokoro, Hiroshi; Kobayashi, Kunio
2004-03-01
Abstract-We studied the chronic effects of methyltestosterone (MT) on reproductive status of medaka (Oryzias latipes) over two generations under continuous exposure to verify the applicability of the fish full life-cycle test (FFLC) for this androgen with this species. The exposure of parental (F0) medaka to MT was begun on embryos within 12 h postfertilization and continued for up to 101 d; assessment endpoints included embryological development, hatching, posthatch survival, growth, sexual differentiation, reproduction, and hepatic vitellogenin (VTG) levels under flow-through exposure to MT at each mean measured concentration of 0.35, 1.09, 3.29, 9.98, and 27.75 ng/L. Eggs (F1) spawned from the F0 fish at 98, 99, and 100 d posthatch were examined for hatchability, survival after hatching, growth, sexual differentiation, and hepatic VTG level until 60 d posthatch. In the FFLC with medaka, MT induced masculinization of both secondary sex characteristics and gonads. We observed that all F0 fish in the 27.75-ng/L treatment group showed male secondary sex characteristics in which no fish with ovary could be discerned. Several fish with ovaries in F0 and F1 generations treated with 9.98 ng/L showed male secondary sex characteristics. We also observed swollen abdomens in the F0 and F1 female fish in the 9.98-ng/L treatment group. These swollen abdomens were induced by enlarged ovaries and were accompanied with declined fecundity and fertility in the F0 generation. These results indicate that MT reduces the reproductive potential of medaka and that the FFLC with this species is applicable to the evaluation of androgens.
Davis, Anne R; Horvath, Sarah K; Castaño, Paula M
2017-03-01
Screening for fetal aneuploidy has evolved over the past 2 decades. Whether these advances impact gestational age at abortion has received little study. We sought to describe trends in the gestational age at the time of abortion by fetal diagnosis over an 11-year study period. We hypothesized that gestational age at time of abortion would decrease for fetal aneuploidy but remain unchanged for structural abnormalities. We conducted a retrospective case series of all women undergoing surgical abortion for fetal aneuploidy or structural abnormalities up to 24 weeks' gestation from 2004 through 2014 in a hospital operating room setting at a single, urban medical center. We excluded labor induction abortions (<1% of abortions at our medical center) and suction aspirations performed in the office practice. We performed suction aspiration up to 14 weeks and dilation and evacuation after that gestational age. We describe the median gestational age at abortion by fetal indication and year. For women undergoing abortion for fetal aneuploidy (n = 392), the median gestational age at time of abortion decreased from 19.0 weeks (interquartile range 18.0-21.0) in 2004 to 14.0 weeks (interquartile range 13.0-17.0) in 2014 (Kruskal-Wallis P < .0001). For women undergoing abortion for fetal structural abnormalities (n = 586), the median gestational age was ≥20 weeks for each year during the study interval (P = .1). As gestational age decreased in the fetal aneuploidy group, fewer women underwent dilation and evacuation and more became eligible for suction aspiration (<14 weeks). In 2004, >90% of women underwent dilation and evacuation for either indication. By 2014, 31% of women with fetal aneuploidy were eligible for suction aspiration compared to 11% of those with structural anomalies. Gestational age at the time of abortion for fetal aneuploidy decreased substantially from 2004 through 2014; earlier abortion is safer for women. In contrast, women seeking abortion for fetal structural abnormalities did not experience a change in timing. Legislation restricting gestational age at the time of abortion could disproportionately affect women with fetal structural abnormalities. Copyright © 2016 Elsevier Inc. All rights reserved.
Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.
Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O
2014-08-01
Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.
Early Embryonic Androgen Exposure Induces Transgenerational Epigenetic and Metabolic Changes
Xu, Ning; Chua, Angela K.; Jiang, Hong; Liu, Ning-Ai
2014-01-01
Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study. PMID:24992182
Van Dijk, Aimée E; Van Eijsden, Manon; Stronks, Karien; Gemke, Reinoud J B J; Vrijkotte, Tanja G M
2012-06-01
Prenatal exposure to maternal stress may program the fetal HPA axis, potentially leading to altered metabolism in later life, associated with adiposity and diabetes. This association is little studied in humans, and thus we explore whether high maternal job strain during early pregnancy, as well as maternal cortisol levels are associated with increased body mass index (BMI), central adiposity or body fat mass in the offspring at age five. Additionally, we explore whether these associations are modified by gender or mediated by gestational age and fetal growth restriction. 2939 pregnant women (ABCD cohort study) completed a questionnaire around gestational week 16 including the Job Content Questionnaire, assessing job strain. Serum total cortisol was assessed in a subsample (n=1320). Gestational age (≥37 weeks), standardized birth weight and information on many covariates were available. At the age five health check, height, weight (BMI, kg/m(2)), waist circumference (waist-to-height ratio, WHtR) and Fat Mass Index (FMI, kg/m(2)) were assessed. Job strain was not associated with higher BMI, WHtR or FMI. Higher maternal cortisol was independently associated with marginally higher FMI in girls, but marginally lower FMI in boys (β 0.09 and β -0.10 per 100 unit increase in serum cortisol, respectively. p<0.01). This association was not mediated by gestational age or fetal growth restriction. Results show that prenatal maternal job strain and cortisol may not program obesity and adiposity in the next generation in humans, but gender differences should always be considered. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Use of atypical antipsychotics in pregnancy and maternal gestational diabetes.
Panchaud, Alice; Hernandez-Diaz, Sonia; Freeman, Marlene P; Viguera, Adele C; MacDonald, Sarah C; Sosinsky, Alexandra Z; Cohen, Lee S
2017-12-01
Second generation antipsychotic medications (SGAs) are widely used by reproductive-age women to treat a number of psychiatric illnesses. Some SGAs have been associated with an increased risk of developing diabetes, although information regarding their diabetogenic effect in pregnant women is scarce. To evaluate the risk of gestational diabetes (GDM) among women treated with SGA. The Massachusetts General Hospital (MGH) National Pregnancy Registry for Atypical Antipsychotics (NPRAA) collects data on drug use, pregnancy outcomes, and other characteristics from pregnant women, ages 18-45 years, using 3 phone interviews conducted at (1) enrollment during pregnancy, (2) 7 months' gestation, and (3) 2-3 months postpartum. Information on GDM was abstracted from obstetric and delivery medical records. The study population was restricted to women without pre-gestational diabetes. Pregnancies exposed to SGAs during the first trimester were compared with a reference group of women with psychiatric conditions but not treated with SGAs during pregnancy. Generalized linear models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for GDM. Of 303 women exposed to SGAs, 33 (10.9%) had GDM compared to 16 (10.7%) in the 149 non-exposed women. The crude OR of GDM for SGA was 1.02 (95% CI, 0.54-1.91). After adjustment for maternal age, race, marital status, employment status, level of education, smoking, and primary psychiatric diagnosis, the OR moved to 0.79 (0.40-1.56). Findings did not suggest an increased risk of GDM associated with exposure to SGAs during pregnancy in women who had used SGA before pregnancy without developing diabetes, compared to psychiatrically ill women who were not exposed to SGA. ClinicalTrials.gov identifier: NCT01246765. Copyright © 2017 Elsevier Ltd. All rights reserved.
Meyer, A M; Hess, B W; Paisley, S I; Du, M; Caton, J S
2014-09-01
We hypothesized that gestational nutrition would affect calf feed efficiency and small intestinal biology, which would be correlated with feed efficiency. Multiparous beef cows (n = 36) were individually fed 1 of 3 diets from d 45 to 185 of gestation: native grass hay and supplement to meet NRC recommendations (control [CON]), 70% of CON NEm (nutrient restricted [NR]), or a NR diet with a RUP supplement (NR+RUP) to provide similar essential AA as CON. After d 185 of gestation, cows were managed as a single group, and calf individual feed intake was measured with the GrowSafe System during finishing. At slaughter, the small intestine was dissected and sampled. Data were analyzed with calf sex as a block. There was no effect (P ≥ 0.33) of maternal treatment on residual feed intake, G:F, DMI, ADG, or final BW. Small intestinal mass did not differ (P ≥ 0.38) among treatments, although calf small intestinal length tended (P = 0.07) to be greater for NR than NR+RUP. There were no differences (P ≥ 0.20) in calf small intestinal density or jejunal cellularity, proliferation, or vascularity among treatments. Jejunal soluble guanylate cyclase mRNA was greater (P < 0.03) for NR+RUP than CON and NR. Residual feed intake was positively correlated (P ≤ 0.09) with small intestinal mass and relative mass and jejunal RNA content but was negatively correlated (P ≤ 0.09) with jejunal mucosal density and DNA concentration. Gain:feed was positively correlated (P ≤ 0.09) with jejunal mucosal density, DNA, protein, and total cells and was negatively correlated (P ≤ 0.05) with small intestinal relative mass, jejunal RNA, and RNA:DNA. Dry matter intake was positively correlated (P ≤ 0.09) with small intestinal mass, relative mass, length, and density as well as jejunal DNA and protein content, total cells, total vascularity, and kinase insert domain receptor and endothelial nitric oxide synthase 3 mRNA and was negatively correlated (P = 0.02) with relative small intestinal length. In this study, calf performance and efficiency during finishing as well as most measures of small intestinal growth were not affected by maternal nutrient restriction during early and midgestation. Results indicate that offspring small intestinal gene expression may be affected by gestational nutrition even when apparent tissue growth is unchanged. Furthermore, small intestinal size and growth may explain some variation in efficiency of nutrient utilization in feedlot cattle.
Cansu, A; Ozgur, H; Guven, S; Dinc, G; Dinc, H
2014-01-01
To develop a nomogram for estimating nasal bone length (NBL) at 11(+0) - 13(+6) weeks of gestation in 554 consecutive cases and to determine the value of NBL measurement in screening for chromosomal abnormalities. NBL and crown-rump length (CRL) were examined in 554 fetuses at 11(+0) - 13(+6) weeks' gestation. A nomogram for NBL was developed with data from 479 healthy fetuses in which fetal profile examination was possible. Reference values, including percentiles, weie calculated for each gestational age. A linear correlation was noted between CRL and NBL in healthy fetuses at 11(+0) - 11(+6), 12(+0) - 12(+6) and 13(+0) - 13(+6) weeks of gestation. Mean NBL was 2.18 +/- 0.53 mm, 2.46 +/- 0.45 mm, and 2.91 +/- 0.55 mm in healthy fetuses, for these time frames, respectively. NBL increased significantly with CRL from respective means of 2.26 +/- 0.43, 2.60 +/- 0.48, 2.77 +/- 0.43, and 3.16 +/- 0.52 mm at 45 - 54.9, 55 - 64.9, 65 +/- 74.9, and 75 - 84 mm. The authors developed a NBL nomogram with data from normal, healthy Turkish fetuses at 11(+0) - 13(+6) weeks of gestation. These reference ranges may prove useful in prenatal screening and diagnosis of syndromes known to be associated with nasal hypoplasia.
Fetal eyeball volume: relationship to gestational age and biparietal diameter.
Odeh, Marwan; Feldman, Yulia; Degani, Shimon; Grinin, Vitali; Ophir, Ella; Bornstein, Jacob
2009-08-01
To measure and determine normal values of the fetal eyeball volume between 14 and 40 weeks of gestation. The volume of the fetal eyeball was measured with three-dimensional ultrasound between 14 and 40 weeks of gestation using the VOCAL software.Only singleton pregnancies without fetal growth restriction, diabetes mellitus, hypertension or major fetal malformation were included. Over all, 203 women were studied. In 125 both eyeballs were measured while in 78 only one eyeball was measured. The volume of the eyeball correlated strongly with gestational age (right: R = 0.946, P < 0.001, n = 171. left: R = 0.945, P < 0.001, n = 156), and with the biparietal diameter (BPD) (right: R = 0.949, P < 0.001, n = 171. left: R = 0.953, P < 0.001, n = 156). Using regression analysis the best correlation between eyeball volume and the BPD were: square of right eyeball = -0.180 + 0.187 BPD, square of left eyeball = -0.182 + 0.187 BPD. The volume of the eyeball has strong positive correlations with gestational age and BPD. Our data may be helpful in fetuses suspected of having eye anomalies.
Pereira, Gavin; Jacoby, Peter; de Klerk, Nicholas; Stanley, Fiona J
2014-01-01
Objective To re-evaluate the causal effect of interpregnancy interval on adverse birth outcomes, on the basis that previous studies relying on between mother comparisons may have inadequately adjusted for confounding by maternal risk factors. Design Retrospective cohort study using conditional logistic regression (matching two intervals per mother so each mother acts as her own control) to model the incidence of adverse birth outcomes as a function of interpregnancy interval; additional unconditional logistic regression with adjustment for confounders enabled comparison with the unmatched design of previous studies. Setting Perth, Western Australia, 1980-2010. Participants 40 441 mothers who each delivered three liveborn singleton neonates. Main outcome measures Preterm birth (<37 weeks), small for gestational age birth (<10th centile of birth weight by sex and gestational age), and low birth weight (<2500 g). Results Within mother analysis of interpregnancy intervals indicated a much weaker effect of short intervals on the odds of preterm birth and low birth weight compared with estimates generated using a traditional between mother analysis. The traditional unmatched design estimated an adjusted odds ratio for an interpregnancy interval of 0-5 months (relative to the reference category of 18-23 months) of 1.41 (95% confidence interval 1.31 to 1.51) for preterm birth, 1.26 (1.15 to 1.37) for low birth weight, and 0.98 (0.92 to 1.06) for small for gestational age birth. In comparison, the matched design showed a much weaker effect of short interpregnancy interval on preterm birth (odds ratio 1.07, 0.86 to 1.34) and low birth weight (1.03, 0.79 to 1.34), and the effect for small for gestational age birth remained small (1.08, 0.87 to 1.34). Both the unmatched and matched models estimated a high odds of small for gestational age birth and low birth weight for long interpregnancy intervals (longer than 59 months), but the estimated effect of long interpregnancy intervals on the odds of preterm birth was much weaker in the matched model than in the unmatched model. Conclusion This study questions the causal effect of short interpregnancy intervals on adverse birth outcomes and points to the possibility of unmeasured or inadequately specified maternal factors in previous studies. PMID:25056260
Gestational syphilis and stillbirth in Latin America and the Caribbean.
Arnesen, Lauren; Martínez, Gerardo; Mainero, Luis; Serruya, Suzanne; Durán, Pablo
2015-03-01
To measure the association between gestational syphilis and stillbirth in Latin America and the Caribbean. In a retrospective study, data on stillbirth and gestational syphilis extracted from the Sistema Informático Perinatal database were analyzed for deliveries in 11 countries between January 1, 2009, and December 31, 2012. Potential confounders were examined, and binary logistic regression analysis was performed to assess the association between gestational syphilis and stillbirth. Among 368 151 deliveries, 3875 (1.1%) were by women with a positive syphilis test, and 1461 (0.4%) were stillbirths. Among the stillbirths, 29 (2.0%) were delivered by women with a positive syphilis test. After controlling for country, congenital anomalies, gestational age at labor, maternal age, and previous stillbirth, gestational syphilis was significantly associated with stillbirth (odds ratio 1.88, 95% confidence interval 1.25-2.83; P=0.002). Gestational syphilis contributes to stillbirth in Latin America and the Caribbean. Interventions targeting gestational syphilis are highly cost-effective and should be implemented across the region. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Immortal time bias in the study of stillbirth risk factors: the example of gestational diabetes.
Hutcheon, Jennifer A; Kuret, Verena; Joseph, K S; Sabr, Yasser; Lim, Kenneth
2013-11-01
Current understanding of the increased risk for stillbirth in gestational diabetes mellitus is often based on large cohort studies in which the risk of stillbirth in women with this disease is compared with the risk in women without. However, such studies could be susceptible to immortal time bias because, although many cohorts begin at 20 weeks' gestation, pregnancies must "survive" until 24-28 weeks in order to be screened and diagnosed with gestational diabetes. We describe the theoretical potential for immortal time bias in studies of stillbirth and gestational diabetes and then quantify the magnitude of the bias using 2006 United States vital statistics data. Although gestational diabetes was protective against stillbirth when including all births (relative risk = 0.88 [95% confidence interval = 0.79-0.99]), restricting analyses to births at >28 weeks' gestation reversed the effect and diabetes became associated with an increased risk of stillbirth (1.25 [1.11-1.41]). Immortal time before diagnosis of gestational diabetes may bias our understanding of the stillbirth risk associated with this condition.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hoshino, K.; Kameyama, Y.
1988-03-01
Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopesmore » of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.« less
Anand, Sonia S.; Gupta, Milan; Teo, Koon K.; Schulze, Karleen M.; Desai, Dipika; Abdalla, Nora; Zulyniak, Michael; de Souza, Russell; Wahi, Gita; Shaikh, Mateen; Beyene, Joseph; de Villa, Eileen; Morrison, Katherine; McDonald, Sarah D.; Gerstein, Hertzel
2017-01-01
Background: The reasons for the increased risk of gestational diabetes among South Asian women are not well understood. We sought to identify the determinants of gestational diabetes and its impact on newborn health in a prospective birth cohort of South Asian women and their babies. Methods: As part of the South Asian Birth Cohort (START) prospective birth cohort study in Ontario, we recruited 1012 South Asian women with singleton pregnancies in the second trimester of pregnancy between July 11, 2011, and Nov. 10, 2015. We collected health information and physical measurements and administered an oral glucose tolerance test. Birth weight and skinfold thickness measurements were obtained from their newborns, and cord blood glucose and insulin levels were measured. Results: The incidence of gestational diabetes was 36.3% (95% confidence interval [CI] 33.3%-39.3%); the age-standardized rate was 40.7%. Factors associated with gestational diabetes included maternal age (odds ratio [OR] 1.08 [95% CI 1.04-1.12]), family history of diabetes (OR 1.65 [95% CI 1.26-2.17]), prepregnancy weight (OR 1.025 [95% CI 1.01-1.04]) and low diet quality (OR 1.57 [95% CI 1.16-2.12]). Maternal height was protective against gestational diabetes (OR 0.97 [95% CI 0.95-0.99]). The population attributable risk due to prepregnancy body mass index and low diet quality was 37.3%. Compared to newborns of women without gestational diabetes, those of women with gestational diabetes had a significantly higher birth weight (3267 [standard error (SE) 23] g v. 3181 [SE 17] g, p = 0.005), greater skinfold thickness (11.7 [SE 0.1] mm v. 11.2 [SE 0.1] mm, p = 0.007) and lower insulin sensitivity (glucose/insulin ratio 0.092 [SE 0.009] mmol/pmol v. 0.129 [SE 0.006] mmol/pmol, p = 0.001). Interpretation: The modifiable risk factors of prepregnancy weight and low diet quality accounted for 37% of the population attributable risk of gestational diabetes in our cohort. Intervention studies to lower prepregnancy weight and to prevent gestational diabetes among South Asian women in high-income countries are needed. PMID:28800568
Boghossian, Nansi S; McDonald, Scott A; Bell, Edward F; Carlo, Waldemar A; Brumbaugh, Jane E; Stoll, Barbara J; Laptook, Abbot R; Shankaran, Seetha; Walsh, Michele C; Das, Abhik; Higgins, Rosemary D
2016-06-01
Little is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples. To examine if use of ANS is associated with improvement in major outcomes in extremely preterm multiples. Infants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables. Antenatal corticosteroids. In-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment. A total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01). Compared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.
Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data.
Sunkara, Sesh Kamal; Antonisamy, Belavendra; Selliah, Hepsy Y; Kamath, Mohan S
2017-12-01
Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared. No difference was found in the risk of PTB and LBW after gestational surrogacy compared with autologous fresh IVF-ICSI: PTB (adjusted OR 0.90, 95% CI 0.56 to 1.42), LBW (adjusted OR 0.90, 95% CI 0.57 to 1.43) and gestational surrogacy compared with autologous frozen embryo transfers: PTB (adjusted OR 0.96, 95% CI 0.58 to 1.60), LBW (adjusted OR 1.16, 95% CI 0.69 to 1.96). The incidence of HBW was significantly higher after gestational surrogacy compared with fresh IVF-ICSI (adjusted OR 1.94, 95% CI 1.38 to 2.75); no difference was found in HBW between gestational surrogacy and autologous frozen embryo transfers. The dataset is limited by lack of information on confounders, i.e. ethnicity, body mass index, underlying medical history, which could result in residual confounding. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Brough, Louise; Rees, Gail A; Crawford, Michael A; Morton, R Hugh; Dorman, Edgar K
2010-08-01
Poor nutrient intake during pregnancy can adversely affect both infant and maternal health. The aim was to investigate the efficacy of multiple-micronutrient supplementation during pregnancy in a socially deprived population in the developed world. We conducted a randomised, double-blind, placebo-controlled trial of multiple-micronutrient supplementation including 20 mg Fe and 400 microg folic acid, from the first trimester of pregnancy in 402 mothers, in East London, UK. Nutrient status was measured at recruitment, and at 26 and 34 weeks of gestation. Infants were weighed at birth. At recruitment the prevalence of anaemia was 13 %, vitamin D insufficiency 72 %, thiamin deficiency 12 % and folate deficiency 5 %, with no differences between groups. Only 39 % of women completed the study; rates of non-compliance were similar in both groups. Intention-to-treat analysis showed that participants receiving treatment had higher mean Hb at 26 weeks of gestation (110 (sd 10) v.108 (sd 10) g/l; P = 0.041) and 34 weeks of gestation (113 (sd 12) v.109 (sd 10) g/l; P = 0.003) and packed cell volume concentrations at 26 weeks of gestation (0.330 (sd 0.025) v. 0.323 (sd 0.026) l/l; P = 0.011) and 34 weeks of gestation (0.338 (sd 0.029) v. 0.330 (sd 0.028) l/l; P = 0.014) compared with controls. Analysis of compliant women showed supplemented women had higher median concentrations of serum ferritin, erythrocyte folate and 25-hydroxyvitamin D later in gestation than controls. In the compliant subset (n 149), placebo mothers had more small-for-gestational age (SGA) infants (eight SGA v. thirteen; P = 0.042) than treatment mothers. Baseline micronutrient deficiencies were common; the multiple-micronutrient supplement was well-tolerated and improved nutrient status. Multiple-micronutrient supplements from early pregnancy may be beneficial and larger studies are required to assess impact on birth outcomes and infant development.
Unshielded fetal magnetocardiography system using two-dimensional gradiometers
NASA Astrophysics Data System (ADS)
Seki, Yusuke; Kandori, Akihiko; Kumagai, Yukio; Ohnuma, Mitsuru; Ishiyama, Akihiko; Ishii, Tetsuko; Nakamura, Yoshiyuki; Horigome, Hitoshi; Chiba, Toshio
2008-03-01
We developed a fetal magnetocardiography (fMCG) system that uses a pair of two-dimensional gradiometers to achieve high signal-to-noise ratio. The gradiometer, which is based on a low-Tc superconducting quantum interference device, detects the gradient of a magnetic field in two orthogonal directions. Gradiometer position is easy to adjust by operating the gantry to drive the cryostat in both the swinging and axial directions. As a result, a fMCG waveform for 25weeks' gestation was measured under an unshielded environment in real time. Moreover, the P and T waves for 25 and 34weeks' gestation, respectively, were obtained by averaging. These results indicate that this two-dimensional gradiometer is one of the most promising techniques for measuring fetal heart rate and diagnosing fetal arrhythmia.
Does pre-pregnancy BMI determine blood pressure during pregnancy? A prospective cohort study
Zuithoff, Peter; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M
2016-01-01
Objectives To evaluate if pre-pregnancy body mass index (BMI) determines blood pressure throughout pregnancy and to explore the role of gestational weight gain in this association. In addition, the effects of pre-pregnancy BMI and gestational weight gain on the occurrence of gestational hypertension and pre-eclampsia were investigated. Design Prospective cohort study. Setting Maternal and child health primary care referral centre, Jakarta, Indonesia. Population and measurements 2252 pregnant women visiting Budi Kemuliaan Hospital and its branch for regular antenatal care visits from July 2012 to April 2015. Pre-pregnancy BMI (kg/m2) was based on self-reported pre-pregnancy weight and measured height at first visit. Gestational weight gain was calculated as weight at the day of delivery minus the pre-pregnancy weight. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured during pregnancy at every visit. Linear mixed models were used to analyse this relation with repeated blood pressure measures as the outcome and pre-pregnancy BMI as the predictor. When looking at gestational hypertension and pre-eclampsia as outcomes, (multiple) logistic regression was used in the analysis. Results Independent of pre-pregnancy BMI, SBP and DBP increased by 0.99 mm Hg/month and 0.46 mm Hg/month, respectively. Higher pre-pregnancy BMI was associated with higher pregnancy SBP (0.25 mm Hg/kg/m2; 95% CI 0.17 to 0.34; p<0.01) and DBP (0.18 mm Hg/kg/m2; 0.13 to 0.24; p<0.01) in adjusted analysis. Every 1 kg/m2 higher pre-pregnancy BMI was associated with 6% and 9% higher odds for gestational hypertension (adjusted OR (aOR) 1.06; 95% CI 1.03 to 1.09; p<0.01) and pre-eclampsia (aOR 1.09; 1.04 to 1.14; p<0.01). Accounting for gestational weight gain did not attenuate these associations. Conclusions Pre-pregnancy BMI determines the level, but not the change, of blood pressure in pregnancy and is linked to higher odds for gestational hypertension and pre-eclampsia, independent of gestational weight gain. PMID:27515754
Gonzalez-Rodriguez, Pablo; Cantu, Jessica; O'Neil, Derek; Seferovic, Maxim D; Goodspeed, Danielle M; Suter, Melissa A; Aagaard, Kjersti M
2016-05-01
The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P < .05); however, essential nutrient supplementation diet abrogates this difference (4.995 vs 5.100; P > .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P < .05) on the control diet, an effect that was repressed with essential nutrient supplementation. Heritable growth restriction is associated with changes in H19 gene expression; these changes are reversible with diet supplementation to favorably impact adult metabolic syndrome. Copyright © 2016. Published by Elsevier Inc.
Localized wear of compomer restorative materials.
Latta, M A; Barkmeier, W W; Wilwerding, T M; Blake, S M
2001-08-01
To determine and compare the localized wear of six compomer restorative materials. Ten specimens of Dyract, Dyract AP, F2000, Compoglass F, Elan and Hytac were prepared in a custom fixture and polished. A pretest surface profile was generated using an MTS 3-D surface profilometer and the specimens were subjected to 400,000 cycles in a Leinfelder wear machine equipped with a conical stylus tip to simulate localized wear. A post-test profile was generated and the before and after profiles were fitted and analyzed using AnSur 3-D software. The total volume loss and depth of the wear facet on each specimen was calculated and statistical analysis was accomplished (ANOVA and Tukey's test). Volume loss (mm3) was as follows: F2000, 0.027 +/- 0.002; Hytac, 0.007 +/- 0.023; Elan, 0.054 +/- 0.013; Compoglass F, 0.135 +/- 0.006; Dyract AP, 0.135 +/- 0.023; Dyract, 0.185 +/- 0.032. Maximum depth of the wear facets (microm) was as follows: F2000, 112.2 +/- 10.2; Hytac, 132.8 +/- 9.3; Elan, 144.3 +/- 23. 1; Compoglass F, 168.3 +/- 13.0; Dyract AP, 194.0 +/- 19.7; Dyract, 220.6 +/- 15.8. There was not a difference (P > 0.05) in volumetric loss between F2000 and Hytac or between Hytac and Elan. The volume loss and maximum depth of the wear facets of F2000, Hytac and Elan was significantly less (P< 0.05) than Compoglass F, Dyract AP and Dyract The results of this study indicate that there are significant differences in the in vitro wear rates of compomer materials.
Neonatal outcomes according to different therapies for gestational diabetes mellitus.
Silva, Amanda L da; Amaral, Augusto R do; Oliveira, Daniela S de; Martins, Lisiane; Silva, Mariana R E; Silva, Jean Carl
To compare different neonatal outcomes according to the different types of treatments used in the management of gestational diabetes mellitus. This was a retrospective cohort study. The study population comprised pregnant women with gestational diabetes treated at a public maternity hospital from July 2010 to August 2014. The study included women aged at least 18 years, with a singleton pregnancy, who met the criteria for gestational diabetes mellitus. Blood glucose levels, fetal abdominal circumference, body mass index and gestational age were considered for treatment decision-making. The evaluated neonatal outcomes were: type of delivery, prematurity, weight in relation to gestational age, Apgar at 1 and 5min, and need for intensive care unit admission. The sample consisted of 705 pregnant women. The neonatal outcomes were analyzed based on the treatment received. Women treated with metformin were less likely to have children who were small for gestational age (95% CI: 0.09-0.66) and more likely to have a newborn adequate for gestational age (95% CI: 1.12-3.94). Those women treated with insulin had a lower chance of having a preterm child (95% CI: 0.02-0.78). The combined treatment with insulin and metformin resulted in higher chance for a neonate to be born large for gestational age (95% CI: 1.14-11.15) and lower chance to be born preterm (95% CI: 0.01-0.71). The type of treatment did not affect the mode of delivery, Apgar score, and intensive care unit admission. The pediatrician in the delivery room can expect different outcomes for diabetic mothers based on the treatment received. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Tetraquark mixing framework for isoscalar resonances in light mesons
NASA Astrophysics Data System (ADS)
Kim, Hungchong; Kim, K. S.; Cheoun, Myung-Ki; Oka, Makoto
2018-05-01
Recently, a tetraquark mixing framework has been proposed for light mesons and applied more or less successfully to the isovector resonances, a0(980 ) , a0(1450 ) , as well as to the isodoublet resonances, K0*(800 ),K0*(1430 ). In this work, we present a more extensive view on the mixing framework and apply this framework to the isoscalar resonances, f0(500 ), f0(980 ), f0(1370 ), f0(1500 ). Tetraquarks in this framework can have two spin configurations containing either spin-0 diquark or spin-1 diquark and each configuration forms a nonet in flavor space. The two spin configurations are found to mix strongly through the color-spin interactions. Their mixtures, which diagonalize the hyperfine masses, can generate the physical resonances constituting two nonets, which, in fact, coincide roughly with the experimental observation. We identify that f0(500 ), f0(980 ) are the isoscalar members in the light nonet, and f0(1370 ), f0(1500 ) are the similar members in the heavy nonet. This means that the spin configuration mixing, as it relates the corresponding members in the two nonets, can generate f0(500 ) , f0(1370 ) among the members in light mass, and f0(980 ) , f0(1500 ) in heavy mass. The complication arises because the isoscalar members of each nonet are subject to an additional flavor mixing known as Okubo-Zweig-Iizuka rule so that f0(500 ) , f0(980 ) , and similarly f0(1370 ) , f0(1500 ) , are the mixture of two isoscalar members belonging to an octet and a singlet in SUf(3 ) . The tetraquark mixing framework including the flavor mixing is tested for the isoscalar resonances in terms of the mass splitting and the fall-apart decay modes. The mass splitting among the isoscalar resonances is found to be consistent qualitatively with their hyperfine mass splitting strongly driven by the spin configuration mixing, which suggests that the tetraquark mixing framework works. The fall-apart modes from our tetraquarks also seem to be consistent with the experimental modes. We also discuss possible existence of the spin-1 tetraquarks that can be constructed by the spin-1 diquark.
Yaqub, Lukuman Surakat; Ayo, Joseph Olusegun; Kawu, Muhammad Umar; Rekwot, Peter Ibrahim
2017-08-01
The study investigated concomitant effect of gestation and high ambient temperature under a tropical environment on rectal temperature (RT), respiratory rate (RR) and heart rate (HR) responses in Yankasa ewes. Twenty Yankasa ewes, consisting of ten pregnant and ten non-pregnant ewes, were used for the study. Ewes were synchronised and bred, such that each gestation phase coincided with different periods of the dry-seasons, early-gestation (cold/harmattan), mid-gestation (peak hot-dry) and late-gestation (late hot-dry). The RT, RR and HR were recorded thrice, 2 days apart at middle of each gestation period at 06:00, 14:00 and 18:00 h, concurrently with dry- (DBT) and wet-bulb temperatures of the experimental pen. The DBT was positively correlated with RT, RR during the different gestation stages. The RT significantly (P < 0.001) increased with the hour of day, regardless of the physiological status of the ewes, with peak at 14:00 h. Values of RT and RR were higher (P < 0.05) in pregnant than non-pregnant ewes at mid- and late-gestation, respectively. Mean RT was lower (P < 0.001) at 06:00 h in pregnant than non-pregnant ewes at early-gestation (cold-dry). The HR was (P < 0.05) higher in pregnant than non-pregnant ewes during the different gestation phases. In conclusion, ambient temperature and gestation concomitantly modulate diurnal thermoregulatory responses of the ewes to hot-dry season. Adequate measures should be adopted to mitigate adverse impact of prolonged high RR on the dam and the foetus during the peak of ambient temperature prevailing in the tropical Savannah environment.
Zhang, Ya-Jie; Jin, Hua; Qin, Zhen-Li; Ma, Jin-Long; Zhao, Han; Zhang, Ling; Chen, Zi-Jiang
2016-01-01
This study aims to explore the independent predictors of gestational diabetes mellitus (GDM) in Chinese women with polycystic ovary syndrome (PCOS). This cross-sectional study analyzed primigravid women with PCOS and classified them as those with and without GDM. Independent risk factors and model performance were analyzed using multivariate logistic regression and the area under the curve (AUC) of receiver operating characteristic (ROC), respectively. Maternal body mass index, waist circumference, waist-to-hip ratio (WHR), fasting glucose, insulin, sex hormone-binding globulin (SHBG), homeostasis model assessment-insulin resistance (HOMA-IR) before pregnancy, gestation weight gain before 24 weeks and the incidence of family history of diabetes were different in the 2 groups. Logistic regression analysis showed that pre-pregnancy WHR, SHBG, HOMA-IR and gestation weight gain before 24 weeks were the independent predictors of GDM. ROC curve analysis confirmed that gestation weight gain before 24 weeks (AUC 0.767, 95% CI 0.688-0.841), pre-pregnant WHR (AUC 0.725, 95% CI 0.649-0.802), HOMA-IR (AUC 0.711, 95% CI 0.632-0.790) and SHBG levels (AUC 0.709, 95% CI 0.625-0.793) were the strong risk factors. In Chinese women with PCOS, factors of gestation weight gain before 24 weeks, pre-pregnant WHR, HOMA-IR and SHBG levels are strongly associated with subsequent development of GDM. © 2015 S. Karger AG, Basel.
Nishina, Hidenori; Green, Lucy R; McGarrigle, Hugh H G; Noakes, David E; Poston, Lucilla; Hanson, Mark A
2003-01-01
Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid-gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein-restricted group fetuses (P < 0.05). Maximal relaxation (P < 0.01) and sensitivity (P < 0.05) to acetylcholine were markedly reduced in protein-restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve, P < 0.05). The dilator response (P < 0.05) and sensitivity (P < 0.05) to the α2 agonist UK14304 was lower in protein-, but not in globally restricted group fetuses. The response (P < 0.05) and sensitivity (P < 0.05) to the nitric oxide donor sodium nitroprusside were reduced in protein-restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial-dependent and -independent relaxation in systemic arteries from the mid-gestation fetus. These changes may precede perturbed late-gestation fetal and postnatal cardiovascular control. PMID:12949230
De Felice, Alessia; Greco, Anita; Calamandrei, Gemma; Minghetti, Luisa
2016-06-14
Autism spectrum disorders (ASD) are emerging as polygenic and multifactorial disorders in which complex interactions between defective genes and early exposure to environmental stressors impact on the correct neurodevelopment and brain processes. Organophosphate insecticides, among which chlorpyrifos (CPF), are widely diffused environmental toxicants associated with neurobehavioral deficits and increased risk of ASD occurrence in children. Oxidative stress and dysregulated immune responses are implicated in both organophosphate neurodevelopmental effects and ASD etiopathogenesis. BTBR T+tf/J mice, a well-studied model of idiopathic autism, show several behavioral and immunological alterations found in ASD children, and we recently showed that CPF gestational exposure strengthened some of these autistic-like traits. In the present study, we aimed at investigating whether the behavioral effects of gestational CPF administration are associated with brain increased oxidative stress and altered lipid mediator profile. Brain levels of F2-isoprostanes (15-F2t-IsoP), as index of in vivo oxidative stress, and prostaglandin E2 (PGE2), a major arachidonic acid metabolite released by immune cells and by specific glutamatergic neuron populations mainly in cortex and hippocampus, were assessed by specific enzyme-immuno assays in brain homogenates from BTBR T+tf/J and C57Bl6/J mice, exposed during gestation to either vehicle or CPF. Measures were performed in mice of both sexes, at different postnatal stages (PNDs 1, 21, and 70). At birth, BTBR T+tf/J mice exhibited higher baseline 15-F2t-IsoP levels as compared to C57Bl6/J mice, suggestive of greater oxidative stress processes. Gestational treatment with CPF-enhanced 15-F2t-IsoP and PGE2 levels in strain- and age-dependent manner, with 15-F2t-IsoP increased in BTBR T+tf/J mice at PNDs 1 and 21, and PGE2 elevated in BTBR T+tf/J mice at PNDs 21 and 70. At PND 21, CPF effects were sex-dependent being the increase of the two metabolites mainly associated with male mice. CPF treatment also induced a reduction of somatic growth, which reached statistical significance at PND 21. These findings indicate that the autistic-like BTBR T+tf/J strain is highly vulnerable to environmental stressors during gestational period. The results further support the hypothesis that oxidative stress might be the link between environmental neurotoxicants such as CPF and ASD. The increased levels of oxidative stress during early postnatal life could result in delayed and long-lasting alterations in specific pathways relevant to ASD, of which PGE2 signaling represents an important one.
Predictive factors for birth weight of newborns of mothers with gestational diabetes mellitus.
Silva, Sara de Oliveira Corrêa da; Saunders, Cláudia; Zajdenverg, Lenita; Moreira, Luciana Novaes; Heidelmann, Sonaly Petronilho; Pereira, Ariane Cristine Dos Santos; Padilha, Patricia de Carvalho
2018-04-01
To evaluate the predictive factors of birth weight (BW) of newborns of women with gestational diabetes mellitus (GDM). A cross-sectional study was performed among pregnant women with GDM treated in a public maternity unit, Brazil. We selected 283 pregnant women, with nutritional follow-up initiated till the 28th gestational week, singleton pregnancy, without chronic diseases and with birth weight information of the newborns. The predictive factors of BW were identified by multivariate linear regression. Mean maternal age was 31.2 ± 5.8 years; 64.4% were non-white; 70.1% were pre-gestational overweight or obese. Mean BW was 3234.3 ± 478.8 g. An increase of 1 kg of weight in the first and third trimesters increased BW by 21 g (p = 0.01) and 27 g (p = 0.03), respectively. Similarly, the other predictive factors of BW were pre-gestational body mass index (β = 17.16, p = 0.02) and postprandial plasma glucose in the third trimester (β = 4.14, p = 0.008), in the model adjusted by gestational age at delivery (β = 194.68, p < 0.001). The best predictors of BW were gestational age at birth, and maternal pre-gestational and gestational anthropometric characteristics. Maternal glycaemic levels may also influence BW. The results may contribute to a review of prenatal routines for pregnant women with GDM. Copyright © 2018 Elsevier B.V. All rights reserved.
Velkoska Nakova, V; Krstevska, B; Dimitrovski, Ch; Simeonova, S; Hadzi-Lega, M; Serafimoski, V
2010-01-01
The aim of the present study was to determine the prevalence of abnormal thyroid function and antithyroid antibodies during pregnancy in women with diabetes type 1 and gestational diabetes mellitus (GDM). The study group included 83 pregnant women who attended the Outpatient Department of the Endocrinology, Diabetes and Metabolic Disorders Clinic in the period from 05.2009 to 11.2009. The one hundred-g. oral glucose tolerance test (OGTT) was conducted on the pregnant women except for women with diabetes type 1. Thyroid functions were evaluated in all the pregnant women. After routine screening for GDM, thirty of the pregnant women were healthy and GDM was diagnosed in forty of them. The rest, thirteen women, had diabetes type 1. The women who developed GDM showed a mean free thyroxin concentration (fT4) significantly lower than that observed in the healthy pregnant women and women with diabetes type 1. Among the pregnant women with GDM, 10 women or 25% had fT4 concentrations below the lower cut-off with normal thyroid-stimulating hormone concentrations (TSH). A statistically significant difference was found in the prevalence of antithyroid antibodies (anti-TPO) between the (30%) women with diabetes type 1 and (10%) healthy pregnant women (p<0.05). In the women positive for anti-TPO, TSH was significantly higher (p<0.05). The significantly higher prevalence of hypothyroxinemia in GDM pregnancies and anti-TPO titres in pregnancies with diabetes type 1, than in healthy pregnant women warrants routine screening for thyroid abnormalities in these groups of pregnant women.
Nasr, Mohammed A F
2017-08-01
The current study was aimed to investigate the impact of THI on productive and reproductive indices of PE and F 1 crosses (50% PE and 50% Italian buffaloes) and back crosses (BC) (75% PE and 25% Italian buffaloes) under hot conditions. In this study, 8385 records used PE (1914, 1518, and 1737), F 1 (387, 447, and 657), and BC (495, 585, and 645) for low, medium, and high THI, respectively. The high THI reduced the conception rate after first insemination in PE, F 1 , and BC ((odds ratio, OR) = 1.187, P = 0.007; 2.361, <0.0001 and 1.603, <0.0001, respectively) when compared with low THI. But, stillbirth and calving condition were not significantly influenced by different THI levels in BC and F 1 . BC was more bearable to the harsh environment; they possessed the highest incidence of conception after first insemination (72.70, 72.60, and 62.40%), producing live calves (98.50, 100, and 99.40%) with easy calving condition (98.50, 100, and 99.40%) when compared to PE and F 1 at different levels of THI, respectively. The average daily milk yield and peak of milk production were decreased in PE (4.02 and 5.12%), BC (13.33 and 10.95%), and F 1 (25.29 and 12.20%) from low to high THI. However, BC revealed no significant changes in days open, dry period, calving interval, gestation length, service per conception, and the first service post-partum at different levels of THI when compared with PE and F 1 . Therefore, rearing BC is recommended for improving buffalo productive and reproductive performance under hot conditions.
Ebert, T; Hindricks, J; Kralisch, S; Lossner, U; Jessnitzer, B; Richter, J; Blüher, M; Stumvoll, M; Fasshauer, M
2014-08-01
Fractalkine has recently been introduced as an adipokine that improves glucose tolerance. Regulation of fractalkine in gestational diabetes, as well as its association with markers of obesity, glucose and lipid metabolism, inflammation and renal function, has not been elucidated. Circulating fractalkine was quantified by enzyme-linked immunosorbent assay in 74 women with gestational diabetes and 74 healthy, pregnant control subjects matched for age, BMI, and gestational age. Median (interquartile range) levels of fractalkine were not significantly different between the two groups [gestational diabetes: 2.24 (2.16) μg/l; control: 2.45 (1.38) μg/l] (P = 0.461). In multivariate linear regression analysis, fractalkine remained independently associated with homeostasis model assessment of insulin resistance (β = -0.253, P = 0.002) and the proinflammatory adipokine progranulin (β = 0.218, P = 0.007). Circulating fractalkine is not different between women with gestational diabetes and control subjects, but the adipokine is independently associated with markers of insulin resistance and proinflammatory progranulin in pregnancy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.
Validation of Self-reported Diagnosis of Gestational Diabetes at 6-weeks Postpartum.
Hinkle, Stefanie N; Rawal, Shristi; Zhu, Yeyi; Grewal, Jagteshwar; Albert, Paul S; Zhang, Cuilin
2017-09-01
Self-report is often used in identifying gestational diabetes events in epidemiologic studies; however, validity data are limited, with little to no data on self-reported severity or treatment. We aimed to assess the validity of self-reported gestational diabetes diagnosis and evaluate the accuracy of glucose diagnosis results and gestational diabetes treatment self-reported at 6-week postpartum. Data were from 82 and 83 women with and without gestational diabetes, respectively, within the prospective National Institute Child Health and Human Development Fetal Growth Studies-Singletons (2009-2013). Medical record data were considered the gold standard. Sensitivity was 95% (95% confidence interval [CI] = 88, 98), and specificity was 100% (95% CI = 96, 100); four women with gestational diabetes incorrectly reported not having the disease, and none of the women without gestational diabetes reported having gestational diabetes. Sensitivity did not vary substantially across maternal characteristics including race/ethnicity. For women who attempted to recall their values (84/159 women), self-reported glucose challenge test results did not differ from the medical records (median difference: 0; interquartile range: 0-0 mg/dl). Medical records indicated that 42 (54%) of 78 women with confirmed gestational diabetes were treated by diet only and 33 (42%) were treated by medication. All 42 women with diet-treated gestational diabetes correctly reported having had diet and lifestyle modification, and 28 (85%) of 33 women with medication-treated gestational diabetes indicated postpartum that they had medication treatment. At 6-week postpartum, regardless of race/ethnicity or socioeconomic status, women accurately recalled whether they had gestational diabetes and, as applicable, their treatment method.
The Sortie-Generation Model System. Volume VI. Spares Subsystem,
1981-09-01
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He, Fang; He, Hua; Liu, Wenqi; Lin, Junyu; Chen, Bingjun; Lin, Yucong; Zhao, Yitao; Tao, Wen; Xia, Xuefeng
2017-03-01
A large neck circumference might be an indicator of metabolic syndrome and its components, and for certain patients is more practical as an index than waist circumference. The demarcation value for neck circumference that suggests metabolic syndrome appears to vary by ethnic group. Gestational diabetes mellitus is considered a component of metabolic syndrome in pregnant women. We investigated whether neck circumference in Han Chinese women is associated with gestational diabetes mellitus in early pregnancy, and determined a predictive demarcation value. A nested case-control study was carried out with 255 women aged 18-35 years. Gestational diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association through a 2-h, 75-g oral glucose tolerance test. Of the total population, 41 (16%) women developed gestational diabetes mellitus by 24-28 weeks of gestation. Neck circumference at gestational week 16 positively correlated with pre-pregnancy waist circumference, bodyweight and body mass index, and maternal age (P = 0.029) and hemoglobin A1c at gestational week 24 (P ≤ 0.001). By binary logistic regression, neck circumference was an independent predictor of gestational diabetes mellitus (odds ratio 1.840, 95% confidence interval 1.040-3.254; P = 0.036). According to the receiver operating characteristic curve, for predicting gestational diabetes mellitus the optimal demarcation for neck circumference at gestational week 16 was 35.15 cm. Neck circumference is a viable tool to screen for gestational diabetes mellitus. In this population of pregnant Han Chinese women, a neck circumference of ≥35.15 cm was a predictor of gestational diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Axelsson, Josefin; Larsson, Irene; Johansson, Martin; Wester-Rosenlöf, Lena; Mörgelin, Matthias; Casslén, Vera; Gram, Magnus; Åkerström, Bo; Hansson, Stefan R.
2015-01-01
Preeclampsia is one of the most serious pregnancy-related diseases and clinically manifests as hypertension and proteinuria after 20 gestational weeks. The worldwide prevalence is 3-8% of pregnancies, making it the most common cause of maternal and fetal morbidity and mortality. Preeclampsia lacks an effective therapy, and the only “cure” is delivery. We have previously shown that increased synthesis and accumulation of cell-free fetal hemoglobin (HbF) in the placenta is important in the pathophysiology of preeclampsia. Extracellular hemoglobin (Hb) and its metabolites induce oxidative stress, which may lead to acute renal failure and vascular dysfunction seen in preeclampsia. The human endogenous protein, α1-microglobulin (A1M), removes cell-free heme-groups and induces natural tissue repair mechanisms. Exogenously administered A1M has been shown to alleviate the effects of Hb-induced oxidative stress in rat kidneys. Here we attempted to establish an animal model mimicking the human symptoms at stage two of preeclampsia by administering species-specific cell-free HbF starting mid-gestation until term, and evaluated the therapeutic effect of A1M on the induced symptoms. Female pregnant rabbits received HbF infusions i.v. with or without A1M every second day from gestational day 20. The HbF-infused animals developed proteinuria and a significantly increased glomerular sieving coefficient in kidney that was ameliorated by co-administration of A1M. Transmission electron microscopy analysis of kidney and placenta showed both intracellular and extracellular tissue damages after HbF-treatment, while A1M co-administration resulted in a significant reduction of the structural and cellular changes. Neither of the HbF-treated animals displayed any changes in blood pressure during pregnancy. In conclusion, infusion of cell-free HbF in the pregnant rabbits induced tissue damage and organ failure similar to those seen in preeclampsia, and was restored by co-administration of A1M. This study provides preclinical evidence supporting further examination of A1M as a potential new therapy for preeclampsia. PMID:25955715
Shin, Eun Hee; Roh, Jong Yul; Park, Won Il; Song, Bong Gu; Chang, Kyu-Sik; Lee, Wook-Gyo; Lee, Hee Il; Park, Chan; Park, Mi-Yeoun; Shin, E-Hyun
2014-01-01
Transovarial transmission of Orientia tsutsugamushi in colonies of Leptotrombidium palpale was studied in the parent and F1 and F2 generations. Both transovarial transmission and filial infection rates were 100% in the parent and F1 generations of Leptotrombidium palpale. The filial infection rate in the F1 generation was 100%, but it declined to 94.3% in the F2 progeny. The sex ratio of the F1 generation from infected L. palpale was 1∶0.8 (male:female) and the proportion of males was relatively high. This study is the first to report on the transovarial transmission of O. tsutsugamushi in L. palpale. High transovarial transmission rates in L. palpale suggest that this species might be one of the major vectors of tsutsugamushi disease in Korea.
Shin, Eun Hee; Roh, Jong Yul; Park, Won Il; Song, Bong Gu; Chang, Kyu-Sik; Lee, Wook-Gyo; Lee, Hee Il; Park, Chan; Park, Mi-Yeoun; Shin, E-Hyun
2014-01-01
Transovarial transmission of Orientia tsutsugamushi in colonies of Leptotrombidium palpale was studied in the parent and F1 and F2 generations. Both transovarial transmission and filial infection rates were 100% in the parent and F1 generations of Leptotrombidium palpale. The filial infection rate in the F1 generation was 100%, but it declined to 94.3% in the F2 progeny. The sex ratio of the F1 generation from infected L. palpale was 1∶0.8 (male:female) and the proportion of males was relatively high. This study is the first to report on the transovarial transmission of O. tsutsugamushi in L. palpale. High transovarial transmission rates in L. palpale suggest that this species might be one of the major vectors of tsutsugamushi disease in Korea. PMID:24721932
Zimmer, J; Takahashi, T; Hofmann, A D; Puri, Prem
2016-12-01
High mortality and morbidity in infants born with congenital diaphragmatic hernia (CDH) are attributed to pulmonary hypoplasia and pulmonary hypertension (PH). Forkhead box (Fox) transcription factors are known to be crucial for cell proliferation and homeostasis. FoxF1 is essential for lung morphogenesis, vascular development, and endothelial proliferation. Mutations in FoxF1 and also the Fox family member FoxC2 have been identified in neonates with PH. In human and experimental models of arterial PH, the Fox protein FoxO1 was found to be downregulated. We hypothesized that Fox expression is altered in the lungs of the nitrofen-induced CDH rat model and investigated the expression of FoxF1, FoxC2, and FoxO1. Following ethical approval (Rec 913b), time-pregnant Sprague-Dawley rats received nitrofen or vehicle on gestational day (D9). Fetuses were sacrificed on D21, inspected for CDH and divided into CDH (n = 11) and control group (n = 11). Gene expression of FoxF1, FoxC2, and FoxO1 was evaluated with qRT-PCR. Detected alterations of mRNA levels were subsequently assessed on the protein level by performing western blot analysis and laser scanning confocal microscopy. The relative mRNA level of FoxF1 was significantly downregulated in CDH lungs compared to controls (FoxF1 CDH 1.047 ± 0.108, FoxF1 Ctrl 1.419 ± 0.01, p = 0.014). Relative mRNA levels of FoxC2 and FoxO1 were not found to be altered between the experimental groups (FoxC2 CDH 30.74 ± 8.925, FoxC2 Ctrl 27.408 ± 7.487, p = 0.776; FoxO1 CDH 0.011 ± 0.002, FoxO1 Ctrl 0.011 ± 0.001, p = 0.809). On the protein level, western blotting demonstrated a reduced pulmonary protein expression of FoxF1 in CDH lungs. Confocal microscopy showed a markedly diminished expression of FoxF1 in the pulmonary vasculature of CDH lungs compared to controls. Our study demonstrates a strikingly reduced expression of FoxF1 in the pulmonary vasculature of nitrofen-induced CDH. Altered FoxF1 gene expression during embryogenesis may participate in vascular maldevelopment resulting in PH in this animal model.
NASA Astrophysics Data System (ADS)
Sun, Dong; Chen, Qi; He, Ning; Diao, Pan-Pan; Jia, Li-Xing; Duan, Shun-Shan
2017-02-01
Nonylphenol (NP) is a persistent environmental chemical that can disrupt the organism’s endocrine system, and is detected in the surface water and sea. In this study, we investigated whether NP can alter transcriptional expression of sexual differentiation-related genes. Three generations of zebrafish were exposed to 0, 2, 20 and 200 μg·L-1 of NP, and transcriptional expression of sexual differentiation genes were assessed in 10, 20 and 40 dpf in the F1 and F2 generations. Growth of zebrafish exposed to 200 μg·L-1 of NP was inhibited at 125 dpf in the F1 generation. 20 μg·L-1 of NP resulted in 80% females in the F1 generation, but had no effect on the F2 generation. In terms of the sexual differentiation genes, the transcriptional expression of cyp19a1a and esr1 genes were upregulated in 20 μg·L-1 of NP in the F1 generation. But expression of the sexual differentiation genes were not affected in the F2 generation. Overall, NP could affect sexual differentiation and gene transcriptional expression in the F1 generation. The tolerance of contaminant in the offsprings was improved at low concentration.
Melot, A; Labarre, A; Vanhulle, C; Rondeau, S; Brasseur, M; Gilard, V; Castel, H; Marret, S; Proust, F
2016-04-01
To assess long-term neurodevelopmental outcome in children with hydrocephalus requiring neurosurgical treatment during the neonatal period. This prospective longitudinal population-based study included 43 children with neonatal shunted hydrocephalus. The 43 children were prospectively reviewed in the presence of their parents at the outpatient clinic. Cognitive and motor outcomes were assessed respectively using different Wechsler scales according to age and Gross Motor Function Classification System (GMFCS). Postoperative MRI was routinely performed. The mean gestational age at birth of the 43 consecutive children with neonatal hydrocephalus (sex ratio M/F: 1.39) was 34.5±5.4 weeks of gestation. At mean follow-up of 10.4±4 years, mean total IQ was 73±27.7, with equivalent results in mean verbal and mean performance IQ. Of the 33 children with IQ evaluation, 18 presented an IQ≥85 (41.9%). Efficiency in walking without a mobility device (GMFCS≤2) was obtained in 37 children (86%). Only severity of postoperative ventricular dilation was significantly associated with unfavorable outcome (Evans index>0.37; odds ratio: 0.16, P=0.03). This information could be provided to those families concerned who often experience anxiety when multi-disciplinary management of neonatal hydrocephalus is required. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Neville, T L; Caton, J S; Hammer, C J; Reed, J J; Luther, J S; Taylor, J B; Redmer, D A; Reynolds, L P; Vonnahme, K A
2010-11-01
Lambs born from feed-restricted or overfed ewes can be lighter at birth, whereas maternal Se supplementation can increase fetal size near term. We hypothesized that birth weight would be inversely related to feed efficiency and growth rates during postnatal development. To examine the effects of maternal dietary Se and nutrient restriction or excess on postnatal lamb growth, diet digestibility, and N retention, 82 ewe lambs (52.2 ± 0.8 kg) were allotted randomly to 1 of 6 treatments in a 2 × 3 factorial arrangement. Factors were dietary Se [adequate Se (9.5 μg/kg of BW; ASe) vs. high Se (Se-enriched yeast; 81.8 μg/kg of BW; HSe)] and maternal nutritional intake [60% (restricted, RES), 100% (control, CON), or 140% (high, HI) of NRC requirements]. Selenium treatments began at breeding. Nutritional treatments began on d 50 of gestation. Lambs were immediately removed from their dams at parturition, provided artificial colostrum, and fed milk replacer until weaning. After weaning, lambs were maintained using common management and on common diets until necropsy at 180 d. Male and female lambs from RES-fed ewes were lighter (P ≤ 0.03) at birth than lambs from CON-fed ewes, with lambs from HI-fed ewes being intermediate. Although maternal nutritional intake influenced (P < 0.06) BW gain before weaning on d 57, both maternal nutritional intake and sex of offspring influenced (P ≤ 0.09) BW gain from d 57 to 180. Although maternal nutritional intake did not influence (P ≥ 0.35) female lamb BW gain, male lambs from RES-fed ewes were lighter (P ≤ 0.09) than those from CON-fed ewes until d 162. By d 180, male lambs from RES- and HI-fed ewes were lighter (P ≤ 0.09) than those from CON-fed ewes. In a subset of lambs used in a feed efficiency study, namely, those born to ASe ewes, HI maternal nutritional intake decreased (P ≤ 0.09) ADG and G:F compared with lambs born to RES- and CON-fed ewes, which did not differ (P ≥ 0.60). Conversely, when lambs were born to HSe ewes, HI maternal nutritional intake increased (P ≤ 0.01) ADG and G:F compared with CON, with RES being intermediate. Moreover, lambs born to ASe-HI ewes had decreased (P < 0.01) ADG and G:F compared with lambs born to HSe-HI ewes. Furthermore, male lambs had a greater (P < 0.01) G:F than female lambs. Maternal diet did not affect (P ≥ 0.11) N retention in male lambs. These data indicate that maternal nutrition during gestation and sex of the offspring alter postnatal growth and efficiency of growth in offspring despite similar postnatal management.
Bayoglu Tekin, Yesim; Guvendag Guven, Emine Seda; Mete Ural, Ulku; Yazici, Zihni Acar; Kirbas, Aynur; Kir Sahin, Figen
2016-01-01
The aim of this study was to evaluate maternal neutrophil gelatinase-asssociated lipocalin (NGAL) levels and fetal renal artery (fRA) Doppler flow indices in pregnant women fasting in Ramadan in respect of dehydration in long hot summer days as a marker of hypoperfusion and early renal injury. A cross-sectional observational study was carried out at a University Hospital. Fasting pregnant women and non-fasting age, gravidity and gestational age-matched women were evaluated for hematologic, blood biochemistry and urine parameters in the first and fourth weeks of the Ramadan. Umbilical artery and fRA Doppler flows were studied in each evaluation. Blood urea nitrogen, potassium and hematocrit levels, blood and urine NGAL levels were significantly higher, and fRA Doppler indices increased in fasting women (p < 0.05) during the second visit in the last week of the Ramadan, while non-fasting women had no significant alterations in each evaluation (p > 0.05). Adequate maternal vascular volume is essential for the maintenance of healthy pregnancy. Fasting during the long and hot summer days leads to fluid deprivation and dehydration which was found to be related to subclinical maternal renal dysfunction and increased fRA Doppler indices.
Lamichhane, Kiran; Garcia, Santos N; Huggett, Duane B; DeAngelis, Donald L; La Point, Thomas W
2013-04-01
Trace quantities of pharmaceuticals are continuously being discharged into the environment through domestic and industrial wastewater effluents, causing concern among scientists and regulators regarding potential long-term impacts on aquatic ecosystems. These compounds and their metabolites are constantly interacting with organisms at various life-cycle stages and may differentially influence the development of embryonic, larval, juvenile, and adult stages. To understand the possible cumulative effects of exposure to carbamazepine (CBZ), a multigenerational approach was taken in which survival, reproduction, respiration, growth, brood size, and biomass of Ceriodaphnia dubia were assessed at sublethal concentrations over the course of three successive generations. CBZ exposure significantly decreased fecundity at 196.7 μg/L in the F0 and F1 generations over 2 weeks and acclimatized at 264.6 μg/L in the F2 generation. Similarly, a significant decrease of neonate dry weight was observed at the 196.7 μg/L CBZ treatment in the F1 generation, and it acclimatized at 264.6 μg/L treatment level in the F2 generation. Median time to first brood release was significantly delayed at 264.6 μg/L in the F2 generation, indicating slower maturation. Results over three successive generations are not different than what one would obtain by testing simply the F0 generation. Furthermore, the effects measured were observed at concentrations two orders of magnitude higher than are environmentally relevant, and it is unlikely that CBZ poses a substantial risk to the environment regarding the end points measured in this study. However, additional research through laboratory and field multigenerational studies may be required to understand the overall risk of CBZ to other nontarget organisms.
Carcass composition of market weight pigs subjected to heat stress in utero and during finishing.
Cruzen, S M; Boddicker, R L; Graves, K L; Johnson, T P; Arkfeld, E K; Baumgard, L H; Ross, J W; Safranski, T J; Lucy, M C; Lonergan, S M
2015-05-01
Objectives were to investigate the effects of prolonged gestational and/or postnatal heat stress on performance and carcass composition of market weight pigs. Pregnant gilts were exposed to gestational heat stress (GHS, 28°C to 34°C, diurnal) or thermal neutral (18°C to 22°C, diurnal) conditions during the entire gestation or during the first or second half of gestation. At 14 wk of age (58 ± 5 kg), barrows were housed in heat stress (32°C, HS) or thermal neutral (21°C, TN) conditions. Feed intake and BW were recorded weekly, and body temperature parameters were monitored twice weekly until slaughter (109 ± 5 kg). Organs were removed and weighed, and loin eye area (LEA) and back fat thickness (BF) were measured after carcass chilling. Carcass sides were separated into lean, separable fat, bone, and skin components and were weighed. Moisture, lipid, and protein content were determined in the LM at the 10th rib. Data were analyzed using a split plot with random effect of dam nested within gestational treatment. Carcass measurements included HCW as a covariate to control for weight. Planned orthogonal contrast statements were used to evaluate the overall effect of GHS in the first half, second half, or any part of gestation. Gestational heat stress did not alter postnatal performance or most body temperature parameters (P > 0.10). However, ADFI in the finishing period was increased (P < 0.05) in response to GHS, particularly in pigs receiving GHS in the first half of gestation. Gestational heat stress during the first half of gestation decreased head weight as a percent of BW (P = 0.02), whereas GHS in the second half of gestation decreased bone weight as a percent of BW (P = 0.02). Heat stress reduced ADG, BW, and HCW (P < 0.0001). Lean tissue was increased in HS pigs on both a weight and percentage basis (P < 0.0001), but LEA was similar to TN carcasses (P = 0.38). Carcasses from HS barrows also had less carcass separable fat (P < 0.01) and tended to have less BF (P = 0.06) compared with those from TN barrows, even after controlling for HCW. However, percent intramuscular fat did not differ between treatments (P = 0.48). The LM from HS carcasses had a greater moisture to protein ratio (P = 0.04). HS barrows also had decreased heart (P < 0.001) and kidney (P < 0.0001) as a percent of BW compared with TN pigs. In summary, GHS may affect head and bone development, subsequently affecting carcass composition. Chronic HS during finishing results in longer times to reach market weight and a leaner carcass once market weight is achieved.
Lavretsky, Philip; Peters, Jeffrey L; Winker, Kevin; Bahn, Volker; Kulikova, Irina; Zhuravlev, Yuri N; Wilson, Robert E; Barger, Chris; Gurney, Kirsty; McCracken, Kevin G
2016-02-01
Estimating the frequency of hybridization is important to understand its evolutionary consequences and its effects on conservation efforts. In this study, we examined the extent of hybridization in two sister species of ducks that hybridize. We used mitochondrial control region sequences and 3589 double-digest restriction-associated DNA sequences (ddRADseq) to identify admixture between wild lesser scaup (Aythya affinis) and greater scaup (A. marila). Among 111 individuals, we found one introgressed mitochondrial DNA haplotype in lesser scaup and four in greater scaup. Likewise, based on the site-frequency spectrum from autosomal DNA, gene flow was asymmetrical, with higher rates from lesser into greater scaup. However, using ddRADseq nuclear DNA, all individuals were assigned to their respective species with >0.95 posterior assignment probability. To examine the power for detecting admixture, we simulated a breeding experiment in which empirical data were used to create F1 hybrids and nine generations (F2-F10) of backcrossing. F1 hybrids and F2, F3 and most F4 backcrosses were clearly distinguishable from pure individuals, but evidence of admixed histories was effectively lost after the fourth generation. Thus, we conclude that low interspecific assignment probabilities (0.011-0.043) for two lesser and nineteen greater scaup were consistent with admixed histories beyond the F3 generation. These results indicate that the propensity of these species to hybridize in the wild is low and largely asymmetric. When applied to species-specific cases, our approach offers powerful utility for examining concerns of hybridization in conservation efforts, especially for determining the generational time until admixed histories are effectively lost through backcrossing. © 2015 John Wiley & Sons Ltd.
Ayton, Jennifer; Hansen, Emily; Quinn, Stephen; Nelson, Mark
2012-11-26
To investigate and examine the factors associated with initiation of, and exclusive breastfeeding at hospital discharge of, late preterm (34 0/7 - 36 6/7 weeks) compared to 37 week gestation (37 0/7 - 37 6/7 week) mother and baby pairs. A retrospective population-based cohort study using a Perinatal National Minimum Data Set and clinical medical records review, at the Royal Hobart Hospital, Tasmania, Australia in 2006. Late preterm and 37 week gestation infants had low rates of initiation of breastfeeding within one hour of birth, 31 (21.1%) and 61 (41.5%) respectively. After multiple regression analysis, late preterm infants were less likely to initiate breastfeeding within one hour of birth (OR 0.3 95% CI 0.1, 0.7 p = 0.009) and were less likely to be discharged exclusively breastfeeding from hospital (OR 0.4 95% CI 0.1, 1.0 p = 0.04) compared to 37 week gestation infants. A late preterm birth is predictive of breastfeeding failure, with late preterm infants at greater risk of not initiating breastfeeding and/or exclusively breastfeeding at hospital discharge, compared with those infants born at 37 weeks gestation. Stratifying breastfeeding outcomes by gestational age groups may help to identify those sub-populations at greatest risk of premature cessation of breastfeeding.
NASA Astrophysics Data System (ADS)
Moura, André L.; Carreño, Sandra J. M.; Pincheira, Pablo I. R.; Fabris, Zanine V.; Maia, Lauro J. Q.; Gomes, Anderson S. L.; de Araújo, Cid B.
2016-06-01
Ultraviolet and blue light were obtained by nonlinear frequency conversion in a random laser (RL) based on Nd0.10Y0.90Al3(BO3)4 nanocrystalline powder. RL operation at 1062 nm, due to the 4F3/2 → 4I11/2 transition of neodymium ions (Nd3+), was achieved by exciting the Nd3+ with a tunable beam from 680 to 920 nm covering the ground state absorption transitions to the 4F9/2, (4F7/2,4S3/2), (4F5/2,2H9/2), and 4F3/2 states. Light from 340 to 460 nm was obtained via the second-harmonic generation of the excitation beam while tunable blue light, from 417 to 486 nm, was generated by self-sum-frequency mixing between the excitation beam and the RL emission.
Bouthoorn, Selma H.; van Lenthe, Frank J.; Hokken-Koelega, Anita C. S.; Moll, Henriëtte A.; Tiemeier, Henning; Hofman, Albert; Mackenbach, Johan P.; Jaddoe, Vincent W. V.; Raat, Hein
2012-01-01
Objective Head circumference (HC) reflect growth and development of the brain in early childhood. It is unknown whether socioeconomic differences in HC are present in early childhood. Therefore, we investigated the association between socioeconomic position (SEP) and HC in early childhood, and potential underlying factors. Methods The study focused on Dutch children born between April 2002 and January 2006 who participated in The Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Maternal educational level was used as indicator of SEP. HC measures were concentrated around 1, 3, 6 and 11 months. Associations and explanatory factors were investigated using linear regression analysis, adjusted for potential mediators. Results The study included 3383 children. At 1, 3 and 6 months of age, children of mothers with a low education had a smaller HC than those with a high education (difference at 1 month: −0.42 SD; 95% CI: −0.54,−0.30; at 3 months: −0.27 SD; 95% CI −0.40,−0.15; and at 6 months: −0.13 SD; 95% CI −0.24,−0.02). Child’s length and weight could only partially explain the smaller HC at 1 and 3 months of age. At 6 months, birth weight, gestational age and parental height explained the HC differences. At 11 months, no HC differences were found. Conclusion Educational inequalities in HC in the first 6 months of life can be mainly explained by pregnancy-related factors, such as birth weight and gestational age. These findings further support public health policies to prevent negative birth outcomes in lower socioeconomic groups. PMID:22768125
Impact of Antenatal Steroids on Intraventricular Hemorrhage in Very Low Birth Weight Infants
Wei, Julia C.; Catalano, Ralph; Profit, Jochen; Gould, Jeffrey B.; Lee, Henry C.
2016-01-01
Objective To determine the association between antenatal steroids administration and intraventricular hemorrhage rates. Methods We used cross-sectional data from the California Perinatal Quality Care Collaborative during 2007-2013 for infants ≤ 32 weeks gestational age. Using multivariable logistic regression, we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by gestational age. Results In 25,979 very low birth weight infants, antenatal steroid use was associated with a reduction in incidence of any grade of intraventricular hemorrhage (odds ratio = 0.51, 95% confidence interval: 0.45, 0.58) and a reduction in incidence of severe intraventricular hemorrhage (odds ratio = 0.62, 95% confidence interval: 0.57, 0.67). This association was seen across gestational ages ranging from 22 to 29 weeks. Conclusions While current guidelines recommend coverage for preterm birth at 24 to 34 weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even before 24 weeks of gestational age. PMID:27010109
Weerwind, Patrick W; Lindhout, Theo; Caberg, Nicole EH; de Jong, Dick S
2003-01-01
Background In spite of using heparin-coated extracorporeal circuits, cardiopulmonary bypass (CPB) is still associated with an extensive thrombin generation, which is only partially suppressed by the use of high dosages of heparin. Recent studies have focused on the origins of this thrombotic stimulus and the possible role of retransfused suctioned blood from the thoracic cavities on the activation of the extrinsic coagulation pathway. The present study was designed to find during CPB an association between retransfusion of suctioned blood from the pericardium and pleural space, containing activated factor VIIa and systemic thrombin generation. Methods Blood samples taken from 12 consenting patients who had elective cardiac surgery were assayed for plasma factor VIIa, prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin (TAT) concentrations. Blood aspirated from the pericardium and pleural space was collected separately, assayed for F1+2, TAT, and factor VIIa and retransfused to the patient after the aorta occlusion. Results After systemic heparinization and during CPB thrombin generation was minimal, as indicated by the lower than base line plasma levels of F1+2, and TAT after correction for hemodilution. In contrast, blood aspirated from the thoracic cavities had significantly higher levels of factor VIIa, F1+2, and TAT compared to the simultaneous samples from the blood circulation (P < 0.05). Furthermore, after retransfusion of the suctioned blood (range, 200–1600 mL) circulating levels of F1+2, and TAT rose significantly from 1.6 to 2.9 nmol/L (P = 0.002) and from 5.1 to 37.5 μg/L (P = 0.01), respectively. The increase in both F1+2, and TAT levels correlated significantly with the amount of retransfused suctioned blood (r = 0.68, P = 0.021 and r = 0.90, P = 0.001, respectively). However, the circulating factor VIIa levels did not correlate with TAT and F1+2 levels. Conclusions These data suggest that blood aspirated from the thoracic cavities during CPB is highly thrombogenic. Retransfusion of this blood may, therefore, promote further systemic thrombin generation during CPB. PMID:12904260
Brewer, H B
1979-01-01
Lebistes reticulatus (guppy) was subjected to a continuous treatment of a 500-G homogeneous magnetic field within a specially designed horseshoe magnet encompassing a small aquarium. The experiment was carried through several generations with the following results: in the first generation, the brood size was normal but the gestation period was reduced by 30%; the second generation had an average reduction of spawn rate of 50% and a reduction of the gestation period of 30%; and in the third generation, reproduction was completely inhibited as long as the fish remained within the magnetic field. Images FIGURE 5 FIGURE 6 PMID:262552
Gybel-Brask, Dorte; Høgdall, Estrid; Johansen, Julia; Christensen, Ib Jarle; Skibsted, Lillian
2014-08-01
To test if serum YKL-40 is increased in women developing preeclampsia or small-for-gestational age fetuses. We also assessed the association between uterine artery pulsatility index, notching and serum YKL-40 levels. Prospective cohort study. A primary referral unit for obstetric ultrasound. A total of 1214 unselected pregnant women enrolled at nuchal translucency examination between 11(+3) and 13(+6) weeks of gestation. All women had ultrasound and blood sample collection at the nuchal translucency scan, a 20-week malformation scan and 25-week and 32-week fetal growth examinations. Uterine artery Doppler was assessed and outcome was registered from medical records. Preeclampsia, hypertension, small-for-gestational age. Serum YKL-40 was associated with increasing maternal age (p < 0.0001), body mass index (p = 0.0002), primiparity (p = 0.0003), and hypertension (p = 0.015). Serum YKL-40 increased from 12 to 20 weeks and decreased from 20-25 and 25-32 weeks of gestation. No association was found between preeclampsia and serum YKL-40. Small-for-gestational-age at birth was significantly associated with a 5.4% increase in serum YKL-40 at 32 weeks of gestation (95% CI 1.5-9.3, p = 0.005). An association was found between uterine artery pulsatility index at 32 weeks and small-for-gestational age (p = 0.0015) but not between YKL-40 and uterine artery notching (p = 0.83). Serum YKL-40 was not associated with preeclampsia. Increasing serum YKL-40 was related to maternal age, body mass index and small-for-gestational age and may reflect an exaggerated inflammatory response. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.
Santos, R M C; do Rêgo, E R; Borém, A; Nascimento, M F; Nascimento, N F F; Finger, F L; Rêgo, M M
2014-10-31
Two accessions of ornamental pepper Capsicum annuum L., differing in most of the characters studied, were crossed, resulting in the F1 generation, and the F2 generation was obtained through self-fertilization of the F1 generation. The backcross generations RC1 and RC2 were obtained through crossing between F1 and the parents P1 and P2, respectively. Morpho-agronomic characterization was performed based on the 19 quantitative descriptors of Capsicum. The data obtained were subjected to generation analysis, in which the means and additive variance (σa(2)), variance due to dominance deviation (σd(2)), phenotypic variance (σf(2)), genetic variance (σg(2)) and environmental variance (σm(2)) were calculated. For the full model, we estimated the mean effects of all possible homozygotes, additives, dominants, and epistatics: additive-additive, additive-dominant, and dominant-dominant. For the additive-dominant model, we estimated the additive effects, dominant effects and mean effects of possible homozygotes. The character fruit dry matter had the lowest value for broad sense heritability (0.42), and the highest values were found for fresh matter and fruit weight, 0.91 and 0.92, respectively. The lowest value for narrow sense heritability was for the minor fruit diameter character (0.33), and the highest values were found for seed yield per fruit and fresh matter, 0.87 and 0.84, respectively. The additive-dominant model explained only the variation found in plant height, canopy width, stem length, corolla diameter, leaf width, and pedicel length, but in the other characters, the epistatic effects showed significant values.
Factors predicting labor induction success: a critical analysis.
Crane, Joan M G
2006-09-01
Because of the risk of failed induction of labor, a variety of maternal and fetal factors as well as screening tests have been suggested to predict labor induction success. Certain characteristics of the woman (including parity, age, weight, height and body mass index), and of the fetus (including birth weight and gestational age) are associated with the success of labor induction; with parous, young women who are taller and lower weight having a higher rate of induction success. Fetuses with a lower birth weight or increased gestational age are also associated with increased induction success. The condition of the cervix at the start of induction is an important predictor, with the modified Bishop score being a widely used scoring system. The most important element of the Bishop score is dilatation. Other predictors, including transvaginal ultrasound (TVUS) and biochemical markers [including fetal fibronectin (fFN)] have been suggested. Meta-analyses of studies identified from MEDLINE, PubMed, and EMBASE and published from 1990 to October 2005 were performed evaluating the use of TVUS and fFN in predicting labor induction success in women at term with singleton gestations. Both TVUS and Bishop score predicted successful induction [likelihood ratio (LR)=1.82, 95% confidence interval (CI)=1.51-2.20 and LR=2.10, 95%CI=1.67-2.64, respectively]. As well, fFN and Bishop score predicted successful induction (LR=1.49, 95%CI=1.20-1.85, and LR=2.62, 95%CI=1.88-3.64, respectively). Although TVUS and fFN predicted successful labor induction, neither has been shown to be superior to Bishop score. Further research is needed to evaluate these potential predictors and insulin-like growth factor binding protein-1 (IGFBP-1), another potential biochemical marker.
Podestà, Marina; Bruschettini, Matteo; Cossu, Claudia; Sabatini, Federica; Dagnino, Monica; Romantsik, Olga; Spaggiari, Grazia Maria; Ramenghi, Luca Antonio; Frassoni, Francesco
2015-01-01
Background Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. Methods and Results Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15–4.8) vs 0.3% (0.032–2.23) p = 0.0001 and in neonates <32 weeks of gestational age (GA) compared to those ≥32 wks GA: 0.95% (range 0.18–4.8) and 0.36% (0.15–3.2) respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP) did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL) resulted higher compared to term (p = 0.004) and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168). Conclusions We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144)The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies. PMID:26417990
Podestà, Marina; Bruschettini, Matteo; Cossu, Claudia; Sabatini, Federica; Dagnino, Monica; Romantsik, Olga; Spaggiari, Grazia Maria; Ramenghi, Luca Antonio; Frassoni, Francesco
2015-01-01
Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15-4.8) vs 0.3% (0.032-2.23) p = 0.0001 and in neonates <32 weeks of gestational age (GA) compared to those ≥32 wks GA: 0.95% (range 0.18-4.8) and 0.36% (0.15-3.2) respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP) did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL) resulted higher compared to term (p = 0.004) and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168). We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144)The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies.
fMRI Evidence for Dorsal Stream Processing Abnormality in Adults Born Preterm
ERIC Educational Resources Information Center
Chaminade, Thierry; Leutcher, Russia Ha-Vinh; Millet, Veronique; Deruelle, Christine
2013-01-01
We investigated the consequences of premature birth on the functional neuroanatomy of the dorsal stream of visual processing. fMRI was recorded while sixteen healthy participants, 8 (two men) adults (19 years 6 months old, SD 10 months) born premature (mean gestational age 30 weeks), referred to as Premas, and 8 (two men) matched controls (20…
NASA Astrophysics Data System (ADS)
Hild, Kenneth E.; Alleva, Giovanna; Nagarajan, Srikantan; Comani, Silvia
2007-01-01
In this study we compare the performance of six independent components analysis (ICA) algorithms on 16 real fetal magnetocardiographic (fMCG) datasets for the application of extracting the fetal cardiac signal. We also compare the extraction results for real data with the results previously obtained for synthetic data. The six ICA algorithms are FastICA, CubICA, JADE, Infomax, MRMI-SIG and TDSEP. The results obtained using real fMCG data indicate that the FastICA method consistently outperforms the others in regard to separation quality and that the performance of an ICA method that uses temporal information suffers in the presence of noise. These two results confirm the previous results obtained using synthetic fMCG data. There were also two notable differences between the studies based on real and synthetic data. The differences are that all six ICA algorithms are independent of gestational age and sensor dimensionality for synthetic data, but depend on gestational age and sensor dimensionality for real data. It is possible to explain these differences by assuming that the number of point sources needed to completely explain the data is larger than the dimensionality used in the ICA extraction.
Wang, Chen; Wei, Yumei; Zhang, Xiaoming; Zhang, Yue; Xu, Qianqian; Sun, Yiying; Su, Shiping; Zhang, Li; Liu, Chunhong; Feng, Yaru; Shou, Chong; Guelfi, Kym J; Newnham, John P; Yang, Huixia
2017-04-01
Obesity and being overweight are becoming epidemic, and indeed, the proportion of such women of reproductive age has increased in recent times. Being overweight or obese prior to pregnancy is a risk factor for gestational diabetes mellitus, and increases the risk of adverse pregnancy outcome for both mothers and their offspring. Furthermore, the combination of gestational diabetes mellitus with obesity/overweight status may increase the risk of adverse pregnancy outcome attributable to either factor alone. Regular exercise has the potential to reduce the risk of developing gestational diabetes mellitus and can be used during pregnancy; however, its efficacy remain controversial. At present, most exercise training interventions are implemented on Caucasian women and in the second trimester, and there is a paucity of studies focusing on overweight/obese pregnant women. We sought to test the efficacy of regular exercise in early pregnancy to prevent gestational diabetes mellitus in Chinese overweight/obese pregnant women. This was a prospective randomized clinical trial in which nonsmoking women age >18 years with a singleton pregnancy who met the criteria for overweight/obese status (body mass index 24≤28 kg/m 2 ) and had an uncomplicated pregnancy at <12 +6 weeks of gestation were randomly allocated to either exercise or a control group. Patients did not have contraindications to physical activity. Patients allocated to the exercise group were assigned to exercise 3 times per week (at least 30 min/session with a rating of perceived exertion between 12-14) via a cycling program begun within 3 days of randomization until 37 weeks of gestation. Those in the control group continued their usual daily activities. Both groups received standard prenatal care, albeit without special dietary recommendations. The primary outcome was incidence of gestational diabetes mellitus. From December 2014 through July 2016, 300 singleton women at 10 weeks' gestational age and with a mean prepregnancy body mass index of 26.78 ± 2.75 kg/m 2 were recruited. They were randomized into an exercise group (n = 150) or a control group (n = 150). In all, 39 (26.0%) and 38 (25.3%) participants were obese in each group, respectively. Women randomized to the exercise group had a significantly lower incidence of gestational diabetes mellitus (22.0% vs 40.6%; P < .001). These women also had significantly less gestational weight gain by 25 gestational weeks (4.08 ± 3.02 vs 5.92 ± 2.58 kg; P < .001) and at the end of pregnancy (8.38 ± 3.65 vs 10.47 ± 3.33 kg; P < .001), and reduced insulin resistance levels (2.92 ± 1.27 vs 3.38 ± 2.00; P = .033) at 25 gestational weeks. Other secondary outcomes, including gestational weight gain between 25-36 gestational weeks (4.55 ± 2.06 vs 4.59 ± 2.31 kg; P = .9), insulin resistance levels at 36 gestational weeks (3.56 ± 1.89 vs 4.07 ± 2.33; P = .1), hypertensive disorders of pregnancy (17.0% vs 19.3%; odds ratio, 0.854; 95% confidence interval, 0.434-2.683; P = .6), cesarean delivery (except for scar uterus) (29.5% vs 32.5%; odds ratio, 0.869; 95% confidence interval, 0.494-1.529; P = .6), mean gestational age at birth (39.02 ± 1.29 vs 38.89 ± 1.37 weeks' gestation; P = .5); preterm birth (2.7% vs 4.4%, odds ratio, 0.600; 95% confidence interval, 0.140-2.573; P = .5), macrosomia (defined as birthweight >4000 g) (6.3% vs 9.6%; odds ratio, 0.624; 95% confidence interval, 0.233-1.673; P = .3), and large-for-gestational-age infants (14.3% vs 22.8%; odds ratio, 0.564; 95% confidence interval, 0.284-1.121; P = .1) were also lower in the exercise group compared to the control group, but without significant difference. However, infants born to women following the exercise intervention had a significantly lower birthweight compared with those born to women allocated to the control group (3345.27 ± 397.07 vs 3457.46 ± 446.00 g; P = .049). Cycling exercise initiated early in pregnancy and performed at least 30 minutes, 3 times per week, is associated with a significant reduction in the frequency of gestational diabetes mellitus in overweight/obese pregnant women. And this effect is very relevant to that exercise at the beginning of pregnancy decreases the gestational weight gain before the mid-second trimester. Furthermore, there was no evidence that the exercise prescribed in this study increased the risk of preterm birth or reduced the mean gestational age at birth. Copyright © 2017 Elsevier Inc. All rights reserved.
Nutritional status of women with gestational hypertension compared with normal pregnant women.
Kazemian, Elham; Dorosty-Motlagh, Ahmad-Reza; Sotoudeh, Gity; Eshraghian, Mohammad-Reza; Ansary, Samaneh; Omidian, Mahsa
2013-05-01
Some evidence indicated the role of nutrition in the development of hypertensive disorders of pregnancy. This case-control study was conducted on 113 women with gestational hypertension and 150 healthy pregnant women referred to Shahid Akbarabadi Hospital in Tehran. A demographic questionnaire was filled out for all participants. A validated semi-quantitative food frequency questionnaire was used to assess the dietary intakes of the study subjects. All nutrients were adjusted for total energy intake. Logistic regression was used to find the association of energy and nutrient intakes with gestational hypertension. We found that higher intakes of energy (OR, 1.33; 95% CI: 1.17-1.52), monounsaturated fatty acids (OR, 1.34; 95% CI: 1.03-1.74) and polyunsaturated fatty acids (OR, 1.26; 95% CI: 1.00-1.54) were positively associated with the risk of gestational hypertension after adjustment for confounders. We also observed decreased odds of gestational hypertension with increased intakes of vitamin C (OR, 0.87; 95% CI: 0.81-0.94), potassium (OR, 0.45; 95% CI: 0.28-0.71) and magnesium (OR, 0.68; 95% CI: 0.51-0.89). This study demonstrates higher intakes of energy, monounsaturated fatty acids and polyunsaturated fatty acids as well as lower intakes of vitamin C, potassium and magnesium are positively correlated with the risk of developing gestational hypertension.
Ghassabian, Akhgar; Sundaram, Rajeshwari; Wylie, Amanda; Bell, Erin; Bello, Scott C.; Yeung, Edwina
2015-01-01
Aims We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months. Methods We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children’s motor milestone achievement at 4, 8, 12, 18, and 24 months of age. Results After adjustment for covariates (including prepregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support [Hazard Ratio (HR)=0.84, 95%CI:0.75-0.93), walking with assistance (HR=0.88, 95%CI:0.77-0.98) and walking alone (HR=0.88, 95%CI:0.77-0.99) than children of women with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birth weight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors. Interpretation Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity. PMID:26502927
Minsart, Anne-Frederique; N'guyen, Thai-Son Pierre; Dimtsu, Hirut; Ratsimandresy, Rachel; Dada, Fouad; Ali Hadji, Rachid
2014-09-01
The International Association of Diabetes and Pregnancy Study Groups released new recommendations on screening methods and diagnostic criteria for gestational diabetes. The main objectives of the present study were to analyze characteristics of mothers who underwent the new screening test, and to assess the prevalence of gestational diabetes and related pregnancy complications such as the 5-minute Apgar score <7, in a urban maternity clinic in Djibouti. The effect of treating gestational diabetes was also evaluated. Totally, 231 mothers underwent the new screening test, and 106 were diagnosed as having gestational diabetes (45.9%). Mothers with gestational diabetes had an excess risk of low Apgar scores, even after adjustment for socio-economic and medical covariates, with an odds ratio of 6.34 (1.77-22.66), p value <0.005. Only 46.2% of mothers with gestational diabetes followed the recommendations regarding treatment. Among these patients, 18.6% of infants from untreated mothers had a 5-minute Apgar score <7, compared to 3.9% infants from treated mothers (p value = 0.017). After adjustment, untreated mothers still had a high excess risk of low Apgar scores, although non-significant, with an odds ratio of 4.67 (0.78-27.87), p value = 0.09. In conclusion, gestational diabetes is highly prevalent in Djibouti and is related to low Apgar scores.
Norman, Wendy V; Bergunder, Jeannette; Eccles, Lisa
2011-03-01
We sought to quantify the accuracy of estimating gestational age by reported last menstrual period among women seeking surgical abortion. We observed that women seeking surgical abortion underestimated their gestational age when making the appointment, leading to poor allocation of resources. This tendency to underestimate has not previously been reported and differs from the accurate dating reported among women choosing either medical abortion or continuation of the pregnancy. We performed a retrospective review of randomly selected medical records for women with abortions scheduled at 9 to 20 weeks' gestation (n = 415) at two clinics in Vancouver between 2002 and 2008. The mean gestational age calculated by menstrual dates (14.3, SD 3.9) was 1.2 (95% CI 0.9 to 1.4) weeks less than that calculated by ultrasound (15.5, SD 3.4) (P < 0.001). Greater gestational age was associated with a larger discrepancy (r = 0.192, P < 0.001). Variables other than gestational age (maternal age, parity, previous abortions, illicit drug use, and contraceptive method at conception) were not significant predictors of inaccurate menstrual dating. Women seeking surgical abortion for pregnancies of 9 to 20 weeks underreport gestational age by an average of 1.2 weeks using menstrual dating. We found that women who intended to continue with their pregnancy overestimated their gestational age, those seeking very early abortion estimated most accurately, and those seeking surgical abortion at more than nine weeks had a clinically significant underestimation of their gestational age. Clinicians referring and counselling women who are considering surgical abortion must facilitate timely access to clinical or ultrasound dating of their pregnancy.
Bowker, S L; Savu, A; Yeung, R O; Johnson, J A; Ryan, E A; Kaul, P
2017-09-01
To examine patterns of use of different glycaemic control agents for treating gestational diabetes mellitus. This was a large, retrospective, population-based cohort study of pregnant women with gestational diabetes from Alberta, Canada. We linked data from the Alberta Vital Statistics - Birth database with administrative claims data. Alberta Vital Statistics - Birth data were used to identify births that occurred between 1 January 2009 and 31 December 2014. We used International Classification of Diseases version 9/10 codes to identify women with gestational diabetes, and we excluded women with pre-existing diabetes. Our cohort consisted of 16 857 women with gestational diabetes, with a total of 18 761 birth events between 2009 and 2014. Over the study period, the proportion of women with gestational diabetes who were treated with glycaemic control therapies increased from 25.0% to 31.4% (P<0.0001). The number of pregnancies treated with insulin only increased (from 23.6% to 28.3%; P<0.0001), as did the number treated with metformin, +/- insulin (from 1.4% to 3.2%; P<0.0001). Rates of large-for-gestational-age infants were significantly higher among pregnancies treated with insulin only (17%) or metformin (16.5%) than among pregnancies that did not receive any pharmacological treatment (12.8%). Our findings show increasing use of insulin and metformin in women with gestational diabetes. Rates of large-for-gestational-age infants were similar among pregnant women receiving either pharmacological treatment, and higher than among pregnant women who did not receive any pharmacological treatment. Future research should explore the long-term outcomes and safety of metformin as an alternative for treating gestational diabetes. © 2017 Diabetes UK.
Nomura, Roseli Mieko Yamamoto; Paiva, Letícia Vieira; Costa, Verbênia Nunes; Liao, Adolfo Wenjaw; Zugaib, Marcelo
2012-03-01
To analyze the influence of maternal nutritional status, weight gain and energy consumption on fetal growth in high-risk pregnancies. A prospective study from August 2009 to August 2010 with the following inclusion criteria: puerperae up to the 5th postpartum day; high-risk singleton pregnancies (characterized by medical or obstetrical complications during pregnancy); live fetus at labor onset; delivery at the institution; maternal weight measured on the day of delivery, and presence of medical and/or obstetrical complications characterizing pregnancy as high-risk. Nutritional status was assessed by pregestational body mass index and body mass index in late pregnancy, and the patients were classified as: underweight, adequate, overweight and obese. A food frequency questionnaire was applied to evaluate energy consumption. We investigated maternal weight gain, delivery data and perinatal outcomes, as well as fetal growth based on the occurrence of small for gestational age and large for gestational age neonates. We included 374 women who were divided into three study groups according to newborn birth weight: adequate for gestational age (270 cases, 72.2%), small for gestational age (91 cases, 24.3%), and large for gestational age (13 cases, 3.5%). Univaried analysis showed that women with small for gestational age neonates had a significantly lower mean pregestational body mass index (23.5 kg/m², p<0.001), mean index during late pregnancy (27.7 kg/m², p<0.001), and a higher proportion of maternal underweight at the end of pregnancy (25.3%, p<0.001). Women with large for gestational age neonates had a significantly higher mean pregestational body mass index (29.1 kg/m², p<0.001), mean index during late pregnancy (34.3 kg/m², p<0.001), and a higher proportion of overweight (30.8%, p=0.02) and obesity (38.5%, p=0.02) according to pregestational body mass index, and obesity at the end of pregnancy (53.8%, p<0.001). Multivariate analysis revealed the index value during late pregnancy (OR=0.9; CI95% 0.8-0.9, p<0.001) and the presence of hypertension (OR=2.6; 95%CI 1.5-4.5, p<0.001) as independent factors for small for gestational age. Independent predictors of large for gestational age infant were the presence of diabetes mellitus (OR=20.2; 95%CI 5.3-76.8, p<0.001) and obesity according to body mass index during late pregnancy (OR=3.6; 95%CI 1.1-11.7, p=0.04). The maternal nutritional status at the end of pregnancy in high-risk pregnancies is independently associated with fetal growth, the body mass index during late pregnancy is a protective factor against small for gestational age neonates, and maternal obesity is a risk factor for large for gestational age neonates.
COMPLEMENT ACTIVATION FRAGMENT Bb IN EARLY PREGNANCY AND SPONTANEOUS PRETERM BIRTH
LYNCH, ANNE M.; GIBBS, RONALD S.; MURPHY, JAMES R.; BYERS, TIM; NEVILLE, MARGARET C.; GICLAS, PATRICIA C.; SALMON, JANE E.; VAN HECKE, TRISHA M; MICHAEL HOLERS, V.
2008-01-01
Objective To determine if an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks gestation or SPTB between 34 and 37 weeks gestation (late SPTB). Study Design Prospective study of 784 women enrolled at < 20 weeks gestation. Results Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks gestation and 25 (3.2%) a SPTB between 34 and 37 weeks gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks gestation as compared with women who had levels of Bb in the lower three quartiles (95% CI 1.5 to 14, P = 0.003). There was no association between Bb and late SPTB (RR= 0.8, 95% CI = 0.3 to 2). Conclusions A significant relationship was found between an elevated Bb in early pregnancy and SPTB < 34 weeks gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition. PMID:18928972
Boghossian, Nansi S; Do, Barbara T; Bell, Edward F; Dagle, John M; Brumbaugh, Jane E; Stoll, Barbara J; Vohr, Betty R; Das, Abhik; Shankaran, Seetha; Sanchez, Pablo J; Wyckoff, Myra H; Bethany Ball, M
2017-10-01
Optimal management of the patent ductus arteriosus (PDA) in preterm infants remains controversial. Therefore, studies identifying infants who are most likely to benefit from PDA treatment are needed. We sought to examine if significant intrauterine growth restriction, defined by birth weight z-score, reduces the efficacy of PDA closure with indomethacin or ibuprofen and thereby increases the need for surgical closure of PDA after pharmacologic treatment. We studied infants 23-28weeks' gestation born 2006-2013 at NICHD Neonatal Research Network centers. We examined the responses to PDA treatment with indomethacin and/or ibuprofen and whether the PDA was subsequently closed surgically. Logistic regression generated adjusted odds ratios (ORs) for the associations between the z-score groups (<-2, -2 to -0.5, and >-0.5) and PDA surgery following pharmacologic treatment. 5606 infants were diagnosed with PDA; 3587 (64.0%) received indomethacin or ibuprofen or both, and 909 (25.3%) underwent PDA surgery. Mothers of infants with PDA non-closure were less likely to have hypertension (19% vs. 28%). Infants with non-closure were more likely to be female (53% vs. 49%), have lower gestational age and birth weight and to develop sepsis (42% vs. 31%). Compared to infants with z-score>-0.5, PDA surgery was increased among infants with z-score -2 to -0.5 (OR=1.23; 95% CI 1.02-1.47) but not among infants with z-score<-2. Infants with birth weight z-score -2 to -0.5 are more likely than normally grown infants to require PDA surgery following pharmacologic treatment. Copyright © 2017 Elsevier B.V. All rights reserved.
Palacio, M; Cobo, T; Antolín, E; Ramirez, M; Cabrera, F; Mozo de Rosales, F; Bartha, J L; Juan, M; Martí, A; Oros, D; Rodríguez, À; Scazzocchio, E; Olivares, J M; Varea, S; Ríos, J; Gratacós, E
2016-11-01
To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. Multicentre, randomised, double-blind, placebo-controlled trial. Twelve tertiary care centres in Spain. A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. Maintenance progesterone in 258 women after arrested PTL showed no benefit. © 2016 Royal College of Obstetricians and Gynaecologists.
Consecutive repeat miscarriages are likely to occur in the same gestational period.
Yan, Junhao; Saravelos, Sotirios H; Ma, Ning; Ma, Caihong; Chen, Zi-Jiang; Li, Tin-Chiu
2012-06-01
This is a retrospective, observational study to determine how often repeated consecutive miscarriages occur consistently in the same gestational period, including 1589 miscarriages among 543 women with recurrent miscarriage. In women who had two miscarriages only, 49.17% of both miscarriages occurred in the same gestational period, which was significantly higher than the expected probability of 34.54% (P<0.01). The proportions of all miscarriages occurring in the same gestational period in women with three, four and five or more miscarriages were 28.72%, 19.44% and 18.60%, compared with the expected probabilities of 14.36% (P<0.01), 6.57% (P<0.05) and <3.15% (P<0.05). The proportions of miscarriages occurring consistently in the same gestational period are higher than the theoretical probabilities calculated for the whole population. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Blood and urine 8-iso-PGF2α levels in babies of different gestational ages.
Li, Sitao; Hao, Hu; Zhou, Ping; Gao, Ping Ming; Xiao, Xin
2014-01-01
We measured cord blood and urine 8-iso-prostaglandin F2α (8-iso-PGF2α) levels in babies of different gestational ages to determine lipid peroxidation status. Babies at gestational ages of 28-43 weeks were divided into group A (28-32 weeks), group B (33-36 weeks), group C (37-41 weeks), and group D (42-43 weeks). 8-iso-PGF2α in umbilical cord blood (UCB) at birth and urine at 6 hours after birth was and tested by ELISA. UCB and urine 8-iso-PGF2α levels in group C were 130.09 ± 31.73 pg/ml and 27.14 ± 6.73 pg/ml, respectively. UCB 8-iso-PGF2α levels in group A and B were 188.42 ± 59.34 pg/ml and 189.37 ± 68.46 pg/ml, and urine 8-iso-PGF2α were 32.14 ± 7.32 pg/ml and 30.46 ± 8.83 pg/ml, respectively. Blood and urine 8-iso-PGF2α levels in group D (post-term) were 252.01 ± 46.42 pg/ml and 44.00 ± 8.50 pg/ml. For all babies, UCB and urine iso-PGF2α levels were significantly correlated (r = 0.65, P < 0.01). We established blood and urine iso-PGF2α levels in normal full-term babies. Urine 8-iso-PGF2α levels may reflect the extent of lipid peroxidation in babies. In pre-term and post-term babies, there was evidence for increased lipid peroxidation.
Germplasm evaluation in beef cattle-cycle IV: birth and weaning traits.
Cundiff, L V; Gregory, K E; Koch, R M
1998-10-01
Gestation length, unassisted calving percentage, perinatal mortality, calf crop weaned (survival from birth to weaning), birth weight, and 200-d weaning weight of 2,597 calves born and 2,433 calves weaned are reported for F1 crosses resulting from matings of Angus, Hereford, Charolais, Gelbvieh, Pinzgauer, Shorthorn, Galloway, Longhorn, Nellore, Piedmontese, and Salers sires to Angus and Hereford dams (> or = 3 yr of age) in Cycle IV of the Germplasm Evaluation (GPE) Program at the U.S. Meat Animal Research Center. Hereford and Angus sires included 1) reference sires born from 1963 to 1971 used in previous cycles of the GPE Program, 2) sires born from 1982 to 1985 (1980s), and 3) sires born from 1983 to 1985 used in natural service clean-up matings. Effects of sire breed of calf were significant for gestation length, unassisted calving percentage, birth weight, and 200-d weaning weight. Gestation length was significantly longer for Nellore than for Charolais, Galloway, Longhorn, Piedmontese, and Salers, which were in turn longer than for Hereford-Angus and Shorthorn. Rankings for birth weight tended to be inversely related to those for calving ease, except for Shorthorn and Salers sires, which required low assistance relative to their heavy birth weights. Rankings for 200-d weight among AI-sired progeny were as follows: Charolais (231.3), Nellore (229.7), Salers (225.5), Shorthorn (223.8), 1980s Hereford-Angus (223.1), Piedmontese (220.0), Galloway (209.5), reference Hereford-Angus (210.1), and Longhorn (199.0); differences > or = 6.5 kg were significant.
J.N. King; M.J. Carson; G.R. Johnson
1998-01-01
Genetic parameters from a second generation (F2) disconnected diallel progeny test of the New Zealand radiata pine improvement programme are presented. Heritability estimates of growth and yield traits of 0.2 are similar to progeny test results of the previous generation (F1) generation tests. A trend of declining dominance...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Person, F.; Brun, J.
1974-01-01
Chemical mutagens as EMS, acriflavine, acridine, colchicine, nitrous acide and physical mutagens, such as X rays, have been used on the gonochoric mycophagous Nematode Aphelenchoides composticola. They show a nematicid activity due, to their toxicity on treated Nematodes and to the induction of lethal mutations affecting particularly early stages of gametogenesis. They produce abnormal strains dwarfs or giants (up to 25% of the population). Concentrations of chemical mutagens varying from 0.2 to 0.5% correspond to the optimal production of abnormalities. Similar results were obtained by irradiation near to 2000r. The action of the mutagens shows some differences: EMS and Xmore » rays generally produce dwarfs, whereas acriflavine, acridine, colchicine or nitrous acid induced only giants. Abnormal strains appear: in the F$sub 1$, generation by X rays or acridine treatments; in the F$sub 2$ or F$sub 3$ generation by acriflavine, colchicine, nitrous acid or EMS action. The abnormal strains could be either variants or mutants and from these we select: four dwarfs B, C, D, E, induced by EMS 0.5% for 24 hours appearing in the F$sub 3$ generation; or dwarf F induced by irradiation of 1500r appearing in the F$sub 1$ generation. All these selected mutants are autosomal recessive single factors D and C controlled by two alleles of the some locus. (FR)« less
2013-01-01
Background Wolbachia pipientis, a diverse group of α-proteobacteria, can alter arthropod host reproduction and confer a reproductive advantage to Wolbachia-infected females (cytoplasmic incompatibility (CI)). This advantage can alter host population genetics because Wolbachia-infected females produce more offspring with their own mitochondrial DNA (mtDNA) haplotypes than uninfected females. Thus, these host haplotypes become common or fixed (selective sweep). Although simulations suggest that for a CI-mediated sweep to occur, there must be a transient phase with repeated initial infections of multiple individual hosts by different Wolbachia strains, this has not been observed empirically. Wolbachia has been found in the tsetse fly, Glossina fuscipes fuscipes, but it is not limited to a single host haplotype, suggesting that CI did not impact its population structure. However, host population genetic differentiation could have been generated if multiple Wolbachia strains interacted in some populations. Here, we investigated Wolbachia genetic variation in G. f. fuscipes populations of known host genetic composition in Uganda. We tested for the presence of multiple Wolbachia strains using Multi-Locus Sequence Typing (MLST) and for an association between geographic region and host mtDNA haplotype using Wolbachia DNA sequence from a variable locus, groEL (heat shock protein 60). Results MLST demonstrated that some G. f. fuscipes carry Wolbachia strains from two lineages. GroEL revealed high levels of sequence diversity within and between individuals (Haplotype diversity = 0.945). We found Wolbachia associated with 26 host mtDNA haplotypes, an unprecedented result. We observed a geographical association of one Wolbachia lineage with southern host mtDNA haplotypes, but it was non-significant (p = 0.16). Though most Wolbachia-infected host haplotypes were those found in the contact region between host mtDNA groups, this association was non-significant (p = 0.17). Conclusions High Wolbachia sequence diversity and the association of Wolbachia with multiple host haplotypes suggest that different Wolbachia strains infected G. f. fuscipes multiple times independently. We suggest that these observations reflect a transient phase in Wolbachia evolution that is influenced by the long gestation and low reproductive output of tsetse. Although G. f. fuscipes is superinfected with Wolbachia, our data does not support that bidirectional CI has influenced host genetic diversity in Uganda. PMID:23384159
Bloom, Michael S; Neamtiu, Iulia A; Surdu, Simona; Pop, Cristian; Lupsa, Ioana Rodica; Anastasiu, Doru; Fitzgerald, Edward F; Gurzau, Eugen S
2014-10-13
Previous work suggests an increased risk for spontaneous pregnancy loss linked to high levels of inorganic arsenic (iAs) in drinking water sources (>10 μg/L). However, there has been little focus to date on the impact of low-moderate levels of iAs in drinking water (<10 μg/L). To address this data gap we conducted a hospital-based case-control study in Timis County, Romania. We recruited women with incident spontaneous pregnancy loss of 5-20 weeks completed gestation as cases (n = 150), and women with ongoing pregnancies matched by gestational age (±1 week) as controls (n = 150). Participants completed a physician-administered questionnaire and we collected water samples from residential drinking sources. We reconstructed residential drinking water exposure histories using questionnaire data weighted by iAs determined using hydride generation-atomic absorption spectrometry (HG-AAS). Logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) for associations between iAs exposure and loss, conditioned on gestational age and adjusted for maternal age, cigarette smoking, education and prenatal vitamin use. We explored potential interactions in a second set of models. Drinking water arsenic concentrations ranged from 0.0 to 175.1 μg/L, with median 0.4 μg/L and 90th%tile 9.4 μg/L. There were no statistically significant associations between loss and average or peak drinking water iAs concentrations (OR 0.98, 95% CI 0.96-1.01), or for daily iAs intake (OR 1.00, 95% CI 0.98-1.02). We detected modest evidence for an interaction between average iAs concentration and cigarette smoking during pregnancy (P = 0.057) and for daily iAs exposure and prenatal vitamin use (P = 0.085). These results suggest no increased risk for spontaneous pregnancy loss in association with low to moderate level drinking water iAs exposure. Though imprecise, our data also raise the possibility for increased risk among cigarette smokers. Given the low exposures overall, these data should reassure pregnant women and policy makers with regard to the potential effect of drinking water iAs on early pregnancy, though a larger more definitive study to investigate the potential risk increase in conjunction with cigarette smoking is merited.
Law, Graham R; Gilthorpe, Mark S; Secher, Anna L; Temple, Rosemary; Bilous, Rudolf; Mathiesen, Elisabeth R; Murphy, Helen R; Scott, Eleanor M
2017-04-01
This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA 1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA 1c measurements are applicable to pregnant women with diabetes. CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5-7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA 1c measure. In total, 688 average glucose-HbA 1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA 1c . There was a strong association between HbA 1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA 1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA 1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4-7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA 1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. The HbA 1c -average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care.
Raghavan, S; Zhang, W; Yang, I V; Lange, L A; Lange, E M; Fingerlin, T E; Dabelea, D
2017-12-01
To examine the extent to which offspring obesity-associated genetic risk explains the association between gestational diabetes mellitus and childhood adiposity. We studied 282 children aged 7-12 years who were enrolled in the Exploring Perinatal Outcomes in Children Study. A genetic risk score for BMI was calculated as the count of 91 established BMI-raising risk alleles. Multivariable linear and logistic regression models were used to estimate associations between the offspring genetic risk score and exposure to gestational diabetes and childhood adiposity (BMI and waist circumference), adjusting for clinical and demographic covariates. The contribution of offspring genetic risk to associations between maternal gestational diabetes and childhood outcomes was estimated by comparing the regression coefficients for the gestational diabetes variable in models with and without the genetic risk score. The offspring BMI genetic risk score was associated with childhood BMI (P = 0.006) and waist circumference (P = 0.02), and marginally with gestational diabetes (P = 0.05). Offspring BMI genetic risk did not contribute significantly to associations between gestational diabetes and childhood BMI [7.7% (95% CI -3.3, 18.8)] or waist circumference [5.8% (95% CI -3.1, 14.8); P = 0.2 for both]. Offspring obesity genetic risk does not explain a significant proportion of the association between gestational diabetes exposure and childhood adiposity. The association between gestational diabetes and childhood adiposity is probably explained through alternative pathways, including direct intrauterine effects or a shared postnatal environment. © 2017 Diabetes UK.
NASA Astrophysics Data System (ADS)
Philippe, François-Xavier; Laitat, Martine; Wavreille, José; Nicks, Baudouin; Cabaraux, Jean-François
2015-05-01
This study aims to measure under barn conditions the emissions of NH3, N2O, CH4 and CO2 associated with gestating sows (trial 1) and fattening pigs (trial 2) fed either a control diet (CTD) based on cereals or a high-fibre diet (HFD) based on sugar beet pulp (SBP). Three successive batches of 10 Belgian Landrace gestating sows were used for trial 1. Two successive batches of 24 Piétrain × Belgian Landrace fattening pigs were used for trial 2. Animals were kept on slatted floor. The gas emissions were measured by infrared photoacoustic detection and expressed per day and per livestock unit, equals to 500 kg body weight. Similar trends were observed for both animal types. With HFD, the NH3 emissions were reduced (27.2 vs. 36.5 g for the gestating sows, P < 0.001; 23.2 vs. 45.0 g for the fattening pigs, P < 0.001) but the CH4 emissions were increased (41.5 vs. 21.0 g for gestating sows, P < 0.001; 37.9 vs. 27.2 g for fattening pigs, P < 0.001). The fibre content of the diet had not significant impact on N2O emissions (around 1.4 g for gestating sows and 2.1 g for fattening pigs, P > 0.05), and on CO2 emissions (around 6.0 kg for gestating sows and 9.1 kg for fattening pigs, P > 0.05). Most of manure parameters did not statistically differ regarding the treatment. Reproductive performance and body condition of the sows were not affected by the diet. However, growth performance and carcass traits of the HFD-fed fattening pigs were deteriorated compared to CTD.
DHA supplementation and pregnancy outcomes123
Colombo, John; Gajewski, Byron J; Gustafson, Kathleen M; Mundy, David; Yeast, John; Georgieff, Michael K; Markley, Lisa A; Kerling, Elizabeth H; Shaddy, D Jill
2013-01-01
Background: Observational studies associate higher intakes of n−3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy with higher gestation duration and birth size. The results of randomized supplementation trials using various n−3 LCPUFA sources and amounts are mixed. Objective: We tested the hypothesis that 600 mg/d of the n−3 LCPUFA docosahexaenoic acid (DHA) can increase maternal and newborn DHA status, gestation duration, birth weight, and length. Safety was assessed. Design: This phase III, double-blind, randomized controlled trial was conducted between January 2006 and October 2011. Women (n = 350) consumed capsules (placebo, DHA) from <20 wk of gestation to birth. Blood (enrollment, birth, and cord) was analyzed for red blood cell (RBC) phospholipid DHA. The statistical analysis was intent-to-treat. Results: Most of the capsules were consumed (76% placebo; 78% DHA); the mean DHA intake for the treated group was 469 mg/d. In comparison with placebo, DHA supplementation resulted in higher maternal and cord RBC-phospholipid-DHA (2.6%; P < 0.001), longer gestation duration (2.9 d; P = 0.041), and greater birth weight (172 g; P = 0.004), length (0.7 cm; P = 0.022), and head circumference (0.5 cm; P = 0.012). In addition, the DHA group had fewer infants born at <34 wk of gestation (P = 0.025) and shorter hospital stays for infants born preterm (40.8 compared with 8.9 d; P = 0.026) than did the placebo group. No safety concerns were identified. Conclusions: A supplement of 600 mg DHA/d in the last half of gestation resulted in overall greater gestation duration and infant size. A reduction in early preterm and very-low birth weight could be important clinical and public health outcomes of DHA supplementation. This trial was registered at clinicaltrials.gov as NCT00266825. PMID:23426033
The puzzling association between smoking and hypertension during pregnancy.
Zhang, J; Klebanoff, M A; Levine, R J; Puri, M; Moyer, P
1999-12-01
The object of this study was to examine the association between maternal smoking and hypertension during pregnancy. We used data from the Collaborative Perinatal Project, a large prospective cohort study that collected detailed information on blood pressure, proteinuria, smoking, and placental morphologic and histologic characteristics. A total of 9651 healthy primigravid women without chronic hypertension who had been enrolled in the study at the first or second trimester (average 18 weeks' gestation) and had had >/=3 prenatal visits were included. Gestational hypertension was defined as diastolic blood pressure >/=90 mm Hg on 2 occasions from 24 weeks' gestation to 2 weeks post partum. Preeclampsia was defined as gestational hypertension plus >/=2 urine samples containing >/=1+ protein according to dipstick measurement during the same gestational period. After we controlled for prepregnancy body mass, age, socioeconomic status, and race, both past smoking and smoking during pregnancy were associated in a dose-response pattern with reduced risks of gestational hypertension and preeclampsia. For women who smoked >/=10 cigarettes/d the relative risks with respect to women who had never smoked were 0.6 (95% confidence interval, 0.4-0.9) for gestational hypertension and 0.5 (95% confidence interval, 0.4-0.7) for preeclampsia. This protective effect was observed both for mild and severe gestational hypertension and for preeclampsia. The more and the longer a woman had smoked previously, the lower was her risk of development of hypertension during pregnancy. This association could not be explained by confounding factors, by changes in placental morphologic or histopathologic characteristics, by maternal net weight gain, or by elevated liver enzyme bioactivity. Smoking is associated with a reduced risk of hypertension during pregnancy. The protective effect appears to continue even after cessation of smoking. Further basic research on this issue is warranted.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Damilakis, John; Tzedakis, Antonis; Perisinakis, Kostas
Purpose: Current methods for the estimation of conceptus dose from multidetector CT (MDCT) examinations performed on the mother provide dose data for typical protocols with a fixed scan length. However, modified low-dose imaging protocols are frequently used during pregnancy. The purpose of the current study was to develop a method for the estimation of conceptus dose from any MDCT examination of the trunk performed during all stages of gestation. Methods: The Monte Carlo N-Particle (MCNP) radiation transport code was employed in this study to model the Siemens Sensation 16 and Sensation 64 MDCT scanners. Four mathematical phantoms were used, simulatingmore » women at 0, 3, 6, and 9 months of gestation. The contribution to the conceptus dose from single simulated scans was obtained at various positions across the phantoms. To investigate the effect of maternal body size and conceptus depth on conceptus dose, phantoms of different sizes were produced by adding layers of adipose tissue around the trunk of the mathematical phantoms. To verify MCNP results, conceptus dose measurements were carried out by means of three physical anthropomorphic phantoms, simulating pregnancy at 0, 3, and 6 months of gestation and thermoluminescence dosimetry (TLD) crystals. Results: The results consist of Monte Carlo-generated normalized conceptus dose coefficients for single scans across the four mathematical phantoms. These coefficients were defined as the conceptus dose contribution from a single scan divided by the CTDI free-in-air measured with identical scanning parameters. Data have been produced to take into account the effect of maternal body size and conceptus position variations on conceptus dose. Conceptus doses measured with TLD crystals showed a difference of up to 19% compared to those estimated by mathematical simulations. Conclusions: Estimation of conceptus doses from MDCT examinations of the trunk performed on pregnant patients during all stages of gestation can be made using the method developed in the current study.« less
Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study
Heimstad, Runa; Iversen, Ann-Charlotte; Austgulen, Rigmor; Lydersen, Stian; Andersen, Guro L; Irgens, Lorentz M; Vik, Torstein
2013-01-01
Objective To test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age. Design Population based cohort study. Setting Clinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway. Participants All singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616 658 control children). Main outcome measures Cerebral palsy and cerebral palsy subtypes. Results Children exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (≥37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype. Conclusions Exposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age. PMID:23838554
Davies, HR; Visser, J; Tomlinson, M; Rotheram-Borus, MJ; Gissane, C; Harwood, J; LeRoux, I
2014-01-01
Objective The aim of this study was to investigate the ability of the gestational body mass index (BMI) method to screen for adverse birth outcomes and maternal morbidities. Design This was a substudy of a randomised controlled trial, the Philani Mentor Mothers’ study. Setting and subjects The Philani Mentor Mothers’ study took place in a peri-urban settlement, Khayelitsha, between 2009 and 2010. Pregnant women living in the area in 2009-2010 were recruited for the study. Outcome measures Maternal anthropometry (height and weight) and gestational weeks were obtained at baseline to calculate the gestational BMI, which is maternal BMI adjusted for gestational age. Participants were classified into four gestational BMI categories: underweight, normal, overweight and obese. Birth outcomes and maternal morbidities were obtained from clinic cards after the births. Results Pregnant women were recruited into the study (n = 1 058). Significant differences were found between the different gestational BMI categories and the following birth outcomes: maternal (p-value = 0.019), infant hospital stay (p-value = 0.03), infants staying for over 24 hours in hospital (p-value = 0.001), delivery mode (p-value = 0.001), birthweight (p-value = 0.006), birth length (p-value = 0.007), birth head circumference (p-value = 0.007) and pregnancy-induced hypertension (p-value = 0.001). Conclusion To the best of our knowledge, this is the first study that has used the gestational BMI method in a peri-urban South African pregnant population. Based on the findings that this method is able to identify unfavourable birth outcomes, it is recommended that it is implemented as a pilot study in selected rural, peri-urban and urban primary health clinics, and that its ease and effectiveness as a screening tool is evaluated. Appropriate medical and nutritional advice can then be given to pregnant women to improve both their own and their infants’ birth-related outcomes and maternal morbidities. PMID:25324710
Mackay, Euan; Dalman, Christina; Karlsson, Håkan; Gardner, Renee M
2017-04-01
Prenatal exposure to famine is associated with a 2-fold risk for nonaffective psychoses. Less is known about whether maternal nutrition states during pregnancy modify offspring risk for nonaffective psychoses in offspring in well-fed populations. To determine whether gestational weight gain (GWG) during pregnancy and maternal body mass index (BMI) in early pregnancy are associated with risk for nonaffective psychoses in offspring. This population-based cohort study used data from Swedish health and population registers to follow up 526 042 individuals born from January 1, 1982, through December 31, 1989, from 13 years of age until December 31, 2011. Cox proportional hazards regression models adjusted for socioeconomic status and potential risk factors were used to examine the risk for developing nonaffective psychoses. Family-based study designs were used to further test causality. Data were analyzed from February 1 to May 14, 2016. Gestational weight gain during pregnancy, maternal body mass index at the first antenatal visit, and paternal body mass index at the time of conscription into the Swedish military (at 18 years of age). Hazard ratios (HRs) for the diagnosis of nonaffective psychoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20 to F29 and International Classification of Diseases, Ninth Revision [ICD-9] codes 295, 297 and 298, except 298A and 298B) and narrowly defined schizophrenia (ICD-9 code 295 and ICD-10 code F20). The 526 042 individuals in the cohort (48.52% female and 51.47% male; mean [SD] age, 26 [2.3] years) included 2910 persons with nonaffective psychoses at the end of follow-up, of whom 704 had narrowly defined schizophrenia. Among the persons with nonaffective psychosis, 184 (6.32%) had mothers with extremely inadequate GWG (<8 kg for mothers with normal baseline BMI), compared with 23 627 (4.52%) of unaffected individuals. Extremely inadequate GWG was associated with an increased risk for nonaffective psychoses among offspring in adjusted models (HR, 1.32; 95% CI, 1.13-1.54) and in matched-sibling analysis (HR, 1.61; 95% CI, 1.02-2.56). Similar patterns were observed when considering narrowly defined schizophrenia as the outcome. Maternal mild thinness in early pregnancy was weakly associated with an increased risk for nonaffective psychosis in offspring (HR for BMI≥17.0 and <18.5, 1.21; 95% CI, 1.01-1.45), as was paternal severe thinness (HR for BMI<16.0, 2.53; 95% CI, 1.26-5.07) in mutually adjusted models. In matched-sibling analysis, no association was observed between maternal underweight (HR, 1.46; 95% CI, 0.90-2.35), overweight (HR, 1.11; 95% CI, 0.73-1.68), or obesity (HR, 0.56; 95% CI, 0.23-1.38) and risk for nonaffective psychosis in offspring. Inadequate GWG was associated with an increased risk for nonaffective psychosis in offspring, consistent with historical studies on maternal starvation. These findings support the role of maternal undernutrition in nonaffective psychosis pathogenesis.
Quesada-Calderón, Suany; Bacigalupe, Leonardo Daniel; Toro-Vélez, Andrés Fernando; Madera-Parra, Carlos Arturo; Peña-Varón, Miguel Ricardo; Cárdenas-Henao, Heiber
2017-08-01
Water pollution due to human activities produces sedimentation, excessive nutrients, and toxic chemicals, and this, in turn, has an effect on the normal endocrine functioning of living beings. Overall, water pollution may affect some components of the fitness of organisms (e.g., developmental time and fertility). Some toxic compounds found in polluted waters are known as endocrine disruptors (ED), and among these are nonhalogenated phenolic chemicals such as bisphenol A and nonylphenol. To evaluate the effect of nonhalogenated phenolic chemicals on the endocrine system, we subjected two generations (F0 and F1) of Drosophila melanogaster to different concentrations of ED. Specifically, treatments involved wastewater, which had the highest level of ED (bisphenol A and nonylphenol) and treated wastewater from a constructed Heliconia psittacorum wetland with horizontal subsurface water flow (He); the treated wastewater was the treatment with the lowest level of ED. We evaluated the development time from egg to pupa and from pupa to adult as well as fertility. The results show that for individuals exposed to treated wastewater, the developmental time from egg to pupae was shorter in individuals of the F1 generation than in the F0 generation. Additionally, the time from pupae to adult was longer for flies growing in the H. psittacorum treated wastewater. Furthermore, fertility was lower in the F1 generation than in the F0 generation. Although different concentrations of bisphenol A and nonylphenol had no significant effect on the components of fitness of D. melanogaster (developmental time and fertility), there was a trend across generations, likely as a result of selection imposed on the flies. It is possible that the flies developed different strategies to avoid the effects of the various environmental stressors.
Shankaran, Sunita S; Dahlem, Timothy J; Bisgrove, Brent W; Yost, H Joseph; Tristani-Firouzi, Martin
2017-07-05
The ability to perform reverse genetics in the zebrafish model organism has been greatly advanced with the advent of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated) system. The high level of efficiency in generating mutations when using the CRISPR/Cas9 system combined with the rapid generation time of the zebrafish model organism has made the possibility of performing F 0 screens in this organism a reality. This unit describes a detailed protocol for performing an F 0 screen using the CRISPR/Cas9 system in zebrafish starting with the design and production of custom CRISPR/Cas9 reagents for injection. Next, two approaches for determining the efficiency of mutation induction by the custom CRISPR/Cas9 reagents that are easily performed using standard molecular biology protocols are detailed. Finally, screening for F 0 induced phenotypes using the zebrafish flh gene as an example is discussed. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.
Kim, Bang Sil; Son, Chang Ho
2007-09-01
Serial ultrasonographic examinations were performed daily on 9 Miniature Schnauzer bitches from the 15th day of gestation until parturition to determine the time the gestational structures were first detected. The gestational age was timed from the day of ovulation (day 0), which was estimated to occur when the plasma progesterone concentration was >4.0 ng/ml. The gestational length in 9 Miniature Schnauzer bitches was found to be 63.0 +/- 1.7 (range 61-65) days. The initial detection of the fetal and extra-fetal structures were as follows: gestational sac at day 18.0 +/- 0.9 (17-19); zonary placenta in the uterine wall at day 24.9 +/- 1.1 (23-26); yolk sac membrane at day 25.0 +/- 0.9 (24-26); amnionic membrane at day 27.7 +/- 1.0 (26- 29); embryo initial detection at day 22.6 +/- 0.5 (22-23); heartbeat at day 23.4 +/- 0.5 (23-24); fetal movement at day 32.5 +/- 0.8 (32-34); stomach at day 31.2 +/- 1.6 (29-33); urinary bladder at day 32.6 +/- 1.8 (31-35); skeleton at day 34.9 +/- 1.6 (34-38) and kidney at day 42.2 +/- 0.7 (41-43).
A comparison of foetal and infant mortality in the United States and Canada.
Ananth, Cande V; Liu, Shiliang; Joseph, K S; Kramer, Michael S
2009-04-01
Infant mortality rates are higher in the United States than in Canada. We explored this difference by comparing gestational age distributions and gestational age-specific mortality rates in the two countries. Stillbirth and infant mortality rates were compared for singleton births at >or=22 weeks and newborns weighing>or=500 g in the United States and Canada (1996-2000). Since menstrual-based gestational age appears to misclassify gestational duration and overestimate both preterm and postterm birth rates, and because a clinical estimate of gestation is the only available measure of gestational age in Canada, all comparisons were based on the clinical estimate. Data for California were excluded because they lacked a clinical estimate. Gestational age-specific comparisons were based on the foetuses-at-risk approach. The overall stillbirth rate in the United States (37.9 per 10,000 births) was similar to that in Canada (38.2 per 10,000 births), while the overall infant mortality rate was 23% (95% CI 19-26%) higher (50.8 vs 41.4 per 10,000 births, respectively). The gestational age distribution was left-shifted in the United States relative to Canada; consequently, preterm birth rates were 8.0 and 6.0%, respectively. Stillbirth and early neonatal mortality rates in the United States were lower at term gestation only. However, gestational age-specific late neonatal, post-neonatal and infant mortality rates were higher in the United States at virtually every gestation. The overall stillbirth rates (per 10,000 foetuses at risk) among Blacks and Whites in the United States, and in Canada were 59.6, 35.0 and 38.3, respectively, whereas the corresponding infant mortality rates were 85.6, 49.7 and 42.2, respectively. Differences in gestational age distributions and in gestational age-specific stillbirth and infant mortality in the United States and Canada underscore substantial differences in healthcare services, population health status and health policy between the two neighbouring countries.
Balcells, Ingrid; Castelló, Anna; Mercadé, Anna; Noguera, José L; Fernández-Rodríguez, Amanda; Sànchez, Armand; Tomàs, Anna
2011-10-31
Reproductive traits, such as prolificacy, are of great interest to the pig industry. Better understanding of their genetic architecture should help to increase the efficiency of pig productivity through the implementation of marker assisted selection (MAS) programmes. The Mucin 4 (MUC4) gene has been evaluated as a candidate gene for a prolificacy QTL described in an Iberian × Meishan (Ib × Me) F2 intercross. For association analyses, two previously described SNPs (DQ124298:g.243A>G and DQ124298:g.344A>G) were genotyped in 347 pigs from the Ib × Me population. QTL for the number of piglets born alive (NBA) and for the total number of piglets born (TNB) were confirmed on SSC13 at positions 44 cM and 51 cM, respectively. The MUC4 gene was successfully located within the confidence intervals of both QTL. Only DQ124298:g.344A>G MUC4 polymorphism was significantly associated with both NBA and TNB (P-value < 0.05) with favourable effects coming from the Meishan origin. MUC4 expression level was determined in F2 sows displaying extreme phenotypes for the number of embryos (NE) at 30-32 days of gestation. Differences in the uterine expression of MUC4 were found between high (NE ≥ 13) and low (NE ≤ 11) prolificacy sows. Overall, MUC4 expression in high prolificacy sows was almost two-fold increased compared with low prolificacy sows. Our data suggest that MUC4 could play an important role in the establishment of an optimal uterine environment that would increase embryonic survival during pig gestation.
Han, Yun; Zheng, Yan-Li; Wu, Ai-Min; Liu, Hong-Bin; Su, Jian-Bin; Lu, Xiao-Yan; Han, Yu-Wen; Ji, Jin-Long; Ji, Ju-Hua; Shi, Yue
2016-12-01
A great quantity of gestational diabetes mellitus with normal prepregnancy body mass index have emerged with the new criteria of gestational diabetes mellitus in China based on the International Diabetes in Pregnancy Consensus group criteria, and understanding placental changes and how they affect outcomes are necessary in order to develop effective management approach. The aim of this study was to prospectively explore the effect of active management starting from the late second trimester in gestational diabetes mellitus women with normal prepregnancy body mass index on pregnancy outcomes and placental ultrastructures, and to provide scientific evidences for optimizing the management of gestational diabetes mellitus in China. Gestational diabetes mellitus women with normal prepregnancy body mass index in the same period of this prospective cohort study were divided into intervention group (n = 51) and control group (n = 55). The intervention group was managed rigorously, while the control group received conventional prenatal cares. The glucose profile, gestational weight gain and pregnancy outcomes were followed up and placental ultrastructures were observed and recorded by transmission electron microscopy. The blood glucose level and gestational weight gain in intervention group were significantly better controlled than those in control group (P < 0.01). The incidences of fetal distress, cesarean section and large for gestational age were significantly lower in intervention group than in control group (P < 0.05). There was a significant reduction in the incidence of abnormal placental ultrastructure in the intervention group (P < 0.01). After adjustment for confounding factors, the undesirable glycemic control and conventional management were related to abnormal placental ultrastructure (P < 0.05). Meanwhile, the undesirable glycemic control, abnormal placental ultrastructure and conventional management made sense in the incidence of fetal distress (P < 0.05), and the target glycemic control, recommend weight gain and active management were associated with reductions in the prevalence of cesarean delivery and large for gestational age (P < 0.05). The active management of gestational diabetes mellitus women with normal prepregnancy body mass index can improve pregnancy outcomes and placental ultrastructures, and the abnormal placental ultrastructure might be closely associated with the undesirable glycemic control and adverse pregnancy outcomes.
Analogues of Chernoff's theorem and the Lie-Trotter theorem
NASA Astrophysics Data System (ADS)
Neklyudov, Alexander Yu
2009-10-01
This paper is concerned with the abstract Cauchy problem \\dot x=\\mathrm{A}x, x(0)=x_0\\in\\mathscr{D}(\\mathrm{A}), where \\mathrm{A} is a densely defined linear operator on a Banach space \\mathbf X. It is proved that a solution x(\\,\\cdot\\,) of this problem can be represented as the weak limit \\lim_{n\\to\\infty}\\{\\mathrm F(t/n)^nx_0\\}, where the function \\mathrm F\\colon \\lbrack 0,\\infty)\\mapsto\\mathscr L(\\mathrm X) satisfies the equality \\mathrm F'(0)y=\\mathrm{A}y, y\\in\\mathscr{D}(\\mathrm{A}), for a natural class of operators. As distinct from Chernoff's theorem, the existence of a global solution to the Cauchy problem is not assumed. Based on this result, necessary and sufficient conditions are found for the linear operator \\mathrm{C} to be closable and for its closure to be the generator of a C_0-semigroup. Also, we obtain new criteria for the sum of two generators of C_0-semigroups to be the generator of a C_0-semigroup and for the Lie-Trotter formula to hold. Bibliography: 13 titles.
A two-component Bayesian mixture model to identify implausible gestational age.
Mohammadian-Khoshnoud, Maryam; Moghimbeigi, Abbas; Faradmal, Javad; Yavangi, Mahnaz
2016-01-01
Background: Birth weight and gestational age are two important variables in obstetric research. The primary measure of gestational age is based on a mother's recall of her last menstrual period. This recall may cause random or systematic errors. Therefore, the objective of this study is to utilize Bayesian mixture model in order to identify implausible gestational age. Methods: In this cross-sectional study, medical documents of 502 preterm infants born and hospitalized in Hamadan Fatemieh Hospital from 2009 to 2013 were gathered. Preterm infants were classified to less than 28 weeks and 28 to 31 weeks. A two-component Bayesian mixture model was utilized to identify implausible gestational age; the first component shows the probability of correct and the second one shows the probability of incorrect classification of gestational ages. The data were analyzed through OpenBUGS 3.2.2 and 'coda' package of R 3.1.1. Results: The mean (SD) of the second component of less than 28 weeks and 28 to 31 weeks were 1179 (0.0123) and 1620 (0.0074), respectively. These values were larger than the mean of the first component for both groups which were 815.9 (0.0123) and 1061 (0.0074), respectively. Conclusion: Errors occurred in recording the gestational ages of these two groups of preterm infants included recording the gestational age less than the actual value at birth. Therefore, developing scientific methods to correct these errors is essential to providing desirable health services and adjusting accurate health indicators.
Liu, Hong; Shao-Gang, Ma; Liang, Cheng; Feng, Bai; Wei, Xu
2015-01-01
To investigate whether serum levels of butyrylcho-linesterase activity, cystatin C, and pre-albumin has the potential value as γ-glutamyl transferase in reflecting gestational diabetes mellitus and its fetal outcome. Seventy-six gestational diabetes mellitus women and 76 pregnancies with normal glucose tolerance in the second trimester were enrolled. Maternal serum parameters of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C, and pre-albumin were detected and evaluated. The pregnant complications and fetal outcome were also evaluated. Levels of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C, pre-albumin and glycemic variables were higher in the gestational diabetes mellitus patients than in the controls. Levels of butyrylcholinesterase activity were significantly correlated to the levels of fasting plasma glucose, cystatin C, and γ- glutamyl transferase (p < 0.05) in the gestational diabetes mellitus group. There were statistical differences in cases of preterm delivery, preeclampsia and postpartum hemorrhage. Higher levels of γ-glutamyl transferase and pre-albumin were risk markers for gestational diabetes mellitus (p < 0.05). The diagnosis curve demonstrated that γ-glutamyl transferase had a significant advantage over other markers (p < 0.001) but no significance compared with pre-albumin (p = 0.096). None of the detected markers showed predictive value for fetal outcome. Serum levels of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C and pre-albumin were correlated with gestational diabetes mellitus status but not with the fetal outcome. Pre-albumin can be equivalent as γ-glutamyl transferase in reflecting the presence of gestational diabetes mellitus.
Lactation is associated with altered metabolomic signatures in women with gestational diabetes.
Much, Daniela; Beyerlein, Andreas; Kindt, Alida; Krumsiek, Jan; Stückler, Ferdinand; Rossbauer, Michaela; Hofelich, Anna; Wiesenäcker, David; Hivner, Susanne; Herbst, Melanie; Römisch-Margl, Werner; Prehn, Cornelia; Adamski, Jerzy; Kastenmüller, Gabi; Theis, Fabian; Ziegler, Anette-G; Hummel, Sandra
2016-10-01
Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures postpartum. We enrolled 197 women with gestational diabetes at a median of 3.6 years (interquartile range 0.7-6.5 years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3 months and women who lactated for ≤3 months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks. Lactation for >3 months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branched-chain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3 months and have been linked to the pathophysiology of type 2 diabetes in previous studies. Lactation for >3 months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes.
Matsuda, Yoshio; Ogawa, Masaki; Nakai, Akihito; Hayashi, Masako; Satoh, Shoji; Matsubara, Shigeki
2015-01-01
The "inappropriately heavy placenta" has been considered to be associated with various pregnancy disorders; however, data is scarce what factors affect it. To determine whether the following three affect it; (1) infant gender and mother's parity, (2) growth restriction, and (3) preeclampsia. We employed fetal/placental weight ratio (F/P). Subjects consisted of 53,650 infants and their placentas from women who vaginally delivered singleton live term infants. First, we examined whether F/P differs among the infant's gender or mother's parity. We classified the population into 4 categories according to gender and parity: male, nulliparous (n=7,431), male, multiparous (n=7,859), female, nulliparous (n=7,559), female, multiparous (n=7,800), and, compared F/P among the four groups. Next, we determined whether F/P differs in "small" or "large" for gestational age (SGA or LGA) infants, compared with appropriate for gestational age infants. Last, we determined whether preeclampsia (representative disorder of SGA) affects F/P. (1) F/P significantly differed according to infant gender and parity: female and nulliparity had significantly smaller F/P. F/P was significantly smaller in (2) SGA infants, and (3) infants from preeclamptic mothers. We for the first time showed that in Japanese term vaginally-delivered singleton population, the following three had significantly smaller F/P than controls thus had "inappropriately heavy placenta": (1) female gender and nulliparity, (2) SGA infants, and (3) infants from preeclamptic mothers. We recommend that these factors should be taken into account in evaluating placental weight. These data may also be useful for further clarifying the fetal-placental pathophysiology in these conditions.
Phasomkusolsil, Siriporn; Tanskul, Panita; Ratanatham, Supaporn; Watcharapichat, Pochaman; Phulsuksombati, Duangporn; Frances, Stephen P; Lerdthusnee, Kriangkrai; Linthicum, Kenneth J
2012-11-01
Leptotrombidium chiangraiensis Tanskul & Linthicum, and Leptotrombidium imphalum Vercammen-Grandjean are important vectors of scrub typhus in rice field habitats in northern Thailand. The developmental biology of all stages of the life cycle of two generations of these species of mites infected with Orientia tsutsugamushi (Hayashi) and uninfected mites is reported. The development of the infected lines of both F1 and F2 L. chiangraiensis were significantly longer than their respective uninfected lines (P < 0.05). The developmental times of uninfected and infected F1 lines of L. imphalum were not significantly different; however, F2 infected lines took significantly longer to develop (P < 0.05). Both F1 and F2 generations of infected L. imphalum and L. chiangraiensis oviposited on average >150 fewer eggs than uninfected mites.
Lappen, Justin R; Hackney, David N; Bailit, Jennifer L
2015-07-01
To evaluate outcomes of induction of labor, compared with expectant management, in women attempting trial of labor after cesarean delivery (TOLAC) in a large obstetric cohort. We performed a secondary analysis of data from the Consortium on Safe Labor that included women with term (37 weeks of gestation or greater) singleton gestations and a history of one prior cesarean delivery who attempted TOLAC. Induction of labor was compared with expectant management by week of gestation from 37 to 40 weeks in both high- and low-risk cohorts. The primary outcome was failed TOLAC. Secondary outcomes included composite maternal morbidity (hysterectomy, transfusion, intensive care unit (ICU) transfer, venous thromboembolism, death), composite neonatal morbidity (5-minute Apgar score less than 5, cord pH less than 7.0, asphyxia, hypoxic ischemic encephalopathy, neonatal death), and neonatal ICU admission. Multivariate logistic regression was performed with adjustment for confounding factors. We identified 6,033 women attempting TOLAC of whom 1,626 (27.0%) underwent induction of labor and 4,407 (73.0%) did not. Compared with expectant management, induction was associated with an increased risk of failed TOLAC at 37-39 weeks of gestation but not at 40 weeks of gestation (37 weeks of gestation, 48.5% compared with 34.3%, adjusted odds ratio [OR] 1.53, 95% confidence interval [CI] 1.02-2.28]; 38 weeks of gestation, 47.0% compared with 33.0%, adjusted OR 1.74, 95% CI 1.29-2.34; 39 weeks of gestation, 45.6% compared with 29.8%, adjusted OR 2.16, 95% CI 1.76-2.67; 40 weeks of gestation, 37.9% compared with 29.4%, adjusted OR 1.21, 95% CI 0.90-1.66). Induction was associated with an increased risk of composite maternal morbidity at 39 weeks of gestation (adjusted OR 1.87, 95% CI 1.22-2.87) and neonatal ICU admission at 37 weeks of gestation (adjusted OR 2.51, 95% CI 1.62-3.90). Induction was not associated with an increased risk of neonatal morbidity. Induction of labor in women with one prior cesarean delivery, compared with expectant management, is associated with an increased risk of failed TOLAC. Apart from small increases in maternal morbidity at 39 weeks and neonatal ICU admission at 37 weeks of gestation, induction is not associated with an increased risk of severe maternal or neonatal morbidity. II.
Bellad, M B; Goudar, S S; Edlavitch, S A; Mahantshetti, N S; Naik, V; Hemingway-Foday, J J; Gupta, M; Nalina, H R; Derman, R; Moss, N; Kodkany, B S
2012-06-01
To determine whether consanguinity adversely influences pregnancy outcome in South India, where consanguinity is a common means of family property retention. Data were collected from a prospective cohort of 647 consenting women, consecutively registered for antenatal care between 14 and 18 weeks gestation, in Belgaum district, Karnataka in 2005. Three-generation pedigree charts were drawn for consanguineous participants. χ (2)-Test and Student's t-test were used to assess categorical and continuous data, respectively, using SPSS version 14. Multivariate logistic regression adjusted for confounding variables. Overall, 24.1% of 601 women with singleton births and outcome data were consanguineous. Demographic characteristics between study groups were similar. Non-consanguineous couples had fewer stillbirths (2.6 vs 6.9% P=0.017; adjusted P=0.050), miscarriages (1.8 vs 4.1%, P=0.097; adjusted P=0.052) and lower incidence of birth weight <2500 g (21.8 vs 29.5%, P=0.071, adjusted P=0.044). Gestation <37 weeks was 6.2% in both the groups. Adjusted for consanguinity and other potential confounders, age <20 years was protective of stillbirth (P=0.01), pregnancy loss (P=0.023) and preterm birth (P=0.013), whereas smoking (P=0.015) and poverty (P=0.003) were associated with higher rates of low birth weight. Consanguinity significantly increases pregnancy loss and birth weight <2500 g.
[Body composition in women with gestational diabetes mellitus].
Moreno Martinez, Socorro; Tufiño Olivares, Edith; Chávez Loya, Vicente; Rodríguez Morán, Martha; Guerrero Romero, Fernando; Levario Carrillo, Margarita
2009-06-01
Several techniques have been used to determine body composition during pregnancy. To determine the characteristics of body composition in women with gestational diabetes mellitus in comparison with women with normal glucose tolerance and pre-gestacional diabetes. Pregnant women with gestational diabetes mellitus, pre-gestacional diabetes, and normal glucose tolerance, between 24 to 32 weeks of single gestation, were enrolled in a cross-sectional study. Screening of DMG was carried out using 50 g of glucose load; diagnosis was confirmed by oral glucose tolerance test. Evaluation of body composition was carried out by bioelectrical impedance. The Kruskal Wallis test was used for statistical analysis. A total of 79 women were included; of these, diagnosis of gestational diabetes mellitus, pre-gestacional diabetes, and normal glucose tolerance was established in 14, 9, and 56 women, respectively. Pre-gestational body mass index was greater in women with diabetes (p < 0.01). Fat free mass and total body water were similar in the studied groups. Fat mass was greater in women with gestational diabetes mellitus (range 21.0-29.4 kg) and patients with pre-gestacional diabetes (range 26.4-32.7 kg) than in the women with normal glucose tolerance (range 150.8-25.9 kg), p < 0.01. The body composition of women, between 24 to 32 weeks of single gestation, is different in the women with gestational diabetes mellitus compared with women with normal glucose tolerance. Women with gestational diabetes mellitus show a significant increase in fat mass without significant changes in the fat free mass and total body water.
Bakhireva, Ludmila N; Cano, Sandra; Rayburn, William F; Savich, Renate D; Leeman, Lawrence; Anton, Raymond F; Savage, Daniel D
2012-01-01
Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients. Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method. At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as 'positive' for this biomarker at recruitment and at term, respectively (P = 0.011 ). These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further.
The impact of diabetes mellitus on the course and outcome of pregnancy during a 5-year follow-up.
Mitrović, Milena; Stojić, Siniša; Tešić, Dragan S; Popović, Djordje; Rankov, Olivera; Naglić, Dragana Tomić; Paro, Jovanka Novaković; Pejin, Radoslav; Bulatović, Sanja; Veljić, Mašsa Todorović; Zavišić, Branka Kovarev
2014-10-01
Women with diabetes, especially diabetes type 1, have worse pregnancy outcomes, as well as increased incidence of spontaneous abortions, pre-eclampsia, fetal macrosomia, preterm delivery, congenital anomalies and perinatal mortality. The aim of this study was to analyze the course and outcome of pregnancy in the patients with diabetes in relation to the group of healthy women regarding preterm delivery, perinatal morbidity and mortality. Also, the aim was to compare pregnancy outcomes in the patients with pre-existing diabetes type 1 and the patients with gestational and diabetes type 2. This retrospective study included 156 diabetic women treated at the Clinic of Endocrinology, Diabetes and Metabolic Diseases and Gynecology and Obstetrics Clinic of the Clinical Center of Vojvodina from 2006 to 2010. There were 94 patients with gestational diabetes, 48 with type 1 diabetes, and 14 patients with type 2 diabetes. The control group included 106 healthy women hospitalized at the Gynecology and Obstetrics Clinic. The women with type 1 diabetes presented with a statistically significantly higher incidence of cesarean section than those without diabetes, or with type 2 or gestational diabetes (p < 0.0001); the women with type 1 diabetes delivered at an earlier week of gestation (WG) in regard to women without diabetes, or with type 2 or gestational diabetes (p = 0.0017 and p = 0.02, respectively). The incidence of perinatal morbidity: hypoglycemia (p < 0.001), pathological jaundice (p = 0.0021), and other neonatal pathologies at birth (p = 0.0031), was statistically significantly higher and Apgar scores after 1 minute (p = 0.0142) and after 5 minutes (p = 0.0003) were statistically significantly lower in the patients with diabetes compared to the healthy women. The women with type 2 and gestational diabetes were statistically significantly older than those with type 1 diabetes (p = 0.001). A higher incidence of fetal macrosomia in the women with gestational and type 2 diabetes compared to those with type 1 diabetes was at the borderline of statistical significance (p = 0.07), whereas the incidence of hypoglycemia of newborn was statistically significantly higher in the patients with type 1 diabetes (p < 0.0001). Glycosylated hemoglobin (HbA1c) levels were statistically significantly higher in the diabetic women giving birth during and before the week of gestation 36 (p = 0.0087), but there were no differences in HbA1lc levels in regard to fetal macrosomia (p = 0.45) and congenital abnormalities (p = 0.32). The results of our study show a higher incidence of perinatal fetal morbidity (hypoglycemia, jaundice, respiratory distress syndrome) in the patients with type 1, type 2 and gestation diabetes than in the healthy controls. Also, we found a higher incidence of cesarean section in the patients with type 1 diabetes than in those with type 2, gestation diabetes and healthy controls. Although delivery in the patients with type 1, type 2 and gestational diabetes was completed approximately one to two weeks earlier compared to the healthy controls there was no statistically significant difference in the incidence of preterm delivery (≤ 36th week of gestation) between the women with diabetes and healthy controls. Preterm delivery associated with poorer glycaemic control reflected through higher values of HbA1c in third trimester. Risks from adverse pregnancy outcomes may be reduced to minimum by adequate preconception counseling of diabetic patients and early diagnosis of diabetes in pregnancy, in order to achieve glycemic control during organogenesis and within pregnancy and through the teamwork of endocrinologists, gynecologists and pediatricians.
Mahawong, Phitsanu; Sinclair, Adriane; Li, Yi; Schlomer, Bruce; Rodriguez, Esequiel; Max, Ferretti M.; Liu, Baomei; Baskin, Laurence S.; Cunha, Gerald R.
2014-01-01
Potential trans-generational influence of diethylstilbestrol (DES) exposure emerged with reports of effects in grandchildren of DES-treated pregnant women and of reproductive tract tumors in offspring of mice exposed in utero to DES. Accordingly, we examined the trans-generational influence of DES on development of external genitalia (ExG) and compared effects of in utero DES exposure in CD-1 and C57BL/6 mice injected with oil or DES every other day from gestational days 12 to 18. Mice were examined at birth, and on 5 to 120 days postnatal to evaluate ExG malformations. Of 23 adult (≥60 days) prenatally DES-exposed males, features indicative of urethral meatal hypospadias (see text for definitions) ranged from 18 to 100% in prenatally DES-exposed CD-1 males and 31 to 100% in prenatally DES-exposed C57BL/6 males. Thus, the strains differed in the incidence of male urethral hypospadias. Ninety-one percent of DES-exposed CD-1 females and 100% of DES-exposed C57BL/6 females had urethral-vaginal fistula. All DES-exposed CD-1 and C57BL/6 females lacked an os clitoris. None of the prenatally oil-treated CD-1 and C57BL/6 male and female mice had ExG malformations. For the second-generation study, 10 adult CD-1 males and females, from oil- and DES-exposed groups, respectively, were paired with untreated CD-1 mice for 30 days, and their offspring evaluated for ExG malformations. None of the F1 DES-treated females were fertile. Nine of 10 prenatally DES-exposed CD-1 males sired offspring with untreated females, producing 55 male and 42 female pups. Of the F2 DES-lineage adult males, 20% had exposed urethral flaps, a criterion of urethral meatal hypospadias. Five of 42 (11.9%) F2 DES lineage females had urethral-vaginal fistula. In contrast, all F2 oil-lineage males and all oil-lineage females were normal. Thus, prenatal DES exposure induces malformations of ExG in both sexes and strains of mice, and certain malformations are transmitted to the second-generation. PMID:25449352
NASA Astrophysics Data System (ADS)
Ramli, Nur Hasyimah; Yaakop, Salmah
2018-04-01
Tenebrio molitor known as darkling beetle is burrowing insects and can be found all over the world. Tenebrio molitor samples were put in Open Roof Ventilation System, Free Air CO2 Enrichment and Rearing Room system. The development of Tenebrio molitor adult parents (P) and first generation (F1) that more exposed to high level of CO2 were studied. As the results, parent and first generation (F1) of T. molitor shows that there are no significant effects of CO2 on their development. But, decreased development pattern showed between parent and F1 can be used to estimate that prolonged exposure of CO2 will change their development. The highest development of parent showed by OFVSP (0.1708±0.0013) mm, while the lowest showed by FACEP (0.1686±0.0013) mm. For F1, the highest development showed by OFVS F1 (0.1705±0.0015) mm, while RR F1 becomes the lowest (0.1649±0.0023) mm. No significant difference shown by ANOVA test. Unfortunately, the data cannot be used to prove that the development of parent and F1 were affected by CO2 because no significant difference recorded between them. Correlation coefficient analysis of OFVSP and OFVS F1 presented to support the results. It shows that the correlation coefficient among characters from parents and F1 are different. Further study should be done in future to increase our knowledge of the climate change on insects.
Chen, Ling-Wei; Lim, Ai Lin; Colega, Marjorelee; Tint, Mya-Thway; Aris, Izzuddin M; Tan, Chuen Seng; Chong, Yap-Seng; Gluckman, Peter D; Godfrey, Keith M; Kwek, Kenneth; Saw, Seang-Mei; Yap, Fabian; Lee, Yung Seng; Chong, Mary Foong-Fong; van Dam, Rob M
2015-01-01
Maternal folate, vitamin B-12, and vitamin B-6 concentrations during pregnancy have been shown to influence birth outcomes, but the evidence is inconclusive. We aimed to examine the associations of maternal B-vitamin status with gestational age, birth weight, and length in a birth cohort study in Singapore. Maternal blood samples (n = 999) collected during weeks 26-28 of gestation were assayed for plasma folate, vitamin B-12, and vitamin B-6 concentrations. Birth weight and gestational age data were obtained from hospital records, and other anthropometric variables were measured within 72 h after birth. Relations between B-vitamin status and birth outcomes were assessed by linear or logistic regression with adjustment for potential confounders. Median (IQR) plasma concentrations were 34.4 (24.5-44.6) nmol/L for folate, 209 (167-258) pmol/L for vitamin B-12, and 61.8 (25.9-113) nmol/L for vitamin B-6. We found that higher plasma folate concentrations were associated with a longer gestational age (0.12 wk per SD increase in folate; 95% CI: 0.02, 0.21) and tended to be associated with lower risk of all preterm birth (delivery at <37 wk of gestation; OR: 0.79; 95% CI: 0.63, 1.00) and spontaneous preterm birth (OR: 0.76; 95% CI: 0.56, 1.04). Overall, concentrations of maternal folate, vitamin B-12, and vitamin B-6 were not independently associated with birth weight or being born small for gestational age (SGA; birth weight <10th percentile for gestational age). Higher maternal folate concentrations during late pregnancy were associated with longer gestational age and tended to be associated with a lower risk of preterm birth in this multiethnic Asian population. In contrast, the results of our study suggested little or no benefit of higher folate concentrations for reducing the risk of SGA or of higher vitamin B-6 and vitamin B-12 concentrations for reducing the risk of preterm birth or SGA. © 2015 American Society for Nutrition.
Estimation of Gestational Age, Using Neonatal Anthropometry: A Cross-sectional Study in India
Thawani, Rajat; Faridi, M.M.A.; Arora, Shilpa Khanna; Kumar, Rajeev
2013-01-01
Prematurity is a significant contributor to neonatal mortality in India. Conventionally, assessment of gestational age of newborns is based on New Ballard Technique, for which a paediatric specialist is needed. Anthropometry of the newborn, especially birthweight, has been used in the past to predict the gestational age of the neonate in peripheral health facilities where a trained paediatrician is often not available. We aimed to determine if neonatal anthropometric parameters, viz. birthweight, crown heel-length, head-circumference, mid-upper arm-circumference, lower segment-length, foot-length, umbilical nipple distance, calf-circumference, intermammary distance, and hand-length, can reliably predict the gestational age. The study also aimed to derive an equation for the same. We also assessed if these neonatal anthropometric parameters had a better prediction of gestational age when used in combination compared to individual parameters. We evaluated 1,000 newborns in a cross-sectional study conducted in Guru Teg Bahadur Hospital in Delhi. Detailed anthropometric estimation of the neonates was done within 48 hours after birth, using standard techniques. Gestational age was estimated using New Ballard Scoring. Out of 1,250 consecutive neonates, 1,000 were included in the study. Of them, 800 randomly-selected newborns were used in devising the model, and the remaining 200 newborns were used in validating the final model. Quadratic regression analysis using stepwise selection was used in building the predictive model. Birthweight (R=0.72), head-circumference (R=0.60), and mid-upper arm-circumference (R=0.67) were found highly correlated with gestation. The final equation to assess gestational age was as follows: Gestational age (weeks)=5.437×W–0.781×W2+2.815×HC–0.041×HC2+0.285×MUAC–22.745 where W=Weight, HC=Head-circumference and MUAC=Mid-upper arm-circumference; Adjusted R=0.76. On validation, the predictability of this equation is 46% (±1 week), 75.5% (+2 weeks), and 91.5% (+3 weeks). This mathematical model may be used in identifying preterm neonates. PMID:24592594
Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.
Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M
2007-03-15
Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.
The role of prenatal nutrition assistance on the prevalence of night blindness in pregnant adults.
Ribeiro Neves, Paulo Augusto; Ramalho, Andrea; De Carvalho Padilha, Patricia; Saunders, Cláudia
2014-05-01
In developing countries, night blindness is a very common public health problem among pregnant women. Evaluate the effect of the changes occurred on prenatal care concerning prenatal nutritional care on the occurrence of night blindness (XN) in adult pregnant women in public maternity hospital in Rio de Janeiro between 1999-2001 and between 2007-2008. Two cross-sectional studies were conducted, been the first one conducted between 1999-2001 and the second one between 2007-2008. Were studied 402 puerperal women, 225 between 1999-2001 (GI) and 177 between 2007-2008 (GII). The gestational XN was investigated during the immediate puerperium (GI) and during the prenatal/puerperium (GII), diagnosed by the World Health Organization. The study collected sociodemographic, clinical, obstetric, anthropometric and prenatal care information. It verified significant reduce of prevalence of gestational XN (GI = 18.7% e GII = 0.6%, p < 0.001). The occurrence of gestational XN was associated to sanitary conditions, education level, more than six prenatal consultations, miscarriage at last pregnancy, higher average number of deliveries, average number of prenatal care consultations and prenatal nutritional (p < 0.05). There was no association between gestational XN and marital status, skin color, pre-gestational nutritional status, adequacy of gain of total gestational weight, gestational anaemia and average number of pregnancies (p > 0.05). The inclusion of nutritional care in routine prenatal care may have contributed to the reduction of gestational XN. Studies to assess the nutritional intervention in the prevention and treatment of gestational XN at regions at greatest risk are suggested. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Body Mass Index, Overweight, and Obesity in Swedish Women Born Post-term.
Derraik, José G B; Lundgren, Maria; Cutfield, Wayne S; Ahlsson, Fredrik
2016-07-01
There is increasing evidence that post-term birth (≥42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood. Data were collected at first antenatal visit (~10-12 weeks of gestation) on singleton Swedish women aged ≥18 years in 1991-2009 (mean age 26.1 years), who were born post-term (n = 27 153) or at term (37-41 weeks of gestation; n = 184 245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very post-term (≥43 weeks of gestation; n = 5761) to those born within a narrower term window (38-40 weeks of gestation; n = 130 110). Increasing gestational age was associated with greater adult weight and body mass index (BMI). Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m(2) greater than those born at term. Differences were more marked between women born very post-term (≥43 weeks) vs. a narrower term group (38-40 weeks): 1.0 kg and 0.3 kg/m(2) . The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term. Post-term birth is associated with greater BMI and increased risk of overweight and obesity in adulthood, particularly among women born ≥43 weeks of gestation. © 2016 John Wiley & Sons Ltd.
Cruz-Martinez, R; Tenorio, V; Padilla, N; Crispi, F; Figueras, F; Gratacos, E
2015-10-01
To estimate the value of gestational age at birth and fetal Doppler parameters in predicting the risk of neonatal cranial abnormalities in intrauterine growth-restricted (IUGR) fetuses born between 28 and 34 weeks' gestation. Fetal Doppler parameters including umbilical artery (UA), middle cerebral artery (MCA), aortic isthmus, ductus venosus and myocardial performance index were evaluated in a cohort of 90 IUGR fetuses with abnormal UA Doppler delivered between 28 and 34 weeks' gestation and in 90 control fetuses matched for gestational age. The value of gestational age at birth and fetal Doppler parameters in predicting the risk of ultrasound-detected cranial abnormalities (CUA), including intraventricular hemorrhage, periventricular leukomalacia and basal ganglia lesions, was analyzed. Overall, IUGR fetuses showed a significantly higher incidence of CUA than did control fetuses (40.0% vs 12.2%, respectively; P < 0.001). Within the IUGR group, all predictive variables were associated individually with the risk of CUA, but fetal Doppler parameters rather than gestational age at birth were identified as the best predictor. MCA Doppler distinguished two groups with different degrees of risk of CUA (48.5% vs 13.6%, respectively; P < 0.01). In the subgroup with MCA vasodilation, presence of aortic isthmus retrograde net blood flow, compared to antegrade flow, allowed identification of a subgroup of cases with the highest risk of CUA (66.7% vs 38.6%, respectively; P < 0.05). Evaluation of fetal Doppler parameters, rather than gestational age at birth, allows identification of IUGR preterm fetuses at risk of neonatal brain abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Zhang, Yiting; Jin, Lei; Liu, Jian-meng; Ye, Rongwei; Ren, Aiguo
2016-01-01
Objective To examine the relationship between maternal hemoglobin (Hb) concentration and the risk of anemia in infancy. Study design This analysis included 17,193 women who entered the trial when they were 20 years of age or older, no more than 20 weeks of gestation, had mild or no anemia, and delivered singleton live births. Maternal Hb concentrations were measured in the first trimester and during 24-28 weeks of gestation; infant Hb concentrations were measured at 5-7 months and 11-13 months of life. The associations between maternal Hb concentrations and infant Hb concentrations were examined. Results Maternal Hb concentrations measured during 24-28 weeks of gestation, but not in the first trimester, were correlated with infant Hb concentrations measured at either of the two post-partum periods. The risk of infant anemia at 5-7 months increased when maternal Hb concentration was ≤109 g/L during 24-28 weeks of gestation ([AOR: 1.95, 95% CI: 1.59-2.40] and 11-13 months [AOR: 1.72, 95% CI: 1.36-2.18]); whereas the risk of anemia during 5-7 months as well as 11-13 months in infancy decreased when maternal Hb level at 24-28 weeks of gestation was 120-129 g/L (AOR for 5-7 months: 0.74, 95% CI: 0.64-0.85; AOR for 11-13 months: 0.72, 95% CI: 0.61-0.85) or ≥130 g/L (AOR for 5-7 months: 0.75, 95% CI: 0.63-0.90; AOR for 11-13 months: 0.89, 95% CI: 0.73-1.08). Conclusion Low maternal Hb concentration during 24-28 weeks of gestation was associated with an increased risk of anemia in infancy, whereas high maternal Hb concentration was associated with a reduced risk of anemia. PMID:27263403
Qiu, Y H; Xu, Y L; Zhang, W H
2016-06-03
We investigate the role of the GSTM1, GSTT1, and GSTP1 IIe105Val genetic polymorphisms in the susceptibility to gestational diabetes mellitus. A total of 223 pregnant women with gestational diabetes mellitus and 265 healthy pregnant women were examined at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2013 to November 2013. Genotyping for detection of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms was conducted using the restriction fragment length polymorphism-polymerase chain reaction. There were statistically significant differences between patients with gestational diabetes mellitus and control subjects in terms of age (χ(2) = 6.68, P = 0.01) and BMI (t = 7.56, P < 0.001) levels of HDL-C (t = 2.62, P = 0.005) and LDL-C (t = 3.98, P < 0.001). By the chi-square test, we found significant differences between the present and null genotype distributions of GSTM1 (χ(2) = 10.95, P = 0.0009). Null genotype of GSTM1 could influence the susceptibility to gestational diabetes mellitus compared to the present genotype [adjusted OR (95%CI) = 1.85 (1.26-2.72)]. However, the unconditional logistic analysis revealed that GSTT1 and GSTP1 IIe105Val polymorphisms could not influence the risk of gestational diabetes mellitus in a Chinese population. In summary, we suggest that the GSTM1 gene polymorphism could influence the susceptibility to gestational diabetes mellitus in a Chinese population.
Fetal kidney length as a useful adjunct parameter for better determination of gestational age.
Ugur, Mete G; Mustafa, Aynur; Ozcan, Huseyin C; Tepe, Neslihan B; Kurt, Huseyin; Akcil, Emre; Gunduz, Reyhan
2016-05-01
To determine the validity of fetal kidney length and amniotic fluid index (AFI) in labor dating. This prospective study included 180 pregnant women followed up in the outpatient clinic at the Department of Obstetrics and Gynecology, Gaziantep University, Turkey, between January 2014 and January 2015. The gestational age (GA) was estimated by early fetal ultrasound measures and last menstrual period. Routine fetal biometric parameters, fetal kidney length, and amniotic fluid index were measured. We studied the correlation between fetal kidney length, amniotic fluid index, and gestational age. The mean gestational age depending on last menstrual period and early ultrasound was 31.98±4.29 (24-39 weeks). The mean kidney length was 35.66±6.61 (19-49 mm). There was a significant correlation between gestational age and fetal kidney length (r=0.947, p=0.001). However, there was a moderate negative correlation between GA and AFI. Adding fetal kidney length to the routine biometrics improved the effectiveness of the model used to estimate GA (R2=0.965 to R2=0.987). Gestational age can be better predicted by adding fetal kidney length to other routine parameters.
Stirrat, Laura I; O'Reilly, James R; Barr, Sarah M; Andrew, Ruth; Riley, Simon C; Howie, Alexander F; Bowman, Maria; Smith, Roger; Lewis, John G; Denison, Fiona C; Forbes, Shareen; Seckl, Jonathan R; Walker, Brian R; Norman, Jane E; Reynolds, Rebecca M
2016-01-01
The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation. Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects. Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation). In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Effects of competition among fertility centers on pregnancy and high-order multiple gestation rates.
Steiner, Anne Z; Paulson, Richard J; Hartmann, Katherine E
2005-05-01
To measure the effect of competition among fertility centers on pregnancy and high-order multiple (HOM) gestation rates after IVF. Retrospective cohort study. Four hundred eight fertility clinics registered with the Society for Assisted Reproductive Technology as providing IVF services in 2000. Competition was defined as number of clinics in a geographically defined area. Demand for services was based on the population of reproductive-aged women. Three hundred eighty-one fertility clinics reporting clinical outcomes. Pregnancy rates, HOM gestation rates, population of reproductive-aged women, and number of competing clinics were calculated for each clinic from Society for Assisted Reproductive Technology and census data. The clinic HOM gestation rate (percentage of pregnancies that were HOM) and age-adjusted pregnancy rate. The number of clinics in an area of competition ranged from 1 to 22. The HOM gestation rate per clinic ranged from 0% to 50%. As demand increased, competition increased. As competition increased, the number of HOM pregnancies per clinic decreased. In areas of low competition (1 to 2 clinics) the clinic HOM gestation rate was 8.43%, in areas of intermediate competition (3-7 clinics) 8.39%, and in areas of high competition (8-22 clinics) 8.24%. In areas with intermediate demand, high levels of competition resulted in fewer HOM pregnancies than intermediate competition (relative risk 0.56, 95% confidence interval 0.36-0.89) or low levels of competition (RR 0.57, 95% confidence interval 0.35-0.94). Age-adjusted pregnancy rates did not differ by level of competition. According to these data, the risk of HOM gestation decreases with increasing competition among clinics; however, pregnancy rates are unaffected.
Maternal and placental risk factors for light-for-gestational-age births.
Aoyama, Keiko; Endo, Toshiaki; Saito, Tsuyoshi; Izumi, Hisako; Asakura, Sumiyo; Mori, Mitsuru
2016-07-01
We conducted a cross-sectional study to investigate risk factors for births of light-for-gestational-age (LGA) infants. A survey was conducted at the Department of Obstetrics and Gynecology at Sapporo Medical University Hospital in Sapporo, Japan from 2013 to 2014. LGA and appropriate for gestational age (AGA) are defined as having a birthweight below the 10th percentile and between the 10th percentile and 90th percentile for gestational age at birth in the population standard of gestational age, sex, and parity, respectively. An odds ratio (OR) and its 95% confidence interval (95%CI) for LGA were calculated by analysis using the logistic regression model. In total, 307 inpatients (94.2%) participated in the study out of 326 consecutive post-partum inpatients. Among them, 37 infants and 237 infants were classified into the LGA and AGA groups, respectively. As a result of multivariable analysis, prevalence of gestational hypertension (OR = 8.96, 95%CI 1.81-44.35) and the presence of placental infarction (OR = 9.65, 95%CI 1.76-53.01) were significantly associated with an increased risk of LGA. Placentas weighing 510-603 g and ≥604 g were significantly associated with reduced risk of LGA (OR = 0.04, 95%CI 0.01-0.29 and OR = 0.03, 95%CI 0.01-0.32, respectively), and higher placental weights were significantly observed in the trend for reduced LGA risk (P for trend < 0.001). We found that the prevalence of gestational hypertension, lower placental weight, and the presence of placental infarctions were all independently associated with the risk of LGA. Placental abnormalities may be etiologically important for LGA risk, though further research is necessary. © 2016 Japan Society of Obstetrics and Gynecology.
Gernand, Alison D; Paul, Rina Rani; Ullah, Barkat; Taher, Muhammad A; Witter, Frank R; Wu, Lee; Labrique, Alain B; West, Keith P; Christian, Parul
2016-10-21
The best method of gestational age assessment is by ultrasound in the first trimester; however, this method is impractical in large field trials in rural areas. Our objective was to assess the validity of gestational age estimated from prospectively collected date of last menstrual period (LMP) using crown-rump length (CRL) measured in early pregnancy by ultrasound. As part of a large, cluster-randomized, controlled trial in rural Bangladesh, we collected dates of LMP by recall and as marked on a calendar every 5 weeks in women likely to become pregnant. Among those with a urine-test confirmed pregnancy, a subset with gestational age of <15 weeks (n = 353) were enrolled for ultrasound follow-up to measure CRL. We compared interview-assessed LMP with CRL gestational age estimates and classification of preterm, term, and post-term births. LMP-based gestational age was higher than CRL by a mean (SD) of 2.8 (10.7) days; differences varied by maternal education and preterm birth (P < 0.05). Lin's concordance correlation coefficient was good at ultrasound [0.63 (95 % CI 0.56, 0.69)] and at birth [0.77 (95 % CI 0.73, 0.81)]. Validity of classifying preterm birth was high but post-term was lower, with specificity of 96 and 89 % and sensitivity of 86 and 67 %, respectively. Results were similar by parity. Prospectively collected LMP provided a valid estimate of gestational age and preterm birth in a rural, low-income setting and may be a suitable alternative to ultrasound in programmatic settings and large field trials. ClinicalTrials.gov NCT00860470.
Christian, Lisa M.; Blair, Lisa M.; Porter, Kyle; Lower, Mary; Cole, Rachel M.; Belury, Martha A.
2016-01-01
Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20–27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio. PMID:26859301
Risk factors for classical hysterotomy by gestational age.
Osmundson, Sarah S; Garabedian, Matthew J; Lyell, Deirdre J
2013-10-01
To examine the likelihood of classical hysterotomy across preterm gestational ages and to identify factors that increase its occurrence. This is a secondary analysis of a prospective observational cohort collected by the Maternal-Fetal Medicine Network of all women with singleton gestations who underwent a cesarean delivery with a known hysterotomy. Comparisons were made based on gestational age. Factors thought to influence hysterotomy type were studied, including maternal age, body mass index, parity, birth weight, small for gestational age (SGA) status, fetal presentation, labor preceding delivery, and emergent delivery. Approximately 36,000 women were eligible for analysis, of whom 34,454 (95.7%) underwent low transverse hysterotomy and 1,562 (4.3%) underwent classical hysterotomy. The median gestational age of women undergoing a classical hysterotomy was 32 weeks and the incidence peaked between 24 0/7 weeks and 25 6/7 weeks (53.2%), declining with each additional week of gestation thereafter (P for trend <.001). In multivariable regression, the likelihood of classical hysterotomy was increased with SGA (n=258; odds ratio [OR] 2.71; confidence interval [CI] 1.78-4.13), birth weight 1,000 g or less (n=467; OR 1.51; CI 1.03-2.24), and noncephalic presentation (n=783; OR 2.03; CI 1.52-2.72). The likelihood of classical hysterotomy was decreased between 23 0/7 and 27 6/7 weeks of gestation and after 32 weeks of gestation when labor preceded delivery, and increased between 28 0/7 and 31 6/7 weeks of gestation and after 32 weeks of gestation by multiparity and previous cesarean delivery. Emergent delivery did not predict classical hysterotomy. Fifty percent of women at 23-26 weeks of gestation who undergo cesarean delivery have a classical hysterotomy, and the risk declines steadily thereafter. This likelihood is increased by fetal factors, especially SGA and noncephalic presentation. : II.
Tobi, Elmar W; Slieker, Roderick C; Stein, Aryeh D; Suchiman, H Eka D; Slagboom, P Eline; van Zwet, Erik W; Heijmans, Bastiaan T; Lumey, LH
2015-01-01
Background: The manipulation of pregnancy diets in animals can lead to changes in DNA methylation with phenotypic consequences in the offspring. Human studies have concentrated on the effects of nutrition during early gestation. Lacking in humans is an epigenome-wide association study of DNA methylation in relation to perturbations in nutrition across all gestation periods. Methods: We used the quasi-experimental setting of the Dutch famine of 1944–45 to evaluate the impact of famine exposure during specific 10-week gestation periods, or during any time in gestation, on genome-wide DNA methylation levels at age ∼ 59 years. In addition, we evaluated the impact of exposure during a shorter pre- and post-conception period. DNA methylation was assessed using the Illumina 450k array in whole blood among 422 individuals with prenatal famine exposure and 463 time- or sibling-controls without prenatal famine exposure. Results: Famine exposure during gestation weeks 1–10, but not weeks 11–20, 21–30 or 31-delivery, was associated with an increase in DNA methylation of CpG dinucleotides cg20823026 (FAM150B), cg10354880 (SLC38A2) and cg27370573 (PPAP2C) and a decrease of cg11496778 (OSBPL5/MRGPRG) (P < 5.9 × 10−7, PFDR < 0.031). There was an increase in methylation of TACC1 and ZNF385A after exposure during any time in gestation (P < 2.0 × 10−7, PFDR = 0.034) and a decrease of cg23989336 (TMEM105) after exposure around conception. These changes represent a shift of 0.3–0.6 standard deviations and are linked to genes involved in growth, development and metabolism. Conclusion: Early gestation, and not mid or late gestation, is identified as a critical time-period for adult DNA methylation changes in whole blood after prenatal exposure to famine. PMID:25944819
Determining gestational age and preterm birth in rural Guatemala: A comparison of methods.
Weinstein, John R; Thompson, Lisa M; Díaz Artiga, Anaité; Bryan, Joe P; Arriaga, William E; Omer, Saad B; McCracken, John P
2018-01-01
Preterm birth is the leading cause of death among children <5 years of age. Accurate determination of prematurity is necessary to provide appropriate neonatal care and guide preventive measures. To estimate the most accurate method to identify infants at risk for adverse outcomes, we assessed the validity of two widely available methods-last menstrual period (LMP) and the New Ballard (NB) neonatal assessment-against ultrasound in determining gestational age and preterm birth in highland Guatemala. Pregnant women (n = 188) were recruited with a gestational age <20 weeks and followed until delivery. Ultrasound was performed by trained physicians and LMP was collected during recruitment. NB was performed on infants within 96 hours of birth by trained study nurses. LMP and NB accuracy at determining gestational age and identifying prematurity was assessed by comparing them to ultrasound. By ultrasound, infant mean gestational age at birth was 38.3 weeks (SD = 1.6) with 16% born at less than 37 gestation. LMP was more accurate than NB (mean difference of +0.13 weeks for LMP and +0.61 weeks for NB). However, LMP and NB estimates had low agreement with ultrasound-determined gestational age (Lin's concordance<0.48 for both methods) and preterm birth (κ<0.29 for both methods). By LMP, 18% were judged premature compared with 6% by NB. LMP underestimated gestational age among women presenting later to prenatal care (0.18 weeks for each additional week). Gestational age for preterm infants was overestimated by nearly one week using LMP and nearly two weeks using NB. New Ballard neuromuscular measurements were more predictive of preterm birth than those measuring physical criteria. In an indigenous population in highland Guatemala, LMP overestimated prematurity by 2% and NB underestimated prematurity by 10% compared with ultrasound estimates. New, simple and accurate methods are needed to identify preterm birth in resource-limited settings worldwide.
Determining gestational age and preterm birth in rural Guatemala: A comparison of methods
Thompson, Lisa M.; Díaz Artiga, Anaité; Bryan, Joe P.; Arriaga, William E.; Omer, Saad B.; McCracken, John P.
2018-01-01
Background Preterm birth is the leading cause of death among children <5 years of age. Accurate determination of prematurity is necessary to provide appropriate neonatal care and guide preventive measures. To estimate the most accurate method to identify infants at risk for adverse outcomes, we assessed the validity of two widely available methods—last menstrual period (LMP) and the New Ballard (NB) neonatal assessment—against ultrasound in determining gestational age and preterm birth in highland Guatemala. Methods Pregnant women (n = 188) were recruited with a gestational age <20 weeks and followed until delivery. Ultrasound was performed by trained physicians and LMP was collected during recruitment. NB was performed on infants within 96 hours of birth by trained study nurses. LMP and NB accuracy at determining gestational age and identifying prematurity was assessed by comparing them to ultrasound. Results By ultrasound, infant mean gestational age at birth was 38.3 weeks (SD = 1.6) with 16% born at less than 37 gestation. LMP was more accurate than NB (mean difference of +0.13 weeks for LMP and +0.61 weeks for NB). However, LMP and NB estimates had low agreement with ultrasound-determined gestational age (Lin’s concordance<0.48 for both methods) and preterm birth (κ<0.29 for both methods). By LMP, 18% were judged premature compared with 6% by NB. LMP underestimated gestational age among women presenting later to prenatal care (0.18 weeks for each additional week). Gestational age for preterm infants was overestimated by nearly one week using LMP and nearly two weeks using NB. New Ballard neuromuscular measurements were more predictive of preterm birth than those measuring physical criteria. Conclusion In an indigenous population in highland Guatemala, LMP overestimated prematurity by 2% and NB underestimated prematurity by 10% compared with ultrasound estimates. New, simple and accurate methods are needed to identify preterm birth in resource-limited settings worldwide. PMID:29554145
Maternity leave in the ninth month of pregnancy and birth outcomes among working women.
Guendelman, Sylvia; Pearl, Michelle; Graham, Steve; Hubbard, Alan; Hosang, Nap; Kharrazi, Martin
2009-01-01
The health effects of antenatal maternity leave have been scarcely evaluated. In California, women are eligible for paid benefits up to 4 weeks before delivery. We explored whether leave at > or =36 weeks gestation increases gestation and birthweight, and reduces primary cesarean deliveries among full-time working women. Drawing from a 2002--2003 nested case-control study of preterm birth and low birthweight among working women in Southern California, we compared a cohort of women who took leave (n = 62) or worked until delivery (n = 385). Models weighted for probability of sampling were used to calculate hazards ratios for gestational age, odds ratios (OR) for primary cesarean delivery, and multilinear regression coefficients for birthweight. Leave-takers were similar to non-leave-takers on demographic and health characteristics, except that more clerical workers took leave (p = .02). Compared with non-leave-takers, leave-takers had almost 4 times lower odds of cesarean delivery after adjusting for covariates (OR, 0.27; 95% confidence interval [CI], 0.08-0.94). Overall, there were no marked differences in length of gestation or mean birthweight. However, in a subgroup of women whose efforts outstripped their occupational rewards, gestation was prolonged (hazard ratio for delivery each day between 36 and 41 weeks, 0.56; 95% CI, 0.34-0.93). Maternity leave in late pregnancy shows promise for reducing cesarean deliveries and prolonging gestation in occupationally strained women.
Velickovic, Ksenija; Cvoro, Aleksandra; Srdic, Biljana; Stokic, Edita; Markelic, Milica; Golic, Igor; Otasevic, Vesna; Stancic, Ana; Jankovic, Aleksandra; Vucetic, Milica; Buzadzic, Biljana; Korac, Bato; Korac, Aleksandra
2014-01-01
Brown adipose tissue (BAT) has the unique ability of generating heat due to the expression of mitochondrial uncoupling protein 1 (UCP1). A recent discovery regarding functional BAT in adult humans has increased interest in the molecular pathways of BAT development and functionality. An important role for estrogen in white adipose tissue was shown, but the possible role of estrogen in human fetal BAT (fBAT) is unclear. The objective of this study was to determine whether human fBAT expresses estrogen receptor α (ERα) and ERβ. In addition, we examined their localization as well as their correlation with crucial proteins involved in BAT differentiation, proliferation, mitochondriogenesis and thermogenesis including peroxisome proliferator-activated receptor γ (PPARγ), proliferating cell nuclear antigen (PCNA), PPARγ-coactivator-1α (PGC-1α), and UCP1. The fBAT was obtained from 4 human male fetuses aged 15, 17, 20, and 23 weeks gestation. ERα and ERβ expression was assessed using Western blotting, immunohistochemistry, and immunocytochemistry. Possible correlations with PPARγ, PCNA, PGC-1α, and UCP1 were examined by double immunofluorescence. Both ERα and ERβ were expressed in human fBAT, with ERα being dominant. Unlike ERβ, which was present only in mature brown adipocytes, we detected ERα in mature adipocytes, preadipocytes, mesenchymal and endothelial cells. In addition, double immunofluorescence supported the notion that differentiation in fBAT probably involves ERα. Immunocytochemical analysis revealed mitochondrial localization of both receptors. The expression of both ERα and ERβ in human fBAT suggests a role for estrogen in its development, primarily via ERα. In addition, our results indicate that fBAT mitochondria could be targeted by estrogens and pointed out the possible role of both ERs in mitochondriogenesis.
Intrauterine position affects fetal weight and crown-rump length throughout gestation.
Jang, Y D; Ma, Y L; Lindemann, M D
2014-10-01
To investigate the effect of intrauterine positions on fetal growth throughout gestation, data from a total of 65 gilts (n = 784 fetuses) that were slaughtered at assigned days of gestation (d 43, 58, 73, 91, 101, and 108) on a project to evaluate fetal mineral deposition were used. Placenta units were removed from the uterus, and position, sex, weight, and crown-rump length (CRL) of each fetus were recorded. Fetuses were classified into 5 categories within a uterine horn for the absolute intrauterine position: the ovarian end (OE) of the uterine horn, next to the ovarian end (NOE), the middle (MD), next to the cervical end (NCE), and the cervical end (CE), and also classified for the relative fetal position with respect to the sex of adjacent fetuses. Fetuses at the OE and NOE of the uterine horn tended to be heavier (P = 0.06) and longer (P < 0.05) than those at the MD of the uterine horn at d 58 of gestation. Fetuses at the OE of the uterine horn were also heavier and longer than those at the MD and NCE of the uterine horn at d 101 and 108 of gestation (P < 0.05). Fetuses at the CE of the uterine horn were intermediate in weight and length. There were no major effects of adjacent fetal sex (fetuses surrounded by the opposite sexes) in weight or length. Male fetuses were heavier than female fetuses at d 43, 58, 73, and 108 of gestation (P < 0.05) and longer than female fetuses at d 58 (P = 0.06), 73 (P < 0.05), 101 (P = 0.07), and 108 (P < 0.05) of gestation. Fetal weight was highly correlated with CRL at all gestational ages (P < 0.01). These results indicate that 1) the absolute intrauterine position affects fetal growth more than the sex of the adjacent fetus in the uterine horn, 2) each end of the uterine horn (OE and CE) has heavier fetuses than the MD, and 3) male pigs grow faster than female pigs even before birth.
Influence of Gestational Age and Body Weight on the Pharmacokinetics of Labetalol in Pregnancy
Fischer, James H.; Sarto, Gloria E.; Hardman, Jennifer; Endres, Loraine; Jenkins, Thomas M.; Kilpatrick, Sarah J.; Jeong, Hyunyoung; Geller, Stacie; Deyo, Kelly; Fischer, Patricia A.; Rodvold, Keith A.
2015-01-01
Background and Objectives Labetalol is frequently prescribed for treatment of hypertension during pregnancy. However, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol during and after pregnancy in women receiving labetalol for hypertension. Methods Data were collected from 57 women receiving the drug for hypertension from the 12th week of pregnancy through 12 weeks postpartum using a prospective, longitudinal design. A sparse sampling strategy guided collection of plasma samples. Samples were assayed for labetalol by high performance liquid chromatography. Estimation of population pharmacokinetic parameters and covariate effects was performed by nonlinear mixed effects modeling using NONMEM. Final population model was validated by bootstrap analysis and visual predictive check. Simulations were performed with the final model to evaluate the appropriate body weight to guide labetalol dosing. Results Lean body weight (LBW) and gestational age, i.e., weeks of pregnancy, were identified as significantly influencing oral clearance (CL/F) of labetalol, with CL/F ranging from 1.4-fold greater than postpartum values at 12 weeks gestational age to 1.6-fold greater at 40 weeks. Doses adjusted for LBW provide more consistent drug exposure than doses adjusted for total body weight. The apparent volumes of distribution for the central compartment and at steady-state were 1.9-fold higher during pregnancy. Conclusions Gestational age and LBW impact the pharmacokinetics of labetalol during pregnancy and have clinical implications for adjusting labetalol doses in these women. PMID:24297680
Maerdan, Malipati; Shi, Chunyan; Zhang, Xiaoxiao; Fan, Lixin
2017-07-01
The objective of this study is to understand the prevalence of short cervical length between 20 and 24 weeks gestation in China and to evaluate the efficacy of micronized progesterone for prolonging gestation in nulliparous patients with a short cervix. From May 2010 to May 2015, a total of 25 328 asymptomatic women with singleton pregnancies at Peking University First Hospital had their cervical length routinely measured between 20 and 24 weeks of gestation. A cervical length of 25 mm or less was defined as a shortened cervical length. The therapies prescribed include vaginal micronized progesterone capsules (200 mg each night) or bed rest from 20 to 34 weeks of gestation. The primary outcome was spontaneous delivery before 33 weeks. (1) One hundred fourteen women had a cervical length of ≤25 mm (0.45%). (2) Twenty-nine of which with previous spontaneous preterm delivery or late pregnancy loss had cervical cerclage, the remaining 85 women by the use of vaginal progesterone or simply resting activity restriction to prevent preterm birth. (3) In 85 nulliparous women treated by progesterone or bed rest, progesterone use in cervical length between 10 and 20 mm was associated with a statistically significant reduction in the incidence of preterm birth at <33 weeks of gestation (9.5% versus 45.5%, p = 0.02) compared with bed rest. There were no significant differences in cervical length between 20 and 25 mm in their rates of spontaneous preterm delivery at <33 (5.3% versus 3.2%, p = 0.72), <37 (33.3% versus 54.5%, p = 0.25), or <35 weeks (14.3% versus 45.5, p = 0.06) of gestation between vaginal progesterone and bed rest. The rate of short cervical length was less than expected. Vaginal progesterone is efficacious for the prolonging of gestation in women with a cervical length of 10-20 mm in the mid-trimester for a singleton gestation and nulliparous women. For a cervical length of 20-25 mm in the mid trimester, vaginal progesterone compared with bed rest did not prolong pregnancy.
Kim, Bang-Sil
2007-01-01
Serial ultrasonographic examinations were performed daily on 9 Miniature Schnauzer bitches from the 15th day of gestation until parturition to determine the time the gestational structures were first detected. The gestational age was timed from the day of ovulation (day 0), which was estimated to occur when the plasma progesterone concentration was >4.0 ng/ml. The gestational length in 9 Miniature Schnauzer bitches was found to be 63.0 ± 1.7 (range 61-65) days. The initial detection of the fetal and extra-fetal structures were as follows: gestational sac at day 18.0 ± 0.9 (17-19); zonary placenta in the uterine wall at day 24.9 ± 1.1 (23-26); yolk sac membrane at day 25.0 ± 0.9 (24-26); amnionic membrane at day 27.7 ± 1.0 (26-29); embryo initial detection at day 22.6 ± 0.5 (22-23); heartbeat at day 23.4 ± 0.5 (23-24); fetal movement at day 32.5 ± 0.8 (32-34); stomach at day 31.2 ± 1.6 (29-33); urinary bladder at day 32.6 ± 1.8 (31-35); skeleton at day 34.9 ± 1.6 (34-38) and kidney at day 42.2 ± 0.7 (41-43). PMID:17679777
Exercise during pregnancy and its association with gestational weight gain.
Harris, Shericka T; Liu, Jihong; Wilcox, Sara; Moran, Robert; Gallagher, Alexa
2015-03-01
We examined the association between exercise during pregnancy and meeting gestational weight gain recommendations. Data came from the 2009 South Carolina Pregnancy Risk Assessment Monitoring System (n = 856). Women reported their participation in exercise/sports activities before and during pregnancy, including the number of months and types of exercise. We developed an exercise index (EI), the product of the number of months spent in exercise and average metabolic equivalents for specific exercise. The 2009 Institute of Medicine's guideline was used to categorize gestational weight gain into three classes: inadequate, adequate, and excessive. Multinomial logistic regression models were used to adjust for confounders. Over 46 % of women exceeded the recommended weight gain during pregnancy. Nearly one third (31.9 %) of women reported exercising ≥3 times a week at any time during pregnancy. Compared to women who did not report this level of exercise during pregnancy, exercising women were more likely to meet gestational weight gain recommendations (32.7 vs. 18.7 %) and had a lower odds of excessive gestational weight gain [adjusted odds ratio (AOR) 0.43, 95 % confidence interval 0.24-0.78]. Women with an EI above the median value of those women who exercised or women who exercised ≥3 times a week for 6-9 months during pregnancy had lower odds of excessive gestational weight gain (AOR for EI 0.20, 0.08-0.49; AOR for months 0.26, 0.12-0.56, respectively). Our findings support the need to promote or increase exercise during pregnancy to reduce the high proportion of women who are gaining excessive weight.
Swift, Judy A; Langley-Evans, Simon C; Pearce, Jo; Jethwa, Preeti H; Taylor, Moira A; Avery, Amanda; Ellis, Sarah; McMullen, Sarah; Elliott-Sale, Kirsty J
2017-06-01
to investigate women's physical activity levels, diet and gestational weight gain, and their experiences and motivations of behavior change. analysis of cross-sectional data collected during a longitudinal, cohort study examining physiological, psychological, sociodemographic, and self-reported behavioural measures relating to bodyweight. women recruited from routine antenatal clinics at the Nottingham University Hospitals NHS Trust. 193 women ≤27 weeks gestation and aged 18 years or over. MEASUREMENTS & FINDINGS: measurements included weight and height, the Dietary Instrument for Nutrition Education (Brief Version), the International Physical Activity Questionnaire (Short Form), and open questions of perceptions of behaviour change. 50.3% (n=97) were overweight/obese, and women gained 0.26kg/wk (IQR 0.34kg/wk) since conception. The majority consumed low levels of fat (n=121; 63.4%), high levels of unsaturated fat (n=103; 53.9%), and used a dietary supplement (n=166; 86.5%). However, 41% (n=76) were inactive, 74.8% (n=143) did not consume high levels of fibre, and 90.0% (n=171) consumed less than 5 portions of fruit and vegetables a day. Body mass index category was not associated with diet, physical activity levels, or gestational weight gain. Themes generated from open-questions relating to behaviour change were: (1) Risk management, (2) Coping with symptoms, (3) Self-control, (4) Deviation from norm, (5) Nature knows best. early pregnancy is a period of significant and heterogeneous behaviour change, influenced by perceptions of risk and women's lived experience. Behaviour was influenced not only by perceptions of immediate risk to the fetus, but also by the women's lived experience of being pregnant. There are exciting opportunities to constructively reframe health promotion advice relating to physical activity and diet in light of women's priorities. The need for individualized advice is highlighted, and women across all body mass index categories would benefit from improved diet and physical activity levels. Copyright © 2017 Elsevier Ltd. All rights reserved.
Resuscitation of neonates at 23 weeks' gestational age: a cost-effectiveness analysis.
Partridge, J Colin; Robertson, Kathryn R; Rogers, Elizabeth E; Landman, Geri Ottaviano; Allen, Allison J; Caughey, Aaron B
2015-01-01
Resuscitation of infants at 23 weeks' gestation remains controversial; clinical practices vary. We sought to investigate the cost effectiveness of resuscitation of infants born 23 0/7-23 6/7 weeks' gestation. Decision-analytic modeling comparing universal and selective resuscitation to non-resuscitation for 5176 live births at 23 weeks in a theoretic U.S. cohort. Estimates of death (77%) and disability (64-86%) were taken from the literature. Maternal and combined maternal-neonatal utilities were applied to discounted life expectancy to generate QALYs. Incremental cost-effectiveness ratios were calculated, discounting costs and QALYs. Main outcomes included number of survivors, their outcome status and incremental cost-effectiveness ratios for the three strategies. A cost-effectiveness threshold of $100 000/QALY was utilized. Universal resuscitation would save 1059 infants: 138 severely disabled, 413 moderately impaired and 508 without significant sequelae. Selective resuscitation would save 717 infants: 93 severely disabled, 279 moderately impaired and 343 without significant sequelae. For mothers, non-resuscitation is less expensive ($19.9 million) and more effective (127 844 mQALYs) than universal resuscitation ($1.2 billion; 126 574 mQALYs) or selective resuscitation ($845 million; 125 966 mQALYs). For neonates, both universal and selective resuscitation were cost-effective, resulting in 22 256 and 15 134 nQALYS, respectively, versus 247 nQALYs for non-resuscitation. In sensitivity analyses, universal resuscitation was cost-effective from a maternal perspective only at utilities for neonatal death <0.42. When analyzed from a maternal-neonatal perspective, universal resuscitation was cost-effective when the probability of neonatal death was <0.95. Over wide ranges of probabilities for survival and disability, universal and selective resuscitation strategies were not cost-effective from a maternal perspective. Both strategies were cost-effective from a maternal-neonatal perspective. This study offers a metric for counseling and decision-making for extreme prematurity. Our results could support a more permissive response to parental requests for aggressive intervention at 23 weeks' gestation.
Generation of the Starting Plane Flowfield for Supersonic Flow over a Spherically Capped Body
1985-05-09
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Wang, Chao-Xian; Chen, Fang; Zhang, Wen-Fei; Zhang, Shi-Hai; Shi, Kui; Song, Han-Qing; Wang, Yi-Jiang; Kim, Sung Woo; Guan, Wu-Tai
2018-04-18
Leucine (Leu) plays an important role in protein synthesis and metabolism. The present study tested whether Leu supplementation in the diet for sows during late pregnancy could improve piglet birth weight, and it also investigated the possible underlying mechanism. Two hundred sows at day 70 of pregnancy were selected and assigned to four groups fed with following four diets until farrowing, respectively: corn and soybean meal-based diet group (CON), CON + 0.40% Leu, CON + 0.80% Leu, and CON + 1.20% Leu. We found that supplementing with 0.80% Leu significantly increased mean piglet birth weight ( P < 0.05). Supplementation with 0.40, 0.80, and 1.20% Leu increased the plasma concentration of Leu, while decreasing the plasma concentrations of valine (Val) and isoleucine (Ile) in both farrowing sows and newborn piglets ( P < 0.05). The protein expressions of amino acid transporters (including LAT1, SNAT1, SNAT2, 4F2hc, and rBAT) in duodenum, jejunum, ileum, longissimus dorsi muscle of newborn piglets, and placenta of sows showed a difference among the CON group and Leu supplemented groups. Expressions of p-mTOR, p-4E-BP1, and p-S6K1 in longissimus dorsi muscle were also enhanced in each of the supplemental Leu groups compared to CON ( P < 0.05). Collectively, these results indicated that 0.40-0.80% Leu supplementation during late gestation enhanced birth weight of fetal pigs by increasing protein synthesis through modulation of the plasma amino acids profile, amino acid transporters expression, and mTOR signaling pathway.
The influence of prophylactic factor VIII in severe hemophilia A
Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E
2013-01-01
Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation (maximum level and rate) in both empirical and computational systems increased as the level of fVIII increased. FXIII activation rates also increased as the fVIII level increased. Upon suppression of fVIII, thrombin generation became comparable in both systems. Plasma composition analysis showed a negative correlation between bleeding history and computational thrombin generation in the absence of fVIII. Conclusion Residual prophylactic fVIII directly causes an increase in thrombin generation and fibrin cross-linking in individuals with clinically severe hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664
Saccone, Gabriele; Berghella, Vincenzo
2015-08-01
The purpose of this study was to evaluate the efficacy of omega-3 supplementation for the prevention of recurrent preterm birth (PTB) in asymptomatic singleton gestations with previous PTB. We searched fish oil, long chain polyunsaturated fatty acids, pregnancy, and omega-3 in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials from inception of each database to December 2014 with no limit for language. In addition the reference lists of all identified articles were examined to identify studies that were not captured by electronic searches. We performed a metaanalysis of randomized controlled trials of asymptomatic singleton gestations with previous PTB who were assigned randomly to prophylactic omega-3 supplementation vs control (either placebo or no treatment). The primary outcome was predefined as PTB at <37 weeks of gestation. The pooled results were reported as relative risk (RR) with 95% confidence interval (95% CI). The protocol of this review was registered with PROSPERO (registration number: CRD42015016371). Two randomized controlled trials that included 1080 women were analyzed. The mean gestational age at randomization was approximately 134 days in both groups (mean difference, 0.01 days; 95% CI, -0.13 to 0.14). Women who received omega-3 had similar rates of PTB at <37 weeks of gestation (34.5% vs 39.8%; RR, 0.81; 95% CI, 0.59-1.12) and PTB at <34 weeks of gestation (12.0% vs 15.4%; RR, 0.62; 95% CI, 0.26-1.46) compared with control subjects. The omega-3 groups had a statistically significantly longer latency (mean difference, 2.10 days; 95% CI, 1.98-2.22) and higher birthweight (mean difference, 102.52 g; 95% CI, 20.09-184.95) compared with control subjects; the other secondary outcomes (which included gestational age at delivery, spontaneous PTB at <37 and 34 weeks of gestation, admission to the intensive care unit, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, and perinatal death) were similar. Omega-3 supplementation during pregnancy does not prevent recurrent PTB in asymptomatic singleton gestations with previous PTB. The benefits in longer latency and higher birth weight may deserve further study. Copyright © 2015 Elsevier Inc. All rights reserved.
Ashwal, Eran; Shinar, Shiri; Wertheimer, Avital; Reina, Luciena; Miremberg, Hadas; Aviram, Amir; Yogev, Yariv; Hiersch, Liran
2017-10-01
To evaluate the association between gestational age at presentation and interval to delivery in women with early spontaneous preterm delivery (PTD). A retrospective cohort study of women who presented with threatened preterm labor (tPTL) and intact membranes and had a spontaneous PTD <34 weeks in a university-affiliated hospital (2009-2015). The interval from presentation to delivery was compared between different gestational age subgroups. Of 67 550 deliveries during the study period, 252 met inclusion criteria. This cohort was divided to three gestational age subgroups at presentation: 24-28 6/7 weeks (n = 83), 29-31 6/7 weeks (n = 61) and 32-33 6/7 weeks (n = 108). Median time from presentation to delivery was 24.5 h. An inverse relation was observed between gestational age at presentation and admission-delivery interval (group A: 74.7 h, group B: 21.0 h, group C: 14.0 h, p < 0.001). Gestational age at presentation is inversely related to admission-delivery interval in women with tPTL and intact membranes.
Pregnant women lack accurate knowledge of their BMI and recommended gestational weight gain.
Jeffs, Emma; Haszard, Jillian J; Sharp, Benjamin; Gullam, Joanna; Paterson, Helen
2016-08-05
To investigate pregnant women's knowledge of their body mass index (BMI) and their knowledge of gestational weight gain guidelines. Participants were recruited when attending their nuchal translucency scan at between 11 and 13 weeks, 6-days gestation in Dunedin or Christchurch, New Zealand. Recruitment staff measured participants' weight and height. By way of a self-administered, paper-based survey, participants were asked to identify their body size (including: underweight (BMI <18.5 kg/m2); normal weight (18.5-24.9); overweight (25-29.9); and obese (≥30)), and recommended gestational weight gain (including the 2009 Institute of Medicine guidelines for healthy weight gain in pregnancy, along with the options: "I should not gain any weight in my pregnancy", plus "It does not matter how much weight I gain"). Participant-measured BMI was compared to responses for perceived BMI and recommended gestational weight gain to assess accuracy. Demographic predictors of accuracy were also investigated. In total, 644 women were included. Sixty-six percent of these correctly identified their BMI category, however only 31% identified their correct gestational weight gain recommendation. Overweight and obese women were much more likely to underestimate their BMI than normal weight women (p<0.001 for both). Overweight and obese women were also more likely to overestimate their weight gain recommendation (OR=4, p<0.001; OR=18, p<0.001, respectively) while normal weight women were more likely to underestimate their weight gain recommendation (p<0.001). Independent of BMI, women of New Zealand European ethnicity were less likely to underestimate their recommended gestational weight gain compared to other women of non-Māori/non-Pacific Island ethnicity (p=0.001), whereas younger women (p=0.012) were more likely to underestimate recommended gestational weight gain. The present study indicates that New Zealand women, particularly those who are overweight and obese, lack accurate knowledge of their own body size, and this may lead to an under- or over-estimation of appropriate gestational weight gain, which may in turn lead to increased risk of poor health outcomes in pregnancy. Education strategies related to healthy weight gain in pregnancy are urgently required.
Bhandari, Ramji K.; vom Saal, Frederick S.; Tillitt, Donald E.
2015-01-01
The transgenerational consequences of environmental contaminant exposures of aquatic vertebrates have the potential for broad ecological impacts, yet are largely uninvestigated. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are two ubiquitous estrogenic chemicals present in aquatic environments throughout the United States and many other countries. Aquatic organisms, including fish, are exposed to varying concentrations of these chemicals at various stages of their life history. Here, we tested the ability of embryonic exposure to BPA or EE2 to cause adverse health outcomes at later life stages and transgenerational abnormalities in medaka fish. Exposures of F0 medaka to either BPA (100 μg/L) or EE2 (0.05 μg/L) during the first 7 days of embryonic development, when germ cells are differentiating, did not cause any apparent phenotypic abnormalities in F0 or F1 generations, but led to a significant reduction in the fertilization rate in offspring two generations later (F2) as well as a reduction of embryo survival in offspring three generations later (F3). Our present observations suggest that BPA or EE2 exposure during development induces transgenerational phenotypes of reproductive impairment and compromised embryonic survival in fish of subsequent generations. These adverse outcomes may have negative impacts on populations of fish inhabiting contaminated aquatic environments.
Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort
2013-01-01
Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p < 0.05 for all comparisons). At 18 + 0 to 20 + 0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p = 0.0007, 95% CI 99.0-100.0). At 26 + 0 to 28 + 0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease. PMID:23663420
Li-Fei, Zhu; Hong-Xiong, Liu; Ying, H E
2016-11-01
Our study aimed to investigate the measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease (CHD) at different gestational weeks using three dimensional (3-D) ultrasonography and its clinical value. Then, 238 pregnant women who received obstetric ultrasonography in ultrasound department of Internal Medicine of our hospital were enrolled between March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD by prenatal fetal echocardiography, and the other 153 fetuses were normal. Frontal lobe volume, thalamic volume and cerebral blood flow was determined by color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of MCA-PI and CPR in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05), but the level of UA-PI performed significantly higher than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in thalamic volume and frontal lobe volume between the two groups (P<0.05); when gestational age <30 weeks, the level of CHD fetus group performed significantly lower thalamic volume and frontal lobe volume than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in BPD, HC, and GA between the two groups (P<0.05); when gestational age <30 weeks, the level of BPD, HC and GA in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05). If gestational age <30 weeks, CHD performed a small impact on fetal frontal lobe volume and thalamic volume; if gestational age <30 weeks, the level of frontal lobe volume and thalamic volume in fetuses with CHD performed significantly lower than that in normal fetuses.
Hemophagocytic syndrome secondary to tuberculosis at 24-week gestation.
Fernández, Alexandra Arteaga; de Velasco Pérez, David Fernández; Fournier, M C Jiménez; Moreno Del Prado, J C; Torras, B Paraíso; Cañete Palomo, M L
2017-01-01
Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement. At 27 weeks and 5 days, premature rupture of the membranes occurred, and because of the high probability of reactivating the hemophagocytic syndrome, a cesarean section was performed at 29-week and 2-day gestation. Hemophagocytic syndrome is an uncommon disease which rarely appears during pregnancy. Early diagnosis and treatment can save both maternal and fetal lives.
Replication of a Genome-Wide Association Study of Birth Weight in Preterm Neonates
Ryckman, Kelli K; Feenstra, Bjarke; Shaffer, John R.; Bream, Elise NA; Geller, Frank; Feingold, Eleanor; Weeks, Daniel E; Gadow, Enrique; Cosentino, Viviana; Saleme, Cesar; Simhan, Hyagriv N; Merrill, David; Fong, Chin-To; Busch, Tamara; Berends, Susan K; Comas, Belen; Camelo, Jorge L; Boyd, Heather; Laurie, Cathy; Crosslin, David; Zhang, Qi; Doheny, Kim F; Pugh, Elizabeth; Melbye, Mads; Marazita, Mary L; Dagle, John M; Murray, Jeffrey C
2011-01-01
Objective To examine associations in a preterm population between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight. Both markers were associated with birth weight in a term population in a recent genome-wide association (GWA) study by Freathy et al. Study design A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the U.S., 265 families from Argentina and 735 mother-infant pairs from Denmark. Z scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. Results Each additional C allele of rs900400 (LEKR1/CCNL1) in infants was marginally associated with a 0.069 standard deviation (SD) lower birth weight (95% CI = −0.159 – 0.022, P = 0.068). This result was slightly more pronounced after adjusting for smoking (P = 0.036). There were no significant associations identified with rs9883204 or in maternal samples. Conclusions These results indicate the potential importance of this marker on birth weight irrespective of gestational age. PMID:21885063
Yamamoto, Lidia; Targa, Lília S; Sumita, Laura M; Shimokawa, Paulo T; Rodrigues, Jonatas C; Kanunfre, Kelly A; Okay, Thelma S
2017-08-01
To correlate neonatal and infant clinical outcome with parasite load in amniotic fluid (AF). We conducted a retrospective cohort study of 122 children whose mothers had toxoplasmosis during pregnancy. The children were monitored from birth to 12 months old. Stored AF samples were obtained at maternal diagnosis and tested by quantitative polymerase chain reaction. Gestational age at maternal infection, quantitative polymerase chain reaction results, neonatal anti-Toxoplasma gondii immunoglobulin (Ig) M, and clinical outcome at 12 months were correlated. Maternal infection occurred in 18 of 122 (14.7%) and 104 of 122 (85.2%) women in the first and second trimesters, respectively. At birth, IgM was present in 107 of 122 (87.7%) neonates and 36 (29.5%) were symptomatic. Of these, half occurred in the first and the other half in the second trimester and 6 of 36 had severe infections (16.7% of symptomatic, 4.9% of total), all infected in the first trimester. Parasite load levels were highly variable (median 35 parasites/mL, range 2-30,473). Logistic regression correlated symptomatic infection with gestational age (odds ratio [OR] 0.47, CI 0.31-0.73) and parasite load (OR 2.04, CI 1.23-3.37), but not with positive IgM (OR 6.81, CI 0.86-53.9). Negative correlations were found between gestational age and parasite load (rs -0.780, CI -0.843 to -0.696), gestational age and symptoms (rs -0.664, CI -0.755 to -0.547), but not gestational age and IgM (rs -0.136, CI -0.311 to 0.048). Parasite load levels distributed by percentile showed that all symptomatic patients appeared from the 75th percentile and all severe infections from the 95th percentile. Load rankings showed doubled the OR for each 20 parasite/mL increment. Parasite load was associated with symptomatic infections (area under the curve 0.959, CI 0.908-0.987) as well as gestational age (area under the curve 0.918, CI 0.855-0.960) and both parameters combined (area under the curve 0.969, CI 0.920-0.992). Parasite load in AF is associated with the clinical outcome in congenital toxoplasmosis, irrespective of gestational age at maternal infection.
Berggren, Erica K; Groh-Wargo, Sharon; Presley, Larraine; Hauguel-de Mouzon, Sylvie; Catalano, Patrick M
2016-06-01
Weight gain in pregnancy is an essential physiologic adaptation that supports growth and development of a fetus and is distributed among lean mass that includes total body water and fat mass gains. Although gestational weight gain provides a source of energy for the mother and fetus, excess gestational weight gain may underlie reported associations between parity and future metabolic disorders and is linked to postpartum weight retention and insulin resistance. Although weight gain often is proposed as a modifiable variable to mitigate adverse maternal and offspring health outcomes, our knowledge of specific maternal body composition changes with weight gain and the potential metabolic consequences is limited. Furthermore, although gestational weight gain alters maternal body composition, the impact of excess weight gain on fat and lean mass is not well-studied. Understanding the accrual of fat and lean body mass may improve our understanding of the role of excessive gestational weight gain and metabolic dysfunction. The purpose of our study was to quantify the relationship between gestational weight gain and maternal fat and lean body mass accrual and to compare fat and lean body mass accrual according to the 2009 Institute of Medicine Guidelines for Gestational Weight Gain in Pregnancy adherence. We hypothesized that exceeding current weight gain guidelines would be associated with greater fat, compared with lean body, mass accrual. This is a secondary analysis of a randomized controlled trial of 49 overweight/obese women; all 49 are included in this secondary analysis. Maternal weight and body composition were collected in early (13 0/6 to 16 6/7 weeks gestation) and late (34 0/7 to 36 6/7 weeks gestation) pregnancy with the use of air densitometry. Correlations were drawn between gestational weight gain and change in fat and lean body mass. We compared change in fat and lean body mass by adherence to the 2009 Institute of Medicine Guidelines for Gestational Weight Gain in Pregnancy. Nonparametric tests and chi-square analyses were performed; a probability value of <.05 was significant. Early pregnancy body mass index was 30.3 kg/m(2) (interquartile range [IQR], 28.5-35.2 kg/m(2)); women gained 9.0 kg (IQR, 5.3-13.2 kg). Overweight and obese women were equally likely to gain excess weight (48% vs 35%; P = .6). Weight gain correlated strongly with fat mass change (r = 0.87; P < .001); women with excess vs adequate vs inadequate weight gain had greater fat mass change overall (5.2 [IQR, 4.2-8.1] vs 0.2 [IQR, -0.4-2.2] vs -2.7 [IQR, -5.2- -0.7] kg, respectively; P < .001) and in all pairwise comparisons. Weight gain also correlated with lean body mass change (r = 0.52; P = .001), but women with excess vs adequate weight gain had similar lean body mass change (8.4 [IQR, 7.2-10.1] vs 7.8 [IQR, 6.0-8.7] kg; P = .1). Excess gestational weight gain is associated primarily with maternal fat, but not with lean body mass accrual. Our results may help explain the reason that excess gestational weight gain or fat mass accrual is associated with long-term obesity, metabolic dysfunction, and cardiovascular disease risk. Copyright © 2015 Elsevier Inc. All rights reserved.
Bond, R; Pace, R; Rahme, E; Dasgupta, K
2017-12-01
To investigate whether polycystic ovary syndrome further increases postpartum diabetes risk in women with gestational diabetes mellitus and to explore relationships between polycystic ovary syndrome and incident diabetes in women who do not develop gestational diabetes. This retrospective cohort study (Quebec Physician Services Claims; Hospitalization Discharge Databases; Birth and Death registries) included 34 686 women with gestational diabetes during pregnancy (live birth), matched 1:1 to women without gestational diabetes by age group, year of delivery and health region. Diagnostic codes were used to define polycystic ovary syndrome and incident diabetes. Cox regression models were used to examine associations between polycystic ovary syndrome and incident diabetes. Polycystic ovary syndrome was present in 1.5% of women with gestational diabetes and 1.2% of women without gestational diabetes. There were more younger mothers and mothers who were not of white European ancestry among those with polycystic ovary syndrome. Those with polycystic ovary syndrome more often had a comorbidity and a lower proportion had a previous pregnancy. Polycystic ovary syndrome was associated with incident diabetes (hazard ratio 1.52; 95% CI 1.27, 1.82) among women with gestational diabetes. No conclusive associations between polycystic ovary syndrome and diabetes were identified (hazard ratio 0.94; 95% CI 0.39, 2.27) in women without gestational diabetes. In women with gestational diabetes, polycystic ovary syndrome confers additional risk for incident diabetes postpartum. In women without gestational diabetes, an association between PCOS and incident diabetes was not observed. Given the already elevated risk of diabetes in women with a history of gestational diabetes, a history of both polycystic ovary syndrome and gestational diabetes signal a critical need for diabetes surveillance and prevention. © 2017 Diabetes UK.
Behboudi-Gandevani, Samira; Safary, Kolsum; Moghaddam-Banaem, Lida; Lamyian, Minoor; Goshtasebi, Azita; Goshtasbi, Azita; Alian-Moghaddam, Narges
2013-07-01
The aim of this study was to investigate the association between maternal iron/zinc serum levels and their nutritional intake in early pregnancy with gestational diabetes. The maternal serum zinc/iron levels were measured in 1,033 healthy singleton pregnant women aged 20-35 between 14 and 20 weeks of gestation, within two groups: namely, normal and gestational diabetes, and participants were followed up to 24-28 weeks of gestation. Food frequency questionnaire was used to assess nutritional intakes of iron/zinc. The main outcome was gestational diabetes screened with the 50-g glucose challenge test and diagnosed with oral glucose tolerance test at 24-28 weeks of gestation. Gestational diabetes occurred in 72 (6.96 %) of 1,033 women in study. There was a statistical relationship between early pregnancy maternal serum iron and gestational diabetes, mean (SD), 143.8 (48.7) vs. 112.5 (83.5) μg/dl, P value of <0.0001. There was no statistical significant difference in zinc levels and iron/zinc nutritional intake between groups. The results remained unchanged after using regression model for adjustment of potential risk factors with an adjusted OR of 1.006 (95 % CI 1.002 to 1.009; P = 0.001) for early pregnancy maternal serum iron to cause gestational diabetes. The receiver-operator characteristic curve identified that a maternal serum iron above 100 μg/dl in early pregnancy is the optimum cutoff value for predicting gestational diabetes, which showed a sensitivity and specificity of 80.6 and 50.7 %, respectively. In conclusion, high maternal serum iron in early pregnancy could increase the risk of gestational diabetes. Also, it could be used as a sensitive and specific predictor for gestational diabetes.
Trends and outcomes of gestational surrogacy in the United States.
Perkins, Kiran M; Boulet, Sheree L; Jamieson, Denise J; Kissin, Dmitry M
2016-08-01
To evaluate trends and reproductive outcomes of gestational surrogacy in the United States. Retrospective cohort study. Infertility clinics. IVF cycles transferring at least one embryo. Use of a gestational carrier. Trends in gestational carrier cycles during 1999-2013, overall and for non-U.S. residents; reproductive outcomes for gestational carrier and nongestational carrier cycles during 2009-2013, stratified by the use of donor or nondonor oocytes. Of 2,071,984 assisted reproductive technology (ART) cycles performed during 1999-2013, 30,927 (1.9%) used a gestational carrier. The number of gestational carrier cycles increased from 727 (1.0%) in 1999 to 3,432 (2.5%) in 2013. Among gestational carrier cycles, the proportion with non-U.S. residents declined during 1999-2005 (9.5% to 3.0%) but increased during 2006-2013 (6.3% to 18.5%). Gestational carrier cycles using nondonor oocytes had higher rates of implantation (adjusted risk ratio [aRR], 1.22; 95% confidence interval [CI], 1.17-1.26), clinical pregnancy (aRR, 1.14; 95% CI, 1.10-1.19), live birth (aRR, 1.17; 95% CI, 1.12-1.21), and preterm delivery (aRR, 1.14; 95% CI, 1.05-1.23) compared with nongestational carrier cycles. When using donor oocytes, multiple birth rates were higher among gestational carrier compared with nongestational carrier cycles (aRR, 1.13; 95% CI, 1.08-1.19). Use of gestational carriers increased during 1999-2013. Gestational carrier cycles had higher rates of ART success than nongestational carrier cycles, but multiple birth and preterm delivery rates were also higher. These risks may be mitigated by transferring fewer embryos given the higher success rates among gestational carrier cycles. Published by Elsevier Inc.
Direct reading inductance meter
NASA Technical Reports Server (NTRS)
Kolby, R. B. (Inventor)
1977-01-01
A direct reading inductance meter comprised of a crystal oscillator and an LC tuned oscillator is presented. The oscillators function respectively to generate a reference frequency, f(r), and to generate an initial frequency, f(0), which when mixed produce a difference equal to zero. Upon connecting an inductor of small unknown value in the LC circuit to change its resonant frequency to f(x), a difference frequency (f(r)-f(x)) is produced that is very nearly a linear function of the inductance of the inductor. The difference frequency is measured and displayed on a linear scale in units of inductance.
Essley, B.; McNanley, T.; Cooper, B.; McIntyre, A.; Witter, F.; Harris, Z.; O’Brien, K.
2014-01-01
Osteoprotegerin (OPG) is involved in the regulation of bone turnover, but little is known about this protein during pregnancy or among neonates. We undertook a prospective longitudinal study to identify relationships between OPG, markers of bone turnover and birth outcomes in 155 pregnant adolescents (13–18 years) and their newborns. Maternal blood samples were collected at mid-gestation and at delivery. Cord blood was obtained at delivery. Serum OPG, estradiol and markers of bone formation (osteocalcin) and resorption (N-telopeptide) were assessed in all samples. Placental OPG expression was assessed in placental tissue obtained at delivery. Bone markers and OPG increased significantly from mid-gestation (26.0 ± 3.4 weeks) to delivery (39.3 ± 2.6 weeks). Neonatal OPG was significantly lower, but bone turnover markers were significantly higher than maternal values at mid-gestation and at parturition (P < 0.001). African-American adolescents had higher concentrations of OPG than Caucasian adolescents at mid-gestation (P = 0.01) and delivery (P = 0.04). Gestational age and estradiol were also predictors of maternal OPG at mid-gestation and delivery. OPG concentrations in cord blood were correlated with maternal OPG concentrations and were negatively associated with infant birth weight z-score (P = 0.02) and ponderal index (P = 0.02). In conclusion, maternal OPG concentrations increased across gestation and were significantly higher than neonatal OPG concentrations. Maternal and neonatal OPG concentrations were not associated with markers of bone turnover or placental OPG expression, but neonatal OPG was inversely associated with neonatal anthropometric measures. Additional research is needed to identify roles of OPG during pregnancy. PMID:25141264
Rahman, Sajjad; Salameh, Khalil; Al-Rifai, Hilal; Masoud, Ahmed; Lutfi, Samawal; Salama, Husam; Abdoh, Ghassan; Omar, Fahmi; Bener, Abdulbari
2011-09-01
To analyze and compare the current gestational age specific neonatal survival rates between Qatar and international benchmarks. An analytical comparative study. Women's Hospital, Hamad Medical Corporation, Doha, Qatar, from 2003-2008. Six year's (2003-2008) gestational age specific neonatal mortality data was stratified for each completed week of gestation at birth from 24 weeks till term. The data from World Health Statistics by WHO (2010), Vermont Oxford Network (VON, 2007) and National Statistics United Kingdom (2006) were used as international benchmarks for comparative analysis. A total of 82,002 babies were born during the study period. Qatar's neonatal mortality rate (NMR) dropped from 6/1000 in 2003 to 4.3/1000 in 2008 (p < 0.05). The overall and gestational age specific neonatal mortality rates of Qatar were comparable with international benchmarks. The survival of < 27 weeks and term babies was better in Qatar (p=0.01 and p < 0.001 respectively) as compared to VON. The survival of > 32 weeks babies was better in UK (p=0.01) as compared to Qatar. The relative risk (RR) of death decreased with increasing gestational age (p < 0.0001). Preterm babies (45%) followed by lethal chromosomal and congenital anomalies (26.5%) were the two leading causes of neonatal deaths in Qatar. The current total and gestational age specific neonatal survival rates in the State of Qatar are comparable with international benchmarks. In Qatar, persistently high rates of low birth weight and lethal chromosomal and congenital anomalies significantly contribute towards neonatal mortality.
Altorjay, Ábel T; Surányi, Andrea; Nyári, Tibor; Németh, Gábor
2017-04-14
We aimed to investigate correlations between uterine artery peak systolic velocity (AUtPSV), and placental vascularization in groups of normal blood pressure (NBP) and hypertensive disorders of pregnancy (chronic hypertension (CHT), gestational hypertension (GHT) and preeclampsia (PE)) alone or in combination with gestational diabetes mellitus (GDM), and hypothesized that AUtPSV rises when GDM complicates pregnancy hypertension. Placental 3-dimensional power Doppler indices, such as vascularization index (VI), flow index (FI), and vascularization-flow index (VFI), and uterine artery peak systolic velocity (AUtPSV) were measured in CHT (N=43), CHT+GDM (N=15), GHT (N=57), GHT+GDM (N=23) and PE (N=17) pregnancies, and compared to NBP (N=109). Correlations were analyzed between vascularization indices, AUtPSV, pregestational BMI and adverse pregnancy outcome rates. In our results VI was higher in CHT (P=0.010), while FI was lower in CHT (P=0.009), GHT and PE (P=0.001) compared to NBP. In case of VFI, significant difference was found between CHT and GHT (P=0.002), and NBP and PE (P=0.001). FI was found prognostic for umbilical pH and neonatal birth weight. Pre-gestational BMI was significantly higher in GHT+GDM compared to GHT, and in CHT+GDM compared to the CHT group. As for AUtPSV, significant difference was found between NBP and CHT (P=0.012), NBP and CHT+GDM (P=0.045), NBP and GHT+GDM (P=0.007), NBP and PE (P=0.032), and GHT and GHT+GDM (P=0.048) groups. Our study revealed that vascularization indices and AUtPSV show significant differences due to gestational pathology, and can be useful in detection of pregnancies at risk.
Ouyang, Fengxiu; Parker, Margaret; Cerda, Sandra; Pearson, Colleen; Fu, Lingling; Gillman, Matthew W.; Zuckerman, Barry; Wang, Xiaobin
2012-01-01
Elevated pre-pregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre-pregnancy BMI, GWG, and GDM with birthweight-for-gestational age, and whether the relationships differ by preterm status. We examined 1035 mother-infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status. We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. 41% were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking and stress during pregnancy, birthweight-for-gestational age z-score was 0.55 (0.30, 0.80) units higher for pre-pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre-pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre-pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birthweight-for-gestational age z-score, but pre-pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM. These results suggest that placental weight partially mediates the effects of pre-pregnancy obesity, GDM and excessive GWG on fetal growth among term infants. PMID:23592670
Ali, Mohammed K; Abbas, Ahmed M; Abdelmagied, Ahmed M; Mohammed, Ghada E; Abdalmageed, Osama S
2017-12-01
The study aims to assess the efficacy of single versus double-daily oral iron dose on prevention of iron deficiency anemia in women with twin gestations. A randomized controlled trial (NCT02858505) conducted at Woman's Health Hospital, Assiut, Egypt, between August 2015 and June 2016 included 120 non-anemic pregnant women with twin gestations in the first trimester. Women were randomly assigned to either group I (27 mg elemental iron) or group II (54 mg elemental iron) daily starting from 12 weeks of pregnancy till 36 weeks. The primary outcomes included the mean level of hemoglobin, hematocrit and serum ferritin at 36 weeks' gestation. Both iron doses maintained the mean hemoglobin and hematocrit within the normal level from 12 weeks to 36 weeks (p = 0.378 and p = 0.244, respectively). However, the mean serum ferritin level was higher in group II than group I (p = 0.000) at 36 weeks' gestation. Moreover, women in group II reported more side effects than group I at 36 weeks' gestation. Doubling the prophylactic iron dose is comparable to single dose in the prevention of iron deficiency anemia among women with twin gestations with more side effects.
Monier, Isabelle; Ancel, Pierre-Yves; Ego, Anne; Jarreau, Pierre-Henri; Lebeaux, Cécile; Kaminski, Monique; Goffinet, François; Zeitlin, Jennifer
2017-05-01
Fetal growth restriction is defined using ultrasound parameters during pregnancy or as a low birthweight for gestational age after birth, but these definitions are not always concordant. The purpose of this study was to investigate fetal and neonatal outcomes based on antenatal vs postnatal assessments of growth restriction. From the EPIPAGE 2 population-based prospective study of very preterm births in France in 2011, we included 2919 singleton nonanomalous infants 24-31 weeks gestational age. We constituted 4 groups based on whether the infant was suspected with fetal growth restriction during pregnancy and/or was small for gestational age with a birthweight <10th percentile of intrauterine norms by sex: 1) suspected with fetal growth restriction/small for gestational age 2) not suspected with fetal growth restriction/small for gestational age 3) suspected with fetal growth restriction/not small for gestational age and 4) not suspected with fetal growth restriction/not small for gestational age. We estimated relative risks of perinatal mortality and morbidity for these groups adjusting for maternal and neonatal characteristics. We found that 22.2% of infants were suspected with fetal growth restriction/small for gestational age, that 11.4% infants were not suspected with fetal growth restriction/small for gestational age, that 3.0% infants were suspected with fetal growth restriction/not small for gestational age, and that 63.4% infants were not suspected with fetal growth restriction/not small for gestational age. Compared with infants who were not suspected with fetal growth restriction/not small-for-gestational-age infants, small-for-gestational-age infants suspected and not suspected with fetal growth restriction had higher risks of stillbirth or termination of pregnancy (adjusted relative risk, 2.0 [95% confidence interval, 1.6-2.5] and adjusted relative risk, 2.8 [95% confidence interval, 2.2-3.4], respectively), in-hospital death (adjusted relative risk, 2.8 [95% confidence interval, 2.0-3.7] and adjusted relative risk, 2.0 [95% confidence interval, 1.5-2.8], respectively), and bronchopulmonary dysplasia (adjusted relative risk, 1.3 [95% confidence interval, 1.2-1.4] and adjusted relative risk, 1.3 [95% confidence interval, 1.1-1.4], respectively), but not severe brain lesions. Risks were not increased for infants suspected with fetal growth restriction but not small-for-gestational-age. Antenatal and postnatal assessments of fetal growth restriction were not concordant for 14% of very preterm infants. In these cases, birthweight appears to be the more relevant parameter for the identification of infants with higher risks of adverse short-term outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
Maternal and fetal outcome of mothers with gestational diabetes mellitus attending BIRDEM Hospital.
Sajani, T T; Rahman, M T; Karim, M R
2014-04-01
Gestational diabetes mellitus, most of which progress to type-2 diabetes mellitus is increasing worldwide. Identification of gestational diabetes and control of glucose can reduce such complications and improve maternal and neonatal health. A hospital based cross sectional study was conducted to find out maternal and fetal outcome of gestational diabetes from January to July 2011. Data were collected from 109 gestational diabetes mothers attending Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) hospital for delivery. Study revealed that gestational diabetes was more common among mothers aged >25 years old and multiparaous women. Mean gestational age of diagnosis was 16.82±9.54 weeks. Sixty eight (68%) mothers were diagnosed before 20 weeks of gestation and more than 90% mothers with gestational diabetes delivered by caesarean section. Mean pregnancy weight gain was 6.8±1.18kg. Adverse maternal outcome observed in 24% cases and adverse fetal outcome was present in 34% cases. In univariate analysis weeks of delivery and fasting blood sugar were statistically significantly associated with adverse pregnancy outcome. Babies born to mothers with only diet restriction had less birth weight than mothers with insulin therapy. Pregnancy thought to be the most vulnerable stage of women's life and protecting her health along with her fetus during this period yields a positive impact on the health of future generation. Particular attention should be given during antenatal period to initiate screening programme and treatment protocol for gestational diabetic mothers.
Starr, Lisa M; Scott, Marilyn E; Koski, Kristine G
2015-01-01
Protein deficiency (PD) and intestinal nematode infections commonly co-occur during pregnancy and impair fetal growth, but the complex network of signals has not been explored. Our objective was to assess those stress hormones, growth factors, and cytokines affected by maternal PD and nematode infection and associated with fetal growth. Using a 2 × 2 factorial design, CD-1 mice, fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets, were either uninfected or infected every 5 d with Heligmosomoides bakeri, beginning on gestational day (GD) 5. Biomarker concentrations were measured on GD 18 in maternal serum (m), fetal serum (f), and amniotic fluid (af) by using Luminex. Maternal PD lowered fetal body mass (PS/uninfected 1.25 ± 0.02 g, PS/infected 1.19 ± 0.02 g vs. PD/uninfected 1.11 ± 0.02 g, PD/infected 0.97 ± 0.02 g; P = 0.02), fetal lung (P = 0.005), and liver (P = 0.003) but not brain mass, whereas maternal infection lowered fetal length (PS/uninfected 2.28 ± 0.02 cm, PD/uninfected 2.27 ± 0.03 cm vs. PS/infected 2.21 ± 0.03 cm, PD/infected 2.11 ± 0.02 cm; P = 0.05) and kidney mass (P = 0.04). PD elevated stress hormones (m-adrenocortiotropic hormone, f-corticosterone, af-corticosterone) and reduced insulin-like growth factor 1 in all compartments (P ≤ 0.01), but these were unassociated with fetal mass or length. Fetal mass was positively associated with f-leptin (R(2) = 0.71, P = 0.0001) and negatively with fetal cytokines [tumor necrosis factor-α: R(2) = 0.62, P = 0.001; interleukin-4 (IL-4): R(2) = 0.63, P = 0.0004]. In contrast, maternal infection lowered f-prolactin (P = 0.02) that was positively associated with fetal length (R(2) = 0.43; P = 0.03); no other biomarker was affected by infection. Regression analyses showed associations between organ growth, cytokines, and growth factors: 1) thymus, spleen, heart, and brain with m-IL-10; 2) brain and kidney with f-vascular endothelial growth factor, af-monocyte chemotactic protein 1, af-interferon-γ, and af-eotaxin; and 3) liver and lung with f-leptin and af-corticosterone (all P ≤ 0.02). PD and nematode infection impaired fetal mass and linear growth, respectively. Fetal mass, length, and individual organ masses were regulated by different hormones, growth factors, and cytokines. © 2015 American Society for Nutrition.
Changes in rates of salivary estriol increases before parturition at term.
Hedriana, H L; Munro, C J; Eby-Wilkens, E M; Lasley, B L
2001-01-01
The aim of this study was to characterize the increases of salivary estriol concentrations before the onset of labor at term. Salivary estriol concentrations were measured in weekly patient-collected samples by means of a sensitive (mean +/- SD threshold, 0.025 +/- 0.001 ng/mL; coefficient of variation, 3.8%) direct enzyme immunoassay in a microtiter plate format. The salivary estriol concentrations in 16 healthy pregnant women were characterized from 30 weeks' gestation until the time of parturition and delivery. Samples were stored frozen at collection and analyzed in batches after delivery. The median salivary estriol concentration profile revealed a nonlinear rise beginning from 30 weeks' gestation (0.89 ng/mL) until term (2.70 ng/mL, an increase of 201%). At 35 weeks' gestation the salivary estriol concentration median value increased sharply (positive inflection point, 50%-93% increase) at a demarcation between a slower increase during early pregnancy and a more rapid increase during late pregnancy. This positive inflection point associated with a late pregnancy increase characterized subgroups of pregnancies according to the lengths of gestation as follows: early term (delivered at <38 weeks 1 day's gestation), middle term (delivered at 38 weeks 1 day-40 weeks' gestation), and late term (delivered at >40 weeks' gestation). Five weeks before delivery the mean (+/-SEM) rate of rise in salivary estriol concentration was 0.50 +/- 0.13 ng/mL per week to 0.84 +/- 0.26 ng/mL per week in the early term group. The increase in rate for the middle term group was 0.32 +/- 0.06 ng/mL per week to 0.37 +/- 0.26 ng/mL per week, whereas in the late term group the rate of salivary estriol concentration rise was 0.37 +/- 0.03 ng/mL per week to -0.03 +/- 0.25 ng/mL per week. These data demonstrate in normal pregnancies (1) that a direct, nonradiometric measure of salivary estriol concentration can be used to monitor the late pregnancy increase in estriol production, (2) that 35 weeks' gestation marks a positive inflection point of the onset of increased estriol production, and (3) that the late pregnancy rise in salivary estriol concentration shows distinct patterns that tend to be characteristic of the length of pregnancy. These data support the concept that the rate of increase of estriol production is related to the timing of the onset of labor.
Farina, Antonio; Sekizawa, Akihiko; Rizzo, Nicola; Concu, Manuela; Banzola, Irina; Carinci, Paolo; Simonazzi, Giuliana; Okai, Takashi
2004-04-01
To determine (1) if fetal DNA (fDNA) in the maternal circulation in women affected by preeclampsia correlates with the time elapsed from the onset of symptoms to the time of blood collection, and (2) if the inclusion of this variable improves the discrimination between affected and unaffected patients by using fDNA distributions. Plasma were collected from 34 women at 33.7 +/- 3.9 weeks' gestation, affected by preeclampsia, and bearing a single male fetus. fDNA was extracted from 1.5-mL plasma samples, and the SRY and beta-globin gene were analyzed by real-time quantitative PCR. MoMs (multiple of the control median) were calculated by using a log equation of 102 normal cases. Log MoMs were then plotted against the time elapsed from onset of symptoms to blood collection (expressed in days) by means of a log-linear regression. Adjusted MoMs were then calculated. ROC curves were used to test the discrimination obtained by using adjusted MoMs. The median MoMs of controls and preeclamptic patients were 1.00 +/- 1.53 and 2.62 +/- 2.70 respectively. By plotting log MoM fDNA against the time elapsed from onset of symptoms to blood collection, we found a significant positive correlation, (p-value < 0.001, R2 = 0.55, F = 38.97, from 1 to 50 days). The adjusted median fDNA MoM was 2.66 +/- 2.50. Areas under the curves, as estimated by ROC curves, were 76.7 for unadjusted and 85.5 for adjusted MoMs respectively (p-value = 0.02). The effect of a further covariate showed that (1) fDNA passage from trophoblasts to maternal circulation for unit of time is proportional to the duration of the damage and that (2) increased discrimination can be obtained in comparison to normal subjects. Copyright 2004 John Wiley & Sons, Ltd.
Yang, Yue; Wei, Qiong; Yu, Hong; Wang, Pin; Xia, Wenqing; Huang, Rong; Cai, Rongrong; Sun, Haixia; Wang, Shaohua
2016-05-01
To assess how pre-pregnancy body mass index (BMI) affects pregnancy outcome and total gestational weight gain (GWG) in a cohort of women with gestational diabetes (GDM). Pregnant women at 24-28 gestational weeks diagnosed with GDM were classified as normal weight (pre-pregnancy BMI, 18.5-24.9 kg/m(2) ) or overweight (pre-pregnancy BMI, 25.0-29.9 kg/m(2) ). GWG was derived from the self-reported pre-pregnancy and pre-delivery weights, and analyzed using 2009 Institute of Medicine categories. A total of 106 GDM women were categorized as normal weight (n = 79) or overweight (n = 27). No statistically significant differences were found between the groups in terms of various obstetrical and neonatal outcomes. Higher pre-pregnancy BMI, however, was associated with excessive GWG during pregnancy (difference between groups, P = 0.013). Furthermore, pre-pregnancy BMI (OR, 0.529; 95%CI: 0.377-0.742; P = 0.000) and pre-pregnancy overweight (OR, 3.825; 95%CI: 1.469-9.959; P = 0.006) were independent factors of GWG. Among Chinese GDM women, overweight GDM mothers gain excessive weight during pregnancy. Regulation of pre-pregnancy bodyweight might be an appropriate precaution against excessive GWG. © 2016 Japan Society of Obstetrics and Gynecology.
Zhang, Yongkang; Li, Meng; Li, Shuying; Wang, Qiangwei; Zhu, Guonian; Su, Guanyong; Letcher, Robert J; Liu, Chunsheng
2018-05-14
Previous studies reported that exposure to environmentally relevant concentrations of TDCIPP significantly decreased the number of cumulative eggs in zebrafish, but effects on the quantity of eggs and sperms remained unknown. Therefore, in this study, effects of TDCIPP on yolk diameter, surface morphology of eggs, sperm density and total motility were evaluated. First generation (F0) zebrafish larvae (Danio rerio) were exposed to 0, 50, 500 or 5000 ng/L tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) from 14 days post fertilization (dpf) to 120 dpf. The F0 generation of zebrafish were paired and F1 generation of embryos were collected and continuously exposed to the same concentrations of TDCIPP until 150 dpf. TDCIPP bioconcentration in the whole body as well as effects on survival and fecundity were evaluated in F1 generation. Exposure to TDCIPP resulted in an accumulation of the chemical and decreased survival of F1 generation of zebrafish. TDCIPP decreased cumulative production and changed surface morphology of eggs in females. In males, TDCIPP decreased total motility of sperm but did not affect sperm density. These effects on quality of egg and sperm might be responsible for the decreased hatching rates observed in cross mating experiments. Furthermore, TDCIPP exposure resulted in down-regulated gene expression related to gonadal development and maturation of germ cells in females or/and males, and the down-regulation was correlated to decreased fecundity. Taken together, the results suggested that exposure to TDCIPP could decrease the quantity of eggs and sperms by down-regulating the expression of genes related to gonadal development and maturation of germ cells in zebrafish. Copyright © 2018 Elsevier B.V. All rights reserved.
Evaluation of the Friction of Self-Ligating and Conventional Bracket Systems
Tecco, Simona; Di Iorio, Donato; Nucera, Riccardo; Di Bisceglie, Beatrice; Cordasco, Giancarlo; Festa, Felice
2011-01-01
Objectives: This in vitro study evaluated the friction (F) generated by aligned stainless steel (SS) conventional brackets, self-ligating Damon MX© brackets (SDS Ormco, Glendora, California, USA), Time3© brackets (American Orthodontics, Sheboygan, Wisconsin, USA), Vision LP© brackets (American Orthodontics), and low-friction Slide© ligatures (Leone, Firenze, Italy) coupled with various SS, nickel-titanium (NiTi), and beta-titanium (TMA) archwires. Methods: All brackets had a 0.022-inch slot, and the orthodontic archwires were 0.014-inch, 0.016-inch, 0.014×0.025-inch, 0.018×0.025-inch, and 0.019×0.025-inch NiTi; 0.017×0.025-inch TMA; and 0.019×0.025-inch SS. Each bracket-archwire combination was tested 10 times. In the test, 10 brackets of the same group were mounted in alignment on a metal bar. The archwires moved through all the 10 brackets at a crosshead speed of 0.5 mm/min (each run lasted approximately 5 min). The differences among 5 groups of brackets were analyzed through the Kruskal-Wallis test, and a Mann-Whitney test was calculated as post hoc analysis. The P value was set at 0.05. Results: Coupled with 0.014-inch NiTi and 0.016-inch NiTi, Victory Series© brackets generated the greatest F, while Damon MX© and Vision LP© brackets generated the lowest (P<.05); no significant differences were observed between Time3© brackets and Slide© ligatures. Coupled with all the rectangular archwires, Victory Series© brackets, Slide© ligatures, and Vision LP© self-ligating brackets generated significantly lower F than did Time3© and Damon MX© self-ligating brackets (P<.05). Conclusions: These findings suggest that self-ligating brackets are a family of brackets that, in vitro, can generate different levels of F when coupled with thin or thick, rectangular, or round archwires. Clinical conclusions based on our results are not possible due to the limitations of the experimental conditions. PMID:21769273
The effect of fetal gender on nuchal translucency at 10-14 weeks of gestation.
Lam, Y H; Tang, M H; Lee, C P; Sin, S Y; Tang, R; Wong, H S; Wong, S F
2001-08-01
Recent data have suggested that fetal nuchal translucency (NT) is affected by fetal gender. We investigated the size of this effect in 12 189 unselected pregnancies with known normal outcomes that had undergone NT measurements between 10 and 14 weeks of gestation. NT increased with gestation and was converted to multiples of the median (MoM) for the gestational day. The median NT MoM (95% CI) for female fetuses was 0.98 (0.97-0.99). This was significantly lower than that of the male fetuses (1.03; range 1.02-1.04) (p<0.0005; Wilcoxon rank-sum test). The gender difference was not observed at 10 weeks but was observed from 11 weeks onwards. There is no obvious explanation for the above findings. Copyright 2001 John Wiley & Sons, Ltd.
Carnero, AM; Mejía, CR; García, PJ
2014-01-01
Objective To examine the shape (functional form) of the association between the rate of gestational weight gain, pre-pregnancy body mass index (BMI), and preterm birth and its subtypes. Design Retrospective cohort study. Setting National reference obstetric centre in Lima, Peru. Population Pregnant women who delivered singleton babies during the period 2006–2009, resident in Lima, and beginning prenatal care at ≤12 weeks of gestation (n = 8964). Methods Data were collected from the centre database. The main analyses consisted of logistic regression with fractional polynomial modelling. Main outcome measures Preterm birth and its subtypes. Results Preterm birth occurred in 12.2% of women, being mostly idiopathic (85.7%). The rate of gestational weight gain was independently associated with preterm birth, and the shape of this association varied by pre-pregnancy BMI. In women who were underweight, the association was linear (per 0.1 kg/week increase) and protective (OR 0.88; 95% CI 0.82–1.00). In women of normal weight or who were overweight, the association was U-shaped: the odds of delivering preterm increased exponentially with rates <0.10 or >0.66 kg/week, and <0.04 or >0.50 kg/week, respectively. In women who were obese, the association was linear, but nonsignificant (OR 1.01; 95% CI 0.95–1.06). The association described for preterm birth closely resembled that of idiopathic preterm birth, although the latter was stronger. The rate of gestational weight gain was not associated with indicated preterm birth or preterm prelabour rupture of membranes. Conclusions In Peruvian pregnant women starting prenatal care at ≤12 weeks of gestation, the rate of gestational weight gain is independently associated with preterm birth, mainly because of its association with idiopathic preterm birth, and the shape of both associations varies by pre-pregnancy BMI. PMID:22607522
Wiśniewski, Andrzej; Stupnicki, Romuald; Milde, Katarzyna; Szufladowicz-Woźniak, Jolanta
2006-01-01
Body mass deficit at birth is one of the characteristic features observed in Turner's syndrome (TS). Body mass is lower than expected for gestational age in about 90% of TS-babies, and is below -2 SD (i.e. "small for gestational age") in about 20% of patients. The aim of the study was to compare the growth courses of TS-girls born with normal and deficient body mass. A group of 157 TS-girls, delivered at term (> or =38 weeks of gestation), were studied. Body mass of 80 girls ranged from -0.5 to +0.5 SD and body length was above -2 SD (AGA group); another 54 girls had body mass below -2 SD and body length above -2 SD (disproportional SGA group), and 23 girls had both body mass and length below -2 SD (proportional SGA group). Turner's syndrome was confirmed by chromosome analysis. Body mass at birth (BMB) was related to the norms for gestational age (GA) designed by Usher and McLean. Newborns, whose BMB was lower than -2 SD for GA, were considered small for gestational age (SGA). Postnatal body height and mass values were related to Polish norms for females with Turner's syndrome and to the norms for healthy female population. In the spontaneously growing TS-girls from the AGA group, a total of 275 measurements of body mass and height were carried out, the respective numbers for DSGA and PSGA groups were 176 and 100. Mean differences between the actual and expected body height for the AGA, DSGA and PSGA groups amounted to 0.40+/- 1.02, -0.21+/-0.88 and -0.95+/-0.80 SD TS, respectively, all means differing highly significantly (p<0.001) from each other. It may be concluded that spontaneously growing girls with Turner's syndrome, who had a normal (for gestational age) body mass at birth, attain a higher stature than girls with body mass deficit.
Carnero, A M; Mejía, C R; García, P J
2012-07-01
To examine the shape (functional form) of the association between the rate of gestational weight gain, pre-pregnancy body mass index (BMI), and preterm birth and its subtypes. Retrospective cohort study. National reference obstetric centre in Lima, Peru. Pregnant women who delivered singleton babies during the period 2006-2009, resident in Lima, and beginning prenatal care at ≤ 12 weeks of gestation (n=8964). Data were collected from the centre database. The main analyses consisted of logistic regression with fractional polynomial modelling. Preterm birth and its subtypes. Preterm birth occurred in 12.2% of women, being mostly idiopathic (85.7%). The rate of gestational weight gain was independently associated with preterm birth, and the shape of this association varied by pre-pregnancy BMI. In women who were underweight, the association was linear (per 0.1 kg/week increase) and protective (OR 0.88; 95% CI 0.82-1.00). In women of normal weight or who were overweight, the association was U-shaped: the odds of delivering preterm increased exponentially with rates <0.10 or >0.66 kg/week, and <0.04 or >0.50 kg/week, respectively. In women who were obese, the association was linear, but non-significant (OR 1.01; 95% CI 0.95-1.06). The association described for preterm birth closely resembled that of idiopathic preterm birth, although the latter was stronger. The rate of gestational weight gain was not associated with indicated preterm birth or preterm prelabour rupture of membranes. In Peruvian pregnant women starting prenatal care at ≤ 12 weeks of gestation, the rate of gestational weight gain is independently associated with preterm birth, mainly because of its association with idiopathic preterm birth, and the shape of both associations varies by pre-pregnancy BMI. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.
Income inequality, parental socioeconomic status, and birth outcomes in Japan.
Fujiwara, Takeo; Ito, Jun; Kawachi, Ichiro
2013-05-15
The purpose of this study was to investigate the impact of income inequality and parental socioeconomic status on several birth outcomes in Japan. Data were collected on birth outcomes and parental socioeconomic status by questionnaire from Japanese parents nationwide (n = 41,499) and then linked to Gini coefficients at the prefectural level in 2001. In multilevel analysis, z scores of birth weight for gestational age decreased by 0.018 (95% confidence interval (CI): -0.029, -0.006) per 1-standard-deviation (0.018-unit) increase in the Gini coefficient, while gestational age at delivery was not associated with the Gini coefficient. For dichotomous outcomes, mothers living in prefectures with middle and high Gini coefficients were 1.24 (95% CI: 1.05, 1.47) and 1.23 (95% CI: 1.02, 1.48) times more likely, respectively, to deliver a small-for-gestational-age infant than mothers living in more egalitarian prefectures (low Gini coefficients), although preterm births were not significantly associated with income distribution. Parental educational level, but not household income, was significantly associated with the z score of birth weight for gestational age and small-for-gestational-age status. Higher income inequality at the prefectural level and parental educational level, rather than household income, were associated with intrauterine growth but not with shorter gestational age at delivery.
Polymorphism of the renalase gene in gestational diabetes mellitus.
Fatima, Syeda Sadia; Jamil, Zehra; Alam, Faiza; Malik, Hajira Zafar; Madhani, Sarosh Irfan; Ahmad, Muhammad Saad; Shabbir, Tayyab; Rehmani, Muhammed Noman; Rabbani, Amna
2017-01-01
Renalase is considered as a novel candidate gene for type 2 diabetes. In this study, we aimed to investigate the relationship of serum renalase and two single nucleotide polymorphisms with gestational diabetes mellitus. One hundred and ninety-eight normotensive pregnant females (n = 99 gestational diabetes mellitus; n = 99 euglycemic pregnant controls) were classified according to the International Association of the Diabetes and Pregnancy Study criteria. Fasting and 2-h post glucose load blood levels and anthropometric assessment was performed. Serum renalase was measured using enzyme-linked immunosorbent assay, whereas DNA samples were genotyped for renalase single nucleotide polymorphisms rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment length polymorphism method. In an age-matched case control study, no difference was observed in the serum levels of renalase (p > 0.05). The variant rs10887800 showed an association with gestational diabetes mellitus and remained significant after multiple adjustments (p < 0.05), whereas rs2576178 showed weak association (p = 0.030) that was lost after multiple adjustments (p = 0.09). We inferred a modest association of the rs10887800 polymorphism with gestational diabetes. Although gestational diabetes mellitus is self-reversible, yet presence of this minor G allele might predispose to metabolic syndrome phenotypes in near the future.
Caesarean delivery before 39 weeks associated with selecting an auspicious time for birth in Taiwan.
Chu, Kuei-Hui; Lee, Yu-Hsiang; Tai, Chen-Jei; Lin, Yu-Hung; Huang, Chiu-Mieh; Chien, Li-Yin
2015-09-01
Caesarean delivery before 39 weeks of gestation increases the risk of morbidity among infants. Taiwan has one of the highest caesarean rates in the world, but little attention has been paid to this issue. This study aimed to describe the rate of caesarean delivery before 39 weeks gestation among women who did not have labour signs and had a non-emergency caesarean delivery in Taiwan and to examine whether the phenomenon was associated with the Chinese cultural practice of selecting an auspicious time for birth. We recruited women at 15-28 weeks of pregnancy at 5 hospitals in northern Taiwan and followed them at 4 or 5 weeks after delivery using structured questionnaires. This analysis included 150 primiparous mothers with a singleton pregnancy who had a non-emergency caesarean delivery without the presence of labour signs. Ninety-three of these women (62.0%) had caesarean deliveries before 39 weeks of gestation. Logistic regression analysis showed that women who had selected an auspicious time for delivery (OR=2.82, 95% CI: 1.15-6.95) and delivered in medical centres (OR=5.26, 95% CI: 2.25-12.26) were more likely to deliver before 39 weeks of gestation. Non-emergency caesarean delivery before 39 weeks of gestation was common among the study women, and was related to the Chinese cultural practice of selecting an auspicious time for birth. Further studies are needed to examine the risks and benefits associated with timing of caesarean delivery in Taiwan in order to generate a consensus among obstetricians and give pregnant women appropriate information. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
Santos, Marta Maria Antonieta de Souza; Baião, Mirian Ribeiro; de Barros, Denise Cavalcante; Pinto, Alessandra de Almeida; Pedrosa, Priscila La Marca; Saunders, Claudia
2012-03-01
To identify the association between pre-gestational nutritional status, maternal weight gain, and prenatal care with low birth weight (LBW) and prematurity outcomes in infants of adolescent mothers. Cross-sectional study with 542 pairs of adolescent mothers and their children attending a public maternity hospital in Rio de Janeiro. Data were collected from medical records. To determine the association between independent variables and the outcomes studied, odds ratio (OR) and a 95% confidence interval (CI) were estimated With respect to pre-pregnancy nutritional status of adolescents, 87% had normal weight, 1% were underweight, 10% were overweight, and 2% obese. Inadequate total gestational weight gain (72%) exceeded adequacy (28%). Birth weight was favored with greater gestational weight gain, and reduced with late onset of prenatal care. The comparison between the low birth weight and normal birth weight groups revealed significant differences between variable means: interval between the past pregnancy and current pregnancy (p = 0.022), pre-gestational weight (p = 0.018); pre-gestational body mass index (p < 0.001), and total gestational weight gain (p = 0.047). The odds of LBW (OR 2.70, 95% CI 1.45 to 5.06) and prematurity (OR 5.82, 95% CI 3.10 to 10.92) fell when the adolescent received six or more prenatal visits. Birth weight was associated with inter-gestational interval, pre-pregnancy weight and body mass index before pregnancy. The minimum frequency of six prenatal care visits was a protective factor against LBW and prematurity.
Thompson, Shirley; Sawyer, Jennifer; Bonam, Rathan; Valdivia, J E
2009-07-01
The German EPER, TNO, Belgium, LandGEM, and Scholl Canyon models for estimating methane production were compared to methane recovery rates for 35 Canadian landfills, assuming that 20% of emissions were not recovered. Two different fractions of degradable organic carbon (DOC(f)) were applied in all models. Most models performed better when the DOC(f) was 0.5 compared to 0.77. The Belgium, Scholl Canyon, and LandGEM version 2.01 models produced the best results of the existing models with respective mean absolute errors compared to methane generation rates (recovery rates + 20%) of 91%, 71%, and 89% at 0.50 DOC(f) and 171%, 115%, and 81% at 0.77 DOC(f). The Scholl Canyon model typically overestimated methane recovery rates and the LandGEM version 2.01 model, which modifies the Scholl Canyon model by dividing waste by 10, consistently underestimated methane recovery rates; this comparison suggested that modifying the divisor for waste in the Scholl Canyon model between one and ten could improve its accuracy. At 0.50 DOC(f) and 0.77 DOC(f) the modified model had the lowest absolute mean error when divided by 1.5 yielding 63 +/- 45% and 2.3 yielding 57 +/- 47%, respectively. These modified models reduced error and variability substantially and both have a strong correlation of r = 0.92.
Morphological basis for the evolution of acoustic diversity in oscine songbirds.
Riede, Tobias; Goller, Franz
2014-03-22
Acoustic properties of vocalizations arise through the interplay of neural control with the morphology and biomechanics of the sound generating organ, but in songbirds it is assumed that the main driver of acoustic diversity is variation in telencephalic motor control. Here we show, however, that variation in the composition of the vibrating tissues, the labia, underlies diversity in one acoustic parameter, fundamental frequency (F0) range. Lateral asymmetry and arrangement of fibrous proteins in the labia into distinct layers is correlated with expanded F0 range of species. The composition of the vibrating tissues thus represents an important morphological foundation for the generation of a broad F0 range, indicating that morphological specialization lays the foundation for the evolution of complex acoustic repertoires.
Mert, Mustafa Kurthan; Satar, Mehmet; Özbarlas, Nazan; Yaman, Akgün; Özgünen, Fatma Tuncay; Asker, Hüseyin Selim; Çekinmez, Eren Kale; Tetiker, Tamer
2016-01-01
This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p < 0.001). NT proBNP levels were positively correlated with interventricular septum thickness in the pregestational and gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p < 0.01). Both pregestational and gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (<6.1 %) and suboptimal (>6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p < 0.01). In the suboptimal metabolic control diabetic group, NT proBNP was only found to be positively correlated with the left ventricular mass index (r = 0.586, p < 0.01). While there was no correlation in the myocardial performance index between infants of diabetic mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.
Neonatal Arterial Morphology Is Related to Body Size in Abnormal Human Fetal Growth.
Olander, Rasmus F W; Sundholm, Johnny K M; Ojala, Tiina H; Andersson, Sture; Sarkola, Taisto
2016-09-01
Restriction in fetal growth is associated with cardiovascular disease in adulthood. It is unclear whether abnormal intrauterine growth influences arterial morphology during the fetal or neonatal stage. The objective was to study the regional arterial morphology with respect to gestational age and abnormal fetal body size. We studied body anthropometrics and arterial morphology and physiology in 174 neonates born between 31 and 42 weeks of gestation, including neonates with birth weights appropriate, small, and large for age, with very high resolution vascular ultrasound (35-55 MHz). In simple linear regressions, parameters of body size (body weight, body surface area, and organ circumference) and gestational age were statistically significantly associated with common carotid, brachial, femoral arterial parameters (lumen diameter [LD], wall layer thickness [intima-media thickness and intima-media-adventitia thickness], and carotid artery wall stress [CAWS]). Male sex was statistically significantly associated with LD and CAWS. In multiple linear regression models, body size, gestational age, and sex explained a large proportion of the arterial variance (R( 2) range, 0.37-0.47 for LD; 0.09-0.35 for intima-media thickness; 0.21-0.41 for intima-media-adventitia thickness; and 0.23 for CAWS; all models P<0.001). Arterial wall layer thickness, LDs, and CAWS were independently and strongly predicted by body size, and no effect of maternal disease was observed when added to the models. Gestational age and male sex were also independently but more weakly associated with arterial LDs and CAWS (P<0.01), but not with arterial wall layers. These results indicate that the intrauterine growth of fetal arterial LD and wall layer thickness are primarily attributed to body growth overall. LD and CAWS show weaker association with gestational age and sex. © 2016 American Heart Association, Inc.
Pasquier, Jean-Charles; Rabilloud, Muriel; Picaud, Jean-Charles; Ecochard, René; Claris, Olivier; Gaucherand, Pascal; Collet, Frédéric; Chabert, Pierre; Mellier, Georges
2005-08-01
Description of mothers' characteristics, obstetricians' practices, and PPROM-linked mortality in all 81 maternity hospitals in the Rhône-Alpes Region, over a period of 2 years. Prospective cohort study of 598 women with PPROM between 24 and 34 weeks' gestation, leading to 680 births. At time of PPROM, collection of mothers' socio-economic characteristics, medical and obstetric histories and PPROM circumstances. Collection of perinatal management, neonates' medical status and postnatal referral. The birth rate after PPROM between 24 and 34 weeks' gestation was 0.47% (95% CI: 0.42-0.48). Sixty percent of PPROM occurred before 32 weeks' gestation and 98% of births before 37 weeks. The incidence of previous PPROM was 14.3%. Antibiotics, corticosteroids, and tocolytics were given to 82, 78, and 52% of women, respectively. The rate of antibiotics and antenatal corticosteroids varied with gestational age (lower rates for antibiotics just after the limit of viability (23-24 weeks) and after 32 weeks, higher rates of corticosteroids between 26 and 30 weeks). The PPROM-birth interval became shorter as gestation advanced. The incidence of C-section was 58.7% (n = 270), C-section before labour being the most frequent mode of delivery. Sixty-seven percent of neonates were born in Level-3 hospitals. The overall neonatal mortality rate at 28 days decreased with gestational age at PPROM, and was 17.2% (16/93), 3% (6/200), and 0.41% (1/241) at 24-27, 28-31 and 32-33 weeks of PPROM, respectively. After PPROM, antibiotics and antenatal corticosteroids were widely used in our cohort, and C-section rates were elevated. With that up-to-date management, the perinatal mortality rate was less than 3% following PPROM after 28 weeks' gestation.
Keir, Amy K; Yang, Junmin; Harrison, Adele; Pelausa, Ermelinda; Shah, Prakesh S
2015-06-01
Knowledge of neonatal transfusion practices remains limited to local cohorts or survey-based studies. This study evaluated the pattern and temporal changes in the types and frequency of blood product use among preterm neonates born at less than 30 weeks' gestation in Canada. A retrospective cohort study of preterm neonates born at less than 30 weeks' gestation and admitted to participating neonatal intensive care units in the Canadian Neonatal Network from 2004 to 2012 was conducted to evaluate blood product usage. The temporal change in red blood cell (RBC) use was evaluated by dividing the study period into three epochs: 2004 to 2006, 2007 to 2009, and 2010 to 2012. Of 14,868 eligible neonates admitted to participating units in Canada during the overall study period, 8252 (56%) received RBCs, 2151 (15%) platelets, 1556 (11%) fresh-frozen plasma, 915 (6%) albumin, and 302 (2%) cryoprecipitate. Temporal evaluation over three epochs revealed a trend toward fewer RBC transfusions among neonates born at 26 to 29 weeks' gestation (p = <0.01-0.04) but use remained unchanged or increased for neonates born at 23 to 25 weeks' gestation (p = 0.02-0.54). Blood product use remains at a very high frequency in preterm neonates born at less than 30 weeks' gestation. Evolutionary practice changes and relative high tolerance for anemia may be associated with a reduction in RBC usage in recent years in neonates born at at least 26 weeks' gestation. This contrasts with the ongoing higher usage of blood products observed at extremely low gestational ages. © 2015 AABB.
Pels, Anouk; Mol, Ben Willem J; Singer, Joel; Lee, Terry; von Dadelszen, Peter; Ganzevoort, Wessel; Asztalos, Elizabeth; Magee, Laura A
2018-06-01
For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight <10th centile ( P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. URL: https://www.isrctn.com. Unique identifier: ISRCTN71416914. © 2018 The Authors.
Hopmans, Tara-Eileen J P; van Houten, Chantal B; Kasius, Annemieke; Kouznetsova, Ouliana I; Nguyen, Ly A; Rooijmans, Sanne V; Voormolen, Daphne N; van Vliet, Elvira O G; Franx, Arie; Koster, M P H Wendy
2015-01-01
To determine the long-term risk of developing type II diabetes (T2D) and cardiovascular disease (CVD) for women with a history of gestational diabetes mellitus. Systematic review and meta-analysis. Two search strategies were used in PubMed and Embase to determine the long-term risks of developing T2D and CVD after a pregnancy complicated by gestational diabetes mellitus. After critical appraisal of the papers found, 11 papers were included, involving a total of 328,423 patients. Absolute and relative risks (RRs) were calculated. Eight studies (n=276,829) reported on the long-term risk of T2D and 4 (n=141,048) on the long-term risk of CVD. Follow-up ranged from 3.5 to 11.5 years for T2D and from 1.2 to 74.0 years for CVD. Women with gestational diabetes had a risk of T2D varying between 9.5% and 37.0% and a risk of CVD of between 0.28% and 15.5%. Women with gestational diabetes were at increased risk of T2D (weighted RR: 13.2; 95% CI: 8.5-20.7) and CVD (weighted RR: 2.0; 95% CI: 1.1-3.7) compared to women without gestational diabetes. Women with prior gestational diabetes mellitus have a significantly increased risk of developing T2D and CVD. It is very important that gestational diabetes is recognised as a cardiovascular risk factor in daily practice. It would be desirable to screen this group of women for the presence of hyperglycaemia and other cardiovascular risk factors. Further research is required to be able to specify the long-term risk of T2D and CVD and to demonstrate whether such screening is cost-effective.
Lee, Anne Cc; Kozuki, Naoko; Cousens, Simon; Stevens, Gretchen A; Blencowe, Hannah; Silveira, Mariangela F; Sania, Ayesha; Rosen, Heather E; Schmiegelow, Christentze; Adair, Linda S; Baqui, Abdullah H; Barros, Fernando C; Bhutta, Zulfiqar A; Caulfield, Laura E; Christian, Parul; Clarke, Siân E; Fawzi, Wafaie; Gonzalez, Rogelio; Humphrey, Jean; Huybregts, Lieven; Kariuki, Simon; Kolsteren, Patrick; Lusingu, John; Manandhar, Dharma; Mongkolchati, Aroonsri; Mullany, Luke C; Ndyomugyenyi, Richard; Nien, Jyh Kae; Roberfroid, Dominique; Saville, Naomi; Terlouw, Dianne J; Tielsch, James M; Victora, Cesar G; Velaphi, Sithembiso C; Watson-Jones, Deborah; Willey, Barbara A; Ezzati, Majid; Lawn, Joy E; Black, Robert E; Katz, Joanne
2017-08-17
Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21 st birth weight standard. Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21 st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. Setting CHERG birth cohorts from 14 population based sites in low and middle income countries. Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Kozuki, Naoko; Cousens, Simon; Stevens, Gretchen A; Blencowe, Hannah; Silveira, Mariangela F; Sania, Ayesha; Rosen, Heather E; Schmiegelow, Christentze; Adair, Linda S; Baqui, Abdullah H; Barros, Fernando C; Bhutta, Zulfiqar A; Caulfield, Laura E; Christian, Parul; Clarke, Siân E; Fawzi, Wafaie; Gonzalez, Rogelio; Humphrey, Jean; Huybregts, Lieven; Kariuki, Simon; Kolsteren, Patrick; Lusingu, John; Manandhar, Dharma; Mongkolchati, Aroonsri; Mullany, Luke C; Ndyomugyenyi, Richard; Nien, Jyh Kae; Roberfroid, Dominique; Saville, Naomi; Terlouw, Dianne J; Tielsch, James M; Victora, Cesar G; Velaphi, Sithembiso C; Watson-Jones, Deborah; Willey, Barbara A; Ezzati, Majid; Lawn, Joy E; Black, Robert E; Katz, Joanne
2017-01-01
Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard. Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. Setting CHERG birth cohorts from 14 population based sites in low and middle income countries. Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries PMID:28819030
Lemley, C O; Meyer, A M; Neville, T L; Hallford, D M; Camacho, L E; Maddock-Carlin, K R; Wilmoth, T A; Wilson, M E; Perry, G A; Redmer, D A; Reynolds, L P; Caton, J S; Vonnahme, K A
2014-01-01
Objectives were to examine effects of selenium (Se) supply and maternal nutritional plane during gestation on placental size at term and maternal endocrine profiles throughout gestation and early lactation. Ewe lambs (n = 84) were allocated to treatments that included Se supply of adequate Se (ASe; 11.5 μg/kg BW) or high Se (HSe; 77 μg/kg BW) initiated at breeding and nutritional plane of 60% (RES), 100% (CON), or 140% (EXC) of requirements beginning on day 40 of gestation. At parturition, lambs were removed from their dams, and ewes were transitioned to a common diet that met requirements of lactation. Blood samples were taken from a subset of ewes (n = 42) throughout gestation, during parturition, and throughout lactation to determine hormone concentrations. Cotyledon number was reduced (P = 0.03) in RES and EXC ewes compared with CON ewes. Placental delivery time tended (P = 0.08) to be shorter in HSe ewes than in ASe ewes, whereas placental delivery time was longer (P = 0.02) in RES ewes than in CON and EXC ewes. During gestation, maternal progesterone, estradiol-17β, and GH were increased (P < 0.05) in RES ewes and decreased (P < 0.05) in EXC ewes compared with CON ewes. In contrast, maternal cortisol, IGF-I, prolactin, triiodothyronine, and thyroxine were decreased in RES ewes and increased in EXC ewes compared with CON ewes during gestation. Selenium supply did not alter maternal hormone profiles during gestation. During parturition and lactation, maternal hormone concentrations were influenced by both Se and maternal nutritional plane. During the parturient process, HSe ewes tended to have greater (P = 0.06) concentrations of estradiol-17β than ASe ewes. Three hours after parturition a surge of GH was observed in ASe-RES ewes that was muted in HSe-RES ewes and not apparent in other ewes. Growth hormone area under the curve during the parturient process was increased (P < 0.05) in ASe-RES vs HSe-RES ewes. Ewes that were overfed during gestation had reduced (P < 0.05) estradiol-17β but greater IGF-I, triiodothyronine, and thyroxine (P < 0.05) compared with RES ewes. Even though ewes were transitioned to a common diet after parturition, endocrine status continued to be affected into lactation. Moreover, it appears that gestational diet may partially affect lactational performance through altered endocrine status. Copyright © 2014 Elsevier Inc. All rights reserved.
Temperature and Term Low Birth Weight in California.
Basu, Rupa; Rau, Reina; Pearson, Dharshani; Malig, Brian
2018-06-12
Few investigations have explored temperature and birth outcomes. In a retrospective cohort study, we examined apparent temperature, a combination of temperature and relative humidity, and term low birth weight (LBW) among 43,629 full-term LBW infants and 2,032,601 normal weight infants in California from 1999 to 2013. The California Department of Public Health provided birth certificate data, while meteorologic data came from the California Irrigation Management Information System, US Environmental Protection Agency, and National Centers for Environmental Information. After considering several temperature metrics, we observed the best model fit for term LBW over the full gestation (13.0% change, 95% confidence interval: 4.1, 22.7 per 10 degrees Fahrenheit (°F) increase in apparent temperature) above 55°F and the greatest association for third trimester exposure above 60°F (15.8%, 95% confidence interval: 5.0, 27.6). Apparent temperature during the first month of pregnancy exhibited no significant risk, while the first trimester had a significantly negative association, and second trimester, last month and last two weeks had slightly increased risks. Mothers who were Black, older, delivered male infants, or gave birth during the warm season conferred the highest risks. This study provides further evidence for adverse birth outcomes from heat exposure for vulnerable subgroups of pregnant women.
Wong, Brian J F; Karimi, Koohyar; Devcic, Zlatko; McLaren, Christine E; Chen, Wen-Pin
2008-06-01
The objectives of this study were to: 1) determine if a genetic algorithm in combination with morphing software can be used to evolve more attractive faces; and 2) evaluate whether this approach can be used as a tool to define or identify the attributes of the ideal attractive face. Basic research study incorporating focus group evaluations. Digital images were acquired of 250 female volunteers (18-25 y). Randomly selected images were used to produce a parent generation (P) of 30 synthetic faces using morphing software. Then, a focus group of 17 trained volunteers (18-25 y) scored each face on an attractiveness scale ranging from 1 (unattractive) to 10 (attractive). A genetic algorithm was used to select 30 new pairs from the parent generation, and these were morphed using software to produce a new first generation (F1) of faces. The F1 faces were scored by the focus group, and the process was repeated for a total of four iterations of the algorithm. The algorithm mimics natural selection by using the attractiveness score as the selection pressure; the more attractive faces are more likely to morph. All five generations (P-F4) were then scored by three focus groups: a) surgeons (n = 12), b) cos-metology students (n = 44), and c) undergraduate students (n = 44). Morphometric measurements were made of 33 specific features on each of the 150 synthetic faces, and correlated with attractiveness scores using univariate and multivariate analysis. The average facial attractiveness scores increased with each generation and were 3.66 (+0.60), 4.59 (+/-0.73), 5.50 (+/-0.62), 6.23 (+/-0.31), and 6.39 (+/-0.24) for P and F1-F4 generations, respectively. Histograms of attractiveness score distributions show a significant shift in the skew of each curve toward more attractive faces with each generation. Univariate analysis identified nasal width, eyebrow arch height, and lip thickness as being significantly correlated with attractiveness scores. Multivariate analysis identified a similar collection of morphometric measures. No correlation with more commonly accepted measures such as the length facial thirds or fifths were identified. When images are examined as a montage (by generation), clear distinct trends are identified: oval shaped faces, distinct arched eyebrows, and full lips predominate. Faces evolve to approximate the guidelines suggested by classical canons. F3 and F4 generation faces look profoundly similar. The statistical and qualitative analysis indicates that the algorithm and methodology succeeds in generating successively more attractive faces. The use of genetic algorithms in combination with a morphing software and traditional focus-group derived attractiveness scores can be used to evolve attractive synthetic faces. We have demonstrated that the evolution of attractive faces can be mimicked in software. Genetic algorithms and morphing provide a robust alternative to traditional approaches rooted in comparing attractiveness scores with a series of morphometric measurements in human subjects.
Dorst, J; Haag, A; Knake, S; Oertel, W H; Hamer, H M; Rosenow, F
2008-10-01
Functional transcranial Doppler sonography (fTCD) during word generation is well established for language lateralization. In this study, we evaluated a fTCD paradigm to reliably identify the non-dominant hemisphere. Twenty-nine right-handed healthy subjects (27.1+/-7.6 years) performed the 'cube perspective test' [Stumpf, H., & Fay, E. (1983). Schlauchfiguren: Ein Test zur Beurteilung des räumlichen Vorstellungsvermögens. Verlag für Psychologie Dr. C. J. Hogrefe, Göttingen, Toronto, Zürich] a spatial orientation task, while the cerebral blood flow velocity (CBFV) was simultaneously measured in both middle cerebral arteries (MCAs). In addition, the established word generation paradigm for language lateralization was performed. Subjects with atypical language representation were excluded. Data were analysed offline with the software Average, which performed a heart-cycle integration and a baseline-correction and calculated a lateralization index (LI) with its standard error of the mean increase in CBFV separately for both MCAs. Twenty-one of 29 subjects (72.4%) lateralized to the right hemisphere (chi2=5.828, p=0.016). The mean LI of the spatial orientation paradigm pointed to the right hemisphere (x =-1.9+/-3.2) and was different from the LI of word generation (x =3.9+/-2.2;p<0.001). There was no correlation between the LI of spatial orientation and word generation (R=0.095, p=0.624). Age of the subjects did not correlate with the LI during spatial orientation (p>0.05) but negatively with the LI during word generation (R=-0.468, p=0.010). The maximum increase of CBFV was greater in the spatial orientation (14.0%+/-3.6%) than in the word generation paradigm (9.4%+/-4.0%; p<0.001). In more than two thirds of the subjects with left-sided language dominance, the spatial orientation paradigm was able to identify the non-dominant hemisphere. The results suggest both paradigms to be independent of each other. The spatial orientation paradigm, therefore, appears to be a non-verbal fTCD paradigm with possible clinical relevance.
Complement activation fragment Bb in early pregnancy and spontaneous preterm birth.
Lynch, Anne M; Gibbs, Ronald S; Murphy, James R; Byers, Tim; Neville, Margaret C; Giclas, Patricia C; Salmon, Jane E; Van Hecke, Trisha M; Holers, V Michael
2008-10-01
The objective of this study was to determine whether an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks' gestation or SPTB between 34 and 37 weeks' gestation (late SPTB). This was a prospective study of 784 women enrolled at less than 20 weeks' gestation. Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks' gestation and 25 (3.2%) a SPTB between 34 and 37 weeks' gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks' gestation as compared with women who had levels of Bb in the lower 3 quartiles (95% confidence interval [CI] 1.5-14, P = .003). There was no association between Bb and late SPTB (relative risk 0.8, 95% CI 0.3-2). A significant relationship was found between an elevated Bb in early pregnancy and SPTB less than 34 weeks' gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition.
Serum zinc levels of cord blood: relation to birth weight and gestational period.
Gómez, Tahiry; Bequer, Leticia; Mollineda, Angel; González, Olga; Diaz, Mireisy; Fernández, Douglas
2015-04-01
Zn-deficiency has been associated with numerous alterations during pregnancy including low birth weight; however, the research relating neonatal zinc status and birth weight has not produced reliable results. To compare the serum Zn-levels of cord blood in healthy newborns and low birth weight newborns, and to assess a possible relationship between zinc concentration and neonatal birth weight and gestational age. 123 newborns divided in "study group" (n=50) with <2500g birth weight neonates and "control group" (n=73) with ≥2500g birth weight neonates were enrolled. Study group was subdivided according to gestational age in preterm (<37 weeks) and full-term (≥37 weeks). Serum cord blood samples were collected and the Zn-levels were analyzed using flame Atomic Absorption Spectrophotometry method and the result was expressed in μmol/L. The Zn-levels were compared between the groups (Mann-Whitney-U test) and the Zn-levels were correlated with the birth weight and gestational age (Spearman's rank correlations). Statistically significant low positive correlation between Zn-levels and birth weight (ρ=0.283; p=0.005) was found. No statistically significant difference between Zn-levels of study and control groups [17.00±0.43 vs. 18.16±0.32 (p=0.053)] was found. Statistically significant low positive correlation between Zn-levels and gestational age (ρ=0.351; p=0.001) was found. No statistically significant difference between Zn-levels of preterm as compare to full-term newborns [16.33±0.42 vs. 18.43±0.93 (p=0.079)] was found. Zn-level of preterm subgroup was significantly lower compared to control group (p=0.001). Despite low birth weight preterm neonates had significantly lower serum zinc levels of cord blood than healthy term neonates, the correlation between cord blood zinc levels and birth weight and gestational age was lower. The results are not enough to relate the change in cord blood zinc concentration to the birth weight values or gestational period. In relation to complicated pregnancies, further studies regarding zinc levels in blood in our population are required. Copyright © 2015 Elsevier GmbH. All rights reserved.
Tomasek, R; Rezac, P; Havlicek, Z
2017-01-01
The objective was to assess the effects of the month of conception, month of calving, sex of the calf, and twins on gestation length (GL) in Holstein cows and heifers in two dairy herds with different milk yields. The study was performed in northeast Czech Republic over a 6-year period on two commercial dairy herds with a mean annual milk production of 11,060 kg per cow in the higher milk-producing herd and 8854 kg per cow in the lower milk-producing herd. Gestation length in cows that conceived in different months of the year was longer in the higher milk-producing herd than that in the lower milk-producing herd throughout the year (P < 0.01), whereas GL in heifers was almost the same in both herds. Gestation length in cows that conceived in different months of the year was longer than that in heifers through the whole year in both herds (P < 0.05). Similar results were found in cows and heifers that calved in different months of the year. Gestation length in cows and heifers that conceived in the first months of the year was longer than in those that conceived in the last months of the year in both herds (P < 0.05). Gestation length in cows and heifers that calved in late fall and throughout winter was longer than in those that calved in spring and summer in both herds (P < 0.05). Gestation length in females carrying male calves was longer than in those carrying female calves (P < 0.0001). Gestation length in cows (P < 0.0001) and heifers (P < 0.05) carrying singles was longer than in those carrying twins in both herds. In conclusion, results indicate that GL in Holstein cattle is associated with the month of conception, month of calving, herd, parity, sex of the calf, and twins. Copyright © 2016 Elsevier Inc. All rights reserved.
Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.
Anway, Matthew D; Memon, Mushtaq A; Uzumcu, Mehmet; Skinner, Michael K
2006-01-01
The current study was designed to examine the actions of a model endocrine disruptor on embryonic testis development and male fertility. Pregnant rats (F0) that received a transient embryonic exposure to an environmental endocrine disruptor, vinclozolin, had male offspring (F1) with reduced spermatogenic capacity. The reduced spermatogenetic capacity observed in the F1 male offspring was transmitted to the subsequent generations (F2-F4). The administration of vinclozolin, an androgen receptor antagonist, at 100 mg/kg/day from embryonic day 8-14 (E8-E14) of pregnancy to only the F0 dam resulted in a transgenerational phenotype in the subsequent male offspring in the F1-F4 generations. The litter size and male/female sex ratios were similar in controls and the vinclozolin generations. The average testes/body weight index of the postnatal day 60 (P60) males was not significantly different in the vinclozolin-treated generations compared to the controls. However, the testicular spermatid number, as well as the epididymal sperm number and motility, were significantly reduced in the vinclozolin generations compared to the control animals. Postnatal day 20 (P20) testis from the vinclozolin F2 generation had no morphological abnormalities, but did have an increase in spermatogenic cell apoptosis. Although the P60 testis morphology was predominantly normal, the germ cell apoptosis was significantly increased in the testes cross sections of animals from the vinclozolin generations. The increase in apoptosis was stage-specific in the testis, with tubules at stages IX-XIV having the highest increase in apoptotic germ cells. The tubules at stages I-V also had an increase in apoptotic germ cells compared to the control samples, but tubules at stages VI-VIII had no increase in apoptotic germ cells. An outcross of a vinclozolin generation male with a wild-type female demonstrated that the reduced spermatogenic cell phenotype was transmitted through the male germ line. An outcross with a vinclozolin generation female with a wild-type male had no phenotype. A similar phenotype was observed in outbred Sprague Dawley and inbred Fisher rat strains. Observations demonstrate that a transient exposure at the time of male sex determination to the antiandrogenic endocrine disruptor vinclozolin can induce an apparent epigenetic transgenerational phenotype with reduced spermatogenic capacity.
Paramel Jayaprakash, Teenus; Wagner, Emily C.; van Schalkwyk, Julie; Albert, Arianne Y. K.; Hill, Janet E.; Money, Deborah M.
2016-01-01
Objective To characterize the vaginal microbiota of women following preterm premature rupture of membranes (PPROM), and determine if microbiome composition predicts latency duration and perinatal outcomes. Design A prospective cohort study Setting Canada Population Women with PPROM between 24+0 and 33+6 weeks gestational age (GA). Methods Microbiome profiles, based on pyrosequencing of the cpn60 universal target, were generated from vaginal samples at time of presentation with PPROM, weekly thereafter, and at delivery. Main Outcome Measures Vaginal microbiome composition, latency duration, gestational age at delivery, perinatal outcomes. Results Microbiome profiles were generated from 70 samples from 36 women. Mean GA at PPROM was 28.8 wk (mean latency 2.7 wk). Microbiome profiles were highly diverse but sequences representing Megasphaera type 1 and Prevotella spp. were detected in all vaginal samples. Only 13/70 samples were dominated by Lactobacillus spp. Microbiome profiles at the time of membrane rupture did not cluster by gestational age at PPROM, latency duration, presence of chorioamnionitis or by infant outcomes. Mycoplasma and/or Ureaplasma were detected by PCR in 81% (29/36) of women, and these women had significantly lower GA at delivery and correspondingly lower birth weight infants than Mycoplasma and/or Ureaplasma negative women. Conclusion Women with PPROM had mixed, abnormal vaginal microbiota but the microbiome profile at PPROM did not correlate with latency duration. Prevotella spp. and Megasphaera type I were ubiquitous. The presence of Mollicutes in the vaginal microbiome was associated with lower GA at delivery. The microbiome was remarkably unstable during the latency period. PMID:27861554
Vásquez, Gustavo; Sanhueza, Felipe; Vásquez, Rodrigo; González, Marcelo; Martín, Rody San; Casanello, Paola; Sobrevia, Luis
2004-01-01
Gestational diabetes is associated with increased l-arginine transport and nitric oxide (NO) synthesis, and reduced adenosine transport in human umbilical vein endothelial cells (HUVEC). Adenosine increases endothelial l-arginine/NO pathway via A2 purinoceptors in HUVEC from normal pregnancies. It is unknown whether the effect of gestational diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter 1 (hENT1), or endothelial NO synthase (eNOS) in HUVEC. Cells were isolated from normal or gestational diabetic pregnancies and cultured up to passage 2. Gestational diabetes increased hCAT-1 mRNA expression (2.4-fold) and activity, eNOS mRNA (2.3-fold), protein level (2.1-fold), and phosphorylation (3.8-fold), but reduced hENT1 mRNA expression (32%) and activity. Gestational diabetes increased extracellular adenosine (2.7 μm), and intracellular l-arginine (1.9 mm) and l-citrulline (0.7 mm) levels compared with normal cells (0.05 μm, 0.89 mm, 0.35 mm, respectively). Incubation of HUVEC from normal pregnancies with 1 μm nitrobenzylthioinosine (NBMPR) mimicked the effect of gestational diabetes, but NBMPR was ineffective in diabetic cells. Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44mapk activation, and were blocked by the A2a purinoceptor antagonist ZM-241385. Thus, gestational diabetes increases the l-arginine/NO pathway involving activation of mitogen-activated protein (MAP) kinases, protein kinase C (PKC) and NO cell signalling cascades following activation of A2a purinoceptors by extracellular adenosine. A functional relationship is proposed between adenosine transport and modulation of l-arginine transport and NO synthesis in HUVEC, which could be determinant in regulating vascular reactivity in diabetes mellitus. PMID:15272035
Fondjo, Linda Ahenkorah; Gmagna, Peter; Ghartey, Frank Naku; Awe, Martin Akilla
2017-01-01
Background Gestational diabetes is a risk factor for perinatal complications; include shoulder dystocia, birth injuries such as bone fractures and nerve palsies. It is associated with later development of type 2 diabetes, the risk of macrosomia and other long-term health effects of infants born to diabetic mothers. The study assesses placental peptides and maternal factors as potential predictors of gestational diabetes among pregnant women. Material and methods A total of 200 pregnant women were recruited for the study, 150 pregnant women without pre gestational diabetes including 50 women with low risk factors of diabetes as controls and 50 other pregnant women with pregestational diabetes as control. Fasting blood glucose and the lipid profile were determined by enzymatic methods using Envoy® 500 reagents (Vital Diagnostics, USA). Glycated haemoglobin was assessed using the Cation Exchange resin method. Leptin and the Human Placenta Lactogen were assayed using the Sandwich-ELISA technique. Beta chorionic gonadotrophin, insulin, progesterone and estradiol were determined using chemilumiscence imunoassay technique on MAGLUMI 600 analyzer. Anthropometry, including BMI and blood pressure were also measured. Results Fasting plasma glucose (FBG), insulin, insulin resistance, glycated haemoglobin and Human Placenta Lactogen(HPL)were significantly (p<0.0001) increased in the pregestational diabetic women whereas progesterone and estradiol were significantly decreased. In the second trimester however, there was no significant difference (p>0.05) in estradiol, insulin, insulin resistance and HPL between the pregnant women who developed gestational diabetes and those who did not. Leptin, progesterone and FBG were significantly increased in those who developed GDM. The risk of developing gestational diabetes increased with overweight (OR = 1.76, P = 0.370) and family history of diabetes (OR = 2.18, P = 0.282). Conclusion Leptin, progesterone, estradiol estimated in this study were increased in the gestational diabetes mellitus women and fairly predicted gestational diabetes in the non-diabetics pregnant women. Obesity, aging and family history of diabetes were strongly predictive of gestational diabetes. PMID:28732072
Ngala, Robert Amadu; Fondjo, Linda Ahenkorah; Gmagna, Peter; Ghartey, Frank Naku; Awe, Martin Akilla
2017-01-01
Gestational diabetes is a risk factor for perinatal complications; include shoulder dystocia, birth injuries such as bone fractures and nerve palsies. It is associated with later development of type 2 diabetes, the risk of macrosomia and other long-term health effects of infants born to diabetic mothers. The study assesses placental peptides and maternal factors as potential predictors of gestational diabetes among pregnant women. A total of 200 pregnant women were recruited for the study, 150 pregnant women without pre gestational diabetes including 50 women with low risk factors of diabetes as controls and 50 other pregnant women with pregestational diabetes as control. Fasting blood glucose and the lipid profile were determined by enzymatic methods using Envoy® 500 reagents (Vital Diagnostics, USA). Glycated haemoglobin was assessed using the Cation Exchange resin method. Leptin and the Human Placenta Lactogen were assayed using the Sandwich-ELISA technique. Beta chorionic gonadotrophin, insulin, progesterone and estradiol were determined using chemilumiscence imunoassay technique on MAGLUMI 600 analyzer. Anthropometry, including BMI and blood pressure were also measured. Fasting plasma glucose (FBG), insulin, insulin resistance, glycated haemoglobin and Human Placenta Lactogen(HPL)were significantly (p<0.0001) increased in the pregestational diabetic women whereas progesterone and estradiol were significantly decreased. In the second trimester however, there was no significant difference (p>0.05) in estradiol, insulin, insulin resistance and HPL between the pregnant women who developed gestational diabetes and those who did not. Leptin, progesterone and FBG were significantly increased in those who developed GDM. The risk of developing gestational diabetes increased with overweight (OR = 1.76, P = 0.370) and family history of diabetes (OR = 2.18, P = 0.282). Leptin, progesterone, estradiol estimated in this study were increased in the gestational diabetes mellitus women and fairly predicted gestational diabetes in the non-diabetics pregnant women. Obesity, aging and family history of diabetes were strongly predictive of gestational diabetes.
Refractive Status at Birth: Its Relation to Newborn Physical Parameters at Birth and Gestational Age
Varghese, Raji Mathew; Sreenivas, Vishnubhatla; Puliyel, Jacob Mammen; Varughese, Sara
2009-01-01
Background Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth. Methods All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, (mean spherical equivalent (MSE), astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters. Results Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age. Conclusion This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher. PMID:19214228
Between-Hospital Variation in Treatment and Outcomes in Extremely Preterm Infants
Rysavy, Matthew A.; Li, Lei; Bell, Edward F.; Das, Abhik; Hintz, Susan R.; Stoll, Barbara J.; Vohr, Betty R.; Carlo, Waldemar A.; Shankaran, Seetha; Walsh, Michele C.; Tyson, Jon E.; Cotten, C. Michael; Smith, P. Brian; Murray, Jeffrey C.; Colaizy, Tarah T.; Brumbaugh, Jane E.; Higgins, Rosemary D.
2015-01-01
BACKGROUND Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. METHODS We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). RESULTS Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation. CONCLUSIONS Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.) PMID:25946279
Hutton, E K; Hannah, M E; Ross, S J; Delisle, M-F; Carson, G D; Windrim, R; Ohlsson, A; Willan, A R; Gafni, A; Sylvestre, G; Natale, R; Barrett, Y; Pollard, J K; Dunn, M S; Turtle, P
2011-04-01
To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. An unblinded multicentred randomised controlled trial. A total of 1543 women were randomised from 68 centres in 21 countries. Women with a singleton breech fetus at a gestational age of 33(0/7) weeks (231 days) to 35(6/7) weeks (251 days) of gestation were included. Participants were randomly assigned to having a first ECV procedure between the gestational ages of 34(0/7) (238 days) and 35(6/7) weeks of gestation (early ECV group) or at or after 37(0/7) (259 days) weeks of gestation (delayed ECV group). The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P=0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P=0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P=0.07) between groups. External cephalic version at 34-35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.
Xinxo, Sonela; Bimbashi, Astrit; Z Kakarriqi, Eduard; Zaimi, Edmond
2013-01-01
Maternal nutritional status of pre pregnancy and gestational weight gain affects the preterm birth. The association between maternal nutritional status of pre pregnancy and preterm birth appears to be complex and varied by studies from different countries, thus this association between the gestational weight gain and preterm birth is more consolidated. The study aims to determine any association between the pre pregnancy maternal nutritional status, gestational weight gain and the preterm birth rate in the Albanian context. In case control study, we analyzed women who have delivered in obstetric institutions in Tirana during the year 2012. Body mass index and gestational weight gain of 150 women who had a preterm delivery were compared with those of 150 matched control women who had a normal delivery regarding the gestation age. The self-reported pre pregnancy weight, height, gestational weight gain, age, education and parity are collected through a structured questioner. The body mass index and gestational weight gain are categorized based on the Institute of Medicine recommendation. The multiple logistic regression is used to measure the association between the nutritional status of pre pregnancy and gestational weight gain and the preterm birth rate. The women which have a underweight status or obese of pre pregnancy are more likely to have a preterm birth compared to the women of a normal pre-pregnancy nutritional status (respectively OR =2.7 and 4.3 p<0.05). Women who do not reach the recommended gestational weight gain are more likely to have a preterm birth compared to the women which reach this weight (OR=1.8 p< 0.05). Maternal nutritional status and gestational weight gain affects the risk for preterm birth. Pre-pregnancy and gestation nutritional assessments should be part of routine prenatal visits.
Mahendru, Amita A; Wilhelm-Benartzi, Charlotte S; Wilkinson, Ian B; McEniery, Carmel M; Johnson, Sarah; Lees, Christoph
2016-10-01
Understanding the natural length of human pregnancy is central to clinical care. However, variability in the reference methods to assign gestational age (GA) confound our understanding of pregnancy length. Assignation from ultrasound measurement of fetal crown-rump length (CRL) has superseded that based on last menstrual period (LMP). Our aim was to estimate gestational length based on LMP, ultrasound CRL, and implantation that were known, compared to pregnancy duration assigned by day of ovulation. Prospective study in 143 women trying to conceive. In 71 ongoing pregnancies, gestational length was estimated from LMP, CRL at 10-14 weeks, ovulation, and implantation day. For each method of GA assignment, the distribution in observed gestational length was derived and both agreement and correlation between the methods determined. Median ovulation and implantation days were 16 and 27, respectively. The gestational length based on LMP, CRL, implantation, and ovulation was similar: 279, 278, 276.5 and 276.5 days, respectively. The distributions for observed gestational length were widest where GA was assigned from CRL and LMP and narrowest when assigned from implantation and ovulation day. The strongest correlation for gestational length assessment was between ovulation and implantation (r = 0.98) and weakest between CRL and LMP (r = 0.88). The most accurate method of predicting gestational length is ovulation day, and this agrees closely with implantation day. Prediction of gestational length from CRL and known LMP are both inferior to ovulation and implantation day. This information could have important implications on the routine assignment of gestational age.
Alberico, Salvatore; Montico, Marcella; Barresi, Valentina; Monasta, Lorenzo; Businelli, Caterina; Soini, Valentina; Erenbourg, Anna; Ronfani, Luca; Maso, Gianpaolo
2014-01-15
It is crucial to identify in large population samples the most important determinants of excessive fetal growth. The aim of the study was to evaluate the independent role of pre-pregnancy body mass index (BMI), gestational weight gain and gestational diabetes on the risk of macrosomia. A prospective study collected data on mode of delivery and maternal/neonatal outcomes in eleven Hospitals in Italy. Multiple pregnancies and preterm deliveries were excluded. The sample included 14109 women with complete records. Associations between exposure variables and newborn macrosomia were analyzed using Pearson's chi squared test. Multiple logistic regression models were built to assess the independent association between potential predictors and macrosomia. Maternal obesity (adjusted OR 1.7, 95% CI 1.4-2.2), excessive gestational weight gain (adjusted OR 1.9, 95% CI 1.6-2.2) and diabetes (adjusted OR 2.1, 95% CI 1.5-3.0 for gestational; adjusted OR 3.0, 95% CI 1.2-7.6 for pre-gestational) resulted to be independent predictors of macrosomia, when adjusted for other recognized risk factors. Since no significant interaction was found between pre-gestational BMI and gestational weight gain, excessive weight gain should be considered an independent risk factor for macrosomia. In the sub-group of women affected by gestational or pre-gestational diabetes, pre-gestational BMI was not significantly associated to macrosomia, while excessive pregnancy weight gain, maternal height and gestational age at delivery were significantly associated. In this sub-population, pregnancy weight gain less than recommended was not significantly associated to a reduction in macrosomia. Our findings indicate that maternal obesity, gestational weight gain excess and diabetes should be considered as independent risk factors for newborn macrosomia. To adequately evaluate the clinical evolution of pregnancy all three variables need to be carefully assessed and monitored.
2014-01-01
Background It is crucial to identify in large population samples the most important determinants of excessive fetal growth. The aim of the study was to evaluate the independent role of pre-pregnancy body mass index (BMI), gestational weight gain and gestational diabetes on the risk of macrosomia. Methods A prospective study collected data on mode of delivery and maternal/neonatal outcomes in eleven Hospitals in Italy. Multiple pregnancies and preterm deliveries were excluded. The sample included 14109 women with complete records. Associations between exposure variables and newborn macrosomia were analyzed using Pearson’s chi squared test. Multiple logistic regression models were built to assess the independent association between potential predictors and macrosomia. Results Maternal obesity (adjusted OR 1.7, 95% CI 1.4-2.2), excessive gestational weight gain (adjusted OR 1.9, 95% CI 1.6-2.2) and diabetes (adjusted OR 2.1, 95% CI 1.5-3.0 for gestational; adjusted OR 3.0, 95% CI 1.2-7.6 for pre-gestational) resulted to be independent predictors of macrosomia, when adjusted for other recognized risk factors. Since no significant interaction was found between pre-gestational BMI and gestational weight gain, excessive weight gain should be considered an independent risk factor for macrosomia. In the sub-group of women affected by gestational or pre-gestational diabetes, pre-gestational BMI was not significantly associated to macrosomia, while excessive pregnancy weight gain, maternal height and gestational age at delivery were significantly associated. In this sub-population, pregnancy weight gain less than recommended was not significantly associated to a reduction in macrosomia. Conclusions Our findings indicate that maternal obesity, gestational weight gain excess and diabetes should be considered as independent risk factors for newborn macrosomia. To adequately evaluate the clinical evolution of pregnancy all three variables need to be carefully assessed and monitored. PMID:24428895
Generation of extremely low frequency chorus in Van Allen radiation belts: ELF CHORUS GENERATION
Xiao, Fuliang; Liu, Si; Tao, Xin; ...
2017-01-01
Recent studies have shown that chorus can efficiently accelerate the outer radiation belt electrons to relativistic energies. Chorus, previously often observed above 0.1 equatorial electron gyrofrequency f ce, was generated by energetic electrons originating from Earth's plasmasheet. Chorus below 0.1 f ce has seldom been reported until the recent data from Van Allen Probes but its origin has not been revealed so far. Because electron resonant energy can approach the relativistic level at extremely low frequency relativistic effects should be considered in the formula for whistler-mode wave growth rate. Here we report high-resolution observations during the 14 October 2014 smallmore » storm and firstly demonstrate, using a fully relativistic simulation, that electrons with the high energy tail population and relativistic pitch angle anisotropy can provide free energy sufficient for generating chorus below 0.1 f ce. The simulated wave growth displays a very similar pattern to the observations. Finally, the current results can be applied to Jupiter, Saturn and other magnetized planets.« less
Mikami, H; Nishibata, R; Kawamoto, Y; Ino, T
1991-04-01
We developed two lines of guinea pigs, one as model animals for bronchial asthma with bronchial hypersensitivity and the other with hyposensitivity as a control. In the last four years, the bronchial hypersensitive line (BHS) and hyposensitive line (BHR), both derived from Hartley strain guinea pigs, have been selected by using bronchial reactivity to acetylcholine and to histamine as parameters. Both lines have reached the F6 generation. The following results were obtained with the two lines: 1) Sib and cous in matings, and mating of selected consanguineous individuals were adopted in breeding BHS and BHR. The breeding started with six families, each, but in the F6 generation the number of families decreased to two in each line. 2) Appearance rates of hyper- or hyposensitivity to acetylcholine and histamine increased with successive generations in both lines, which had been completely separated by the F6 generation. 3) Coefficients of inbreeding in BHS and BHR in the F6 generation ranged from 42% to 45% in the former and 42% in the latter. 4) Heritabilities (h2) of BHS and BHR for the appearance rates of sensitivity to acetylcholine were presumed to be 0.54 in the former and 0.69 in the latter. 5) No difference in the body weight of 0, 20, and 40 day-old BHS was observed in any generation. On the other hand, the body weight of 20 and 40 day-old BHR tended to decrease with successive generations. 6) Mean litter sizes of BHS and BHR in each of the generations ranged from 2.24 to 3.47 animals in the former and from 2.63 to 3.38 animals in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)