Science.gov

Sample records for early fetal growth

  1. Effect of maternal smoking cessation before and during early pregnancy on fetal and childhood growth.

    PubMed

    Suzuki, Kohta; Sato, Miri; Zheng, Wei; Shinohara, Ryoji; Yokomichi, Hiroshi; Yamagata, Zentaro

    2014-01-01

    Maternal smoking during pregnancy is a major cause of intrauterine growth restriction and childhood obesity, but only a few studies have examined the association of smoking cessation before and during pregnancy with fetal and childhood growth. We examined this association in a prospective cohort study in Japan. Our study included children born between 1991 and 2006 and their mothers. Using a questionnaire, maternal smoking status was recorded at pregnancy. The anthropometric data of the children were collected during a medical check-up at age 3 years. Multiple linear and logistic regression models were used for data analysis stratified by sex. In total, 2663 mothers reported their smoking status during early pregnancy, and data were collected from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was associated with a significant reduction in birth weight (approximately 120-150 g). Body mass index at age 3 years was significantly higher among boys born to smoking mothers than among boys born to nonsmoking mothers. Maternal smoking during pregnancy was associated with overweight at age 3 years among boys (adjusted odds ratio, 2.4; 95% CI, 1.03-5.4). However, among women who stopped smoking in early pregnancy, there was no increase in the risks of a small for gestational age birth or childhood overweight at age 3 years. Children born to mothers who stopped smoking before or during early pregnancy had appropriate fetal and childhood growth.

  2. Fetal growth restriction: current knowledge.

    PubMed

    Nardozza, Luciano Marcondes Machado; Caetano, Ana Carolina Rabachini; Zamarian, Ana Cristina Perez; Mazzola, Jaqueline Brandão; Silva, Carolina Pacheco; Marçal, Vivian Macedo Gomes; Lobo, Thalita Frutuoso; Peixoto, Alberto Borges; Araujo Júnior, Edward

    2017-05-01

    Fetal growth restriction (FGR) is a condition that affects 5-10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classification, prediction, diagnosis, and management of the condition, as well as on its neurological complications. The Pubmed, SCOPUS, and Embase databases were searched using the term "fetal growth restriction". Fetal growth restriction (FGR) may be classified as early or late depending on the time of diagnosis. Early FGR (<32 weeks) is associated with substantial alterations in placental implantation with elevated hypoxia, which requires cardiovascular adaptation. Perinatal morbidity and mortality rates are high. Late FGR (≥32 weeks) presents with slight deficiencies in placentation, which leads to mild hypoxia and requires little cardiovascular adaptation. Perinatal morbidity and mortality rates are lower. The diagnosis of FGR may be clinical; however, an arterial and venous Doppler ultrasound examination is essential for diagnosis and follow-up. There are currently no treatments to control FGR; the time at which pregnancy is interrupted is of vital importance for protecting both the mother and fetus. Early diagnosis of FGR is very important, because it enables the identification of the etiology of the condition and adequate monitoring of the fetal status, thereby minimizing risks of premature birth and intrauterine hypoxia.

  3. Cohort profile: effect of malaria in early pregnancy on fetal growth in Benin (RECIPAL preconceptional cohort)

    PubMed Central

    Accrombessi, Manfred; Yovo, Emmanuel; Cottrell, Gilles; Agbota, Gino; Gartner, Agnès; Martin-Prevel, Yves; Fanou-Fogny, Nadia; Djossinou, Diane; Zeitlin, Jennifer; Tuikue-Ndam, Nicaise; Bodeau-Livinec, Florence; Houzé, Sandrine; Jackson, Nicola; Ayemonna, Paul; Massougbodji, Achille; Cot, Michel; Fievet, Nadine; Briand, Valérie

    2018-01-01

    Purpose REtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus. Participants For this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment. Findings to date Pregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively. Future plans REtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future. PMID:29317419

  4. Outcome in early-onset fetal growth restriction is best combining computerized fetal heart rate analysis with ductus venosus Doppler: insights from the Trial of Umbilical and Fetal Flow in Europe.

    PubMed

    Frusca, Tiziana; Todros, Tullia; Lees, Christoph; Bilardo, Caterina M

    2018-02-01

    Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02-1.52) and infant survival without neurodevelopmental impairment at 2

  5. Remodelling of the bovine placenta: Comprehensive morphological and histomorphological characterization at the late embryonic and early accelerated fetal growth stages.

    PubMed

    Estrella, Consuelo Amor S; Kind, Karen L; Derks, Anna; Xiang, Ruidong; Faulkner, Nicole; Mohrdick, Melina; Fitzsimmons, Carolyn; Kruk, Zbigniew; Grutzner, Frank; Roberts, Claire T; Hiendleder, Stefan

    2017-07-01

    Placental function impacts growth and development with lifelong consequences for performance and health. We provide novel insights into placental development in bovine, an important agricultural species and biomedical model. Concepti with defined genetics and sex were recovered from nulliparous dams managed under standardized conditions to study placental gross morphological and histomorphological parameters at the late embryo (Day48) and early accelerated fetal growth (Day153) stages. Placentome number increased 3-fold between Day48 and Day153. Placental barrier thickness was thinner, and volume of placental components, and surface areas and densities were higher at Day153 than Day48. We confirmed two placentome types, flat and convex. At Day48, there were more convex than flat placentomes, and convex placentomes had a lower proportion of maternal connective tissue (P < 0.01). However, this was reversed at Day153, where convex placentomes were lower in number and had greater volume of placental components (P < 0.01- P < 0.001) and greater surface area (P < 0.001) than flat placentomes. Importantly, embryo (r = 0.50) and fetal (r = 0.30) weight correlated with total number of convex but not flat placentomes. Extensive remodelling of the placenta increases capacity for nutrient exchange to support rapidly increasing embryo-fetal weight from Day48 to Day153. The cellular composition of convex placentomes, and exclusive relationships between convex placentome number and embryo-fetal weight, provide strong evidence for these placentomes as drivers of prenatal growth. The difference in proportion of maternal connective tissue between placentome types at Day48 suggests that this tissue plays a role in determining placentome shape, further highlighting the importance of early placental development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  7. Sildenafil Citrate in Fetal Growth Restriction

    PubMed Central

    Panda, Subrat; Das, Ananya; Md Nowroz, Hossain

    2014-01-01

    Background Pregnancies with early onset fetal growth restriction have poor perinatal outcome. Sildenafil citrate (PDE -5 inhibitor) as a vasodilator increases utero-placental blood flow and potentiates fetal growth. Case Presentation In this study, a case was examined and Sildenafil was administered for her. It was found that Sildenafil improved the uterine blood flow with a favorable fetal outcome at delivery. Conclusion Sildenafil, as a vasodilator has emerged as a potential management option in the treatment of Intra Uterine Growth Retardation (IUGR) and preeclampsia by later normalization in velocimetric profile. PMID:25202677

  8. Uterine artery blood flow, fetal hypoxia and fetal growth

    PubMed Central

    Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  9. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants

    PubMed Central

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena

    2018-01-01

    The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

  10. Prenatal Depression Restricts Fetal Growth

    PubMed Central

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

    2009-01-01

    Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

  11. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

    PubMed Central

    Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

    2011-01-01

    Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

  12. The effect of fetal sex on customized fetal growth charts.

    PubMed

    Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

    2016-12-01

    To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

  13. Ultrasound for fetal assessment in early pregnancy

    PubMed Central

    Whitworth, Melissa; Bricker, Leanne; Neilson, James P; Dowswell, Therese

    2014-01-01

    Background Diagnostic ultrasound is a sophisticated electronic technology, which utilises pulses of high frequency sound to produce an image. Diagnostic ultrasound examination may be employed in a variety of specific circumstances during pregnancy such as after clinical complications, or where there are concerns about fetal growth. Because adverse outcomes may also occur in pregnancies without clear risk factors, assumptions have been made that routine ultrasound in all pregnancies will prove beneficial by enabling earlier detection and improved management of pregnancy complications. Routine screening may be planned for early pregnancy, late gestation, or both. The focus of this review is routine early pregnancy ultrasound. Objectives To assess whether routine early pregnancy ultrasound for fetal assessment (i.e. its use as a screening technique) influences the diagnosis of fetal malformations, multiple pregnancies, the rate of clinical interventions, and the incidence of adverse fetal outcome when compared with the selective use of early pregnancy ultrasound (for specific indications). Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (September 2009). Selection criteria Published, unpublished, and ongoing randomised controlled trials that compared outcomes in women who experienced routine versus selective early pregnancy ultrasound (i.e. less than 24 weeks’ gestation). We have included quasi-randomised trials. Data collection and analysis Two review authors independently extracted data for each included study. We used the Review Manager software to enter and analyse data. Main results Routine/revealed ultrasound versus selective ultrasound/concealed: 11 trials including 37505 women. Ultrasound for fetal assessment in early pregnancy reduces the failure to detect multiple pregnancy by 24 weeks’ gestation (risk ratio (RR) 0.07, 95% confidence interval (CI) 0.03 to 0.17). Routine scan is associated with a reduction in

  14. Elsevier Trophoblast Research Award Lecture: Searching for an early pregnancy 3-D morphometric ultrasound marker to predict fetal growth restriction.

    PubMed

    Collins, S L; Stevenson, G N; Noble, J A; Impey, L

    2013-03-01

    Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, even in term babies. An effective screening test to identify pregnancies at risk of FGR, leading to increased antenatal surveillance with timely delivery, could decrease perinatal mortality and morbidity. Placental volume, measured with commercially available packages and a novel, semi-automated technique, has been shown to predict small for gestational age babies. Placental morphology measured in 2-D in the second trimester and ex-vivo post delivery, correlates with FGR. This has also been investigated using 2-D estimates of diameter and site of cord insertion obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL) software. Data is presented describing a pilot study of a novel 3-D method for defining compactness of placental shape. We prospectively recruited women with a singleton pregnancy and BMI of <35. A 3-D ultrasound scan was performed between 11 and 13 + 6 weeks' gestation. The placental volume, total placental surface area and the area of the utero-placental interface were calculated using our validated technique. From these we generated dimensionless indices including sphericity (ψ), standardised placental volume (sPlaV) and standardised functional area (sFA) using Buckingham π theorem. The marker for FGR used was small for gestational age, defined as <10th customised birth weight centile (cSGA). Regression analysis examined which of the morphometric indices were independent predictors of cSGA. Data were collected for 143 women, 20 had cSGA babies. Only sPlaV and sFA were significantly correlated to birth weight (p < 0.001). Regression demonstrated all dimensionless indices were inter-dependent co-factors. ROC curves showed no advantage for using sFA over the simpler sPlaV. The generated placental indices are not independent of placental volume this early in gestation. It is hoped that another placental ultrasound marker based on vascularity can improve the

  15. Fetal acoustic stimulation test for early intrapartum fetal monitoring.

    PubMed

    Goonewardene, M; Hanwellage, K

    2011-03-01

    The fetal acoustic stimulation test (FAST) is a simple cost effective screening test for antenatal fetal monitoring. The aim of the study was to evaluate the FAST as a screening test for early intrapartum fetal well being. An initial non stress test (NST) followed by a FAST using corometric model 146 was carried out in 486 participants in early labour with uncomplicated singleton pregnancies and > 32 weeks gestation. A repeat NST was recorded in the participants who had an initial non reactive NST. The results of the NST and FAST were compared with fetal outcome. Maternal perception of fetal movements after FAST, results of NST before and after FAST, and the babies' 5 minute APGAR scores were measured. Of the 486 participants 413 (85%) noticed fetal movements after FAST. Initial NST was non reactive in 203 (42%) but 149 (31%) became reactive after FAST. Compared to the NST, FAST had a better sensitivity (97% vs 62%, p < 0.001), specificity (100% vs 87%, p = 0.017), positive predictive value (100% vs 98%, p = 0.024), negative predictive value (79% vs 17%, p < 0.001) and accuracy (99%vs 64%, p < 0.001) in predicting 5 minute APGAR < 7 in the baby. FAST is a reliable screening test for assessing fetal well being in early labour. It complements the NST and is better than the NST alone.

  16. Accelerated fetal growth in early pregnancy and risk of severe large-for-gestational-age and macrosomic infant: a cohort study in a low-risk population.

    PubMed

    Simic, Marija; Wikström, Anna-Karin; Stephansson, Olof

    2017-10-01

    Our objective was to examine the association between fetal growth in early pregnancy and risk of severe large-for-gestational-age (LGA) and macrosomia at birth in a low-risk population. Cohort study that included 68 771 women with non-anomalous singleton pregnancies, without history of diabetes or hypertension, based on an electronic database on pregnancies and deliveries in Stockholm-Gotland Region, Sweden, 2008-2014. We performed multivariable logistic regression to estimate the association between accelerated fetal growth occurring in the first through early second trimester as measured by ultrasound and LGA and macrosomia at birth. Restricted analyses were performed in the groups without gestational diabetes and with normal body mass index (18.5-24.9 kg/m 2 ). When adjusting for confounders, the odds of having a severely LGA or macrosomic infant were elevated in mothers with fetuses that were at least 7 days larger than expected as compared with mothers without age discrepancy at the second-trimester scan (adjusted odds ratio 1.80; 95% CI 1.23-2.64 and adjusted odds ratio 2.15; 95% CI 1.55-2.98, respectively). Additionally, mothers without gestational diabetes and mothers with normal weight had an elevated risk of having a severely LGA or macrosomic infant when the age discrepancy by second-trimester ultrasound was at least 7 days. In a low-risk population, ultrasound-estimated accelerated fetal growth in early pregnancy was associated with an increased risk of having a severely LGA or macrosomic infant. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  17. Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction.

    PubMed

    Nagai, S; Kawai, M; Myowa-Yamakoshi, M; Morimoto, T; Matsukura, T; Heike, T

    2017-07-01

    The objective of this study was to estimate gonadotropin concentrations in small for gestational age (SGA) male infants with the reactivation of the hypothalamic-pituitary-gonadal axis during the first few months of life that is important for genital development. We prospectively examined 15 SGA and 15 appropriate for gestational age (AGA) preterm male infants between 2013 and 2014 at Kyoto University Hospital. Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to 168 and compared between SGA and AGA infants using the Mann-Whitney test. A longitudinal analysis showed that SGA infants had higher LH and lower FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants. Male infants who are SGA at birth because of fetal growth restriction have gonadotropin secretion abnormalities in the first few months of life.

  18. Growth assessment in diagnosis of Fetal Growth Restriction. Review.

    PubMed

    Albu, A R; Horhoianu, I A; Dumitrascu, M C; Horhoianu, V

    2014-06-15

    The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories.

  19. Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

    PubMed

    Buck Louis, Germaine M; Grewal, Jagteshwar; Albert, Paul S; Sciscione, Anthony; Wing, Deborah A; Grobman, William A; Newman, Roger B; Wapner, Ronald; D'Alton, Mary E; Skupski, Daniel; Nageotte, Michael P; Ranzini, Angela C; Owen, John; Chien, Edward K; Craigo, Sabrina; Hediger, Mary L; Kim, Sungduk; Zhang, Cuilin; Grantz, Katherine L

    2015-10-01

    Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were

  20. EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

    PubMed

    Spencer, Rebecca; Ambler, Gareth; Brodszki, Jana; Diemert, Anke; Figueras, Francesc; Gratacós, Eduard; Hansson, Stefan R; Hecher, Kurt; Huertas-Ceballos, Angela; Marlow, Neil; Marsál, Karel; Morsing, Eva; Peebles, Donald; Rossi, Carlo; Sebire, Neil J; Timms, John F; David, Anna L

    2017-01-23

    Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel

  1. New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

    PubMed

    Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

    2017-05-01

    The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

  2. Growth assessment in diagnosis of Fetal Growth Restriction. Review

    PubMed Central

    Albu, AR; Horhoianu, IA; Dumitrascu, MC; Horhoianu, V

    2014-01-01

    Abstract The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories. Abbreviations: FGR = Fetal growth restriction; IUGR = Intrauterine Growth Restriction; SGA = small for gestational age fetus; EFW = estimated fetal weight; AC = abdominal circumference; SD = Standard Deviation; SFH = Symphyseal-fundal height; US = ultrasound; 2D = bidimensional; 3D = tridimensional; RCOG = Royal College of Obstetricians and Gynecologists; FL = femur length; BPD = biparietal diameter; BW = birth weight; IGA = Individualized Growth Assessment; PIH = Pregnancy Induced hypertension; PE = Preeclampsia; NICU = Neonatal Intensive Care Unit. PMID:25408718

  3. Fetal Growth and Neurobehavioral Outcomes in Childhood

    PubMed Central

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-01-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  4. Diet quality in early pregnancy and its effects on fetal growth outcomes: the Infancia y Medio Ambiente (Childhood and Environment) Mother and Child Cohort Study in Spain.

    PubMed

    Rodríguez-Bernal, Clara L; Rebagliato, Marisa; Iñiguez, Carmen; Vioque, Jesús; Navarrete-Muñoz, Eva M; Murcia, Mario; Bolumar, Francisco; Marco, Alfredo; Ballester, Ferran

    2010-06-01

    Maternal diet has been associated with fetal growth outcomes; however, evidence is scarce on the role of dietary quality. The objective was to assess the effect of diet quality during the first trimester of pregnancy, as measured by the Alternate Healthy Eating Index (AHEI) adapted for pregnancy, on fetal growth. We studied 787 women and their newborns from a Spanish cohort study. Diet quality was assessed by using a modification of the AHEI. Adjusted birth weight, birth length, and head circumference were used as continuous outcomes. We used a customized model to define fetal growth restriction in weight, length, and head circumference. After adjustment of multivariate models, a positive association was observed between diet quality and adjusted birth weight and adjusted birth length. The greatest differences were found between the fourth and first quintiles of the AHEI. Newborns of women in the fourth quintile were on average 126.3 g (95% CI: 38.5, 213.9 g) heavier and 0.47 cm (95% CI: 0.08, 0.86 cm) longer than those in the lowest quintile (P for trend = 0.009 and 0.013, respectively). Women with the highest AHEI scores had a significantly lower risk of delivering a fetal growth-restricted infant for weight (odds ratio: 0.24; 95% CI: 0.10, 0.55; P for trend = 0.001) than did women in the lowest quintile, but this was not the case for fetal growth restriction in length (P for trend = 0.538) or head circumference (P for trend = 0.070). A high-quality diet in the first trimester of pregnancy is associated with birth size and the risk of fetal growth restriction.

  5. Fetal growth and risk of childhood asthma and allergic disease

    PubMed Central

    Tedner, S G; Örtqvist, A K; Almqvist, C

    2012-01-01

    Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

  6. Early Evaluation of the Fetal Heart.

    PubMed

    Hernandez-Andrade, Edgar; Patwardhan, Manasi; Cruz-Lemini, Mónica; Luewan, Suchaya

    2017-01-01

    Evaluation of the fetal heart at 11-13 + 6 weeks of gestation is indicated for women with a family history of congenital heart defects (CHD), a previous child with CDH, or an ultrasound finding associated with cardiac anomalies. The accuracy for early detection of CHD is highly related to the experience of the operator. The 4-chamber view and outflow tracts are the most important planes for identification of an abnormal heart, and can be obtained in the majority of fetuses from 11 weeks of gestation onward. Transvaginal ultrasound is the preferred route for fetal cardiac examination prior to 12 weeks of gestation, whereas, after 12 weeks, the fetal heart can be reliably evaluated by transabdominal ultrasound. Cardiac defects, such as ventricular septal defects, tetralogy of Fallot, Ebstein's anomaly, or cardiac tumors, are unlikely to be identified at ≤14 weeks of gestation. Additional ultrasound techniques such as spatiotemporal image correlation and the evaluation of volumes by a fetal-heart expert can improve the detection of congenital heart disease. The evaluation of the fetal cardiac function at 11-13 + 6 weeks of gestation can be useful for early identification of fetuses at risk of anemia due to hemoglobinopathies, such as hemoglobin Bart's disease. © 2017 S. Karger AG, Basel.

  7. Fetal growth in muskoxen determined by transabdominal ultrasonography.

    PubMed Central

    Pharr, J W; Rowell, J E; Flood, P F

    1994-01-01

    A 5 MHz commercial sector scanner was used to monitor 13 muskox pregnancies and establish normal fetal growth curves. Examinations were carried out between 40 and 197 days of gestation and pregnancy could be detected throughout the period. Early pregnancies were found by scanning lateral to the udder but as pregnancy progressed the fetus was found closer to the dam's umbilicus. Measurements of cranial and abdominal diameters taken at about two week intervals in seven uncomplicated pregnancies in four cows were used to construct fetal growth curves. These can be reliably used in the reproductive management of muskoxen. In addition a series of regressions based on measurements of the fetuses of muskoxen killed in the Arctic are provided. These allow cranial and abdominal diameters to be related to fetal weight and crown-rump length. Images Fig. 1. Fig. 2. PMID:7954117

  8. Effect of Placenta Previa on Fetal Growth

    PubMed Central

    HARPER, Lorie M.; ODIBO, Anthony O.; MACONES, George A.; CRANE, James P.; CAHILL, Alison G.

    2011-01-01

    Objective To estimate the association between placenta previa and abnormal fetal growth. Study Design Retrospective cohort study of consecutive women undergoing ultrasound between 15–22 weeks. Groups were defined by the presence or absence of complete or partial placenta previa. The primary outcome was intrauterine growth restriction (IUGR), defined as a birth weight <10th percentile by the Alexander growth standard. Univariable, stratified and multivariable analyses were used to estimate the effect of placenta previa on fetal growth restriction. Results Of 59,149 women, 724 (1.2%) were diagnosed with a complete or partial previa. After adjusting for significant confounding factors (black race, gestational diabetes, preeclampsia, and single umbilical artery,), the risk of IUGR remained similar (adjusted odds ratio 1.1, 95% CI 0.9–1.5). The presence of bleeding did not impact the risk of growth restriction. Conclusion Placenta previa is not associated with fetal growth restriction. Serial growth ultrasounds are not indicated in patients with placenta previa. PMID:20599185

  9. Genetic and Environmental Influences on Fetal Growth Vary during Sensitive Periods in Pregnancy.

    PubMed

    Workalemahu, Tsegaselassie; Grantz, Katherine L; Grewal, Jagteshwar; Zhang, Cuilin; Louis, Germaine M Buck; Tekola-Ayele, Fasil

    2018-05-08

    Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34-1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.

  10. Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction

    PubMed Central

    Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.

    2012-01-01

    The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434

  11. Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction.

    PubMed

    Shinohara, Satoshi; Uchida, Yuzo; Kasai, Mayuko; Sunami, Rei

    2017-08-01

    To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.

  12. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  13. Fetal growth velocity and body proportion in the assessment of growth.

    PubMed

    Hiersch, Liran; Melamed, Nir

    2018-02-01

    use of fetal body proportions to classify fetuses as either symmetric or asymmetric using 1 of several ratios; these include the head circumference to abdominal circumference ratio, transverse cerebellar diameter to abdominal circumference ratio, and femur length to abdominal circumference ratio. Although these ratios are associated with small for gestational age at birth and with adverse perinatal outcomes, their predictive accuracy is too low for clinical practice. Furthermore, these associations become questionable when other, potentially more specific measures such as umbilical artery Doppler are being used. Furthermore, these ratios are of limited use in determining the etiology underlying fetal smallness. It is possible that the use of the 2 gestational-age-independent ratios (transverse cerebellar diameter to abdominal circumference and femur length to abdominal circumference) may have a role in the detection of mild-moderate fetal growth restriction in pregnancies without adequate dating. In addition, despite their limited predictive accuracy, these ratios may become abnormal early in the course of fetal growth restriction and may therefore identify pregnancies that may benefit from closer monitoring of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

    PubMed

    Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

    2014-08-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

  15. Fetal Growth Restriction Is Associated With Malaria in Pregnancy: A Prospective Longitudinal Study in Benin.

    PubMed

    Briand, Valérie; Saal, Jessica; Ghafari, Caline; Huynh, Bich-Tram; Fievet, Nadine; Schmiegelow, Christentze; Massougbodji, Achille; Deloron, Philippe; Zeitlin, Jennifer; Cot, Michel

    2016-08-01

    Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based follow-up study of Beninese women. A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with ≥2 malarial parasite infections tended to have lower z scores than uninfected women. Malaria both in early and late pregnancy was associated with a reduction in fetal growth velocity, which occurred either immediately or with a delay after infection. We confirmed the deleterious effect of malaria during both early and late pregnancy on fetal growth. This stresses the importance of starting preventive measures against malaria as early as possible during pregnancy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Effects of induced placental and fetal growth restriction, size at birth and early neonatal growth on behavioural and brain structural lateralization in sheep.

    PubMed

    Hunter, Damien Seth; Hazel, Susan J; Kind, Karen L; Liu, Hong; Marini, Danila; Giles, Lynne C; De Blasio, Miles J; Owens, Julie A; Pitcher, Julia B; Gatford, Kathryn L

    2017-09-01

    Poor perinatal growth in humans results in asymmetrical grey matter loss in fetuses and infants and increased functional and behavioural asymmetry, but specific contributions of pre- and postnatal growth are unclear. We therefore compared strength and direction of lateralization in obstacle avoidance and maze exit preference tasks in offspring of placentally restricted (PR: 10M, 13F) and control (CON: 23M, 17F) sheep pregnancies at 18 and 40 weeks of age, and examined gross brain structure of the prefrontal cortex at 52 weeks of age (PR: 14M, 18F; CON: 23M, 25F). PR did not affect lateralization direction, but 40-week-old PR females had greater lateralization strength than CON (P = .021). Behavioural lateralization measures were not correlated with perinatal growth. PR did not alter brain morphology. In males, cross-sectional areas of the prefrontal cortex and left hemisphere correlated positively with skull width at birth, and white matter area correlated positively with neonatal growth rate of the skull (all P < .05). These studies reinforce the need to include progeny of both sexes in future studies of neurodevelopmental programming, and suggest that restricting in utero growth has relatively mild effects on gross brain structural or behavioural lateralization in sheep.

  17. Fetal growth: a review of terms, concepts and issues relevant to obstetrics.

    PubMed

    Mayer, C; Joseph, K S

    2013-02-01

    The perinatal literature includes several potentially confusing and controversial terms and concepts related to fetal size and growth. This article discusses fetal growth from an obstetric perspective and addresses various issues including the physiologic mechanisms that determine fetal growth trajectories, known risk factors for abnormal fetal growth, diagnostic and prognostic issues related to restricted and excessive growth and temporal trends in fetal growth. Also addressed are distinctions between fetal growth 'standards' and fetal growth 'references', and between fetal growth charts based on estimated fetal weight vs those based on birth weight. Other concepts discussed include the incidence of fetal growth restriction in pregnancy (does the frequency of fetal growth restriction increase or decrease with increasing gestation?), the obstetric implications of studies showing associations between fetal growth and adult chronic illnesses (such as coronary heart disease) and the need for customizing fetal growth standards. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

  18. Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

    PubMed

    Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning

    2010-07-01

    The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

  19. Diagnosis and Management of Fetal Growth Restriction

    PubMed Central

    Bamfo, Jacqueline E. A. K.; Odibo, Anthony O.

    2011-01-01

    Fetal growth restriction (FGR) remains a leading contributor to perinatal mortality and morbidity and metabolic syndrome in later life. Recent advances in ultrasound and Doppler have elucidated several mechanisms in the evolution of the disease. However, consistent classification and characterization regarding the severity of FGR is lacking. There is no cure, and management is reliant on a structured antenatal surveillance program with timely intervention. Hitherto, the time to deliver is an enigma. In this paper, the challenges in the diagnosis and management of FGR are discussed. The biophysical profile, Doppler, biochemical and molecular technologies that may refine management are reviewed. Finally, a model pathway for the clinical management of pregnancies complicated by FGR is presented. PMID:21547092

  20. A uniform management approach to optimize outcome in fetal growth restriction.

    PubMed

    Seravalli, Viola; Baschat, Ahmet A

    2015-06-01

    A uniform approach to the diagnosis and management of fetal growth restriction (FGR) consistently produces better outcome, prevention of unanticipated stillbirth, and appropriate timing of delivery. Early-onset and late-onset FGR represent two distinct clinical phenotypes of placental dysfunction. Management challenges in early-onset FGR revolve around prematurity and coexisting maternal hypertensive disease, whereas in late-onset disease failure of diagnosis or surveillance leading to unanticipated stillbirth is the primary issue. Identifying the surveillance tests that have the highest predictive accuracy for fetal acidemia and establishing the appropriate monitoring interval to detect fetal deterioration is a high priority. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Childhood cognitive development after fetal growth restriction.

    PubMed

    Llurba, E; Baschat, A A; Turan, O M; Harding, J; McCowan, L M

    2013-04-01

    To examine the relationship between prenatal umbilical artery (UA) and internal carotid artery (ICA) Doppler findings and cognitive development at 3 and 6 years in low-birth-weight children. This was a study of 209 low-birth-weight (< 10(th) centile) children born after 28 gestational weeks with UA resistance index (RI) measured within 2 weeks before delivery. Children with normal UA- and ICA-RI were defined as small-for-gestational age (SGA) and those with abnormal UA or ICA Doppler findings as having fetal growth restriction (FGR). Cognitive ability at 3 and 6 years' corrected age was assessed using the fourth edition of the Stanford-Binet Intelligence Scale (SBIS) and compared between SGA and FGR groups. An SBIS score < 85 was considered to indicate delayed development. The median gestational age at diagnosis of abnormal fetal growth was 36.6 (range, 28-41) weeks. There were 87 (41.6%) children classified as having FGR and 122 (58.4%) as SGA. The mean global SBIS score at 3 years was 109.4 (SD, 22.8) and at 6 years it was 110.5 (SD, 13.9). Overall, 22 (10.5%) children had delayed development at 3 years. Total SBIS scores and individual domain scores did not differ between FGR and SGA groups at 3 or 6 years and similar proportions in each group had delayed development. Abnormal prenatal UA and ICA Doppler findings are not associated with lower developmental scores in low-birth-weight children delivered in the third trimester of pregnancy. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

  2. [Fetal and early trauma syndrome-FETS].

    PubMed

    Zoroastro, Gastón A

    2006-01-01

    This is a new clinical description for cases of children whose parents are among those who have disappeared and were given birth by women held prisoners and subjected to torture, humiliation and abuses. This description is considered a special case of early, and in many cases fetal distress. These children felt horror when they were violently separated from their parents immediately after being born in captivity or in early infancy during the last military dictatorship (1976-1983). Afterwards they were sold by their captors and raised as adoptive or as their own children by the purchasers. The fact that these cases be included in the existing WHO categories contained in CIE-10: Posttraumatic stress disorder, F43.1, is discussed as they show late responses on the part of the victims to situations of torture, terrorism and rape. However, it is clarified that cases in which the aftereffects of severe stress become evident after decades will have to be classified as Persistent personality disorders, after catastrophic experience, F62.0. It is concluded that it is necessary to consider FETS as a new combination of manifestations of the Persistent Personality Disorders due to its specific idiosyncratic characteristics that go beyond the available clinical descriptions, to its own etiophatic equation and to its recognizable pathognomonic identification. Its pathognomonic identification in some cases was useful to detect children with these alienated identity problems (understood as legally neglected and clinically alienated). Propedeutic and treatment aspects are mentioned in conjunction with the peculiarities of a therapy that restores the illegally deprived personality of these children, who nowadays are adults of approximately 25 to 29 years of age. Finally, a metapsychologic discussion is presented, which is about the resilience of the truth and the fact that when it is rejected it returns, thus constituting ethics of the truth.

  3. Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

    PubMed

    Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

    2018-02-01

    Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of

  4. Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors.

    PubMed

    Fu, Binqing; Zhou, Yonggang; Ni, Xiang; Tong, Xianhong; Xu, Xiuxiu; Dong, Zhongjun; Sun, Rui; Tian, Zhigang; Wei, Haiming

    2017-12-19

    Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy. However, the role of NK cells in fetal growth is unclear. Here, we have identified a CD49a + Eomes + subset of NK cells that secreted growth-promoting factors (GPFs), including pleiotrophin and osteoglycin, in both humans and mice. The crosstalk between HLA-G and ILT2 served as a stimulus for GPF-secreting function of this NK cell subset. Decreases in this GPF-secreting NK cell subset impaired fetal development, resulting in fetal growth restriction. The transcription factor Nfil3, but not T-bet, affected the function and the number of this decidual NK cell subset. Adoptive transfer of induced CD49a + Eomes + NK cells reversed impaired fetal growth and rebuilt an appropriate local microenvironment. These findings reveal properties of NK cells in promoting fetal growth. In addition, this research proposes approaches for therapeutic administration of NK cells in order to reverse restricted nourishments within the uterine microenvironment during early pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A placenta clinic approach to the diagnosis and management of fetal growth restriction.

    PubMed

    Kingdom, John C; Audette, Melanie C; Hobson, Sebastian R; Windrim, Rory C; Morgen, Eric

    2018-02-01

    Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening

  6. Development of customized fetal growth charts in twins.

    PubMed

    Ghi, Tullio; Prefumo, Federico; Fichera, Anna; Lanna, Mariano; Periti, Enrico; Persico, Nicola; Viora, Elsa; Rizzo, Giuseppe

    2017-05-01

    Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for

  7. Role of placental insufficiency and intrauterine growth restriction on the activation of fetal hepatic glucose production

    PubMed Central

    Wesolowski, Stephanie R.; Hay, William W.

    2016-01-01

    Glucose is the major fuel for fetal oxidative metabolism. A positive maternal-fetal glucose gradient drives glucose across the placenta and is sufficient to meet the demands of the fetus, eliminating the need for endogenous hepatic glucose production (HGP). However, fetuses with intrauterine growth restriction (IUGR) from pregnancies complicated by placental insufficiency have an early activation of HGP. Furthermore, this activated HGP is resistant to suppression by insulin. Here, we present the data demonstrating the activation of HGP in animal models, mostly fetal sheep, and human pregnancies with IUGR. We also discuss potential mechanisms and pathways that may produce and support HGP and hepatic insulin resistance in IUGR fetuses. PMID:26723529

  8. The Influence of Maternal Early to Mid-Gestation Nutrient Restriction of Long Chain Polyunsaturated Fatty Acids in Fetal Sheep

    USDA-ARS?s Scientific Manuscript database

    The early to mid-gestational period (days 28-78) in sheep is the period of most rapid placental development. Maternal nutrient restriction (MNR) in this phase has negative consequences on fetal growth and development, predisposing the fetus to disease in adult life. The influence of MNR on fetal tis...

  9. Fundal Height: An Accurate Indicator of Fetal Growth?

    MedlinePlus

    ... antenatal surveillance, diagnosis, and management. American Journal of Obstetrics and Gynecology. 2011;204:288. Peter JR, et ... Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins — Obstetrics. ACOG Practice Bulletin No. 134: Fetal growth restriction. ...

  10. Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

    PubMed

    Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

    2001-05-01

    Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

  11. Fetal tissue Doppler imaging in pregnancies complicated with preeclampsia with or without intrauterine growth restriction.

    PubMed

    Zhou, Qiongjie; Ren, Yunyun; Yan, Yingliu; Chu, Chen; Gui, Yonghao; Li, Xiaotian

    2012-11-01

    This study's aim was to evaluate the effect of preeclampsia and intrauterine growth restriction (IUGR) on fetal cardiac function, and the relationship of the latter with adverse pregnancy outcomes. We did a cross-sectional study of 132 women with uncomplicated singleton pregnancies, 34 with preeclampsia without IUGR, and 12 with preeclampsia and IUGR. Fetal cardiac structure and function were evaluated using fetal two-dimension ultrasound, pulsed wave Doppler and tissue Doppler imaging (TDI). Data were analyzed by t-tests, ANOVA, Chi-square tests, or Wilcoxon rank-sum test. Compared with the normal pregnancy group, mitral/tricuspid early systolic peak velocity of annulus/late diastolic peak velocity of annulus (Sa) and left ventricular (LV)/right ventricular (RV) early diastolic peak velocity at the annulus (Ea) in TDI decreased in preeclampsia with or without IUGR (P < 0.05). LV/RV Ea underwent a gestational decrease in preeclampsia with or without IUGR (P < 0.05). The changes in mitral/tricuspid Sa and LV Sa associated with preeclampsia were even more pronounced with preterm delivery at less than 34 gestational weeks and stillbirth (P < 0.05). Intrauterine growth restriction influences fetal cardiac function in the presence of preeclampsia, and TDI may be a sensitive and preferable method to detect such changes. Fetal LV/RV Ea is a potential marker for early fetal cardiac diastolic impairment, and mitral/tricuspid Sa and LV Sa may be predictors for adverse pregnancy outcomes. © 2012 John Wiley & Sons, Ltd.

  12. Maternal nutrient restriction in early gestation upregulates myogenic genes in cattle fetal muscle tissue

    USDA-ARS?s Scientific Manuscript database

    Prenatal myogenesis is a critical factor in determining the muscle growth potential of cattle. We hypothesized that maternal nutrient restriction during early gestation would alter the transcriptome of fetal primordial muscle tissue in cattle. A total of 14 Angus-cross heifers were estrus synchroniz...

  13. The effects of smoking and hypertensive disorders on fetal growth

    PubMed Central

    Rasmussen, Svein; Irgens, Lorentz M

    2006-01-01

    Background It is well known that smoking and pregnancy induced hypertension (PIH) are associated with decreased fetal growth. It has been reported that in preeclampsia the fetal growth deficit attributable to smoking is higher, which has been contradicted in other studies. We therefore evaluated the effects on fetal growth of early- and late onset PIH and chronic hypertension and how cigarette smoking modify these effects. We also quantified the proportion of small for gestational age (SGA) cases attributable to PIH, chronic hypertension, and smoking. Methods Population-based study based on record of 215598 singleton pregnancies from the Medical Birth Registry of Norway. Results In severe preeclampsia, mild preeclampsia, transient hypertension, and normotension in term birth, odds ratios (ORs) of SGA in smokers compared with non-smokers were 1.4 (95% confidence interval 0.9, 2.2), 1.6 (1.3, 1.9), 2.3 (1.8, 3.1), and 2.0 (1.9, 2.1), respectively. For preterm births, corresponding ORs were 1.3 (0.9, 2.0), 1.8 (1.1, 3.0), 4.1 (1.9, 9.0), and 1.7 (1.4, 2.0), respectively. The effect of early onset PIH was stronger than that in term births, while the effect of smoking was equal in preterm and term newborns. Only in non-smokers who delivered at term, the rates of SGA significantly increased with the severity of PIH (ORs = 1.3 (1.1, 1.5), 1.8 (1.7, 2.0), and 2.5 (2.2, 3.0) for transient hypertension, mild-, and severe preeclampsia, respectively). The combined effects of smoking and hypertension were generally not synergistic. The effect of smoking was not stronger in women who had chronic hypertension. Nor were the effects of chronic hypertension stronger in smokers. PIH explained 21.9 and 2.5% of preterm and term cases of SGA, respectively, while smoking explained 12% of SGA cases. Conclusion The effects of hypertensive disorder and smoking were generally not synergistic, which suggest that they may exert their main actions on separate sites or work through separate

  14. The World Health Organization fetal growth charts: concept, findings, interpretation, and application.

    PubMed

    Kiserud, Torvid; Benachi, Alexandra; Hecher, Kurt; Perez, Rogelio González; Carvalho, José; Piaggio, Gilda; Platt, Lawrence D

    2018-02-01

    Ultrasound biometry is an important clinical tool for the identification, monitoring, and management of fetal growth restriction and development of macrosomia. This is even truer in populations in which perinatal morbidity and mortality rates are high, which is a reason that much effort is put onto making the technique available everywhere, including low-income societies. Until recently, however, commonly used reference ranges were based on single populations largely from industrialized countries. Thus, the World Health Organization prioritized the establishment of fetal growth charts for international use. New fetal growth charts for common fetal measurements and estimated fetal weight were based on a longitudinal study of 1387 low-risk pregnant women from 10 countries (Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) that provided 8203 sets of ultrasound measurements. The participants were characterized by median age 28 years, 58% nulliparous, normal body mass index, with no socioeconomic or nutritional constraints (median caloric intake, 1840 calories/day), and had the ability to attend the ultrasound sessions, thus essentially representing urban populations. Median gestational age at birth was 39 weeks, and birthweight was 3300 g, both with significant differences among countries. Quantile regression was used to establish the fetal growth charts, which also made it possible to demonstrate a number of features of fetal growth that previously were not well appreciated or unknown: (1) There was an asymmetric distribution of estimated fetal weight in the population. During early second trimester, the distribution was wider among fetuses <50th percentile compared with those above. The pattern was reversed in the third trimester, with a notably wider variation >50th percentile. (2) Although fetal sex, maternal factors (height, weight, age, and parity), and country had significant influence on fetal weight

  15. Occupational exposure to chemicals and fetal growth: the Generation R Study

    PubMed Central

    Snijder, Claudia A.; Roeleveld, Nel; te Velde, Egbert; Steegers, Eric A.P.; Raat, Hein; Hofman, Albert; Jaddoe, Vincent W.V.; Burdorf, Alex

    2012-01-01

    BACKGROUND Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure to chemicals during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight. METHODS Associations between maternal occupational exposure to various chemicals and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Mothers who filled out a questionnaire during mid-pregnancy (response: 77% of enrolment) were included if they conducted paid employment during pregnancy and had a spontaneously conceived singleton live born pregnancy (n = 4680). A job exposure matrix was used, linking job titles to expert judgement on exposure to chemicals in the workplace. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. Placental weight was obtained from medical records and hospital registries. Linear regression models for repeated measurements were used to study the associations between maternal occupational exposure to chemicals and intrauterine growth. RESULTS We observed that maternal occupational exposure to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds and pesticides adversely influenced several domains of fetal growth (fetal weight, fetal head circumference and fetal length). We found a significant association between pesticide and phthalate exposure with a decreased placental weight. CONCLUSIONS Our results suggest that maternal occupational exposure to several chemicals is associated with impaired fetal growth during pregnancy and a decreased placental weight. Further studies are needed to

  16. Maternal hypothyroxinemia during pregnancy and growth of the fetal and infant head.

    PubMed

    van Mil, Nina H; Steegers-Theunissen, Régine P M; Bongers-Schokking, Jacoba J; El Marroun, Hanan; Ghassabian, Akhgar; Hofman, Albert; Jaddoe, Vincent W V; Visser, Theo J; Verhulst, Frank C; de Rijke, Yolanda B; Steegers, Eric A P; Tiemeier, Henning

    2012-12-01

    Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth and corticogenesis. This study focused on the effect of maternal hypothyroxinemia during early pregnancy on growth of the fetal and infant head. In a population-based birth cohort, we assessed thyroid status in early pregnancy (median 13.4, 90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head size of their children at 5 time points. Hypothyroxinemia was defined as normal thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the 10th percentile. Statistical analysis was performed using linear generalized estimating equation. Maternal hypothyroxinemia was associated with larger fetal and infant head size (overall estimate β: 1.38, 95% confidence interval 0.56; 2.19, P = .001). In conclusion, in the general population, even small variations in maternal thyroid function during pregnancy may affect the developing head of the young child.

  17. Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals.

    PubMed

    Portella, André Krumel; Silveira, Patrícia Pelufo

    2014-12-01

    Fetal growth restriction results from a failure to achieve a higher growth potential and has been associated with many maternal conditions, such as chronic diseases (infections, hypertension, and some cases of diabetes and obesity), exposures (tobacco smoke, drugs), and malnutrition. This early adversity induces a series of adaptive physiological responses aimed at improving survival, but imposing increased risk for developing chronic nontransmittable diseases (obesity, type II diabetes, cardiovascular disease) in the long term. Recently, mounting evidence has shown that fetal growth impairment is related to altered feeding behavior and preferences through the life course. When living in countries undergoing nutritional transition, in which individuals experience the coexistence of underweight and overweight problems (the "double burden of malnutrition"), fetal growth-restricted children can be simultaneously growth restricted and overweight-a double burden of malnutrition at the individual level. Considering food preferences as an important aspect of nutrition security, we will summarize the putative neurobiological mechanisms at the core of the relationship between fetal growth and nutrition security over the life course and the evidence linking early life adversity to later food preferences. © 2014 New York Academy of Sciences.

  18. Associations between gestational anthropometry, maternal HIV, and fetal and early infancy growth in a prospective rural/semi-rural Tanzanian cohort, 2012-13.

    PubMed

    Wilkinson, Amanda L; Pedersen, Sarah H; Urassa, Mark; Michael, Denna; Todd, Jim; Kinung'hi, Safari; Changalucha, John; McDermid, Joann M

    2015-10-29

    Healthcare access and resources differ considerably between urban and rural settings making cross-setting generalizations difficult. In resource-restricted rural/semi-rural environments, identification of feasible screening tools is a priority. The objective of this study was to evaluate gestational anthropometry in relation to birth and infant growth in a rural/semi-rural Tanzanian prospective cohort of mothers and their infants. Mothers (n = 114: 44 HIV-positive) attending antenatal clinic visits were recruited in their second or third trimester between March and November, 2012, and followed with their infants through 6-months post-partum. Demographic, clinical, and infant feeding data were obtained using questionnaires administered by a Swahili-speaking research nurse on demographic, socioeconomic, clinical, and infant feeding practices. Second or third trimester anthropometry (mid-upper arm circumference [MUAC], triceps skinfold thickness, weight, height), pregnancy outcomes, birth (weight, length, head circumference) and infant anthropometry (weight-for-age z-score [WAZ], length-for-age z-score [LAZ]) were obtained. Linear regression and mixed effect modeling were used to evaluate gestational factors in relation to pregnancy and infant outcomes. Gestational MUAC and maternal HIV status (HIV-positive mothers = 39%) were associated with infant WAZ and LAZ from birth to 6-months in multivariate models, even after adjustment for infant feeding practices. The lowest gestational MUAC tertile was associated with lower WAZ throughout early infancy, as well as lower LAZ at 3 and 6-months. In linear mixed effects models through 6-months, each 1 cm increase in gestational MUAC was associated with a 0.11 increase in both WAZ (P < 0.001) and LAZ (P = 0.001). Infant HIV-exposure was negatively associated with WAZ (β = -0.65, P < 0.001) and LAZ (β = -0.49, P < 0.012) from birth to 6-months. Lower gestational MUAC, evaluated using only a tape measure and minimal

  19. Fetal growth in different racial groups.

    PubMed Central

    Alvear, J; Brooke, O G

    1978-01-01

    Three racial groups of mothers and their newborn babies-- North European 75, Negro 75, and "Indian" Asian 37--were matched for parity, gestational age, sex, maternal age, maternal smoking habits, and social class. Multiple anthropometric measurements, including skinfold thickness, limb circumferences, and various linear measurements were made on the mothers and their infants to determine the effects of race and smoking on fetal size. Indian-Asian mothers, though shorter and lighter than Europeans and Negroes, had similar skinfold thickness and weight: height2 ratios and gained as much weight during pregnancy. Their infants, however, were lighter than the others, and had smaller head and limb circumferences, although their linear measurements were the same. Negro and European infants were almost identical in size. We found no effect on any of the fetal measurements which could be attributed to smoking. PMID:626515

  20. Fetal growth curves for an ethnically diverse military population: the American Institute of Ultrasound in Medicine-accredited platform experience.

    PubMed

    Elliott, Dawn; Patience, Troy; Boyd, Emily; Hume, Roderick F; Calhoun, Byron C; Napolitano, Peter G; Apodaca, Christina C

    2006-06-01

    To determine which fetal growth curve provided the best estimates of fetal weight for a cohort of ethnically diverse patients at sea level. The study consisted of a population of 1,729 fetuses examined at sea level between January 1, 1997, and June 30, 2000, at 18 weeks, 28 weeks, and term. Gestational age (GA) based on menstrual dates was confirmed or adjusted by crown-rump length or early second-trimester biometry. Fetal weight was estimated by using biparietal diameter, head circumference, abdominal circumference, and femur length. Our fetal growth curves were analyzed with fourth-order polynomial regression analysis, applying four previously defined formulae for fetal growth. Fetal growth curves for estimated fetal weight demonstrated the expected parabolic shape, which varied according to the formulae used. Our curve best fit the following equation: estimated fetal weight = 4.522 - 0.22 x GA age + 0.25 x GA(2) - 0.001 x GA(3) + 5.248 x 10(-6) x GA(4) (R2 = 0.976). SD increased in concordance with GA. Madigan Army Medical Center serves a racially mixed, culturally diverse, military community with unrestricted access to prenatal care. Determination of the optimal population-appropriate growth curve at the correct GA assists clinicians in identifying fetuses at risk for growth restriction or macrosomia and therefore at risk for increased perinatal morbidity and death.

  1. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep.

    PubMed

    Manikkam, Mohan; Crespi, Erica J; Doop, Douglas D; Herkimer, Carol; Lee, James S; Yu, Sunkyung; Brown, Morton B; Foster, Douglas L; Padmanabhan, Vasantha

    2004-02-01

    Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

  2. The importance of fetal gender in intrauterine growth restriction

    PubMed Central

    Radulescu, L; Ferechide, D; Popa, F

    2013-01-01

    One of the most important causes of perinatal mortality and morbidity complicating significant percentage pregnancies is intrauterine growth restriction (IUGR). Fetal growth restriction is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. Numerous studies in different populations reveal an association between intrauterine growth restriction and perinatal and postnatal developments, which differ according to the sex of newborns with intrauterine growth restriction. However, the mechanisms of intrauterine programming, the critical time necessary to cause injury and involvement of other factors are unclear and although several authors’ opinions differ, it seems that females are more likely to develop intrauterine growth restriction. Abbreviations: IUGR=intrauterine growth restriction PMID:23599816

  3. Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

    PubMed

    Segar, Jeffrey L; Volk, Ken A; Lipman, Michael H B; Scholz, Thomas D

    2013-03-01

    Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in

  4. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

    PubMed

    Kiserud, Torvid; Piaggio, Gilda; Carroli, Guillermo; Widmer, Mariana; Carvalho, José; Neerup Jensen, Lisa; Giordano, Daniel; Cecatti, José Guilherme; Abdel Aleem, Hany; Talegawkar, Sameera A; Benachi, Alexandra; Diemert, Anke; Tshefu Kitoto, Antoinette; Thinkhamrop, Jadsada; Lumbiganon, Pisake; Tabor, Ann; Kriplani, Alka; Gonzalez Perez, Rogelio; Hecher, Kurt; Hanson, Mark A; Gülmezoglu, A Metin; Platt, Lawrence D

    2017-01-01

    measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.

  5. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight

    PubMed Central

    Carroli, Guillermo; Widmer, Mariana; Neerup Jensen, Lisa; Giordano, Daniel; Abdel Aleem, Hany; Talegawkar, Sameera A.; Benachi, Alexandra; Diemert, Anke; Tshefu Kitoto, Antoinette; Thinkhamrop, Jadsada; Lumbiganon, Pisake; Tabor, Ann; Kriplani, Alka; Gonzalez Perez, Rogelio; Hecher, Kurt; Hanson, Mark A.; Gülmezoglu, A. Metin; Platt, Lawrence D.

    2017-01-01

    intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. Conclusions This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world. PMID:28118360

  6. Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

    PubMed

    Spiroski, A-M; Oliver, M H; Harding, J E; Bloomfield, F H

    2016-01-01

    Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

  7. Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction

    PubMed Central

    Hillman, Sara; Peebles, Donald M.; Williams, David J.

    2013-01-01

    OBJECTIVE Fathers of low–birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth–restricted offspring were born. RESEARCH DESIGN AND METHODS We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who fathered normal–birth weight offspring (n = 77). All mothers were healthy, nonsmoking, and similar in age, BMI, ethnicity, and parity. Within 4 weeks of offspring birth, all fathers had measures of insulin resistance (HOMA index), blood pressure, waist circumference, endothelial function (flow-mediated dilatation), lipid profile, weight, and smoking habit. Comparison was made using multivariable logistical regression analysis. RESULTS Fathers of fetal growth–restricted offspring [mean (SD) 1.8th (2.2) customized birth centile] were more likely to have insulin resistance, hypertension, central adiposity, and endothelial dysfunction and to smoke cigarettes compared with fathers of normal grown offspring. After multivariable analysis, paternal insulin resistance and smoking remained different between the groups. Compared with fathers of normal grown offspring, men who fathered pregnancies affected by fetal growth restriction had an OR 7.68 (95% CI 2.63–22.40; P < 0.0001) of having a 1-unit higher log HOMA-IR value and 3.39 (1.26–9.16; P = 0.016) of being a smoker. CONCLUSIONS Men who recently fathered growth-restricted offspring have preclinical evidence of the insulin resistance syndrome and are more likely to smoke than fathers of normal grown offspring. Paternal lifestyle may influence heritable factors important for fetal growth. PMID:23315598

  8. A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes.

    PubMed

    McGee, Meghan; Bainbridge, Shannon; Fontaine-Bisson, Bénédicte

    2018-06-01

    The fetal origins of health and disease framework has identified extremes in fetal growth and birth weight as factors associated with the lifelong generation of chronic diseases such as obesity, diabetes, cardiovascular disease, and hypertension. Maternal nutrition plays a critical role in fetal and placental development, in part by providing the methyl groups required to establish the fetus's genome structure and function, notably through DNA methylation. The goal of this narrative review is to describe the role of maternal dietary methyl donor (methionine, folate, and choline) and cofactor (zinc and vitamins B2, B6, and B12) intake in one-carbon metabolism and DNA methylation in the fetus and placenta, as well as their impacts on fetal growth and lifelong health outcomes, with specific examples in animals and humans. Based on the available evidence, it is concluded that intake of different amounts of dietary methyl donors and cofactors during pregnancy may alter fetal growth and development, thus establishing a major link between early environmental exposure and disease development in the offspring later in life.

  9. Maternal Choline Supplementation Alters Fetal Growth Patterns in a Mouse Model of Placental Insufficiency.

    PubMed

    King, Julia H; Kwan, Sze Ting Cecilia; Yan, Jian; Klatt, Kevin C; Jiang, Xinyin; Roberson, Mark S; Caudill, Marie A

    2017-07-18

    Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3 +/- (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3 +/- female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3 +/- mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline.

  10. Maternal Choline Supplementation Alters Fetal Growth Patterns in a Mouse Model of Placental Insufficiency

    PubMed Central

    Kwan, Sze Ting (Cecilia); Yan, Jian; Klatt, Kevin C.; Jiang, Xinyin; Roberson, Mark S.; Caudill, Marie A.

    2017-01-01

    Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/− (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/− female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3+/− mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline. PMID:28718809

  11. Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection.

    PubMed

    Walker, Christie L; Merriam, Audrey A; Ohuma, Eric O; Dighe, Manjiri K; Gale, Michael; Rajagopal, Lakshmi; Papageorghiou, Aris T; Gyamfi-Bannerman, Cynthia; Adams Waldorf, Kristina M

    2018-05-05

    /7, 28-33 6/7, >34 weeks) to analyze time-dependent effects of Zika virus infection on fetal size. Statistical analysis was performed using Wilcoxon signed-rank test on paired data, comparing either abdominal circumference or head circumference to femur length. A total of 56 pregnant women were included in the study with laboratory evidence of a confirmed or possible recent Zika virus infection. Based on the Centers for Disease Control and Prevention definition for microcephaly after congenital Zika virus exposure, microcephaly was diagnosed in 5% (3/56) by both the 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart standards (head circumference Z-score ≤-2 or ≤2.3%). Using 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, intrauterine fetal growth restriction was diagnosed in 18% of pregnancies (10/56; abdominal circumference Z-score ≤-1.3, <10%). Analysis of fetal size using the last ultrasound scan for all subjects revealed a significantly abnormal skewing of fetal biometrics with a smaller abdominal circumference vs femur length by either 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project or World Health Organization Fetal Growth Chart (P < .001 for both). A difference in distribution of fetal abdominal circumference compared to femur length was first apparent in the 24-27 6/7 week strata (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, P = .002; World Health Organization Fetal Growth Chart, P = .001). A significantly smaller head circumference compared to femur length was also observed by 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project as early as the 28-33 6/7 week strata (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, P = .007). Overall, a femur-sparing pattern of growth restriction was detected

  12. Noninvasive monitoring of fetal growth and development in the Siberian polecat (Mustela eversmanni)

    USGS Publications Warehouse

    Wimsatt, Jeffrey; Johnson, Jay D.; Wrigley, Robert H.; Biggins, Dean E.; Godbey, Jerry L.

    1998-01-01

    The Siberian polecat (Mustela eversmanni) is the preferred species to assess procedures and establish normative values for application in the related and endangered black-footed ferret (Mustela nigripes). This study was undertaken to physically, ultrasonographically, and radiographically evaluate fetal development in a spontaneously breeding captive Siberian polecat population. Ultrasonographically, fetal sac enlargement allowed presumptive preg nancy detection as early as 12 days of gestation, the fetal pole was the first definitive sign of pregnancy at about 18 days of gestation, when the fetal heart beat also appeared, and definitive pregnancy detection by ultrasound was essentially 100% accurate after 18 days. The estimation of fetal number by ultrasound was less reliable than by radiography, as it is in other litter-bearing species. Crown-rump growth, organ differentiation, and calcification patterns resembled those of domestic carnivores except that comparable developmental stages in polecats occurred at dispro portionately later times, suggesting that young Siberian polecats are delivered in a less developed state. Careful palpation permitted detection of pregnancy after day 17 but with less certainty than with ultrasound. Radiographic evaluation was insensitive and of limited value for pregnancy detection until near term. Litter number and fetal detail were difficult to assess until ossification could be observed, 3-6 days before parturition.

  13. Noninvasive monitoring of fetal growth and development in the Siberian polecat (Mustela eversmanni).

    PubMed

    Wimsatt, J; Johnson, J D; Wrigley, R H; Biggins, D E; Godbey, J L

    1998-12-01

    The Siberian polecat (Mustela eversmanni) is the preferred species to assess procedures and establish normative values for application in the related and endangered black-footed ferret (Mustela nigripes). This study was undertaken to physically, ultrasonographically, and radiographically evaluate fetal development in a spontaneously breeding captive Siberian polecat population. Ultrasonographically, fetal sac enlargement allowed presumptive pregnancy detection as early as 12 days of gestation, the fetal pole was the first definitive sign of pregnancy at about 18 days of gestation, when the fetal heart beat also appeared, and definitive pregnancy detection by ultrasound was essentially 100% accurate after 18 days. The estimation of fetal number by ultrasound was less reliable than by radiography, as it is in other litter-bearing species. Crown-rump growth, organ differentiation, and calcification patterns resembled those of domestic carnivores except that comparable developmental stages in polecats occurred at disproportionately later times, suggesting that young Siberian polecats are delivered in a less developed state. Careful palpation permitted detection of pregnancy after day 17 but with less certainty than with ultrasound. Radiographic evaluation was insensitive and of limited value for pregnancy detection until near term. Litter number and fetal detail were difficult to assess until ossification could be observed, 3-6 days before parturition.

  14. Growth curve analysis of placental and fetal growth influenced by adjacent fetal sex status under crowded uterine conditions in pigs

    USDA-ARS?s Scientific Manuscript database

    Intrauterine position and sex of adjacent fetuses in litter bearing species have been implicated in physiological and behavioral differences in males and females. Our objective was to establish growth curves for fetal and placental weight gain as influenced by sex status of flanking fetuses under cr...

  15. Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

    PubMed

    Garza, Cutberto

    2015-07-01

    The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age. © 2015 American Society for Nutrition.

  16. Leptin increases growth of primary ossification centers in fetal mice

    PubMed Central

    Bertoni, Laura; Ferretti, Marzia; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Benelli, Augusta; Palumbo, Carla

    2009-01-01

    The effect of peripheral leptin on fetal primary ossification centers during the early phases of bone histogenesis was investigated by administration of leptin to pregnant mice. Fourteen pregnant mice were divided into two groups. The treated pregnant group was subcutaneously injected in the intrascapular region with supraphysiologic doses (2 mg kg−1) of leptin (Vinci Biochem, Firenze, Italy) in a volume of 0.1 mL per 10 g body weight, at the 7th, 9th and 11th day of gestation. The control group was treated with physiological solution in the same manner and same times as the treated group. The new-born mice were killed 1 day after birth and the primary ossification centers were stained with Alizarin Red S after diaphanizing the soft tissues in 1% potassium hydroxide. The development of both endochondral and intramembranous ossification centers was morphometrically analysed in long bones. The results showed that the ossification centers of mice born by mothers treated with leptin grow more rapidly in both length and cross-sectional area compared with mice born by the untreated mothers. As the development of long bones depends on endochondral ossification occurring at proximal and distal epiphyseal plates as well as on intramembranous ossification along the periosteal surface, it appears that leptin activates the differentiation and proliferation of both chondrocytes and osteoblasts. The role of leptin as a growth factor of cartilage and bone is discussed in the light of the data reported in the literature. PMID:19682137

  17. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

    PubMed

    Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2013-11-12

    Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

  18. Fetal Genotype for the Xenobiotic Metabolizing Enzyme "NQO1" Influences Intrauterine Growth among Infants Whose Mothers Smoked during Pregnancy

    ERIC Educational Resources Information Center

    Price, Thomas S.; Grosser, Tilo; Plomin, Robert; Jaffee, Sara R.

    2010-01-01

    Maternal smoking during pregnancy retards fetal growth and depresses infant birth weight. The magnitude of these effects may be moderated by fetal genotype. The current study investigated maternal smoking, fetal genotype, and fetal growth in a large population sample of dizygotic twins. Maternal smoking retarded fetal growth in a dose-dependent…

  19. Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice.

    PubMed

    Watkins, Adam J; Sirovica, Slobodan; Stokes, Ben; Isaacs, Mark; Addison, Owen; Martin, Richard A

    2017-06-01

    Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development is largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Interleukin-10 attenuates experimental fetal growth restriction and demise.

    PubMed

    Rivera, D L; Olister, S M; Liu, X; Thompson, J H; Zhang, X J; Pennline, K; Azuero, R; Clark, D A; Miller, M J

    1998-02-01

    Premature labor, fetal demise, and fetal growth restriction are accompanied by indices of inflammation or infection of the uteroplacental unit. To understand whether these events are causally related, we established an animal model of fetal demise and growth restriction and evaluated the potential utility of the anti-inflammatory cytokine interleukin-10 (IL-10). We administered low-dose endotoxin (lipopolysaccharide, or LPS, 100 microg/kg, i.p.) to third trimester rats (gestational days 14-20). Control rats received normal saline. A third group received IL-10 (100 microg/kg; s.c.) concomitantly with LPS for 7 prenatal days. Cytokine gene expression (IL-10 and TNF-alpha) was evaluated by RT-PCR and tissue levels (TNF-alpha) were determined by ELISA. Apoptosis was evaluated by TdT-mediated dUTP nick end labeling immunohistochemistry, and nitric oxide (NO) levels were quantified by microelectrode electrochemical detection in explants in culture media. LPS exposure resulted in 43% fetal demise and reduced the size of the surviving fetuses. Placental weight was not altered by LPS. IL-10 attenuated the LPS-induced fetal death rate (to 22%) and growth restriction (P<0.05). In normal rats, IL-10 did not affect fetus size or the incidence of resorptions, although placental size was marginally smaller. Increased uterine TNF-alpha content and NO release and apoptosis of uterine epithelia and muscularis were hallmarks of the LPS model. All were normalized by IL-10. IL-10 may represent a new therapeutic option for the treatment of a variety of perinatal complications. Benefit may result from the suppression of TNF-alpha- and NO-mediated cell death.

  1. Physically demanding work, fetal growth and the risk of adverse birth outcomes. The Generation R Study.

    PubMed

    Snijder, Claudia A; Brand, Teus; Jaddoe, Vincent; Hofman, Albert; Mackenbach, Johan P; Steegers, Eric A P; Burdorf, Alex

    2012-08-01

    Work-related risk factors, such as long work hours, and physically demanding work have been suggested to adversely influence pregnancy outcome. The authors aimed to examine associations between various aspects of physically demanding work with fetal growth in different trimesters during pregnancy and the risks of adverse birth outcomes. Associations between physically demanding work and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in The Netherlands (2002-2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment) were included if they conducted paid employment and had a spontaneously conceived singleton live born pregnancy. Questions on physical workload were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on lifting, long periods of standing or walking, night shifts and working hours. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. There were no consistent significant associations between physically demanding work nor working hours in relation to small for gestational age, low birth weight or preterm delivery. Women exposed to long periods of standing had lower growth rates for fetal head circumference (HC), resulting in a reduction of approximately 1 cm (3%) of the average HC at birth. Compared with women working <25 h/week, women working 25-39 h/week and >40 h/week had lower growth rates for both fetal weight and HC, resulting in a difference of approximately 1 cm in HC at birth and a difference of 148-198 g in birth weight. Long periods of standing and long working hours per week during pregnancy seem to negatively influence intrauterine growth.

  2. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

    PubMed

    Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

    2016-05-08

    Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

  3. Biopsychosocial determinants of pregnancy length and fetal growth.

    PubMed

    St-Laurent, Jennifer; De Wals, Philippe; Moutquin, Jean-Marie; Niyonsenga, Theophile; Noiseux, Manon; Czernis, Loretta

    2008-05-01

    The causes and mechanisms related to preterm delivery and intrauterine growth restriction are poorly understood. Our objective was to assess the direct and indirect effects of psychosocial and biomedical factors on the duration of pregnancy and fetal growth. A self-administered questionnaire was distributed to pregnant women attending prenatal ultrasound clinics in nine hospitals in the Montérégie region in the province of Quebec, Canada, from November 1997 to May 1998. Prenatal questionnaires were linked with birth certificates. Theoretical models explaining pregnancy length and fetal growth were developed and tested, using path analysis. In order to reduce the number of variables from the questionnaire, a principal component analysis was performed, and the three most important new dimensions were retained as explanatory variables in the final models. Data were available for 1602 singleton pregnancies. The biophysical score, covering both maternal age and the pre-pregnancy body mass index, was the only variable statistically associated with pregnancy length. Smoking, obstetric history, maternal health and biophysical indices were direct predictors of fetal growth. Perceived stress, social support and self-esteem were not directly related to pregnancy outcomes, but were determinants of smoking and the above-mentioned biomedical variables. More studies are needed to identify the mechanisms by which adverse psychosocial factors are translated into adverse biological effects.

  4. WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component

    PubMed Central

    2014-01-01

    Background In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. Methods This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/− 1 week) to be performed by trained ultrasonographers. The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. Discussion The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use

  5. WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

    PubMed

    Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence

    2014-05-02

    In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

  6. The use of ultrasound measurements in environmental epidemiological studies of air pollution and fetal growth

    PubMed Central

    Smarr, Melissa M.; Vadillo-Ortega, Felipe; Castillo-Castrejon, Marisol; O’Neill, Marie S.

    2015-01-01

    Purpose of review Recently, several international research groups have suggested that studies about environmental contaminants and adverse pregnancy outcomes should be designed to elucidate potential underlying biological mechanisms. The purpose of this review is to examine the epidemiological studies addressing maternal exposure to air pollutants and fetal growth during gestation as assessed by ultrasound measurements. Recent findings The six studies published to date found that exposure to certain ambient air pollutants during pregnancy is negatively associated with the growth rates and average attained size of fetal parameters belonging to the growth profile. Fetal parameters may respond to maternal air pollution exposures uniquely, and this response may vary by pollutant and timing of gestational exposure. Current literature suggests that mean changes in head circumference, abdominal circumference, femur length, and biparietal diameter are negatively associated with early-pregnancy exposures to ambient and vehicle-related air pollution. Summary The use of more longitudinal studies, employing ultrasound measures to assess fetal outcomes, may assist with the better understanding of mechanisms responsible for air pollution-related pregnancy outcomes. PMID:23399571

  7. Effect of Dietary Iron on Fetal Growth in Pregnant Mice

    PubMed Central

    Hubbard, Andrea C; Bandyopadhyay, Sheila; Wojczyk, Boguslaw S; Spitalnik, Steven L; Hod, Eldad A; Prestia, Kevin A

    2013-01-01

    Iron deficiency is the most common nutritional disorder. Children and pregnant women are at highest risk for developing iron deficiency because of their increased iron requirements. Iron-deficiency anemia during pregnancy is associated with adverse effects on fetal development, including low birth weight, growth retardation, hypertension, intrauterine fetal death, neurologic impairment, and premature birth. We hypothesized that pregnant mice fed an iron-deficient diet would have a similar outcome regarding fetal growth to that of humans. To this end, we randomly assigned female C57BL/6 mice to consume 1 of 4 diets (high-iron–low-bioavailability, high-iron–high-bioavailability, iron-replete, and iron-deficient) for 4 wk before breeding, followed by euthanasia on day 17 to 18 of gestation. Compared with all other groups, dams fed the high-iron–high-bioavailability diet had significantly higher liver iron. Hct and Hgb levels in dams fed the iron-deficient diet were decreased by at least 2.5 g/dL as compared with those of all other groups. In addition, the percentage of viable pups among dams fed the iron-deficient diet was lower than that of all other groups. Finally, compared with all other groups, fetuses from dams fed the iron-deficient diet had lower fetal brain iron levels, shorter crown–rump lengths, and lower weights. In summary, mice fed an iron-deficient diet had similar hematologic values and fetal outcomes as those of iron-deficient humans, making this a useful model for studying iron-deficiency anemia during pregnancy. PMID:23582419

  8. Periconceptional growth hormone treatment alters fetal growth and development in lambs.

    PubMed

    Koch, J M; Wilmoth, T A; Wilson, M E

    2010-05-01

    fetal growth and development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.

  9. Impact of placental insufficiency on fetal skeletal muscle growth

    PubMed Central

    Hay, William W.

    2016-01-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

  10. Effects of chronic carbon monoxide exposure on fetal growth and development in mice

    PubMed Central

    2011-01-01

    Background Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse. PMID:22168775

  11. Fetal head circumference growth in children with specific language impairment.

    PubMed

    Whitehouse, Andrew J O; Zubrick, Stephen R; Blair, Eve; Newnham, John P; Hickey, Martha

    2012-01-01

    To characterise fetal brain growth in children with specific language impairment (SLI). A nested case-control study. Perth, Western Australia. Thirty children meeting criteria for SLI at age 10 years were individually matched with a typically developing comparison child on sex, non-verbal ability, fetal gestational age, maternal age at conception, smoking and alcohol intake during pregnancy. Occipitofrontal head circumference (HC) was measured using ultrasonography at approximately 18 weeks gestation. Femur length provided a measure of fetal length. Occipitofrontal HC was measured at birth and at the 1-year postnatal follow-up using a precise paper tape measure, while crown-heel length acted as an index of body length at both time points. Raw data were transformed to z-scores using reference norms. The SLI group had a significantly smaller mean HC than the typically developing comparison children at birth, but there was no group difference at 18 weeks gestation or at the 1-year postnatal follow-up. Individual analyses found that 12 SLI children had an HC z-score less than -1 at birth, with three of these cases meeting criteria for microcephaly. There was no group difference in the indices of overall body size at any time point. Children with SLI are more likely to have a small HC at birth but not at 18 weeks gestation or infancy, suggesting growth asynchrony in brain development during the second half of pregnancy.

  12. Normative biometrics for fetal ocular growth using volumetric MRI reconstruction.

    PubMed

    Velasco-Annis, Clemente; Gholipour, Ali; Afacan, Onur; Prabhu, Sanjay P; Estroff, Judy A; Warfield, Simon K

    2015-04-01

    To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. The 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created using super-resolution volume reconstructions from MRI slice acquisitions. These 3D images were semi-automatically segmented to measure fetal orbit volume, binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD). All biometry correlated with GA (Volume, Pearson's correlation coefficient (CC) = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC = 0.8429), and growth curves were plotted against linear and quadratic growth models. Regression analysis showed quadratic models to best fit BOD, IOD, and OD and a linear model to best fit volume. Orbital volume had the greatest correlation with GA, although BOD and OD also showed strong correlation. The normative data found in this study may be helpful for the detection of congenital fetal anomalies with more consistent measurements than are currently available. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  13. Prenatal Exposure to NO2 and Ultrasound Measures of Fetal Growth in the Spanish INMA Cohort

    PubMed Central

    Iñiguez, Carmen; Esplugues, Ana; Sunyer, Jordi; Basterrechea, Mikel; Fernández-Somoano, Ana; Costa, Olga; Estarlich, Marisa; Aguilera, Inmaculada; Lertxundi, Aitana; Tardón, Adonina; Guxens, Mònica; Murcia, Mario; Lopez-Espinosa, Maria-Jose; Ballester, Ferran

    2015-01-01

    Background Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability. Objective The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study. Methods Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis. Results A 10-μg/m3 increase in average exposure to NO2 during weeks 0–12 was associated with reduced growth at weeks 0–12 in AC (–2.1%; 95% CI: –3.7, –0.6) and EFW (–1.6%; 95% CI: –3.0, –0.3). The same exposure was inversely associated with reduced growth at weeks 20–34 in BPD (–2.6%; 95% CI: –3.9, –1.2), AC (–1.8%; 95% CI: –3.3, –0.2), and EFW (–2.1%; 95% CI: –3.7, –0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers. Conclusions Maternal exposure to NO2 in early pregnancy was associated with reduced fetal growth based on ultrasound measures of growth during pregnancy and measures of size at birth. Citation Iñiguez C, Esplugues A, Sunyer J, Basterrechea M, Fernández-Somoano A, Costa O, Estarlich M, Aguilera I, Lertxundi A, Tardón A, Guxens M, Murcia M, Lopez-Espinosa MJ, Ballester F, on behalf of the INMA Project. 2016. Prenatal exposure

  14. Prenatal exposure to traffic pollution: associations with reduced fetal growth and rapid infant weight gain.

    PubMed

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Koutrakis, Petros; Schwartz, Joel D; Kloog, Itai; Melly, Steven; Coull, Brent A; Zanobetti, Antonella; Gillman, Matthew W; Gold, Diane R; Oken, Emily

    2015-01-01

    Prenatal air pollution exposure inhibits fetal growth, but implications for postnatal growth are unknown. We assessed weights and lengths of US infants in the Project Viva cohort at birth and 6 months. We estimated 3rd-trimester residential air pollution exposures using spatiotemporal models. We estimated neighborhood traffic density and roadway proximity at birth address using geographic information systems. We performed linear and logistic regression adjusted for sociodemographic variables, fetal growth, and gestational age at birth. Mean birth weight-for-gestational age z-score (fetal growth) was 0.17 (standard deviation [SD] = 0.97; n = 2,114), 0- to 6-month weight-for-length gain was 0.23 z-units (SD = 1.11; n = 689), and 17% had weight-for-length ≥95th percentile at 6 months of age. Infants exposed to the highest (vs. lowest) quartile of neighborhood traffic density had lower fetal growth (-0.13 units [95% confidence interval (CI) = -0.25 to -0.01]), more rapid 0- to 6-month weight-for-length gain (0.25 units [95% CI = 0.01 to 0.49]), and higher odds of weight-for-length ≥95th percentile at 6 months (1.84 [95% CI = 1.11 to 3.05]). Neighborhood traffic density was additionally associated with an infant being in both the lowest quartile of fetal growth and the highest quartile of 0- to 6-month weight-for-length gain (Q4 vs. Q1, odds ratio = 3.01 [95% CI = 1.08 to 8.44]). Roadway proximity and 3rd-trimester black carbon exposure were similarly associated with growth outcomes. For 3rd-trimester particulate matter (PM2.5), effect estimates were in the same direction, but smaller and imprecise. Infants exposed to higher traffic-related pollution in early life may exhibit more rapid postnatal weight gain in addition to reduced fetal growth.

  15. Prenatal Exposure to Traffic Pollution: Associations with Reduced Fetal Growth and Rapid Infant Weight Gain

    PubMed Central

    Fleisch, Abby F.; Rifas-Shiman, Sheryl L.; Koutrakis, Petros; Schwartz, Joel D.; Kloog, Itai; Melly, Steven; Coull, Brent A.; Zanobetti, Antonella; Gillman, Matthew W.; Gold, Diane R.; Oken, Emily

    2014-01-01

    Background Prenatal air pollution exposure inhibits fetal growth, but implications for postnatal growth are unknown. Methods We assessed weights and lengths of US infants in the Project Viva cohort at birth and 6 months. We estimated third-trimester residential air pollution exposures using spatiotemporal models. We estimated neighborhood traffic density and roadway proximity at birth address using geographic information systems. We performed linear and logistic regression adjusted for sociodemographic variables, fetal growth, and gestational age at birth. Results Mean birth weight-for-gestational age z-score (fetal growth) was 0.17 (SD = 0.97; n=2,114), 0-6 month weight-for-length gain was 0.23 z-units (SD = 1.11; n=689), and 17% had weight-for-length ≥95th percentile at 6 months of age. Infants exposed to the highest (vs. lowest) quartile of neighborhood traffic density had lower fetal growth (−0.13 units [95% confidence interval (CI) = −0.25 to −0.01]), more rapid 0-6 month weight-for-length gain (0.25 units [95% CI = 0.01 to 0.49]), and higher odds of weight-for-length ≥95th percentile at 6 months (1.84 [95% CI = 1.11 to 3.05]). Neighborhood traffic density was additionally associated with an infant being in both the lowest quartile of fetal growth and highest quartile of 0-6 month weight-for-length gain (Q4 vs. Q1, OR = 3.01 [95% CI = 1.08 to 8.44]). Roadway proximity and third-trimester black carbon exposure were similarly associated with growth outcomes. For third-trimester PM2.5, effect estimates were in the same direction, but smaller and imprecise. Conclusions Infants exposed to higher traffic-related pollution in early life may exhibit more rapid postnatal weight gain in addition to reduced fetal growth. PMID:25437317

  16. Volumetric MRI study of the intrauterine growth restriction fetal brain.

    PubMed

    Polat, A; Barlow, S; Ber, R; Achiron, R; Katorza, E

    2017-05-01

    Intrauterine growth restriction (IUGR) is a pathologic fetal condition known to affect the fetal brain regionally and associated with future neurodevelopmental abnormalities. This study employed MRI to assess in utero regional brain volume changes in IUGR fetuses compared to controls. Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a total of 8 brain regions-supratentorial brain and cavity, cerebral hemispheres, temporal lobes and cerebellum-were measured for volume in 13 fetuses with IUGR due to placental insufficiency and in 21 controls. Volumes and their ratios were assessed for difference using regression models. Reliability was assessed by intraclass correlation coefficients (ICC) between two observers. In both groups, all structures increase in absolute volume during that gestation period, and the rate of cerebellar growth is higher compared to that of supratentorial structures. All structures' absolute volumes were significantly smaller for the IUGR group. Cerebellar to supratentorial ratios were found to be significantly smaller (P < 0.05) for IUGR compared to controls. No other significant ratio differences were found. ICC showed excellent agreement. The cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional research is needed to assess this as a radiologic marker in relation to long-term outcome. • IUGR is a pathologic fetal condition affecting the brain • IUGR is associated with long-term neurodevelopmental abnormalities; fetal characterization is needed • This study aimed to evaluate regional brain volume differences in IUGR • Cerebellar to supratentorial volume ratios were smaller in IUGR fetuses • This finding may play a role in long-term development of IUGR fetuses.

  17. Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth.

    PubMed

    Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A; Romero, Roberto

    2009-01-01

    The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode.

  18. The INTERGROWTH-21st fetal growth standards: toward the global integration of pregnancy and pediatric care.

    PubMed

    Papageorghiou, Aris T; Kennedy, Stephen H; Salomon, Laurent J; Altman, Douglas G; Ohuma, Eric O; Stones, William; Gravett, Michael G; Barros, Fernando C; Victora, Cesar; Purwar, Manorama; Jaffer, Yasmin; Noble, Julia A; Bertino, Enrico; Pang, Ruyan; Cheikh Ismail, Leila; Lambert, Ann; Bhutta, Zulfiqar A; Villar, José

    2018-02-01

    The purpose of the INTERGROWTH-21 st project was to develop international, prescriptive standards for fetal growth assessed by ultrasound and fundal height, preterm postnatal growth, newborn size and body composition, maternal weight gain, and infant development at the age of 2 years. Hence, we have produced, based on World Health Organization recommendations, the first comprehensive set of international standards of optimal fetal and newborn growth that perfectly match the existing World Health Organization child growth standards. Uniquely, the same population was followed up longitudinally from 9 weeks of fetal life to 2 years of age, with growth, health, and nutritional status assessment at 2 years supporting the appropriateness of the population for construction of growth standards. The resulting package of clinical tools allows, for the first time, growth and development to be monitored from early pregnancy to infancy. The INTERGROWTH-21 st fetal growth standards, which are based on observing >4500 healthy pregnancies, nested in a study of >59,000 pregnancies from populations with low rates of adverse perinatal outcomes, show how fetuses should grow-rather than the more limited objective of past references, which describe how they have grown at specific times and locations. Our work has confirmed the fundamental biological principle that variation in human growth across different populations is mostly dependent on environmental, nutritional, and socioeconomic factors. We found that when mothers' nutritional and health needs are met and there are few environmental constraints on growth, <3.5% of the total variability of skeletal growth was due to differences between populations. We propose that not recognizing the concept of optimal growth could deprive the most vulnerable mothers and their babies of optimal care, because local growth charts normalize those at highest risk for growth restriction and overweight, and can be valuable for policymakers to ensure

  19. Genetic factors in fetal growth restriction and miscarriage.

    PubMed

    Yamada, Hideto; Sata, Fumihiro; Saijo, Yasuaki; Kishi, Reiko; Minakami, Hisanori

    2005-06-01

    Recently, several investigations concerning disadvantageous genetic factors in human reproduction have progressed. Inherited thrombophilia, such as factor V Leiden, prothrombin, and methylenetetrahydrofolate reductase mutations; gene polymorphisms of detoxification enzyme (CYP1A1); growth factors (insulin-like growth factor-I); and hormones such as angiotensinogen and CYP17 are involved in the pathogenesis of fetal growth restriction. The inherited thrombophilia, gene polymorphisms of coagulation and anticoagulation factor such as thrombomodulin, endothelial protein C receptor, plasminogen activator inhibitor 1, and factor XIII; human lymphocyte antigen (HLA-G); detoxification enzymes (glutathione- S-transferase M1); cytokines such as interleukin (IL) -1 and IL-6; hormones (CYP17); vasodilators (nitric oxide synthase 3); and vitamins (transcobalamin) are involved in the pathogenesis of sporadic and recurrent miscarriage. It is likely that a gene polymorphism or mutation susceptible to reproductive failure has a beneficial effect on the process of human reproduction with or without the environmental interaction. The factor V Leiden mutation has genetic advantages that are believed to be an improved implantation rate in in vitro fertilization and a reduction of maternal intrapartum blood loss. It has also been demonstrated that the CYP17 A2 allele has bidirectional effects on human reproduction, including increases in susceptibility to recurrent miscarriage and fetal growth enhancement.

  20. Ultrasonographic fetal growth charts: an informatic approach by quantitative analysis of the impact of ethnicity on diagnoses based on a preliminary report on Salentinian population.

    PubMed

    Tinelli, Andrea; Bochicchio, Mario Alessandro; Vaira, Lucia; Malvasi, Antonio

    2014-01-01

    Clear guidance on fetal growth assessment is important because of the strong links between growth restriction or macrosomia and adverse perinatal outcome in order to reduce associated morbidity and mortality. Fetal growth curves are extensively adopted to track fetal sizes from the early phases of pregnancy up to delivery. In the literature, a large variety of reference charts are reported but they are mostly up to five decades old. Furthermore, they do not address several variables and factors (e.g., ethnicity, foods, lifestyle, smoke, and physiological and pathological variables), which are very important for a correct evaluation of the fetal well-being. Therefore, currently adopted fetal growth charts are inadequate to support the melting pot of ethnic groups and lifestyles of our society. Customized fetal growth charts are needed to provide an accurate fetal assessment and to avoid unnecessary obstetric interventions at the time of delivery. Starting from the development of a growth chart purposely built for a specific population, in the paper, authors quantify and analyse the impact of the adoption of wrong growth charts on fetal diagnoses. These results come from a preliminary evaluation of a new open service developed to produce personalized growth charts for specific ethnicity, lifestyle, and other parameters.

  1. The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction.

    PubMed

    Groom, Katie M; David, Anna L

    2018-02-01

    Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology. This renders the study findings less reliable for determining clinical significance. For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0.90, 95% confidence interval, 0.81-1.00) and that a dose of ≥100 mg should be recommended and to start at or before 16 weeks of gestation. These findings support national clinical practice guidelines. In vitro and in vivo studies suggest that low-molecular-weight heparin may prevent fetal growth restriction; however, evidence from randomized control trials is inconsistent. A meta-analysis of multicenter trial data does not demonstrate any positive preventative effect of low-molecular-weight heparin on a primary composite outcome of placenta-mediated complications including fetal growth restriction (18% vs 18%; absolute risk difference, 0.6%; 95% confidence interval, 10.4-9.2); use of low-molecular-weight heparin for the prevention of fetal growth restriction should remain in the research setting. There are even fewer treatment options once fetal growth restriction is diagnosed. At present the only management option if the risk of hypoxia, acidosis, and

  2. A fetal cardiovascular score to predict infant hypertension and arterial remodeling in intrauterine growth restriction.

    PubMed

    Cruz-Lemini, Mónica; Crispi, Fátima; Valenzuela-Alcaraz, Brenda; Figueras, Francesc; Gómez, Olga; Sitges, Marta; Bijnens, Bart; Gratacós, Eduard

    2014-06-01

    Intrauterine growth restricted (IUGR) fetuses experience cardiovascular remodeling that persists into infancy and has been related to cardiovascular outcomes in adulthood. Hypertension in infancy has been demonstrated to be a strong risk factor for later cardiovascular disease. Close monitoring together with dietary interventions have shown to improve cardiovascular health in hypertensive children; however, not all IUGR infants show increased blood pressure. We evaluated the potential of fetal echocardiography for predicting hypertension and arterial remodeling in 6-month-old IUGR infants. One hundred consecutive IUGR and 100 control fetuses were observed into infancy. Fetal assessment included perinatal Doppler imaging, cardiac morphometry, ejection fraction, cardiac output, isovolumic relaxation time (IVRT), tricuspid annular-plane systolic excursion (TAPSE), and tissue Doppler imaging. Infant hypertension and arterial remodeling were defined as mean blood pressure of >95th percentile together with aortic intima-media thickness of >75th percentile at 6 months of age. Odds ratio were obtained for fetal parameters that were associated with infant outcomes. Fetal TAPSE, right sphericity index, IVRT, and cerebroplacental ratio were the strongest predictors for postnatal vascular remodeling. A cardiovascular risk score that was based on fetal TAPSE, cerebroplacental ratio, right sphericity index, and IVRT was highly predictive of infant hypertension and arterial remodeling (area under the curve, 0.87; 95% confidence interval, 0.79-0.93; P < .001). Fetal echocardiographic parameters identify a high-risk group within the IUGR fetuses who could be targeted for early screening of blood pressure and other cardiovascular risk factors and for promoting healthy diet and physical exercise. Copyright © 2014 Mosby, Inc. All rights reserved.

  3. Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children.

    PubMed

    Gishti, Olta; Gaillard, Romy; Manniesing, Rashindra; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Heppe, Denise H M; Steegers, Eric A P; Hofman, Albert; Duijts, Liesbeth; Durmuş, Büşra; Jaddoe, Vincent W V

    2014-07-01

    Higher infant growth rates are associated with an increased risk of obesity in later life. We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months. Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4). We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P < .05). Only infant weight gain was associated with higher fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P < .05). Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P < .05). Growth in both fetal life and infancy affects childhood body mass index, whereas only infant growth directly affects measured total body and abdominal fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.

  4. Imprinted gene expression in fetal growth and development.

    PubMed

    Lambertini, L; Marsit, C J; Sharma, P; Maccani, M; Ma, Y; Hu, J; Chen, J

    2012-06-01

    Experimental studies showed that genomic imprinting is fundamental in fetoplacental development by timely regulating the expression of the imprinted genes to overlook a set of events determining placenta implantation, growth and embryogenesis. We examined the expression profile of 22 imprinted genes which have been linked to pregnancy abnormalities that may ultimately influence childhood development. The study was conducted in a subset of 106 placenta samples, overrepresented with small and large for gestational age cases, from the Rhode Island Child Health Study. We investigated associations between imprinted gene expression and three fetal development parameters: newborn head circumference, birth weight, and size for gestational age. Results from our investigation show that the maternally imprinted/paternally expressed gene ZNF331 inversely associates with each parameter to drive smaller fetal size, while paternally imprinted/maternally expressed gene SLC22A18 directly associates with the newborn head circumference promoting growth. Multidimensional Scaling analysis revealed two clusters within the 22 imprinted genes which are independently associated with fetoplacental development. Our data suggest that cluster 1 genes work by assuring cell growth and tissue development, while cluster 2 genes act by coordinating these processes. Results from this epidemiologic study offer solid support for the key role of imprinting in fetoplacental development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

    PubMed

    Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

    2018-01-01

    Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

  6. Fetal bilateral renal agenesis, phocomelia, and single umbilical artery associated with cocaine abuse in early pregnancy.

    PubMed

    Kashiwagi, Maki; Chaoui, Rabih; Stallmach, Thomas; Hürlimann, Sandra; Lauper, Urs; Hebisch, Gundula

    2003-11-01

    Maternal cocaine abuse in pregnancy is associated with complications such as intrauterine growth retardation, abruptio placentae, and preterm delivery. We report what is, to our knowledge, the first published observation of fetal bilateral renal agenesis associated with a vascular disruption syndrome comprising upper limb reduction defect and a single umbilical artery following maternal cocaine abuse in early pregnancy. This constellation in a fetus aborted at 18 weeks extends the spectrum of complications possibly associated with cocaine abuse in pregnancy. Copyright 2003 Wiley-Liss, Inc.

  7. Impact of gestational weight gain on fetal growth in obese normoglycemic mothers: a comparative study.

    PubMed

    Elhddad, Agzail S; Fairlie, Fiona; Lashen, Hany

    2014-08-01

    To assess the pattern of gestational weight gain (GWG) and its effect on fetal growth among normogylycemic obese and lean mothers. Prospective longitudinal study. Teaching hospitals, Sheffield, UK. Forty-six euglycemic obese and 30 lean mothers and their offspring. The contrast slope of GWG was calculated and its impact on fetal growth trajectory and birth anthropometry examined in both groups. The GWG contrast slope trended significantly upward in both groups but it was steeper among lean mothers (p = 0.003), particularly in second trimester. Lean mothers had a biphasic GWG pattern with a higher early weight gain (p = 0.02), whereas obese mothers had a monophasic GWG. Both groups had similar third trimester GWG. The GWG contrast slope was influenced by early pregnancy maternal anthropometry in the obese group only. Nonetheless, the obese mothers' glucose and insulin indices had no significant relationship to GWG. GWG had a significant positive relationship with intrauterine femur length (r = 0.32, p = 0.04) and abdominal circumference (r = 0.42, p = 0.006) growth trajectories, as well as birthweight standard deviation scores (r = 0.32, p = 0.036) and the ponderal index (r = 0.45, p = 0.003) in the obese mothers. Gestational weight gain among lean mothers is biphasic and significantly higher than their obese counterparts, but without effect on fetal growth. The obese mothers' monophasic weight gain was influenced by their anthropometry, but not by their insulin or glucose indices, and impacted on the growth of their babies. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction.

    PubMed

    Wareing, Mark; Myers, Jenny E; O'Hara, Maureen; Baker, Philip N

    2005-05-01

    Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies. Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate. We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries. We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.

  9. Impact of fetal death reporting requirements on early neonatal and fetal mortality rates and racial disparities.

    PubMed

    Tyler, Crystal P; Grady, Sue C; Grigorescu, Violanda; Luke, Barbara; Todem, David; Paneth, Nigel

    2012-01-01

    Racial disparities in infant and neonatal mortality vary substantially across the U.S. with some states experiencing wider disparities than others. Many factors are thought to contribute to these disparities, but state differences in fetal death reporting have received little attention. We examined whether such reporting requirements may explain national variation in neonatal and fetal mortality rates and racial disparities. We used data on non-Hispanic white and non-Hispanic black infants from the U.S. 2000-2002 linked birth/infant death and fetal death records to determine the degree to which state fetal death reporting requirements explain national variation in neonatal and fetal mortality rates and racial disparities. States were grouped depending upon whether they based the lower limit for fetal death reporting on birthweight alone, gestational age alone, both birthweight and gestational age, or required reporting of all fetal deaths. Traditional methods and the fetuses-at-risk approach were used to calculate mortality rates, 95% confidence intervals, and relative and absolute racial disparity measures in these four groups. States with birthweight-alone fetal death thresholds substantially underreported fetal deaths at lower gestations and slightly overreported neonatal deaths at older gestations. This finding was reflected by these states having the highest neonatal mortality rates and disparities, but the lowest fetal mortality rates and disparities. Using birthweight alone as a reporting threshold may promote some shift of fetal deaths to newborn deaths, contributing to racial disparities in neonatal mortality. The adoption of a uniform national threshold for reporting fetal deaths could reduce systematic differences in live birth and fetal death reporting.

  10. Sexual dimorphism in epigenomicresponses of stem cells to extreme fetal growth

    PubMed Central

    Delahaye, Fabien; Wijetunga, N. Ari; Heo, Hye J.; Tozour, Jessica N.; Zhao, Yong Mei; Greally, John M.; Einstein, Francine H.

    2014-01-01

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction (IUGR) is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age (LGA) growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life. PMID:25300954

  11. Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth.

    PubMed

    Delahaye, Fabien; Wijetunga, N Ari; Heo, Hye J; Tozour, Jessica N; Zhao, Yong Mei; Greally, John M; Einstein, Francine H

    2014-10-10

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34(+) haematopoietic stem/progenitor cells showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.

  12. Growth hormone and early treatment.

    PubMed

    Antoniazzi, F; Cavarzere, P; Gaudino, R

    2015-06-01

    Growth hormone (GH) treatment is approved by the US Food and Drug Administration (FDA) not only for GH deficiency (GHD) but also for other childhood growth disorders with growth failure and/or short stature. GHD is the most frequent endocrine disorder presenting with short stature in childhood. During neonatal period, metabolic effects due to congenital GHD require a prompt replacement therapy to avoid possible life-threatening complications. In childhood and adolescence, growth impairment is the most evident effect of GHD and early treatment has the aim of restore normal growth and to reach normal adult height. We reassume in this review the conditions causing GHD and the diagnostic challenge to reach an early diagnosis, and an early treatment, necessary to obtain the best results. Finally, we summarize results obtained in clinical studies about pediatric patients with GHD treated at an early age, in which a marked early catch-up growth and a normalization of adult height were obtained.

  13. Timing of Gestational Weight Gain on Fetal Growth and Infant Size at Birth in Vietnam

    PubMed Central

    Young, Melissa F.; Hong Nguyen, Phuong; Addo, O. Yaw; Pham, Hoa; Nguyen, Son; Martorell, Reynaldo; Ramakrishnan, Usha

    2017-01-01

    Objective To examine the importance of timing of gestational weight gain during three time periods: 1: ≤ 20 weeks gestation), 2: 21–29 weeks) and 3: ≥ 30 weeks) on fetal growth and infant birth size. Methods Study uses secondary data from the PRECONCEPT randomized controlled trial in Thai Nguyen province, Vietnam (n = 1436). Prospective data were collected on women starting pre-pregnancy through delivery. Maternal conditional weight gain (CWG) was defined as window-specific weight gains, uncorrelated with pre-pregnancy body mass index and all prior body weights. Fetal biometry, was assessed by ultrasound measurements of head and abdomen circumferences, biparietal diameter, and femoral length throughout pregnancy. Birth size outcomes included weight and length, and head, abdomen and mid upper arm circumferences as well as small for gestational age (SGA). Adjusted generalized linear and logistic models were used to examine associations. Results Overall, three-quarters of women gained below the Institute of Medicine guidelines, and these women were 2.5 times more likely to give birth to a SGA infant. Maternal CWG in the first window (≤ 20 weeks), followed by 21–29 weeks, had the greatest association on all parameters of fetal growth (except abdomen circumference) and infant size at birth. For birth weight, a 1 SD increase CWG in the first 20 weeks had 3 times the influence compared to later CWG (≥ 30 weeks) (111 g vs. 39 g) and was associated with a 43% reduction in SGA risk (OR (95% CI): 0.57 (0.46–0.70). Conclusion There is a need to target women before or early in pregnancy to ensure adequate nutrition to maximize impact on fetal growth and birth size. Trial Registration ClinicalTrials.gov, NCT01665378 PMID:28114316

  14. Timing of Gestational Weight Gain on Fetal Growth and Infant Size at Birth in Vietnam.

    PubMed

    Young, Melissa F; Hong Nguyen, Phuong; Addo, O Yaw; Pham, Hoa; Nguyen, Son; Martorell, Reynaldo; Ramakrishnan, Usha

    2017-01-01

    To examine the importance of timing of gestational weight gain during three time periods: 1: ≤ 20 weeks gestation), 2: 21-29 weeks) and 3: ≥ 30 weeks) on fetal growth and infant birth size. Study uses secondary data from the PRECONCEPT randomized controlled trial in Thai Nguyen province, Vietnam (n = 1436). Prospective data were collected on women starting pre-pregnancy through delivery. Maternal conditional weight gain (CWG) was defined as window-specific weight gains, uncorrelated with pre-pregnancy body mass index and all prior body weights. Fetal biometry, was assessed by ultrasound measurements of head and abdomen circumferences, biparietal diameter, and femoral length throughout pregnancy. Birth size outcomes included weight and length, and head, abdomen and mid upper arm circumferences as well as small for gestational age (SGA). Adjusted generalized linear and logistic models were used to examine associations. Overall, three-quarters of women gained below the Institute of Medicine guidelines, and these women were 2.5 times more likely to give birth to a SGA infant. Maternal CWG in the first window (≤ 20 weeks), followed by 21-29 weeks, had the greatest association on all parameters of fetal growth (except abdomen circumference) and infant size at birth. For birth weight, a 1 SD increase CWG in the first 20 weeks had 3 times the influence compared to later CWG (≥ 30 weeks) (111 g vs. 39 g) and was associated with a 43% reduction in SGA risk (OR (95% CI): 0.57 (0.46-0.70). There is a need to target women before or early in pregnancy to ensure adequate nutrition to maximize impact on fetal growth and birth size. ClinicalTrials.gov, NCT01665378.

  15. Prenatal Exposure to Traffic-Related Air Pollution and Ultrasound Measures of Fetal Growth in the INMA Sabadell Cohort

    PubMed Central

    Aguilera, Inmaculada; Garcia-Esteban, Raquel; Iñiguez, Carmen; Nieuwenhuijsen, Mark J.; Rodríguez, Àgueda; Paez, Montserrat; Ballester, Ferran; Sunyer, Jordi

    2010-01-01

    Background Few studies have used longitudinal ultrasound measurements to assess the effect of traffic-related air pollution on fetal growth. Objective We examined the relationship between exposure to nitrogen dioxide (NO2) and aromatic hydrocarbons [benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX)] on fetal growth assessed by 1,692 ultrasound measurements among 562 pregnant women from the Sabadell cohort of the Spanish INMA (Environment and Childhood) study. Methods We used temporally adjusted land-use regression models to estimate exposures to NO2 and BTEX. We fitted mixed-effects models to estimate longitudinal growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW). Unconditional and conditional SD scores were calculated at 12, 20, and 32 weeks of gestation. Sensitivity analyses were performed considering time–activity patterns during pregnancy. Results Exposure to BTEX from early pregnancy was negatively associated with growth in BPD during weeks 20–32. None of the other fetal growth parameters were associated with exposure to air pollution during pregnancy. When considering only women who spent < 2 hr/day in nonresidential outdoor locations, effect estimates were stronger and statistically significant for the association between NO2 and growth in HC during weeks 12–20 and growth in AC, BPD, and EFW during weeks 20–32. Conclusions Our results lend some support to an effect of exposure to traffic-related air pollutants from early pregnancy on fetal growth during mid-pregnancy. PMID:20103496

  16. The association of indicators of fetal growth with visual acuity and hearing among conscripts.

    PubMed

    Olsen, J; Sørensen, H T; Steffensen, F H; Sabroe, S; Gillman, M W; Fischer, P; Rothman, K J

    2001-03-01

    Impaired fetal growth is associated with increased susceptibility to several chronic diseases. We studied the association between birth weight, indicators of disproportional fetal growth, and impaired visual acuity and hearing in 4,300 conscripts from a well-defined region in Denmark from August 1, 1993, to July 31, 1994. From the standard health examination for conscripts, we obtained data on sight based on the Snellen's chart and data on hearing acuity based on audiometry. By means of record linkage, we obtained data on outcomes for the conscripts at birth from the Medical Birth Registry. From this registry, we have data on birth weight, gestational age, and birth length that were recorded from existing computerized registers based on the records of midwives. A birth weight of less than 3,000 gm and a body mass index at birth of less than 3.4 were associated with reduced visual acuity and impaired hearing. The results could be due to fetal brain programming or due to confounding, by early birth trauma or other factors.

  17. Sudden Unexpected Death in Fetal Life Through Early Childhood

    PubMed Central

    Kinney, Hannah C.; Willinger, Marian

    2016-01-01

    In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

  18. The effects of own fetal growth on reported hypertension in parous women aged 33.

    PubMed

    Hennessy, E; Alberman, E

    1997-06-01

    Data from the study of the British 1958 birth cohort, National Child Development Study (NCDS), has allowed wider investigation of the relationship between retarded fetal growth and risk of adult hypertension. A history of self-reported hypertension was related to fetal growth in 3308 parous cohort members. Fetal growth, the measure used, is the difference in actual birthweight from that expected for the gestational age and subsequent adult height. The relationships were investigated both linearly and non-linearly adjusting for potential confounders. After adjustment for confounding factors, including adult weight for height, retarded fetal growth was associated with reported hypertension particularly when not confined to pregnancy. The latter was also associated with accelerated fetal growth, moderate or severe hypertension in the mother when pregnant with the cohort member, being relatively taller than your mother, and lack of educational qualifications. Hypertension confined to pregnancy was more likely among women who were themselves firstborn or older at childbirth. Neither maternal smoking during cohort's gestation nor cohort member's gestational age had a significant effect. The results are consistent with previous reports that fetal growth effects are less marked if gestation is short. The relationships between fetal growth and subsequent hypertension are extremely complex and variable, and need to be studied allowing for deviations from growth potential. Adult weight for height remains the strongest predictor of hypertension. The results suggest that losing weight is likely to have the same proportional benefit in women with and without a history of retarded fetal growth.

  19. Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats.

    PubMed

    Yang, Yuxian; Fan, Xiaorong; Tao, Jianying; Xu, Ting; Zhang, Yingying; Zhang, Wenna; Li, Lingjun; Li, Xiang; Ding, Hongmei; Sun, Miao; Gao, Qinqin; Xu, Zhice

    2018-03-07

    Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling. The results indicated prenatal hypoxia not only delayed fetal skeletal growth, but also increased OVX-induced osteoporosis in the elder offspring probably through down-regulated IGF1 signaling and inhibition of ECM synthesis, providing important information of prenatal hypoxia on functional and molecular bone growth and metabolism in fetal and offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. A neonate with intestinal volvulus without malrotation exhibiting early jaundice with a suspected fetal onset.

    PubMed

    Hara, Kaori; Kinoshita, Mari; Kin, Takane; Arimitsu, Takeshi; Matsuzaki, Yohei; Ikeda, Kazushige; Tomita, Hiroshi; Fujino, Akihiro; Kuroda, Tatsuo

    2015-01-01

    Intestinal volvulus without malrotation is a rare disease that causes volvulus of the small intestine despite normal intestinal rotation and fixation. We encountered a neonate with this disease who developed early jaundice and was suspected to have a fetal onset. This patient was characterized by early jaundice complicating intestinal volvulus without malrotation and is considered to have exhibited reduced fetal movement and early jaundice as a result of volvulus, necrosis, and hemorrhage of the small intestine in the fetal period. If abdominal distention accompanied by early jaundice is noted in a neonate, intestinal volvulus without malrotation and associated intraabdominal hemorrhage should be suspected and promptly treated.

  1. Brief Report: A Preliminary Study of Fetal Head Circumference Growth in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Whitehouse, Andrew J. O.; Hickey, Martha; Stanley, Fiona J.; Newnham, John P.; Pennell, Craig E.

    2011-01-01

    Fetal head circumference (HC) growth was examined prospectively in children with autism spectrum disorder (ASD). ASD participants (N = 14) were each matched with four control participants (N = 56) on a range of parameters known to influence fetal growth. HC was measured using ultrasonography at approximately 18 weeks gestation and again at birth…

  2. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction.

    EPA Science Inventory

    Fetal growth restriction is a major underlying cause of infant mortality worldwide. Unfortunately little is known about the mechanisms that drive compromised growth and the role of placental maladaptation on fetal development. In the current study placentas from male and female r...

  3. Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

    PubMed Central

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

  4. Fetal Growth and Childhood Cancer: A Population-Based Study

    PubMed Central

    Sørensen, Henrik Toft; Grotmol, Tom; Engeland, Anders; Stephansson, Olof; Gissler, Mika; Tretli, Steinar; Troisi, Rebecca

    2013-01-01

    OBJECTIVE: The etiology of childhood cancers is largely unknown. Studies have suggested that birth characteristics may be associated with risk. Our goal was to evaluate the risk of childhood cancers in relation to fetal growth. METHODS: We conducted a case-control study nested within Nordic birth registries. The study included cancer cases diagnosed in Denmark, Finland, Norway, and Sweden among children born from 1967 to 2010 and up to 10 matched controls per case, totaling 17 698 cases and 172 422 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived from conditional logistic regression. RESULTS: Risks of all childhood cancers increased with increasing birth weight (Ptrend ≤ .001). Risks of acute lymphoid leukemia and Wilms tumor were elevated when birth weight was >4000 g and of central nervous system tumors when birth weight was >4500 g. Newborns large for gestational age were at increased risk of Wilms tumor (OR: 2.1 [95% CI: 1.2–3.6]) and connective/soft tissue tumors (OR: 2.1 [95% CI: 1.1–4.4]). In contrast, the risk of acute myeloid leukemia was increased among children born small for gestational age (OR: 1.8 [95% CI: 1.1–3.1]). Children diagnosed with central nervous system tumors at <1 year of age had elevated risk with increasing head circumference (Ptrend < .001). Those with head circumference >39 cm had the highest risk (OR: 4.7 [95% CI: 2.5–8.7]). CONCLUSIONS: In this large, Nordic population-based study, increased risks for several childhood tumors were associated with measures of fetal growth, supporting the hypothesis that tumorigenesis manifesting in childhood is initiated in utero. PMID:24167169

  5. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction

    EPA Science Inventory

    Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularl...

  6. Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy.

    PubMed

    McCowan, Lesley M; Figueras, Francesc; Anderson, Ngaire H

    2018-02-01

    Small for gestational age is usually defined as an infant with a birthweight <10th centile for a population or customized standard. Fetal growth restriction refers to a fetus that has failed to reach its biological growth potential because of placental dysfunction. Small-for-gestational-age babies make up 28-45% of nonanomalous stillbirths, and have a higher chance of neurodevelopmental delay, childhood and adult obesity, and metabolic disease. The majority of small-for-gestational-age babies are not recognized before birth. Improved identification, accompanied by surveillance and timely delivery, is associated with reduction in small-for-gestational-age stillbirths. Internationally and regionally, detection of small for gestational age and management of fetal growth problems vary considerably. The aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines; and identify future research priorities in this field. A search of MEDLINE, Google, and the International Guideline Library identified 6 national guidelines on management of pregnancies complicated by fetal growth restriction/small for gestational age published from 2010 onwards. There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency. All highlight the importance of smoking cessation to prevent small for gestational age. While there is consensus in recommending fundal height measurement in the third trimester, 3 specify the use of a customized growth chart, while 2 recommend McDonald rule. Routine third-trimester scanning is not recommended for small-for-gestational-age screening, while women with major risk factors should have serial scanning in the third

  7. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

    PubMed Central

    Brown, Laura D.

    2014-01-01

    Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present for the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts development of muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or “catch up” postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts towards improving muscle growth early in life in order to prevent the development of chronic metabolic disease later in life. PMID:24532817

  8. Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep.

    PubMed

    Li, S; Sloboda, D M; Moss, T J M; Nitsos, I; Polglase, G R; Doherty, D A; Newnham, J P; Challis, J R G; Braun, T

    2013-04-01

    Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

  9. Fetal growth and perinatal outcome of pregnancies continuing after threatened abortion.

    PubMed

    Das, A G; Gopalan, S; Dhaliwal, L K

    1996-05-01

    The present study was conducted with the aim to find out the effect of threatened abortion in the current pregnancy on the subsequent perinatal outcome and follow the growth pattern of the fetuses of such complicated pregnancies. The study group consisted of 55 women with threatened abortion and 55 women with normal pregnancies formed the control group. Most of the patients presented at 6-12 weeks' gestation. The fetal growth was monitored by both clinical as well as ultrasound (USG) parameters. The mean growth rates were almost identical throughout gestation. The mean values of each parameter of the study group were found lying with 95% confidence limit values of their control group. The apparent increased incidence of low lying placenta in early pregnancy probably contributed to threatened abortion. There was no significant difference in preterm delivery, low birth-weight and overall perinatal outcome.

  10. Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas.

    PubMed

    Chen, Xiaochuan; Rozance, Paul J; Hay, William W; Limesand, Sean W

    2012-05-01

    Placental insufficiency results in intrauterine growth restriction (IUGR), impaired fetal insulin secretion and less fetal pancreatic β-cell mass, partly due to lower β-cell proliferation rates. Insulin-like growth factors (IGFs) and fibroblast growth factors (FGFs) regulate fetal β-cell proliferation and pancreas development, along with transcription factors, such as pancreatic and duodenal homeobox 1 (PDX-1). We determined expression levels for these growth factors, their receptors and IGF binding proteins in ovine fetal pancreas and isolated islets. In the IUGR pancreas, relative mRNA expression levels of IGF-I, PDX-1, FGF7 and FGFR2IIIb were 64% (P < 0.01), 76% (P < 0.05), 76% (P < 0.05) and 52% (P < 0.01) lower, respectively, compared with control fetuses. Conversely, insulin-like growth factor binding protein 2 (IGFBP-2) mRNA and protein concentrations were 2.25- and 1.2-fold greater (P < 0.05) in the IUGR pancreas compared with controls. In isolated islets from IUGR fetuses, IGF-II and IGFBP-2 mRNA concentrations were 1.5- and 3.7-fold greater (P < 0.05), and insulin mRNA was 56% less (P < 0.05) than control islets. The growth factor expression profiles for IGF and FGF signaling pathways indicate that declines in β-cell mass are due to decreased growth factor signals for both pancreatic progenitor epithelial cell and mature β-cell replication.

  11. Sildenafil citrate and uteroplacental perfusion in fetal growth restriction

    PubMed Central

    Dastjerdi, Marzieh Vahid; Hosseini, Sayedehafagh; Bayani, Leila

    2012-01-01

    Background: To determine whether the phosphodiesterase type 5 inhibitor, Sildenafil citrate, affects uteroplacental perfusion. Materials and Methods: Based on a randomized double-blinded and placebo-controlled trial, forty one pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were evaluated for the effect of a single dose of Sildenafil citrate on uteroplacental circulation as determined by Doppler ultrasound study of the umbilical and middle cerebral arteries. Statistical analysis included χ2-test to compare proportions, and independent-samples t-test and paired student's t-test to compare continuous variables. Results: Sildenafil group fetuses demonstrated a significant decrease in systolic/diastolic ratios (0.60 [SD 0.40] [95% Cl 0.37-0.84], P=0.000), and pulsatility index (0.12 [SD 0.15] [95% Cl 0.02-0.22], P=0.019) for the umbilical artery and a significant increase in middle cerebral artery pulsatility index (MCA PI) (0.51 [SD 0.60] [95% Cl 0.16-0.85], P=0.008). Conclusion: Doppler velocimetry index values reflect decreased placental bed vascular resistance after Sildenafil. Sildenafil citrate can improve fetoplacental perfusion in pregnancies complicated by intrauterine growth restriction. It could be a potential therapeutic strategy to improve uteroplacental blood flow in pregnancies with fetal growth restriction (FGR). PMID:23798922

  12. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome.

    PubMed

    Kramer, M S; Olivier, M; McLean, F H; Willis, D M; Usher, R H

    1990-11-01

    Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios

    PubMed Central

    Choudhary, Rana; Desai, Kavita; Parekh, Hetal; Ganla, Kedar

    2016-01-01

    Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course. PMID:27563258

  14. Fetal monitoring indications for delivery and 2-year outcome in 310 infants with fetal growth restriction delivered before 32 weeks' gestation in the TRUFFLE study.

    PubMed

    Visser, G H A; Bilardo, C M; Derks, J B; Ferrazzi, E; Fratelli, N; Frusca, T; Ganzevoort, W; Lees, C C; Napolitano, R; Todros, T; Wolf, H; Hecher, K

    2017-09-01

    In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR) short-term variation (STV) on cardiotocography (CTG); (2) early changes in fetal ductus venosus (DV) waveform (DV-p95); and (3) late changes in fetal DV waveform (DV-no-A). However, many infants per monitoring protocol were delivered because of safety-net criteria, for maternal or other fetal indications, or after 32 weeks of gestation when the protocol was no longer applied. The objective of the present posthoc subanalysis was to investigate the indications for delivery in relation to 2-year outcome in infants delivered before 32 weeks to further refine management proposals. We included all 310 cases of the TRUFFLE study with known outcome at 2 years' corrected age and seven fetal deaths, excluding seven cases with inevitable perinatal death. Data were analyzed according to the allocated fetal monitoring strategy in combination with the indication for delivery. Overall, only 32% of liveborn infants were delivered according to the specified monitoring parameter for indication for delivery; 38% were delivered because of safety-net criteria, 15% for other fetal reasons and 15% for maternal reasons. In the CTG-STV group, 51% of infants were delivered because of reduced STV. In the DV-p95 group, 34% of infants were delivered because of abnormal DV and, in the DV-no-A group, only 10% of infants were delivered accordingly. The majority of infants in the DV groups were delivered for the safety-net criterion of spontaneous decelerations in FHR. Two-year intact survival was highest in the DV groups combined compared with the CTG-STV group (P = 0.05 for live births only, P = 0.21 including fetal death), with no difference between DV groups. A poorer outcome in the CTG-STV group was restricted to

  15. Normal ultrasonic fetal growth ratios evaluated in cases of fetal disproportion.

    PubMed

    Crang-Svalenius, E; Jörgensen, C

    1991-02-01

    During a 2-year period, 5476 normal routine obstetrical ultrasound investigations were performed in the 2nd trimester (16th to 20th week). Data on biparietal diameter (BPD), abdominal diameter (AD) and femur length (FL) have been obtained from this material. Ratios between BPD/AD and BPD/FL have been calculated, and from these ratios, graphs were constructed. Only nine normal fetuses (0.2%) were found to be outside mean +/- 3 SD, and none of the normal cases were +/- 4 SD, so this is perhaps a better guideline for those warranting further investigation. To evaluate if these ratios could better reflect disproportional fetal growth, three cases of triploidy and four cases of dwarfism were tested against these ratios. Triploidy was obvious on the BPD/AD graph and dwarfism on the BPD/FL graph. The ratios were not found to be conclusive in the intrauterine diagnosis of trisomy 21 or of trisomy 18, as only 4 of 17 cases were obvious on the graphs.

  16. Advances in early fetal loss research: importance for risk assessment.

    PubMed Central

    Sweeney, A M; LaPorte, R E

    1991-01-01

    The assessment of early fetal losses (EFLs) in relationship to environmental agents offers unique advantages compared to other end points for hazard assessment. There is a high incidence (greater than 20% of all pregnancies end in an EFL), and the interval between exposure and end point is the short duration between conception and event, i.e., approximately 12 weeks. In contrast, cancer, which is the primary end point evaluated in risk assessment models, occurs with much lower frequency, and the latency period is measured in years or decades. EFLs have not been used effectively for risk assessment because most of the events are not detected. Prospective studies provide the only approach whereby it is possible to link exposure to EFLs. Recent methodologic advancements have demonstrated that it is now possible to conduct population-based studies of EFLs. It is likely that EFLs could serve as sentinels to monitor adverse health effects of many potential environmental hazards. The methodology will be demonstrated using lead exposure in utero as an example. PMID:2050056

  17. [The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

    PubMed

    Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

    2014-06-01

    Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

  18. Physiological alterations associated with intrauterine growth restriction in fetal pigs: Causes and insights for nutritional optimization.

    PubMed

    Wang, Junjun; Feng, Cuiping; Liu, Ting; Shi, Meng; Wu, Guoyao; Bazer, Fuller W

    2017-09-01

    Intrauterine growth restriction (IUGR) remains a major problem in swine production since the associated low birth weight leads to high rates of pre-weaning morbidity and mortality plus permanent retardation of growth and development. Complex biological events-including genetics, epigenetics, maternal maturity, maternal nutrition, placenta efficiency, uterine capacity, and other environmental factors-can affect fetal growth and development during late gestation, as well as maturity of oocytes, duration of estrus, and both implantation and placentation of conceptuses in uteri of sows. Understanding the physiological changes related to initiation and progress of IUGR are, therefore, of great importance to formulate nutritional strategies that can mitigate IUGR in gilts and sows. Altering the nutritional status of sows prior to mating and during early-, mid-, and late-gestation may be effective at increasing the uniformity of oocytes and conceptuses, decreasing variation among conceptuses during elongation and implantation, and preventing increases in within-litter variation in fetal weights during late gestation. This review summarizes current progress on physiological alterations responsible for IUGR fetuses, as well as possible nutritional interventions to prevent the initiation and continuation of IUGR in gilts and sows. © 2017 Wiley Periodicals, Inc.

  19. Arterial stiffness and fetal growth in normotensive pregnancy.

    PubMed

    Elvan-Taspinar, Ayten; Franx, Arie; Bots, Michiel L; Koomans, Hein A; Bruinse, Hein W

    2005-03-01

    Normal pregnancy is characterized by a decrease in peripheral resistance and generalized vasodilation resulting in plasma volume expansion, which is associated with intrauterine growth. Stiffness of the arterial system may be a measure of the degree of plasma volume expansion. Pulse wave velocity (PWV), measured by applanation tonometry, is a validated approach to determine arterial stiffness. Pulse pressure (PP) is considered a surrogate measure for arterial stiffness. The aim of this study was to evaluate the association between arterial stiffness and fetal growth. In 50 normotensive pregnancies, carotid-femoral PWV was measured in the third trimester in 30 degrees lateral position. Blood pressure measurements were performed with conventional auscultatory sphygmomanometry. Birth weight centiles and weight centiles at the age of 6 months were recorded. Linear regression models were used for statistical analyses. There was a significant relationship in PWV with both birth weight centiles and catch-up growth after birth, independent of mean arterial pressure (MAP). An increase of 1 m/sec in PWV was associated with a decrease in birth weight centiles by 17.6% and a catch-up of 22.3% in weight centiles after birth. A stronger association was found for pulse pressure and birth weight centiles. An increase of 1 mm Hg was associated with a decrease in birth weight centiles by 1.8%. There was no association between MAP and birth weight centiles. In normotensive pregnancy arterial stiffness is associated with birth weight centile and catch-up growth after birth, independently from MAP. This suggests that arterial stiffness reflects maternal vascular adaptation to pregnancy better than blood pressure.

  20. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    PubMed

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 *throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cognitive ability in adolescents born small for gestational age: Associations with fetal growth velocity, head circumference and postnatal growth.

    PubMed

    Jensen, Rikke Beck; Juul, Anders; Larsen, Torben; Mortensen, Erik Lykke; Greisen, Gorm

    2015-12-01

    Small size at birth may be associated with impaired cognitive ability later in life. The aim of this study was to examine the effect of being born small for gestational age (SGA), with or without intrauterine growth restriction (IUGR) on cognitive ability in late adolescence. A follow-up study of a former cohort included 123 participants (52 males); 47 born SGA and 76 born appropriate for gestational age (AGA). Fetal growth velocity (FGV) was determined by serial ultrasound measurements during the third trimester. A control group matched for age and birthplace was included. The original Wechsler Adult Intelligence Scale (WAIS) was administered, and verbal, performance and full-scale Intelligence Quotient (IQ) scores were calculated. There was no difference in IQ between adolescents born SGA and AGA. FGV or IUGR during the third trimester did not influence cognitive ability in late adolescence. Full-scale IQ was positively related to head circumference (HC) in adolescence (B: 1.30, 95% CI: 0.32-2.28, p=0.01). HC at birth and three months was positively associated with full-scale IQ. Catch-up growth in the group of SGA children was associated with a significantly increased height, larger HC, increased levels of insulin-like growth factor-I (IGF-I) and increased full-scale IQ compared to those born SGA without catch-up growth. SGA and IUGR may not be harmful for adult cognitive ability, at least not in individuals born at near-term. However, known risk factors of impaired fetal growth may explain the link between early growth and cognitive ability in adulthood. Copyright © 2015. Published by Elsevier Ireland Ltd.

  2. The effect of placenta previa on fetal growth and pregnancy outcome, in correlation with placental pathology.

    PubMed

    Weiner, E; Miremberg, H; Grinstein, E; Mizrachi, Y; Schreiber, L; Bar, J; Kovo, M

    2016-12-01

    To compare the clinical characteristics and placental histopathology between pregnancies complicated by placenta previa and controls. Between 2009 and 2015, cesarean deliveries (CDs) of 119 pregnancies with placenta previa were identified from which maternal outcomes, neonatal outcomes and placental pathology were reviewed. Results were compared with CDs matched for maternal age and pregnancy complications (control group, n=119). Placental lesions were classified into maternal and fetal vascular supply lesions and inflammatory response. Composite neonatal outcome was defined as one or more of early neonatal complications. Small-for-gestational age (SGA) was defined as birth weight ⩽10th percentile. Placentas from the previa group had higher rates of weights <10th percentile (P<0.001) and of maternal and fetal vascular supply lesions (P<0.001, for both). Higher rate of SGA (P=0.003) and worse composite neonatal outcome (P<0.001) were also observed in the previa group as compared with controls. After controlling for potential confounding bias using multivariable logistic regression models, placenta previa remained statistically significantly associated with placental maternal (adjusted odds ratio (aOR) 2.48, 95% confidence interval (CI) 1.2-4.9, P=0.009) and fetal (aOR 7.05, 95% CI 2.4-20.2, P<0.001) vascular supply lesions, SGA (aOR 10, 95% CI 2.3-44.2, P=0.002) and adverse neonatal outcome (aOR 6.87, 95% CI 2.9-11.8, P<0.001). More placental vascular supply lesions, higher rate of SGA and worse neonatal outcome characterized pregnancies with placenta previa in the current study. These findings may suggest that abnormal placentation is accompanied by suboptimal implantation that interferes with fetal growth.

  3. Pregnancy outcome and placental findings in pregnancies complicated by fetal growth restriction with and without preeclampsia.

    PubMed

    Kovo, Michal; Schreiber, Letizia; Elyashiv, Osnat; Ben-Haroush, Avi; Abraham, Golan; Bar, Jacob

    2015-03-01

    To compare pregnancy outcome and placental pathology in pregnancies complicated by fetal growth restriction (FGR) with and without preeclampsia. Labor, fetal/neonatal outcome, and placental pathology parameters from neonates with a birth weight below the 10 th percentile (FGR), born between 24 and 42 weeks of gestation, were reviewed. Results were compared between pregnancies complicated with preeclampsia (hypertensive FGR [H-FGR]) to those without preeclampsia (normotensive FGR [N-FGR]). Composite neonatal outcome, defined as 1 or more of early complication (respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy, or death), Apgar score ≤ 7 at 5 minutes, and days of hospitalization, were compared between the groups. Placental lesions, classified as lesions related to maternal vascular supply, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions, maternal inflammatory response, and fetal inflammatory response, were also compared. Women in the H-FGR group (n = 72) were older, with higher body mass index (BMI) and higher rate of preterm labor (<34 weeks) than in the N-FGR group (n = 270), P < .001 for all. Composite neonatal outcome was worse in the H-FGR than in the N-FGR group, 50% versus 15.5%, P < .001. Higher rate of maternal placental vascular lesions was detected in H-FGR compared with N-FGR, 82% versus 57.7%, P < .001. Using a stepwise logistic regression model, maternal BMI (1.13 odds ratio [OR], confidence interval [CI] 1.035-1.227, P = .006) and neonatal birth weight (0.996 OR, CI 0.995-0.998, P < .001) were independently associated with worse neonatal outcome. Worse neonatal outcome and more maternal placental vascular lesions in pregnancy complicated by FGR with preeclampsia versus FGR without preeclampsia suggest different pathophysiology in these entities. © The Author(s) 2014.

  4. Fetal growth, cognitive function, and brain volumes in childhood and adolescence.

    PubMed

    Rogne, Tormod; Engstrøm, Andreas Aass; Jacobsen, Geir Wenberg; Skranes, Jon; Østgård, Heidi Furre; Martinussen, Marit

    2015-03-01

    To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years. Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25-37, SGA neonates were classified with fetal growth restriction (n=13) or non-fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years. Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, P<.05). Although there were no differences between the SGA non-fetal growth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, P<.05) and 9 years (96.2 compared with 107.5, P<.05) compared with those in the control group. There were some brain volume differences at 15 years between SGA children and those in the control group, but after adjustment for total intracranial volume, age at examination, and sex, there were only significant differences between the SGA fetal growth restriction and control groups for thalamic (17.4 compared with 18.6 cm, P<.01) and cerebellar white matter volumes (21.5 compared with 24.3 cm, P<.01). Small-for-gestational-age children had lower intelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth. II.

  5. [Fetal growth and activity at 20 to 24 weeks of gestation (preliminary study)].

    PubMed

    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.

  6. [Role of placental apoptosis in fetal growth restriction].

    PubMed

    Liu, Yuan; Gao, Peng; Xie, Yingbo; Wang, Shuyun; Dai, Minsheng; Jiang, Sen

    2002-12-01

    To determine the relationship of placental cellular apoptosis and pathophysiology of fetal growth restriction (FGR). Placental samples were obtained from 18 pregnancies complicated by FGR and 14 normal pregnancies. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and transmission electron microscopy were used to confirm the occurrence of apoptosis. In FGR group the placental apoptosis rate was (n = 18) 12.1 per thousand, the average placental weight was (236 +/- 24) g, the average birth weight was (2,071 +/- 428) g; In normal group (n = 14), the placental apoptosis rate was 7.3 per thousand, the average placental weight was (354 +/- 63) g, the average birth weight was (3,411 +/- 588) g (P < 0.05). The incidence of apoptosis was significantly higher in placental samples from pregnancies with FGR compared with normal placental samples (P < 0.05). Under transmission election microscopy, apoptosis was obviously compact and the chromatins were formed as mass. These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of FGR.

  7. Intrauterine Growth Restriction and the Fetal Programming of the Hedonic Response to Sweet Taste in Newborn Infants

    PubMed Central

    Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C.; Silveira, Patrícia Pelufo

    2012-01-01

    Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals. PMID:22851979

  8. Intrauterine growth restriction and the fetal programming of the hedonic response to sweet taste in newborn infants.

    PubMed

    Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C; Silveira, Patrícia Pelufo

    2012-01-01

    Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.

  9. Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe.

    PubMed

    Ma, Yan; Zhu, Mei J; Zhang, Liren; Hein, Sarah M; Nathanielsz, Peter W; Ford, Stephen P

    2010-07-01

    In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were approximately 30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain.

  10. Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe

    PubMed Central

    Ma, Yan; Zhu, Mei J.; Zhang, Liren; Hein, Sarah M.; Nathanielsz, Peter W.

    2010-01-01

    In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were ∼30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain. PMID:20427725

  11. [Physiological significance of IGF-I and its binding proteins on fetal growth and maturation].

    PubMed

    Iwashita, M

    1994-08-01

    Insulin-like growth factor-I (IGF-I) is one of growth factors that circulates bound to specific, high affinity binding proteins (IGFBPs). Physiological significance of IGF-I and IGFBPs on fetal growth is investigated in this study. In mother, circulating levels of IGF-I are increased during pregnancy in which placental hormones take the place of pituitary GH to regulate IGF-I during pregnancy and correlates with fetal birth weight. IGFBPs except IGFBP-1 in the maternal circulation are markedly reduced compared to those of non pregnant women due to increased activity of protease(s) while IGFBP-1 gradually increased throughout pregnancy and negatively correlates with fetal weight. IGF-I stimulated 3H-AIB uptake and release by cultured trophoblast cells in a dose dependent manner. Furthermore, fetal growth and the transfer of 3H-AIB to fetus is inhibited when IGF-I is neutralized by polyclonal antibody. These results indicate that maternal IGF-I stimulates fetal growth by activating placental transport of nutrients to fetus. In contrast, IGFBP-1 inhibits both 125I-IGF-I binding to placental membrane and 3H-glycine uptake of trophoblast cells by IGF-I in a dose dependent manner. Moreover, fetal growth and the transfer of 3H-AIB to fetus are accelerated when IGFBP-1 is neutralized by polyclonal antibody, suggesting that maternal IGFBP-1 inhibits fetal growth by inhibiting IGF-I action on the placenta. IGF-I and four IGFBPs including IGFBP-1, -2, -3, and -4 are localized in cytotrophoblast of term placenta. Similarly IGFBP-1, -2, and -4 are detected in medium conditioned by term decidua cells by Western ligand blot in which release of IGFBP-1 and -4 are diminished by IGF-I and all three IGFBPs are increased by progesterone. Thus, there is a complicated autocrine/paracrine regulation between decidua and placenta and IGF-I action on fetal growth is presumed to be modified by this local regulation. Fetal levels of IGF-I and IGFBP-1 are positively and negatively correlate

  12. Characterization of fetal growth by repeated ultrasound measurements in the wild guinea pig (Cavia aperea).

    PubMed

    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.

  13. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

    PubMed

    Dunford, Louise J; Sinclair, Kevin D; Kwong, Wing Y; Sturrock, Craig; Clifford, Bethan L; Giles, Tom C; Gardner, David S

    2014-11-01

    This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. © FASEB.

  14. Maternal hemodynamics, fetal biometry and Dopplers in pregnancies followed up for suspected fetal growth restriction.

    PubMed

    Roberts, Llinos A; Ling, Hua Zen; Poon, Liona; Nicolaides, Kypros H; Kametas, Nikos A

    2018-04-01

    To assess whether in a cohort of patients with small for gestational age (SGA) foetuses with estimated fetal weight ≤10 th percentile, maternal hemodynamics, fetal biometry and Dopplers at presentation, can predict the subsequent development of abnormal fetal Dopplers or delivery with birthweight <3 rd percentile. The study population comprised of 86 singleton pregnancies with SGA fetuses presenting at a median gestational age of 32 (range 26-35) weeks. We measured maternal cardiac function with a non-invasive transthoracic bioreactance monitor (NICOM, Cheetah), mean arterial pressure, fetal biometry, umbilical artery (UA), middle cerebral artery (MCA) and uterine artery (UT) pulsatility index (PI) and the deepest vertical pool (DVP) of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between those with evidence of abnormal fetal Dopplers at presentation (group 1), those that developed abnormal Dopplers in subsequent visits (group 2) and those who did not develop abnormal Dopplers throughout pregnancy (group 3). Abnormal fetal Dopplers were defined as UAPI >95 th percentile, or MCA PI <5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birthweight <3 rd and ≥3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birthweight <3 rd percentile and evolution from normal fetal Dopplers to abnormal fetal Dopplers in groups 2 and 3. In the study population 14 (16%) cases were in group 1, 19 (22%) in group 2 and 53 (62%) in group 3. The birthweight was <3 rd percentile in 39 (45%) cases and ≥3 rd percentile in 47 (55%). In the study groups, compared to normal populations, there was decreased cardiac output and stroke volume and increased peripheral vascular resistance and mean arterial pressure (MAP) and the deviations from normal were most marked in group 1

  15. [A review of progress in research of effect of air pollutants on fetal growth].

    PubMed

    Wang, W Y; Zhao, R X; Guo, H; Chen, S; Zhang, W H; Yang, S L; Wang, K; Meng, Y; Huang, J; Wei, S

    2017-01-10

    Slow fetal growth is a global public health concern because it might be associated with many diseases later in life. With the progress of technology to measure long-term air pollution exposure. Many epidemiological studies have evaluated the effects of maternal air pollutant exposure on fetal growth. In this paper, we summarize the research progress in this field after the analysis on the related literatures retrieved from the databases of Medline and Web of Science.

  16. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

    PubMed

    Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

    2017-02-01

    Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

  17. L-Citrulline Supplementation Enhances Fetal Growth and Protein Synthesis in Rats with Intrauterine Growth Restriction.

    PubMed

    Bourdon, Aurélie; Parnet, Patricia; Nowak, Christel; Tran, Nhat-Thang; Winer, Norbert; Darmaun, Dominique

    2016-03-01

    Intrauterine growth restriction (IUGR) results from either maternal undernutrition or impaired placental blood flow, exposing offspring to increased perinatal mortality and a higher risk of metabolic syndrome and cardiovascular disease during adulthood. l-Citrulline is a precursor of l-arginine and nitric oxide (NO), which regulates placental blood flow. Moreover, l-citrulline stimulates protein synthesis in other models of undernutrition. The aim of the study was to determine whether l-citrulline supplementation would enhance fetal growth in a model of IUGR induced by maternal dietary protein restriction. Pregnant rats were fed either a control (20% protein) or a low-protein (LP; 4% protein) diet. LP dams were randomly allocated to drink tap water either as such or supplemented with l-citrulline (2 g · kg(-1) · d(-1)), an isonitrogenous amount of l-arginine, or nonessential l-amino acids (NEAAs). On day 21 of gestation, dams received a 2-h infusion of l-[1-(13)C]-valine until fetuses were extracted by cesarean delivery. Isotope enrichments were measured in free amino acids and fetal muscle, liver, and placenta protein by GC-mass spectrometry. Fetal weight was ∼29% lower in the LP group (3.82 ± 0.06 g) than in the control group (5.41 ± 0.10 g) (P < 0.001). Regardless of supplementation, fetal weight remained below that of control fetuses. Yet, compared with the LP group, l-citrulline and l-arginine equally increased fetal weight to 4.15 ± 0.08 g (P < 0.05) and 4.13 ± 0.1 g (P < 0.05 compared with LP), respectively, whereas NEAA did not (4.05 ± 0.05 g; P = 0.07). Fetal muscle protein fractional synthesis rate was 35% lower in the LP fetuses (41% ± 11%/d) than in the control (61% ± 13%/d) fetuses (P < 0.001) and was normalized by l-citrulline (56% ± 4%/d; P < 0.05 compared with LP, NS compared with control) and not by other supplements. Urinary nitrite and nitrate excretion was lower in the LP group (6.4 ± 0.8 μmol/d) than in the control group (17.9

  18. Socioeconomic Status Accounts for Rapidly Increasing Geographic Variation in the Incidence of Poor Fetal Growth

    PubMed Central

    Ball, Stephen J.; Jacoby, Peter; Zubrick, Stephen R.

    2013-01-01

    Fetal growth is an important risk factor for infant morbidity and mortality. In turn, socioeconomic status is a key predictor of fetal growth; however, other sociodemographic factors and environmental effects may also be important. This study modelled geographic variation in poor fetal growth after accounting for socioeconomic status, with a fixed effect for socioeconomic status and a combination of spatially-correlated and spatially-uncorrelated random effects. The dataset comprised 88,246 liveborn singletons, aggregated within suburbs in Perth, Western Australia. Low socioeconomic status was strongly associated with an increased risk of poor fetal growth. An increase in geographic variation of poor fetal growth from 1999–2001 (interquartile odds ratio among suburbs = 1.20) to 2004–2006 (interquartile odds ratio = 1.40) indicated a widening risk disparity by socioeconomic status. Low levels of residual spatial patterns strengthen the case for targeting policies and practices in areas of low socioeconomic status for improved outcomes. This study indicates an alarming increase in geographic inequalities in poor fetal growth in Perth which warrants further research into the specific aspects of socioeconomic status that act as risk factors. PMID:23799513

  19. Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1.

    PubMed

    Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W; Zita, Matteo Moretto; Parast, Mana; Shao, Jianhua

    2016-11-01

    The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Adiponectin knockout (Adipoq (-/-) ) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. The body weight of fetuses from Adipoq (-/-) dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq (-/-) dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq (-/-) and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq (-/-) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq (-/-) dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.

  20. Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

    PubMed Central

    Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W.; Moretto Zita, Matteo; Parast, Mana; Shao, Jianhua

    2016-01-01

    Aims/hypothesis The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Methods Adiponectin knockout (Adipoq−/−) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. Results The body weight of fetuses from Adipoq−/− dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq−/− dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq−/− and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq−/− dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq−/− dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. Conclusions/interpretation These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells. PMID:27495989

  1. Fetal environment and early age at natural menopause in a British birth cohort study

    PubMed Central

    Tom, Sarah E.; Cooper, Rachel; Kuh, Diana; Guralnik, Jack M.; Hardy, Rebecca; Power, Chris

    2010-01-01

    BACKGROUND Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study. METHODS Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44–45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44–45 years, with and without adjustments for confounding factors. RESULTS There was a U-shaped association between birthweight and menopausal status at 44–45 years: women at either extremes of birthweight (<2.5 and ≥4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0–3.49 kg [odds ratio (OR) = 1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44–45 years (OR for fastest quarter versus second fastest quarter = 1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives. CONCLUSIONS These findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further. PMID:20047935

  2. Gestational weight gain and fetal growth in underweight women.

    PubMed

    Zanardo, Vincenzo; Mazza, Alessandro; Parotto, Matteo; Scambia, Giovanni; Straface, Gianluca

    2016-08-05

    Despite the current obesity epidemic, maternal underweight remains a common occurrence with potential adverse perinatal outcomes. We aimed to investigate the relationship between weight gain during pregnancy, and fetal growth in underweight women with low and late fertility. Women body mass index (BMI), defined according to the World Health Organization's definition, gestational weight gain (GWG), defined by the Institute of Medicine and National Research Council and neonatal birth weight were prospectively collected at maternity ward of Policlinico Abano Terme (Italy) in 793 consecutive at term, uncomplicated deliveries. Among those, 96 (12.1 %) were categorized as underweight (BMI < 18.5 kg/m(2)), 551 (69.5 %) as normal weight, 107 (13.4 %) as overweight, and 39 (4.9 %) as obese, respectively. In all mother groups, GWG was within the range recommended by IOM 2009 guidelines. However, underweight women gained more weight in pregnancy (12.8 ± 3.9 kg) in comparison to normal weight (12.3 ± 6.7 kg) and overweight (11.0 ± 4.7 kg) women and their GWG was significantly higher (p < 0.001) with respect to obese women 5.8 ± 6.1 kg). In addition, offspring of underweight women were comparable in size at birth to offspring of normal weight women, whereas they were significantly lighter to offspring of both overweight and obese women. Pre-pregnancy underweight does not impact birth weight of healthy, term neonates in presence of normal GWG. Presumably, medical or personal efforts to reach 'optimal' GWG could be a leading choice for many women living in industrialized and in low-income countries.

  3. Maternal Lipids Are as Important as Glucose for Fetal Growth

    PubMed Central

    Kulkarni, Smita R.; Kumaran, Kalyanaraman; Rao, Shobha R.; Chougule, Suresh D.; Deokar, Tukaram M.; Bhalerao, Ankush J.; Solat, Vishnu A.; Bhat, Dattatray S.; Fall, Caroline H.D.; Yajnik, Chittaranjan S.

    2013-01-01

    OBJECTIVE To study the relationship between maternal circulating fuels and neonatal size and compare the relative effects of glucose and lipids. RESEARCH DESIGN AND METHODS The Pune Maternal Nutrition Study (1993–1996) investigated the influence of maternal nutrition on fetal growth. We measured maternal body size and glucose and lipid concentrations during pregnancy and examined their relationship with birth size in full-term babies using correlation and regression techniques. RESULTS The mothers (n = 631) were young (mean age 21 years), short (mean height 151.9 cm), and thin (BMI 18.0 kg/m2) but were relatively more adipose (body fat 21.1%). Their diet was mostly vegetarian. Between 18 and 28 weeks’ gestation, fasting glucose concentrations remained stable, whereas total cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations decreased. The mean birth weight of the offspring was 2666 g. Total cholesterol and triglycerides at both 18 and 28 weeks and plasma glucose only at 28 weeks were associated directly with birth size. One SD higher maternal fasting glucose, cholesterol, and triglyceride concentrations at 28 weeks were associated with 37, 54, and 36 g higher birth weights, respectively (P < 0.05 for all). HDL-cholesterol concentrations were unrelated to newborn measurements. The results were similar if preterm deliveries also were included in the analysis (total n = 700). CONCLUSIONS Our results suggest an influence of maternal lipids on neonatal size in addition to the well-established effect of glucose. Further research should be directed at defining the clinical relevance of these findings. PMID:23757425

  4. Brief report: a preliminary study of fetal head circumference growth in autism spectrum disorder.

    PubMed

    Whitehouse, Andrew J O; Hickey, Martha; Stanley, Fiona J; Newnham, John P; Pennell, Craig E

    2011-01-01

    Fetal head circumference (HC) growth was examined prospectively in children with autism spectrum disorder (ASD). ASD participants (N = 14) were each matched with four control participants (N = 56) on a range of parameters known to influence fetal growth. HC was measured using ultrasonography at approximately 18 weeks gestation and again at birth using a paper tape-measure. Overall body size was indexed by fetal femur-length and birth length. There was no between-groups difference in head circumference at either time-point. While a small number of children with ASD had disproportionately large head circumference relative to body size at both time-points, the between-groups difference did not reach statistical significance in this small sample. These preliminary findings suggest that further investigation of fetal growth in ASD is warranted.

  5. Assessment of Fetal Kidney Growth and Birth Weight in an Indigenous Australian Cohort.

    PubMed

    Diehm, Christopher J; Lumbers, Eugenie R; Weatherall, Loretta; Keogh, Lyniece; Eades, Sandra; Brown, Alex; Smith, Roger; Johnson, Vanessa; Pringle, Kirsty G; Rae, Kym M

    2017-01-01

    Introduction: Indigenous Australians experience higher rates of renal disease and hypertension than non-Indigenous Australians. Low birth weight is recognized as a contributing factor in chronic disease and has been shown to increase the risk of renal failure in adulthood. A smaller kidney volume with fewer nephrons places an individual at risk of hypertension and renal failure. Indigenous Australians have fewer nephrons than non-Indigenous Australians. In this study, intrauterine fetal and kidney growth were evaluated in 174 Indigenous Australian babies throughout gestation in order to record and evaluate fetal growth and kidney size, within a population that is at high risk for chronic illness. Methods: Pregnant women that identified as Indigenous, or non-Indigenous women that were pregnant with a partner who identified as an Indigenous Australian were eligible to participate. Maternal history, smoking status, blood and urine samples and fetal ultrasounds were collected throughout pregnancy. Fetal kidney measurements were collected using ultrasound. Statistical analysis was performed using the Stata 14.1 software package. Results: 15.2% of babies were born prematurely. 44% of the mothers reported smoking in pregnancy. The median birth weight of this cohort was 3,240 g. Male fetuses had higher kidney to body weight ratios than female fetuses ( P = 0.02). The birth weights of term neonates whose mothers smoked during pregnancy were lower (327 g, P < 0.001) than the birth weights of term babies from non-smoking mothers. The kidney volumes of babies whose mothers smoked were also smaller ( P = 0.02), but were in proportion to body weight. Conclusion: In this cohort of Indigenous women smoking was associated with both increased number of preterm births and with a reduction in birth weights, even of term infants. Since kidney volume is a surrogate measure of nephron number and nephrogenesis is complete at birth, babies whose mothers smoked during pregnancy must have

  6. Comparison of Fetal and Neonatal Growth Curves in Detecting Growth Restriction

    PubMed Central

    Marconi, Anna Maria; Ronzoni, Stefania; Bozzetti, Patrizia; Vailati, Simona; Morabito, Alberto; Battaglia, Frederick C

    2009-01-01

    Objective To evaluate the outcome of intrauterine growth restriction (IUGR) infants with abnormal pulsatility index of the umbilical artery according to the neonatal birth weight/gestational age standards and the intrauterine growth charts. Methods We analyzed 53 pregnancies with severe IUGR classified as Group 2 (22 IUGR: abnormal pulsatility index and normal fetal heart rate) and Group 3 (31 IUGR: abnormal pulsatility index and fetal heart rate). Neonatal birth weight/gestational age distribution, body size measurements, maternal characteristics and obstetric outcome, and neonatal major and minor morbidity and mortality were compared with those obtained in 79 singleton pregnancies with normal fetal growth and pulsatility index, matched for gestational age [appropriate for gestational age (AGA) group]. Differences were analyzed with the χ2 test and the Student’s t test. Differences between means corrected for gestational age in the different groups were assessed by analysis of covariance test. A P value <0.05 was considered significant. Results At delivery, utilizing the neonatal standards, 25/53 (47%) IUGR showed a birthweight above the 10th percentile (IUGRAGA) whereas in 28, birthweight was below the 10th percentile (IUGRSGA). All body size measurements were significantly higher in AGA than in IUGRAGA and IUGRSGA. Forty-nine out of 79 (62%) AGA and 49/53 (92%) IUGR were admitted in the neonatal intensive care unit (p<0.001). One out of 79 (1%) AGA and 6/53 (11%) IUGR newborns died within 28 days (p<0.02). Major and minor morbidity was not different. Conclusion This study shows that neonatal outcome is similar in IUGR of the same clinical severity, whether or not they could be defined AGA or SGA according to the neonatal standards. Neonatal curves are misleading in detecting low birthweight infants and should be utilized only when obstetrical data are unavailable. PMID:19037030

  7. The impact of fetal growth restriction on latency in the setting of expectant management of preeclampsia.

    PubMed

    McKinney, David; Boyd, Heather; Langager, Amanda; Oswald, Michael; Pfister, Abbey; Warshak, Carri R

    2016-03-01

    Fetal growth restriction is a common complication of preeclampsia. Expectant management for qualifying patients has been found to have acceptable maternal safety while improving neonatal outcomes. Whether fetal growth restriction influences the duration of latency during expectant management of preeclampsia is unknown. The objective of the study was to determine whether fetal growth restriction is associated with a reduced interval to delivery in women with preeclampsia being expectantly managed prior to 34 weeks. We performed a retrospective cohort of singleton, live-born, nonanomalous deliveries at the University of Cincinnati Medical Center between 2008 and 2013. Patients were included in our analysis if they were diagnosed with preeclampsia prior to 34 completed weeks and if the initial management plan was to pursue expectant management beyond administration of steroids for fetal lung maturity. Two study groups were determined based on the presence or absence of fetal growth restriction. Patients were delivered when they developed persistent neurological symptoms, severe hypertension refractory to medical therapy, renal insufficiency, nonreassuring fetal status, pulmonary edema, or hemolysis elevated liver low platelet syndrome or when they reached 37 weeks if they remained stable without any other indication for delivery. Our primary outcome was the interval from diagnosis of preeclampsia to delivery, measured in days. Secondary outcomes included indications for delivery, rates of induction and cesarean delivery, development of severe morbidities of preeclampsia, and select neonatal outcomes. We performed a multivariate logistic regression analysis comparing those with fetal growth restriction with those with normally grown fetuses to determine whether there is an association between fetal growth restriction and a shortened interval to delivery, neonatal intensive care unit admission, prolonged neonatal stay, and neonatal mortality. A total of 851 patients met

  8. An assessment of early mandibular growth.

    PubMed

    Hutchinson, E F; L'Abbé, E N; Oettlé, A C

    2012-04-10

    Quantification of skeletal data has been shown to be an effective and reliable method of demonstrating variation in human growth as well as for monitoring and interpreting growth. In South Africa as well as internationally, few researchers have assessed mandibular growth in late fetal period and early childhood and therefore standards for growth and age determination in these groups are limited. The purpose of this study was to evaluate growth in the mandible from the period of 31 gestational weeks to 36 months postnatal. A total of 74 mandibles were used. Dried mandibles were sourced from the Raymond A. Dart Collection (University of Witwatersrand), and cadaveric remains were obtained from the Universities of Pretoria and the Witwatersrand. The sample was divided into four groups; 31-40 gestational weeks (group 1), 0-11 months (group 2), 12-24 months (group 3), and 25-36 months (group 4). Twenty-one osteological landmarks were digitized using a MicroScribe G2. Ten standard measurements were created and included: the maximum length of mandible, mandibular body length and width, mandibular notch width and depth, mental foramen to inferior border of mandible, mandibular basilar widths bigonial and biantegonial, bigonial width of mental foramen and mental angle. Data were analyzed using PAST statistical software and Morphologika2 v2.5. Statistically significant differences were noted in the linear measurements for all group comparisons except between groups 3 and 4. The mandible morphologically changed from a round, smooth contour anteriorly to adopt a more sharp and narrow adult shape. A progressive increase in the depth and definition of the mandibular arch was also noted. In conclusion, the mandible initially grows to accommodate the developing tongue (up to 11 months), progressive dental eruption and mastication from 12 to 36 months. Mastication is associated with muscle mass development; this would necessitate an increase in the dimensions of the mandibular notch

  9. Reexamining the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality

    PubMed Central

    Ananth, Cande V; Platt, Robert W

    2004-01-01

    Background Low birth weight (<2,500 g) is a strong predictor of infant mortality. Yet low birth weight, in isolation, is uninformative since it is comprised of two intertwined components: preterm delivery and reduced fetal growth. Through nonparametric logistic regression models, we examine the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality. Methods We derived data on over 10 million singleton live births delivered at ≥ 24 weeks from the 1998–2000 U.S. natality data files. Nonparametric multivariable logistic regression based on generalized additive models was used to examine neonatal mortality (deaths within the first 28 days) in relation to fetal growth (gestational age-specific standardized birth weight), gestational age, and number of cigarettes smoked per day. All analyses were further adjusted for the confounding effects due to maternal age and gravidity. Results The relationship between standardized birth weight and neonatal mortality is nonlinear; mortality is high at low z-score birth weights, drops precipitously with increasing z-score birth weight, and begins to flatten for heavier infants. Gestational age is also strongly associated with mortality, with patterns similar to those of z-score birth weight. Although the direct effect of smoking on neonatal mortality is weak, its effects (on mortality) appear to be largely mediated through reduced fetal growth and, to a lesser extent, through shortened gestation. In fact, the association between smoking and reduced fetal growth gets stronger as pregnancies approach term. Conclusions Our study provides important insights regarding the combined effects of fetal growth, gestational age, and smoking on neonatal mortality. The findings suggest that the effect of maternal smoking on neonatal mortality is largely mediated through reduced fetal growth. PMID:15574192

  10. Early fetal heart ultrasonography as additional indicator for chromosomopathies.

    PubMed

    Dmitrovic, A; Jeremic, K; Babic, U M; Perovic, M; Mihailovic, T; Opric, D; Zecevic, N; Gojnić-Dugalić, M

    2016-01-01

    First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still

  11. Review: Adiponectin – The Missing Link between Maternal Adiposity, Placental Transport and Fetal Growth?

    PubMed Central

    Aye, Irving L. M. H.; Powell, Theresa L.; Jansson, Thomas

    2012-01-01

    Adiponectin has well-established insulin-sensitizing effects in non-pregnant individuals. Pregnant women who are obese or have gestational diabetes typically have low circulating levels of adiponectin, which is associated with increased fetal growth. Lean women, on the other hand, have high circulating levels of adiponectin. As a result, maternal serum adiponectin is inversely correlated to fetal growth across the full range of birth weights, suggesting that maternal adiponectin may limit fetal growth. In the mother, adiponectin is predicted to promote insulin sensitivity and stimulate glucose uptake in maternal skeletal muscle thereby reducing nutrient availability for placental transfer. Adiponectin prevents insulin-stimulated amino acid uptake in cultured primary human trophoblast cells by modulating insulin receptor substrate phosphorylation. Furthermore, chronic administration of adiponectin to pregnant mice inhibits placental insulin and mammalian target of rapamycin complex 1 (mTORC1) signaling, down-regulates the activity and expression of key placental nutrient transporters and decreases fetal growth. Preliminary findings indicate that adiponectin binds to the adiponectin receptor-2 on the trophoblast cell and activates p38 MAPK and PPAR-α, which inhibits the insulin/IGF-1 signaling pathway. In contrast to maternal adiponectin, recent reports suggest that fetal adiponectin may promote expansion of adipose tissue and stimulate fetal growth. Regulation of placental function by adiponectin constitutes a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth. These findings may help us better understand the factors determining birth weight in normal pregnancies and in pregnancy complications associated with altered maternal adiponectin levels such as obesity and gestational diabetes. PMID:23245987

  12. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.

    PubMed

    Wang, Kimberley C W; Zhang, Lei; McMillen, I Caroline; Botting, Kimberley J; Duffield, Jaime A; Zhang, Song; Suter, Catherine M; Brooks, Doug A; Morrison, Janna L

    2011-10-01

    Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

  13. Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

    PubMed

    Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

    2014-08-25

    Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. [Peruvian newborn fetal growth according to its sex, geographical area, and maternal parity and height].

    PubMed

    Rendón, Manuel Ticona; Apaza, Diana Huanco

    2008-09-01

    Birth weight is the most important indicator of fetal growth, fetal development, and nutritional estate of newborn, and several factors affect it. To know the fetal growth of Peruvian newborns according to fetal sex, maternal parity and height, and geographical area. Prospective and cross sectional study. Successive newborn data of 29 hospitals of Ministerio de Salud del Peru was obtained during 2005 year, all of them without intrauterine growth delay. Student ttest was used to compare: male and female, primiparous and multiparous, and coast, mountain, and rainforest newborn average weight (meaningful difference: p < 0.05). Maternal height was related to newborn weight, height, cephalic perimeter, and gestational age. From 50,568 selected alive newborns, male had an average weight from 19 to 41 g higher than female, and multiparous newborns had from 22 to 53 g more than primiparous newborns. Maternal height has a direct connection with newborn weight, height, and cephalic perimeter. Coast newborns had an average weight from 133 to 210 g higher than those from mountain, and from 76 to 142 g higher than those from rainforest; average weight of rainforest newborns was from 19 to 83 g higher to those from mountain. Weight differences due to fetal sex, maternal parity and height, and geographic region were meaningful among 36 to 42 weeks of gestation. Fetal sex, maternal parity and height, and geographical region affect newborn weight. It is recommended to use weight and gestational age as correction factors to appropriately classify Peruvian newborns.

  15. Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development.

    PubMed

    Conover, Cheryl A; Bale, Laurie K; Overgaard, Michael T; Johnstone, Edward W; Laursen, Ulla H; Füchtbauer, Ernst-Martin; Oxvig, Claus; van Deursen, Jan

    2004-03-01

    Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting. Mice homozygous for targeted disruption of the PAPPA gene were viable but 60% the size of wild-type littermates at birth. The impact of the mutation was exerted during the early embryonic period prior to organogenesis, resulting in proportional dwarfism. PAPPA, IGF2 and IGFBP4 transcripts co-localized in wild-type embryos, and expression of IGF2 and IGFBP4 mRNA was not altered in PAPPA-deficient embryos. However, IGFBP4 proteolytic activity was completely lacking in fibroblasts derived from PAPPA-deficient embryos, and IGFBP4 effectively inhibited IGF-stimulated mitogenesis in these cells. These results provide the first direct evidence that PAPPA is an essential growth regulatory factor in vivo, and suggest a novel mechanism for regulated IGF bioavailability during early fetal development.

  16. Glucocorticoid-induced changes in glucocorticoid receptor mRNA and protein expression in the human placenta as a potential factor for altering fetal growth and development.

    PubMed

    Bivol, Svetlana; Owen, Suzzanne J; Rose'Meyer, Roselyn B

    2016-02-05

    Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth.

  17. Preliminary analysis of in utero low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports.

    PubMed

    Davis, Matthew A; Higgins, John; Li, Zhigang; Gilbert-Diamond, Diane; Baker, Emily R; Das, Amar; Karagas, Margaret R

    2015-03-30

    Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value < 0.05). Although, associations were attenuated in adjusted analyses - among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: -0.151, 0.007) decrease in biparietal head diameter Z-score. Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation.

  18. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.

    PubMed

    Roberge, Stéphanie; Nicolaides, Kypros; Demers, Suzanne; Hyett, Jon; Chaillet, Nils; Bujold, Emmanuel

    2017-02-01

    . Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66-0.99; P = .04) without relationship with aspirin dosage (R 2 , 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64-1.14; P = .28; R 2 , 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86-1.05; P = .34; R 2 , not available; P = .563). Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose-response effect. Low-dose aspirin initiated at >16 weeks' gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

    PubMed Central

    Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

    2012-01-01

    Background Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. Conclusions/Significance Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes. PMID:23152876

  20. In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

    USDA-ARS?s Scientific Manuscript database

    Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

  1. Fetal growth restriction promotes physical inactivity and obesity in female mice.

    PubMed

    Baker, M S; Li, G; Kohorst, J J; Waterland, R A

    2015-01-01

    Environmental exposures during critical periods of prenatal and early postnatal life affect the development of mammalian body weight regulatory mechanisms, influencing lifelong risk of obesity. The specific biological processes that mediate the persistence of such effects, however, remain poorly understood. The objectives of this study were to determine the developmental timing and physiological basis of the obesity-promoting effect previously reported in offspring of obese agouti viable yellow (A(vy)/a) mothers. Newborn offspring of obese A(vy)/a and lean (a/a) mothers were cross-fostered shortly after birth to study separately the effects of in utero or suckling period exposure to A(vy)/a dams. Body composition, food intake, physical activity and energy expenditure were measured in offspring shortly after weaning and in adulthood. Offspring of obese A(vy)/a dams paradoxically experienced fetal growth restriction, which was followed by adult-onset obesity specifically in females. Our main analyses focused on wild-type (a/a) offspring, because a subset of adult A(vy)/a offspring contracted a kidney disease resembling diabetic nephropathy. Detailed physiological characterization demonstrated that, both shortly after weaning and in adulthood, female wild-type mice born to A(vy)/a mothers are not hyperphagic but have reduced physical activity and energy expenditure. No such coordinated changes were detected in male offspring. Mediational regression analysis of our longitudinal data supported a causal pathway in which fetal growth restriction persistently reduces physical activity, leading to adult obesity. Our data are consistent with several recent human epidemiological studies showing female-specific effects of perinatal nutritional restriction on later obesity, and provide the novel mechanistic insight that this may occur via permanent and sex-specific changes in one's inherent propensity for physical activity.

  2. Early stages of zeolite growth

    NASA Astrophysics Data System (ADS)

    Kumar, Sandeep

    Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

  3. Ultrasonographic evaluation of equine fetal growth throughout gestation in normal mares using a convex transducer.

    PubMed

    Murase, Harutaka; Endo, Yoshiro; Tsuchiya, Takeru; Kotoyori, Yasumitsu; Shikichi, Mitsumori; Ito, Katsumi; Sato, Fumio; Nambo, Yasuo

    2014-07-01

    It has not been common to perform regular ultrasound examination of the fetus in equine practice, due to the increasing volume of the uterus caused by fetal development. The convex three-dimensional transducer is bulb-shaped and is able to observe wide areas. In addition, its operation is simple, making it easy to create appropriate angles for various indices using a transrectal approach. The aim of this study was to measure Thoroughbred fetal growth indices throughout gestation using a convex transducer and to clarify the detectable period of some indices for clinical use. We demonstrated changes in fetal indices, such as crown rump length (CRL), fetal heart rate (FHR), fetal eye and kidney and the combined thickness of uterus and placenta (CTUP). CTUP increased from 30 weeks of gestation, and FHR peaked at 8 weeks and then decreased to term. CRL could be observed until 13 weeks due to its wide angle, longer than in previous reports. Fetal eye and kidney could be observed from 10 and 28 weeks, respectively, and these increased with pregnancy progress. The present results showed the advantage of transrectal examination using a convex transducer for evaluation of normal fetal development. Although ultrasonographic examination in mid- to late-gestation is not common in equine reproductive practice, our comprehensive results would be a useful basis for equine pregnancy examination.

  4. The effect of ambient air pollution during early pregnancy on fetal ultrasonic measurements during mid-pregnancy.

    PubMed

    Hansen, Craig A; Barnett, Adrian G; Pritchard, Gary

    2008-03-01

    Over the past decade there has been mounting evidence that ambient air pollution during pregnancy influences fetal growth. This study was designed to examine possible associations between fetal ultrasonic measurements collected from 15,623 scans (13-26 weeks gestation) and ambient air pollution during early pregnancy. We calculated mothers' average monthly exposures over the first 4 months of pregnancy for the following pollutants: particulate matter < 10 microm aerodynamic diameter (PM10), ozone, nitrogen dioxide, and sulfur dioxide. We examined associations with fetal femur length (FL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC). Final analyses included scans from only those women within 2 km of an air pollution monitoring site. We controlled for long-term trend, season, temperature, gestation, mother's age, socioeconomic status, and fetal sex. A reduction in fetal AC was associated with O3 during days 31-60 [-1.42 mm; 95% confidence interval (CI), -2.74 to -0.09], SO2 during days 61-90 (-1.67 mm; 95% CI, -2.94 to -0.40), and PM10 during days 91-120 (-0.78 mm; 95% CI, -1.49 to -0.08). Other results showed a reduction in BPD (-0.68 mm; 95% CI, -1.09 to -0.27) associated with SO2 during days 0-30, a reduction in HC (-1.02 mm; 95% CI, -1.78 to -0.26) associated with PM10 during days 91-120, and a reduction in FL associated with PM10 during days 0-30 (-0.28 mm; 95% CI, -0.48 to -0.08) and 91-120 (-0.23; 95% CI, -0.42 to -0.04). We found strong effects of ambient air pollution on ultrasound measures. Future research, including more individually detailed data, is needed to confirm our results.

  5. International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

    PubMed

    Papageorghiou, Aris T; Ohuma, Eric O; Altman, Douglas G; Todros, Tullia; Cheikh Ismail, Leila; Lambert, Ann; Jaffer, Yasmin A; Bertino, Enrico; Gravett, Michael G; Purwar, Manorama; Noble, J Alison; Pang, Ruyan; Victora, Cesar G; Barros, Fernando C; Carvalho, Maria; Salomon, Laurent J; Bhutta, Zulfiqar A; Kennedy, Stephen H; Villar, José

    2014-09-06

    In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd

  6. The relationship between fetal growth restriction and small placenta in 6-mercaptopurine exposed rat.

    PubMed

    Furukawa, Satoshi; Hayashi, Seigo; Usuda, Koji; Abe, Masayoshi; Ogawa, Izumi

    2011-01-01

    In order to investigate the effect of placental size on fetal intrauterine growth retardation (IURG), we examined the morphology and alterations in the expression of glucose transporter in the placentas of rats exposed to 6-mercaptopurine (6-MP). 6-MP was administered orally at 0 and 60 mg/kg/day on gestation day (GD) 9, 11, 13 or 15, and the placentas were sampled on GDs 17 and 21. The main findings in the treated groups were small placenta caused by mitotic inhibition and apoptosis, fetal resorption and IUGR with or without some malformations. The most sensitive period to 6-MP-induced fetal mortality was found to be in the GD9-treated group, and the small placenta and fetal abnormalities in the GD11-treated group, respectively. However, the litters in a quarter of the dams with the treatment on GD 11 had no fetotoxicity despite 25% decline in the placental weight. Histopathologically, the expression of glucose transporter GLUT3 was increased in the trophoblastic septa in all treated groups, particularly remarkable with proliferation of trophoblasts in the above litters, where the fetal-placental weight ratio was increased. Thus, we consider that the normal fetal growth and development can be maintained caused by adaptive change, even if the placental weight decreased by approximately 25% in 6-MP exposed rats. Copyright © 2009 Elsevier GmbH. All rights reserved.

  7. Different Indices of Fetal Growth Predict Bone Size and Volumetric Density at 4 Years of Age

    PubMed Central

    Harvey, Nicholas C; Mahon, Pamela A; Robinson, Sian M; Nisbet, Corrine E; Javaid, M Kassim; Crozier, Sarah R; Inskip, Hazel M; Godfrey, Keith M; Arden, Nigel K; Dennison, Elaine M; Cooper, Cyrus

    2011-01-01

    We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks’ gestation from ultrasound measurements in participants in the Southampton Women’s Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks’ gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density. PMID:20437610

  8. Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow, Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

    PubMed Central

    2015-01-01

    Study Overview The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Conclusion and Significance Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system. PMID:25915506

  9. Gestational dietary protein is associated with sex specific decrease in blood flow, fetal heart growth and post-natal blood pressure of progeny.

    PubMed

    Hernandez-Medrano, Juan H; Copping, Katrina J; Hoare, Andrew; Wapanaar, Wendela; Grivell, Rosalie; Kuchel, Tim; Miguel-Pacheco, Giuliana; McMillen, I Caroline; Rodgers, Raymond J; Perry, Viv E A

    2015-01-01

    The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14 mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60 d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98 dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36 dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60 d up to 23 dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system.

  10. Down-regulation of placental neuropilin-1 in fetal growth restriction.

    PubMed

    Maulik, Dev; De, Alok; Ragolia, Louis; Evans, Jodi; Grigoryev, Dmitry; Lankachandra, Kamani; Mundy, David; Muscat, Jolene; Gerkovich, Mary M; Ye, Shui Qing

    2016-02-01

    Fetal growth restriction (FGR) is associated with adverse outcomes extending from fetal to adult life, and thus, constitutes a major health care challenge. Fetuses with progressive growth restriction show increasing impedance in the umbilical artery flow, which may become absent during end-diastole. Absent end-diastolic flow (AEDF) is associated with adverse perinatal outcomes including stillbirths and perinatal asphyxia. Placentas from such pregnancies demonstrate deficient fetoplacental vascular branching. Current evidence, moreover, indicates an antiangiogenic state in maternal circulation in several pregnancy complications including preeclampsia, small-for-gestational-age births, fetal death, and preterm labor. The angiogenic mediators in maternal circulation are predominantly of placental origin. Information, however, on the role of specific proangiogenic and antiangiogenic mechanisms operating at the placental level remains limited. Elucidation of these placenta-specific angiogenic mechanisms will not only extend our understanding of the causal pathway for restricted fetal growth but may also lead to the development of biomarkers that may allow early recognition of FGR. We sought to test the hypothesis that fetoplacental angiogenic gene expression is altered in pregnancies complicated with FGR and umbilical artery Doppler AEDF. Placental samples were collected from FGR pregnancies complicated with umbilical artery Doppler AEDF (study group, n = 7), and from uncomplicated pregnancies (control group, n = 7), all delivered by cesarean during the last trimester of pregnancy. Angiogenic oligonucleotide microarray analysis was performed and was corroborated by quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. The Student t test with Bonferroni correction was used with P < .05 considered statistically significant. Independent groups t test was used to analyze the immunostain intensity scores with a P < .05 considered

  11. Uterine and fetal dynamics during early pregnancy in mares.

    PubMed

    Griffin, P G; Ginther, O J

    1991-02-01

    Fetal activity and mobility and changes in diameter of the allantoic fluid compartment in the uterine horns were studied in mares between days 69 and 81 of pregnancy by use of transrectal ultrasonography (n = 12) and transcervical videoendoscopy (n = 8). The insertion tube of the videoendoscope was positioned within the allantoic sac to permit viewing of the fetus and entrance to each uterine horn. Each uterine horn was divided ultrasonographically into 3 segments of equal length, and the horns were designated on the basis of side of umbilical attachment (cord vs noncord horns). The diameter of the allantoic fluid compartment in the cornual segments increased (P less than 0.05) over the cranial (18.6 +/- 1.9 mm), middle (35.6 +/- 2.9 mm), and caudal (51.7 +/- 4.4 mm) segments, but differences between cord and noncord horns were not evident. Dynamic changes in diameter of the allantoic fluid compartment in cornual segments (ultrasonography) and at the entrance to each uterine horn (videoendoscopy) were detected (no significant difference between methods). During continuous videoendoscopic viewing (17 to 60 min/mare), extreme changes in allantoic fluid compartment diameter (76 to 100% of maximum to 0 to 25% of maximum or vice-versa) occurred an equivalent of 2.6 times/h/horn entrance; changes had an average duration of 3.4 minutes. A change from 100% (maximal diameter) to 0% (no visible lumen) or vice-versa occurred an equivalent of 1.3 times/h/horn entrance. Sometimes the uterine wall was so closely constricted++ around the fetal-amniotic unit that no intervening allantoic fluid was ultrasonographically detectable whereas at other times the uterus in the same location was widely dilated.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

    PubMed

    Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

    2004-11-01

    To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

  13. Maternal pelvic dimensions and neonatal size: Implications for growth plasticity in early life as adaptation.

    PubMed

    Wells, Jonathan C K; Figueiroa, José N; Alves, Joao G

    2017-01-01

    Patterns of fetal growth predict non-communicable disease risk in adult life, but fetal growth variability appears to have a relatively weak association with maternal nutritional dynamics during pregnancy. This challenges the interpretation of fetal growth variability as 'adaptation'. We hypothesized that associations of maternal size and nutritional status with neonatal size are mediated by the dimensions of the maternal pelvis. We analysed data on maternal height, body mass index (BMI) and pelvic dimensions (conjugate, inter-spinous and inter-cristal diameters) and neonatal gestational age, weight, length, thorax girth and head girth ( n = 224). Multiple regression analysis was used to identify independent maternal predictors of neonatal size, and the mediating role of neonatal head girth in these associations. Pelvic dimensions displaced maternal BMI as a predictor of birth weight, explaining 11.6% of the variance. Maternal conjugate and inter-spinous diameters predicted neonatal length, thorax girth and head girth, whereas inter-cristal diameter only predicted neonatal length. Associations of pelvic dimensions with birth length, but not birth weight, were mediated by neonatal head girth. Pelvic dimensions predicted neonatal size better than maternal BMI, and these associations were mostly independent of maternal height. Sensitivity of fetal growth to pelvic dimensions reduces the risk of cephalo-pelvic disproportion, potentially a strong selective pressure during secular trends in height. Selection on fetal adaptation to relatively inflexible components of maternal phenotype, rather than directly to external ecological conditions, may help explain high levels of growth plasticity during late fetal life and early infancy.

  14. [Early childhood growth and development].

    PubMed

    Arce, Melitón

    2015-01-01

    This article describes and discusses issues related to the process of childhood growth and development, with emphasis on the early years, a period in which this process reaches critical speed on major structures and functions of the human economy. We reaffirm that this can contribute to the social availability of a generation of increasingly better adults, which in turn will be able to contribute to building a better world and within it a society that enjoys greater prosperity. In the first chapter, we discuss the general considerations on the favorable evolution of human society based on quality of future adults, meaning the accomplishments that today’s children will gain. A second chapter mentions the basics of growth and development in the different fields and the various phenomena that occur in it. In the third we refer to lost opportunities and negative factors that can affect delaying the process and thereby result in not obtaining the expected accomplishments. In the fourth, conclusions and recommendations are presented confirming the initial conception that good early child care serves to build a better society and some recommendations are formulated to make it a good practice.

  15. Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth.

    PubMed

    Hinkle, Stefanie N; Johns, Alicia M; Albert, Paul S; Kim, Sungduk; Grantz, Katherine L

    2015-07-01

    Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at 17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed models. Second, the association between maternal weight changes (per 5 kg) and corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. From 0 to 17 weeks, changes in maternal weight were most strongly associated with changes in BPD [β=0.51 per 5 kg (95%CI 0.26, 0.76)] and FL [β=0.46 per 5 kg (95%CI 0.26, 0.65)]. From 17 to 28 weeks, AC [β=2.92 per 5 kg (95%CI 1.62, 4.22)] and EFW [β=58.7 per 5 kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29 kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67 kg

  16. Impacts of maternal dietary protein intake on fetal survival, growth, and development.

    PubMed

    Herring, Cassandra M; Bazer, Fuller W; Johnson, Gregory A; Wu, Guoyao

    2018-03-01

    Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H 2 S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new

  17. Ethnic differences in fetal size and growth in a multi-ethnic population.

    PubMed

    Sletner, Line; Rasmussen, Svein; Jenum, Anne Karen; Nakstad, Britt; Jensen, Odd Harald Rognerud; Vangen, Siri

    2015-09-01

    Impaired or excessive fetal growth is associated with adverse short- and long-term health outcomes that differ between ethnic groups. We explored ethnic differences in fetal size and growth from mid pregnancy until birth. Data are from the multi-ethnic STORK-Groruddalen study, a population-based, prospective cohort of 823 pregnant women and their offspring in Oslo, Norway. Measures were z-scores of estimated fetal weight (EFW), head circumference (HC), abdominal circumference (AC) and femur length (FL), in gestational week 24, 32 and 37, measured by ultrasound, and similar measures at birth. Differences in fetal size and growth were assessed using separate Linear Mixed Models including all four time points, with ethnic Europeans as reference. In week 24 South Asian fetuses had smaller AC, but larger FL than Europeans, and slightly lower EFW (-0.17 SD (-0.33, -0.01), p=0.04). Middle East/North African fetuses also had larger FL, but similar AC, and hence slightly higher EFW (0.18 (0.003, 0.36), p=0.05). Both groups had slower growth of AC, FL and EFW from this time until birth, and had -0.61 SD (-0.73, -0.49) and -0.28 SD (-0.41, -0.15) lower birth weight respectively. Ethnic East Asians, on the other hand, were smaller throughout pregnancy and had -0.58 SD (-0.82, -0.34) lower birth weight. Significant ethnic differences remained after adjusting for maternal factors. We observed ethnic differences in fetal size and body proportions already in gestational week 24, and in fetal growth from this time until birth, which were only partly explained by key maternal factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Mother's educational level and fetal growth: the genesis of health inequalities.

    PubMed

    Silva, Lindsay M; Jansen, Pauline W; Steegers, Eric A P; Jaddoe, Vincent W V; Arends, Lidia R; Tiemeier, Henning; Verhulst, Frank C; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

    2010-10-01

    Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.

  19. Management of fetal growth restriction using the contraction stress test: a case-control study.

    PubMed

    Tanaka, Hiroaki; Furuhashi, Fumi H; Toriyabe, Kuniaki; Matsumoto, Takeshi; Magawa, Shoich; Nii, Masafumi; Watanabe, Junko; Tanaka, Kayo; Umekawa, Takashi; Kamimoto, Yuki; Ikeda, Tomoaki

    2018-04-18

    Fetal growth restriction (FGR) is a concerning health issue. However, studies on FGR management are limited due to its rarity. We aimed to evaluate the efficacy of the contraction stress test (CST) for FGR management. A case-control retrospective study design. Our institute innovated CST in FGR management in 2017. We included women in their 33rd-40th week of pregnancy with a diagnosis of FGR and retrospectively divided them into groups: the CST group (FGR management with CST) and no CST group (FGR management without CST) before and after CST development. Neonatal outcome, pH, and pO 2 of umbilical artery (UA) were compared between the two groups. No significant differences in the rate of birth weight, Apgar score <7 (5 minutes), neonatal death, hospitalization to newborn childhood intensive care unit (NICU), and UA pH were found between groups. Average UA pH was 7.29 ± 0.05 and 7.29 ± 0.04 in the CST and no CST groups, respectively (p = .864). Average UA pO 2 values were 21.1 ± 8.6 and 15.7 ± 5.0 mmHg in the CST and no CST groups, respectively (p = .016), showing significant differences. Neonatal outcomes and UA pH were slightly different between the groups managed with and without CST. However, UA pO 2 values significantly differed between the groups. For FGR management, the use of a CST may allow for early intervention before fetal acidemia and acidosis. For establishing the effects of a CST for FGR management, analysis including several cases and investigation of long-term outcomes of newborn infants is necessary.

  20. Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

    PubMed

    Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

    2017-08-29

    Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

  1. Antenatal betamethasone and fetal growth in prematurely born children: implications for temperament traits at the age of 2 years.

    PubMed

    Pesonen, Anu-Katriina; Räikkönen, Katri; Lano, Aulikki; Peltoniemi, Outi; Hallman, Mikko; Kari, M Anneli

    2009-01-01

    We explored whether repeated dose of antenatal betamethasone and variation in intrauterine growth of prematurely born children predict temperament characteristics at the age of 2 years. The patients (n = 142) were prematurely born children (mean gestational age: 31.0 weeks; range: 24.6-35.0 weeks) who participated in a randomized and blinded trial testing the effects of a repeated dose of antenatal betamethasone in imminent preterm birth. Fetal growth was estimated as weight, length, and head circumference in SDs according to Finnish growth charts. Parents assessed their toddlers' temperament with 201 items of the Early Childhood Temperament Questionnaire (mean child corrected age: 2.1 years). No significant main effects of repeated betamethasone on toddler temperament existed. However, a significant interaction between study group and duration of exposure to betamethasone emerged; those exposed to a repeated dose for >24 hours before delivery were more impulsive. One-SD increases in weight, length, and head circumference at birth were associated with 0.14- to 0.19-SD lower levels of negative affectivity (fearfulness, anger proneness, and sadness); 1-SD increases in length, weight, and head circumference at birth were associated with 0.14- to 0.18-SD higher levels of effortful control (self-regulation). Repeated antenatal betamethasone did not induce alterations in toddler temperament. The results, however, suggest that a longer duration of exposure is associated with higher impulsivity scores. Regardless of betamethasone exposure, slower fetal growth exerted influences on temperament. Our findings indicate prenatal programming of psychological development and imply that more attention is needed to support the development of infants born at the lower end of the fetal growth distribution.

  2. Fetal growth trajectory and risk for eczema in a Saudi population.

    PubMed

    AlMakoshi, Amel; Ellahi, Awaiss; Sallout, Bala; Devereux, Graham; Turner, Steve

    2015-12-01

    Recent studies in Western cohorts have identified associations between increasing fetal abdominal circumference (AC) during mid-pregnancy and increased risk for eczema and atopy. We sought to replicate these findings in a Saudi population where antenatal environmental exposures are different compared with Western countries. A Saudi birth cohort was recruited to relate maternal dietary intake and fetal growth to wheeze, eczema, and rhinitis in the first 2 yrs. Fetal size was determined from routine ultrasound scan measurements in the second and third trimesters and birthweight was noted. Parent-reported outcomes during the first 2 yrs were acquired by telephone-administered questionnaire. There were 1076 mothers recruited. AC was determined in 562 for the second, in 632 for the third, and in 281 for both second and third trimesters. A history of eczema was determined in 814 children at 2 yrs of age. There was an inverse relationship between change in abdominal circumference between the second and third trimesters for eczema (OR 0.66 per z score increase in AC [95% CI 0.49, 0.89]), and the quartile with the greatest faltering growth were at increased risk compared with other groups (p ≤ 0.045). Change in fetal size between the third trimester and birth was not associated with altered eczema risk. There were no associations between fetal growth and wheeze at the age of 2 yrs. Our findings contrast observations made in Western populations but nonetheless suggest that factors associated with changing fetal growth trajectory in the second half of pregnancy are also relevant to atopy development on the global setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Maternal Nutrient Restriction in Guinea Pigs as an Animal Model for Inducing Fetal Growth Restriction.

    PubMed

    Elias, Alexander A; Ghaly, Andrew; Matushewski, Brad; Regnault, Timothy R H; Richardson, Bryan S

    2016-02-01

    We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs on pregnancy outcomes, maternal/fetal growth parameters, and blood analytes to further characterize the utility of this model for inducing fetal growth restriction (FGR). Thirty guinea pig sows were fed ad libitum (Control) or 70% of the control diet prepregnant switching to 90% at midpregnancy (MNR). Animals were necropsied near term with weights obtained on all sows, fetuses, and placenta. Fetal blood sampling and organ dissection were undertaken in appropriate for gestational age (AGA) fetuses from Control litters and FGR fetuses from MNR litters using > or < 80 g which approximated the 10th percentile for the population weight distribution of the Control fetuses. MNR fetal demise rates (1/43) were extremely low in contrast to that seen with uterine artery ligation/ablation models, albeit with increased preterm delivery in MNR sows (3 of 15). We confirm that MNR fetuses are smaller and have increased placental/fetal weight ratios as often seen in human FGR infants. We provide justification for using a fetal weight threshold for categorizing AGA Control and FGR-MNR cohorts reducing population variance, and show that FGR-MNR fetuses have asymmetrical organ growth, and are polycythemic and hypoglycemic which are also well associated with moderate FGR in humans. These findings further support the utility of moderate MNR in guinea pigs for inducing FGR with many similarities to that in humans with moderate growth restriction whether resulting from maternal undernourishment or placental insufficiency. © The Author(s) 2015.

  4. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    SciTech Connect

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il; Shoshani-Dror, Dana; Guillemin, Claire

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy.more » Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth

  5. Maternal psychiatric disease and epigenetic evidence suggest a common biology for poor fetal growth.

    PubMed

    Ciesielski, Timothy H; Marsit, Carmen J; Williams, Scott M

    2015-08-25

    We sought to identify and characterize predictors of poor fetal growth among variables extracted from perinatal medical records to gain insight into potential etiologic mechanisms. In this process we reevaluated a previously observed association between poor fetal growth and maternal psychiatric disease. We evaluated 449 deliveries of >36 weeks gestation that occurred between 9/2008 and 9/2010 at the Women and Infants Hospital in Providence Rhode Island. This study group was oversampled for Small-for-Gestational-Age (SGA) infants and excluded Large-for-Gestational-Age (LGA) infants. We assessed the associations between recorded clinical variables and impaired fetal growth: SGA or Intrauterine Growth Restriction (IUGR) diagnosis. After validating the previously observed association between maternal psychiatric disease and impaired fetal growth we addressed weaknesses in the prior studies by explicitly considering antidepressant use and the timing of symptoms with respect to pregnancy. We then evaluated DNA methylation levels at 27 candidate loci in placenta from a subset of these deliveries (n = 197) to examine if epigenetic variation could provide insight into the mechanisms that cause this co-morbidity. Infants of mothers with prenatal psychiatric disease (Depression, Anxiety, OCD/Panic) had increased odds of poor fetal growth (ORadjusted = 3.36, 95%CI: 1.38-8.14). This relationship was similar among those who were treated with antidepressants (ORadjusted = 3.69, 95%CI: 1.31-10.45) and among those who were not (ORadjusted = 3.19, 95%CI: 1.30-7.83). Among those with a history of psychiatric disease but no active disease in pregnancy the ORadjusted was 0.45 (95%CI: 0.09-2.35). A locus near the transcription start site of the leptin receptor (cg21655790) had methylation levels that were decreased in the presence of: 1) SGA/IUGR, and 2) active but not resolved psychiatric disease (among mothers not on antidepressants). These results validate and

  6. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    PubMed Central

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  7. MARKERS OF INDIVIDUAL SUSCEPTIBILITY AND OUTCOME RELATED TO FETAL AND INFANT GROWTH AND DEVELOPMENT

    EPA Science Inventory

    To evaluate whether exposures to environmental toxins and psychological stress were related to impaired fetal growth or other adverse pregnancy outcomes, we established a prospective epidemiologic study of 187 women who were pregnant and at or near the World Trade Center (...

  8. Prenatal exposure to mercury and longitudinally assessed fetal growth: Relation and effect modifiers.

    PubMed

    Ballester, Ferran; Iñiguez, Carmen; Murcia, Mario; Guxens, Mònica; Basterretxea, Mikel; Rebagliato, Marisa; Vioque, Jesús; Lertxundi, Aitana; Fernandez-Somoano, Ana; Tardon, Adonina; Sunyer, Jordi; Llop, Sabrina

    2018-01-01

    Prenatal mercury exposure has been related to reductions in anthropometry at birth. Levels of mercury have been reported as being relatively elevated in the Spanish population. To investigate the relation between prenatal exposure to mercury and fetal growth. Study subjects were pregnant women and their newborns (n:1867) participating in a population-based birth cohort study set up in four Spanish regions from the INMA Project. Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were measured by ultrasounds at 12, 20, and 34 weeks of gestation. Size at and growth between these points were assessed by standard deviation (SD) scores adjusted for constitutional characteristics. Total mercury (T-Hg) was determined in cord blood. Associations were investigated by linear regression models, adjusted by sociodemographic, environmental, nutritional - including four seafood groups - and lifestyle-related variables in each sub-cohort. Final estimates were obtained using meta-analysis. Effect modification by sex, seafood intake and polychlorinated biphenyl (PCB) congener 153 concentration was assessed. Geometric mean of cord blood T-Hg was 8.2μg/L. All the estimates of the association between prenatal Hg and growth from 0 to 12 weeks showed reductions in SD-scores, which were only statistically significant for BPD. A doubling of cord blood T-Hg was associated with a 0.58% reduction in size of BPD at week 12 (95% confidence interval -CI-: - 1.10, - 0.07). Size at week 34 showed estimates suggestive of a small reduction in EFW, i.e., a doubling of T-Hg levels was associated with a reduction of 0.38% (95% CI: - 0.91, 0.15). An interaction between PCB153 and T-Hg was found, with statistically significant negative associations of T-Hg with AC and EFW in late pregnancy among participants with PCB153 below the median. Exposure to mercury during pregnancy was associated with early reductions in BPD. Moreover, an antagonism with

  9. Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression

    PubMed Central

    Abdel-Hakeem, Ahmed K; Henry, Tasmia Q; Magee, Thomas R; Desai, Mina; Ross, Michael; Mansano, Roy; Torday, John; Nast, Cynthia C.

    2010-01-01

    Objective Maternal food restriction during pregnancy results in growth restricted newborns and reduced glomerular number, contributing to programmed offspring hypertension. We investigated whether reduced nephrogenesis may be programmed by dysregulation of factors controlling ureteric bud branching and mesenchyme to epithelial transformation. Study Design 10 to 20 days gestation, Sprague Dawley pregnant rats (n=6/group) received ad libitum food; FR rats were 50% food restricted. At embryonic day 20, mRNA and protein expression of WT1, Pax2, FGF2, GDNF, cRET, WNT4, WNT11, BMP4, BMP7, and FGF7 were determined by real-time PCR and Western blotting. Results Maternal FR resulted in up-regulated mRNA expression for WT1, FGF2, and BMP7 whereas Pax2, GDNF, FGF7, BMP4, WNT4, and WNT11 mRNAs were down-regulated. Protein expression was concordant for WT1, GDNF, Pax2, FGF7, BMP4 and WNT4. Conclusion Maternal FR altered gene expression of fetal renal transcription and growth factors, and likely contributes to development of offspring hypertension. PMID:18639218

  10. Dietary -carbamylglutamate and rumen-protected -arginine supplementation ameliorate fetal growth restriction in undernourished ewes.

    PubMed

    Zhang, H; Sun, L W; Wang, Z Y; Deng, M T; Zhang, G M; Guo, R H; Ma, T W; Wang, F

    2016-05-01

    This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary -carbamylglutamate (NCG) and rumen-protected -Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower ( < 0.05) in nutrient-restricted ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter ( = 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased ( < 0.05) in RP-Arg-treated and NCG-treated underfed ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced ( < 0.05) concentrations of β-hydroxybutyrate, triglycerides, and ammonia in serum of underfed ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved ( < 0.05) concentrations of AA (particularly arginine-family AA and branched-chain AA) and polyamines in maternal and fetal plasma and in fetal allantoic and amniotic fluids within nutrient-restricted ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production.

  11. Conceptual basis for prescriptive growth standards from conception to early childhood: present and future.

    PubMed

    Uauy, R; Casanello, P; Krause, B; Kuzanovic, J P; Corvalan, C

    2013-09-01

    maternal uterine environment from the time before conception, through embryonic development until fetal growth is complete. The remaining challenge is how 'early' will we be able to act, now that we can better monitor fetal growth. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  12. IGF2 DNA methylation is a modulator of newborn’s fetal growth and development

    PubMed Central

    St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

    2012-01-01

    The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn’s fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn’s weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn’s fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity. PMID:22907587

  13. IGF2 DNA methylation is a modulator of newborn's fetal growth and development.

    PubMed

    St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

    2012-10-01

    The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.

  14. Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study.

    PubMed

    2008-11-03

    To examine the association of maternal caffeine intake with fetal growth restriction. Prospective longitudinal observational study. Two large UK hospital maternity units. 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy. Investigations Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations. Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations. Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06). Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy.

  15. Locally derived traffic-related air pollution and fetal growth restriction: a retrospective cohort study.

    PubMed

    Pereira, Gavin; Cook, Angus G; Haggar, Fatima; Bower, Carol; Nassar, Natasha

    2012-11-01

    Fetal growth restriction has been inconsistently associated with maternal exposure to elevated levels of traffic-related air pollution. We investigated the relationship between an individualised measure of fetal growth and maternal exposure to a specific marker for traffic-related air pollution. We estimated maternal residential exposure to a marker for traffic-related air pollution (nitrogen dioxide, NO2) during pregnancy for 23,452 births using temporally adjusted land-use regression. Logistic regression was used to investigate associations with small for gestational age and sex (SGA) and fetal growth restriction, defined as proportion of optimal birth weight (POBW) below the 10th percentile. Sub-populations investigated were: women who spent most time at home, women who did not move house, women with respiratory or circulatory morbidity, women living in low/middle/high socio-economic areas, women who delivered before 37 weeks gestation, and women who delivered from 37 weeks gestation. An IQR increase in traffic-related air pollution in the second trimester across all women was associated with an OR of 1.31 (95% CI 1.07 to 1.60) for fetal growth restriction. Effects on fetal growth restriction (low POBW) were highest among women who subsequently delivered before 37 weeks of gestation. Effects on SGA were highest among women who did not move house: OR 1.35 (95% CI 1.08 to 1.69). Larger effect sizes were observed for low POBW than for SGA. Exposure to traffic-related air pollution in mid to late pregnancy was associated with risk of SGA and low POBW in this study.

  16. Antenatal Workup of Early Megacystis and Selection of Candidates for Fetal Therapy.

    PubMed

    Fontanella, Federica; Duin, Leonie; Adama van Scheltema, Phebe N; Cohen-Overbeek, Titia E; Pajkrt, Eva; Bekker, Mireille; Willekes, Christine; Bax, Caroline J; Oepkes, Dick; Bilardo, Catia M

    2018-05-17

    To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks' gestation (early megacystis). In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts. © 2018 The Author(s) Published by S. Karger AG, Basel.

  17. Intrauterine growth restriction decreases nuclear factor-kappa B signaling in fetal pulmonary artery endothelial cells of fetal sheep.

    PubMed

    Dodson, R Blair; Powers, Kyle N; Gien, Jason; Rozance, Paul J; Seedorf, Gregory J; Astling, David; Jones, Kenneth Lloyd; Crombleholme, Timothy M; Abman, Steven H; Alvira, Cristina M

    2018-05-03

    Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC. PAECs were isolated from lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NFκB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NFκB targets. In comparison with controls: (i) immunostaining of active NFκB complexes; (ii) NFκB-DNA binding; (iii) baseline expression of NFκB subunits, p65 and p50; and (iv) LPS-mediated inducible activation of NFκB signaling were decreased in IUGR PAEC. Although pharmacologic NFκB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NFκB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NFκB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NFκB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

  18. Smoking in Pregnancy and Fetal Growth: The Case for More Intensive Assessment.

    PubMed

    Shisler, Shannon; Eiden, Rina D; Molnar, Danielle S; Schuetze, Pamela; Huestis, Marilyn; Homish, Gregory

    2017-05-01

    Many studies on prenatal tobacco exposure (PTE) effects have relied on single item retrospective measures of PTE. However, it is unclear how these single item measures may relate to more intensive maternal self-reports and to biological markers of maternal use and/or fetal exposure. It is also unclear whether these measures may be more valid predictors of fetal growth (gestational age, birthweight, head circumference, and birth length). Data were obtained from 258 women during their pregnancy. PTE was assessed by four methods: a single item question, a calendar-based self-report measure from each trimester of pregnancy, maternal salivary cotinine assays, and nicotine and metabolites in infant meconium. We hypothesized that the more intensive measures and biological assays would account for additional variance in birth outcomes, above and beyond the single item measure. The single item self-report measure was not related to fetal growth. However, the more intensive calendar based self-report measure and the biological assays of PTE (ie, maternal salivary assays and infant meconium) were significant predictors of poor fetal growth, even with the single item measure in the model. The negative effects of PTE on important child outcomes may be greatly underestimated in the literature as many studies use single item self-report measures to ascertain PTE. Whereas more intensive self-report measures or biological assays may be cost prohibitive in large scale epidemiological studies, using a combination of measures when possible should be considered given their superiority both identifying prenatal smokers and predicting poor fetal growth. The present work underscores the importance of measurement issues when assessing associations between PTE and fetal growth. Results suggest that we may be greatly underestimating the negative effects of prenatal smoking on fetal growth and other important child outcomes if we rely solely on restricted single item self-report measures of

  19. Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

    PubMed

    Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

    2014-04-01

    Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

  20. Enhanced or Reduced Fetal Growth Induced by Embryo Transfer into Smaller or Larger Breeds Alters Post-Natal Growth and Metabolism in Pre-Weaning Horses

    PubMed Central

    Peugnet, Pauline; Wimel, Laurence; Duchamp, Guy; Sandersen, Charlotte; Camous, Sylvaine; Guillaume, Daniel; Dahirel, Michèle; Dubois, Cédric; Jouneau, Luc; Reigner, Fabrice; Berthelot, Valérie; Chaffaux, Stéphane; Tarrade, Anne; Serteyn, Didier; Chavatte-Palmer, Pascale

    2014-01-01

    In equids, placentation is diffuse and nutrient supply to the fetus is determined by uterine size. This correlates with maternal size and affects intra-uterine development and subsequent post-natal growth, as well as insulin sensitivity in the newborn. Long-term effects remain to be described. In this study, fetal growth was enhanced or restricted through ET using pony (P), saddlebred (S) and draft (D) horses. Control P-P (n = 21) and S-S (n = 28) pregnancies were obtained by AI. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (P-D, n = 6 and S-D, n = 8) or S embryos into P mares (S-P, n = 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively. Weight gain, growth hormones and glucose homeostasis were investigated in the foals from birth to weaning. Fetal growth was enhanced in P-D and these foals remained consistently heavier, with reduced T3 concentrations until weaning compared to P-P. P-D had lower fasting glucose from days 30 to 200 and higher insulin secretion than P-P after IVGTT on day 3. Euglycemic clamps in the immediate post-weaning period revealed no difference in insulin sensitivity between P-D and P-P. Fetal growth was restricted in S-P and these foals remained consistently lighter until weaning compared to S-D, with elevated T3 concentrations in the newborn compared to S-S. S-P exhibited higher fasting glycemia than S-S and S-D from days 30 to 200. They had higher maximum increment in plasma glucose than S-D after IVGTT on day 3 and clamps on day 200 demonstrated higher insulin sensitivity compared to S-D. Neither the restricted nor the enhanced fetal environment affected IGF-1 concentrations. Thus, enhanced and restricted fetal and post-natal environments had combined effects that persisted until weaning. They induced different adaptive responses in post-natal glucose metabolism: an early insulin-resistance was induced in

  1. Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

    PubMed

    Oyston, Charlotte; Stanley, Joanna L; Oliver, Mark H; Bloomfield, Frank H; Baker, Philip N

    2016-09-01

    Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency. © 2016 American Heart Association, Inc.

  2. Placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction.

    PubMed

    Yoshida, Atsumi; Watanabe, Kazushi; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Wakatsuki, Akihiko

    2018-04-01

    The purpose of this study was to investigate the relationship between placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction (FGR). We examined serum concentrations of oxygen free radicals (d-ROMs), maternal angiogenic factor (PlGF), and sFlt-1, placental oxidative DNA damage, and maternal endothelial function in 17 women with early-onset preeclampsia (PE), 18 with late-onset PE, 14 with normotensive FGR, and 21 controls. Flow-mediated vasodilation (FMD) was assessed as a marker of maternal endothelial function. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Maternal serum d-ROM, sFlt-1 concentrations, and FMD did not significantly differ between the control and normotensive FGR groups. The proportion of nuclei staining positive for 8-OHdG was significantly higher in the normotensive FGR group relative to the control group. Our findings demonstrate that, despite the presence of placental oxidative DNA damage as observed in PE patients, pregnant women with normotensive FGR show no increase in the concentrations of sFlt-1 and d-ROMs, or a decrease in FMD.

  3. Intrinsic catch-up growth of hypoplastic fetal lungs is mediated by interleukin-6.

    PubMed

    Nogueira-Silva, Cristina; Moura, Rute S; Esteves, Nuno; Gonzaga, Sílvia; Correia-Pinto, Jorge

    2008-07-01

    Fetal lung hypoplasia is a common finding in several fetal conditions such as congenital diaphragmatic hernia (CDH). Interestingly, previous studies have demonstrated that hypoplastic lungs have the ability to recover to normal size, when relieved from mechanical factors. However, the underlying mechanisms remain largely unknown. Recently, interleukin-6 (IL-6) has been involved in catch-up growth phenomenon in children. Thus, we hypothesized that IL-6 could mediate fetal growth recover from hypoplastic lungs. Control and nitrofen-induced hypoplastic lung explants were cultured either in normal conditions or with IL-6 neutralizing antibodies. The total number of peripheral airway buds, epithelial perimeter, and total explant area were analyzed and daily branching rates were calculated. Additionally, IL-6 mRNA and protein expression was assessed both in qualitative (by in situ hybridization and immunohistochemistry) and in quantitative (by real-time PCR and Western blot) approaches, in control and hypoplastic lungs (nitrofen and CDH groups). Nitrofen-induced hypoplastic lungs showed in vitro, out of systemic environment, the ability to recover from hypoplasia and presented daily branching rates significantly higher than controls. Blocking IL-6 activity significantly diminished the intrinsic capacity of hypoplastic fetal lungs to recover from hypoplasia and attenuated their daily branching rates. Although more exacerbated in CDH, both nitrofen-exposed lungs presented significant IL-6 mRNA and protein over-expression throughout all studied gestational ages. The present study suggests, for the first time, that fetal lung is able to recover from growth retardation through a way that resembles the catch-up growth phenomenon, and it seems to be, at least partially, orchestrated by intrinsic mechanisms implicating IL-6.

  4. Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

    PubMed Central

    Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

  5. Upregulation of Cytokines Is Detected in the Placentas of Cattle Infected with Neospora caninum and Is More Marked Early in Gestation When Fetal Death Is Observed ▿

    PubMed Central

    Rosbottom, Anne; Gibney, E. Helen; Guy, Catherine S.; Kipar, Anja; Smith, Robert F.; Kaiser, Pete; Trees, Alexander J.; Williams, Diana J. L.

    2008-01-01

    The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-γ), IL-12p40, tumor necrosis factor alpha (TNF-α), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4+ T cells and macrophages. IFN-γ protein expression was also highly increased, and a modest increase in transforming growth factor β was detected. A much smaller increase in the same cytokines and IFN-γ protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-α, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle. PMID:18362132

  6. Fetal growth in women with homozygous sickle cell disease: an observational study.

    PubMed

    Thame, Minerva M; Osmond, Clive; Serjeant, Graham R

    2013-09-01

    To assess fetal growth and whether lower birthweight to mothers with homozygous sickle cell (SS) disease is related to maternal body composition or to clinical events in pregnancy. A prospective study of 41 pregnant women with SS disease and 41 women with a normal (AA) phenotype attending the antenatal clinic, University Hospital of the West Indies, Kingston, Jamaica. Maternal anthropometry, body composition and fetal sonographic measurements were assessed at 15, 25, and 35 weeks' gestation from December 2005 to April 2008. Birth measurements were performed within 24h of delivery. Differences between maternal genotypes and between their offspring were assessed using 2-sample t-tests. Multiple linear regression was used to control for baby's gender and gestational age at delivery. Fetal growth was compared in SS mothers with and without admission for sickle-related complications including bone pain crisis, acute chest syndrome, pregnancy-induced hypertension and urinary tract infection. Mothers with SS disease had lower weight, body fat, fat mass and lean body mass throughout pregnancy but correlation with birth size did not reach statistical significance. Sonographically, babies of SS mothers had smaller abdominal circumference, femoral length and a lower estimated fetal weight at 35 weeks. Birth measurements confirm lower birthweight, crown-heel length and head circumference but the differences were no longer significant after adjustment for baby gender and gestational age at delivery. Bone pain crisis in pregnancy was associated with a significantly reduced crown-heel length at birth. Lower birthweight in babies of mothers with SS disease is largely the result of the lower gestational age. Fetal sonography showed no growth differences by maternal genotype until 35 weeks' gestation and a reduced crown-heel length in offspring of SS mothers was associated with bone pain crises in pregnancy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Association of prenatal lipid-based nutritional supplementation with fetal growth in rural Gambia.

    PubMed

    Johnson, William; Darboe, Momodou K; Sosseh, Fatou; Nshe, Patrick; Prentice, Andrew M; Moore, Sophie E

    2017-04-01

    Prenatal supplementation with protein-energy (PE) and/or multiple-micronutrients (MMNs) may improve fetal growth, but trials of lipid-based nutritional supplements (LNSs) have reported inconsistent results. We conducted a post-hoc analysis of non-primary outcomes in a trial in Gambia, with the aim to test the associations of LNS with fetal growth and explore how efficacy varies depending on nutritional status. The sample comprised 620 pregnant women in an individually randomized, partially blinded trial with four arms: (a) iron and folic acid (FeFol) tablet (usual care, referent group), (b) MMN tablet, (c) PE LNS, and (d) PE + MMN LNS. Analysis of variance examined unadjusted differences in fetal biometry z-scores at 20 and 30 weeks and neonatal anthropometry z-scores, while regression tested for modification of intervention-outcome associations by season and maternal height, body mass index, and weight gain. Despite evidence of between-arm differences in some fetal biometry, z-scores at birth were not greater in the intervention arms than the FeFol arm (e.g., birth weight z-scores: FeFol -0.71, MMN -0.63, PE -0.64, PE + MMN -0.62; group-wise p = .796). In regression analyses, intervention associations with birth weight and head circumference were modified by maternal weight gain between booking and 30 weeks gestation (e.g., PE + MMN associations with birth weight were +0.462 z-scores (95% CI [0.097, 0.826]) in the highest quartile of weight gain but -0.099 z-scores (-0.459, 0.260) in the lowest). In conclusion, we found no strong evidence that a prenatal LNS intervention was associated with better fetal growth in the whole sample. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

  8. Gender mix in twins and fetal growth, length of gestation and adult cancer risk.

    PubMed

    Luke, Barbara; Hediger, Mary; Min, Sung-Joon; Brown, Morton B; Misiunas, Ruta B; Gonzalez-Quintero, Victor Hugo; Nugent, Clark; Witter, Frank R; Newman, Roger B; Hankins, Gary D V; Grainger, David A; Macones, George A

    2005-01-01

    This study evaluated the effect of gender mix (the gender combinations of twin pairs) on fetal growth and length of gestation, and reviewed the literature on the long-term effects of this altered fetal milieu on cancer risk. In singletons, it is well established that females weigh less than males at all gestations, averaging 125-135 g less at full term. This gender difference is generally believed to be the result of the effect of androgens on fetal growth. The gender difference in fetal growth is greater before the third trimester and less towards term, with males growing not only more, but also earlier than females. Plurality is a known risk factor for reduced fetal growth and birthweight. Compared with singletons, the mean birthweight percentiles of twins fall substantially (by 10% or more) below the singleton 10th percentile by 28 weeks, below the singleton 50th percentile by 30 weeks, and below the singleton 90th percentile by 34 weeks. In unlike-gender twin pairs, it has been reported that the female prolongs gestation for her brother, resulting in a higher birthweight for the male twin than that of like-gender male twins. Other researchers have demonstrated that females in unlike-gender pairs had higher birthweights than females in like-gender pairs. Analyses from our consortium on 2491 twin pregnancies with known chorionicity showed longer gestations and faster rates of fetal growth in both males and females in unlike-gender pairs compared with like-gender male or female pairs, although these differences were not statistically significant. The post-natal effects for females growing in an androgenic-anabolic environment include increased sensation-seeking behaviour and aggression, lowered visual acuity, more masculine attitudes and masculinising effects of the auditory system and craniofacial growth. In contrast, there is no evidence to suggest that there might be a similar feminising effect on males from unlike-gender pairs. This hormonal exposure in utero

  9. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    PubMed

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  10. Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

    PubMed

    Swanson, Anna M; Rossi, Carlo A; Ofir, Keren; Mehta, Vedanta; Boyd, Michael; Barker, Hannah; Ledwozyw, Agata; Vaughan, Owen; Martin, John; Zachary, Ian; Sebire, Neil; Peebles, Donald M; David, Anna L

    2016-12-01

    In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A 165 or Ad.LacZ (1 × 10 10 vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A 165 -treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A 165 -treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A 165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

  11. A prospective study of fetal head growth, autistic traits and autism spectrum disorder

    PubMed Central

    Blanken, Laura M. E.; Dass, Alena; Alvares, Gail; van der Ende, Jan; Schoemaker, Nikita K.; El Marroun, Hanan; Hickey, Martha; Pennell, Craig; White, Scott; Maybery, Murray T.; Dissanayake, Cheryl; Jaddoe, Vincent W. V.; Verhulst, Frank C.; Tiemeier, Henning; McIntosh, Will; Whitehouse, Andrew

    2018-01-01

    Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population‐based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism‐Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population‐based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602–612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian

  12. Fetal endocrinology

    PubMed Central

    Kota, Sunil Kumar; Gayatri, Kotni; Jammula, Sruti; Meher, Lalit Kumar; Kota, Siva Krishna; Krishna, S. V. S.; Modi, Kirtikumar D.

    2013-01-01

    Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition. PMID:23961471

  13. Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits.

    PubMed

    Li, Ling; Yang, Chen; Feng, Xiuliang; Du, Yongping; Zhang, Zhihong; Zhang, Yueping

    2018-01-01

    This study aimed to study the effects of intratracheal instillation of budesonide on lung maturity of premature fetal rabbits. The developmental pattern of pulmonary alveoli in rabbits is similar to that in humans. Fetal rabbits were taken out from female rabbits on the 28th day of pregnancy (full term = 31 days) by cesarean section (c-section). The fetal rabbits were divided into four groups: control (normal saline, NS), budesonide (budesonide, BUD), calf pulmonary surfactant for injection (pulmonary surfactant, PS), and calf pulmonary surfactant + budesonide for injection (pulmonary surfactant + budesonide, PS + BUD). All premature rabbits were kept warm after c-section. After 15-min autonomous respiration, a tracheal cannula was implemented for instilling NS, BUD, PS, and PS + BUD. The morphology of lung tissues of premature fetal rabbits was analyzed using optical and electron microscopes. Surfactant protein B (SP-B) mRNA and protein levels in lung tissues were determined using polymerase chain reaction and Western blotting, respectively. Intratracheal instillation of BUD could increase the alveolar area of the fetal rabbits (P < 0.01), decrease the alveolar wall thickness (P < 0.01), and increase the mean density of lamellar bodies (P < 0.05) and SP-B protein levels in type II epithelial cells of pulmonary alveoli (P < 0.05). Intratracheal instillation of BUD during early postnatal life is effective in promoting alveolarization and increasing SP-B expression, the pro-pulmonary maturity of BUD combined with PS is superior to that of BUD or PS alone. However, the long-term effect of BUD on lung development needs further exploration. © 2017 Wiley Periodicals, Inc.

  14. Prediction of fetal growth restriction using estimated fetal weight vs a combined screening model in the third trimester.

    PubMed

    Miranda, J; Rodriguez-Lopez, M; Triunfo, S; Sairanen, M; Kouru, H; Parra-Saavedra, M; Crovetto, F; Figueras, F; Crispi, F; Gratacós, E

    2017-11-01

    To compare the performance of third-trimester screening, based on estimated fetal weight centile (EFWc) vs a combined model including maternal baseline characteristics, fetoplacental ultrasound and maternal biochemical markers, for the prediction of small-for-gestational-age (SGA) neonates and late-onset fetal growth restriction (FGR). This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester (32 + 0 to 36 + 6 weeks' gestation) evaluation. Maternal baseline characteristics, mean arterial pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently delivered a SGA neonate (n = 175), defined as birth weight < 10 th centile according to customized standards, and in a control group (n = 875). Among SGA cases, those with birth weight < 3 rd centile and/or abnormal uterine artery pulsatility index (UtA-PI) and/or abnormal cerebroplacental ratio (CPR) were classified as FGR. Logistic regression predictive models were developed for SGA and FGR, and their performance was compared with that obtained using EFWc alone. In SGA cases, EFWc, CPR Z-score and maternal serum concentrations of unconjugated estriol and PlGF were significantly lower, while mean UtA-PI Z-score and lipocalin-2 and inhibin A concentrations were significantly higher, compared with controls. Using EFWc alone, 52% (area under receiver-operating characteristics curve (AUC), 0.82 (95% CI, 0.77-0.85)) of SGA and 64% (AUC, 0.86 (95% CI, 0.81-0.91)) of FGR cases were predicted at a 10% false-positive rate. A combined screening model including a-priori risk (maternal characteristics), EFWc, UtA-PI, PlGF and estriol (with lipocalin-2 for SGA) achieved a detection rate of 61% (AUC, 0.86 (95% CI, 0.83-0.89)) for SGA cases and 77% (AUC, 0.92 (95% CI, 0.88-0.95)) for FGR. The combined model for the

  15. [Weight/head circumference ratio at birth for assessing fetal growth].

    PubMed

    Gonçalves, Fabiana Cristina Lima da Silva Pastich; Lira, Pedro Israel Cabral de; Eickmann, Sophie Helena; Lima, Marilia de Carvalho

    2015-09-01

    The objective of this study was to use weight/head circumference ratio at birth to assess fetal growth. A retrospective cohort study was conducted in Zona da Mata, Pernambuco State, Brazil, with 915 term infants. Infants' anthropometric measurements and data on prenatal care, smoking during pregnancy, family income, and maternal schooling and nutritional status were collected in the first 24 hours after birth. Infants were classified as proportionate (weight/head circumference ratio ≥ 0.90) versus disproportionate (< 0.90). Lower mean weight/head circumference ratio was associated with maternal smoking, younger age, inadequate prenatal care, and low BMI, height, and triceps skinfold thickness. Mean weight, length, head and chest circumference, arm circumference, and triceps skinfold thickness were lower among infants with disproportionate weight/head circumference ratio, independently of sex. In conclusion, weight/head circumference ratio and birth weight are important indicators of fetal growth.

  16. Exposure to Ergot Alkaloids During Gestation Reduces Fetal Growth in Sheep

    NASA Astrophysics Data System (ADS)

    Duckett, Susan; Pratt, Scott; Andrae, John

    2014-08-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: 1) endophyte-infected (Neotyphodium coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and 2) endophyte-free tall fescue seed (E-; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E-. Organ and muscle weights were also lighter for E+ than E-. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development.

  17. Effect of Maternal Obesity on Fetal Growth and Expression of Placental Fatty Acid Transporters.

    PubMed

    Ye, Kui; Li, Li; Zhang, Dan; Li, Yi; Wang, Hai Qing; Lai, Han Lin; Hu, Chuan Lai

    2017-12-15

    To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters. Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot. Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (p<0.05). The fetal/placental weight ratio of DIO dams was significantly reduced compared with the fetal/placental weight ratio of CON-CON dams (p<0.05). The mRNA expression of GLUT-1 and SNAT-2 were not significantly different between groups. The mRNA and protein expression levels of CD36, FATP-1, and FATP-4 in DIO dams were decreased significantly (p<0.05). Maternal obesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.

  18. Neonatal Arterial Morphology Is Related to Body Size in Abnormal Human Fetal Growth.

    PubMed

    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.

  19. Prenatal Lead Exposure and Fetal Growth: Smaller Infants Have Heightened Susceptibility

    PubMed Central

    Rodosthenous, Rodosthenis S.; Burris, Heather H.; Svensson, Katherine; Amarasiriwardena, Chitra J.; Cantoral, Alejandra; Schnaas, Lourdes; Mercado-García, Adriana; Coull, Brent A.; Wright, Robert O.; Téllez-Rojo, Martha M.; Baccarelli, Andrea A.

    2016-01-01

    Background As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth. Objectives To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth. Methods We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders. Results While linear regression showed a negative association between maternal BLL and BWGA z-score (β=−0.06 z-score units per log2 BLL increase; 95% CI: −0.13, 0.003; P=0.06), quantile regression revealed larger magnitudes of this association in the <30th percentiles of BWGA z-score (β range [−0.08, −0.13] z-score units per log2 BLL increase; all P values <0.05). Mothers in the highest BLL quartile had an odds ratio of 1.62 (95% CI: 0.99–2.65) for having a SGA infant compared to the lowest BLL quartile. Conclusions While both linear and quantile regression showed a negative association between prenatal lead exposure and birthweight, quantile regression revealed that smaller infants may represent a more susceptible subpopulation. PMID:27923585

  20. Prenatal lead exposure and fetal growth: Smaller infants have heightened susceptibility.

    PubMed

    Rodosthenous, Rodosthenis S; Burris, Heather H; Svensson, Katherine; Amarasiriwardena, Chitra J; Cantoral, Alejandra; Schnaas, Lourdes; Mercado-García, Adriana; Coull, Brent A; Wright, Robert O; Téllez-Rojo, Martha M; Baccarelli, Andrea A

    2017-02-01

    As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth. To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth. We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders. While linear regression showed a negative association between maternal BLL and BWGA z-score (β=-0.06 z-score units per log 2 BLL increase; 95% CI: -0.13, 0.003; P=0.06), quantile regression revealed larger magnitudes of this association in the <30th percentiles of BWGA z-score (β range [-0.08, -0.13] z-score units per log 2 BLL increase; all P values<0.05). Mothers in the highest BLL quartile had an odds ratio of 1.62 (95% CI: 0.99-2.65) for having a SGA infant compared to the lowest BLL quartile. While both linear and quantile regression showed a negative association between prenatal lead exposure and birthweight, quantile regression revealed that smaller infants may represent a more susceptible subpopulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. A new customized fetal growth standard for African American women: the PRB/NICHD Detroit Study

    PubMed Central

    Tarca, Adi L.; Romero, Roberto; Gudicha, Dereje W.; Erez, Offer; Hernandez-Andrade, Edgar; Yeo, Lami; Bhatti, Gaurav; Pacora, Percy; Maymon, Eli; Hassan, Sonia S.

    2018-01-01

    Background The assessment of fetal growth disorders requires a standard. Current nomograms for the assessment of fetal growth in African American women have been derived either from neonatal (rather than fetal) biometry data or have not been customized for maternal ethnicity, weight, height, parity, and fetal sex. Objective We sought to 1) develop a new customized fetal growth standard for African American mothers; and 2) compare such a standard to three existing standards for the classification of fetuses as small (SGA) or large (LGA) for gestational age. Study Design A retrospective cohort study included 4,183 women (4,001 African American and 182 Caucasian) from the Detroit metropolitan area who underwent ultrasound examinations between 14 and 40 weeks of gestation (the median number of scans per pregnancy was 5, interquartile range 3-7) and for whom relevant covariate data were available. Longitudinal quantile regression was used to build models defining the “normal” estimated fetal weight (EFW) centiles for gestational age in African American women, adjusted for maternal height, weight, parity, and fetal sex, and excluding pathologic factors with a significant effect on fetal weight. The resulting Perinatology Research Branch/Eunice Kennedy Shriver National Institute of Child Health and Human Development (hereinafter, PRB/NICHD) growth standard was compared to 3 other existing standards—the customized gestation-related optimal weight (GROW) standard; the Eunice Kennedy Shriver National Institute of Child Health and Human Development (hereinafter, NICHD) African American standard; and the multinational World Health Organization (WHO) standard—utilized to screen fetuses for SGA (<10th centile) or LGA (>90th centile) based on the last available ultrasound examination for each pregnancy. Results 1) First, the mean birthweight at 40 weeks was 133g higher for neonates born to Caucasian than to African American mothers and 150g higher for male than female

  2. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

    PubMed

    Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

    2013-08-15

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  3. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

    PubMed Central

    Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

    2013-01-01

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. PMID:25206528

  4. Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh

    PubMed Central

    Gernand, Alison D.; Schulze, Kerry J.; Nanayakkara-Bind, Ashika; Arguello, Margia; Shamim, Abu Ahmed; Ali, Hasmot; Wu, Lee; West, Keith P.; Christian, Parul

    2015-01-01

    Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies. Trial Registration ClinicalTrials.gov NCT00860470 PMID:26431336

  5. Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.

    PubMed

    Gernand, Alison D; Schulze, Kerry J; Nanayakkara-Bind, Ashika; Arguello, Margia; Shamim, Abu Ahmed; Ali, Hasmot; Wu, Lee; West, Keith P; Christian, Parul

    2015-01-01

    Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies. ClinicalTrials.gov NCT00860470.

  6. Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains.

    PubMed

    Falcon, M; Pichini, S; Joya, J; Pujadas, M; Sanchez, A; Vall, O; García Algar, O; Luna, A; de la Torre, R; Rotolo, M C; Pellegrini, M

    2012-05-10

    Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and

  7. Maternal Exposure to Bisphenol-A and Fetal Growth Restriction: A Case-Referent Study

    PubMed Central

    Burstyn, Igor; Martin, Jonathan W.; Beesoon, Sanjay; Bamforth, Fiona; Li, Qiaozhi; Yasui, Yutaka; Cherry, Nicola M.

    2013-01-01

    We conducted a case-referent study of the effect of exposure to bisphenol-A on fetal growth in utero in full-term, live-born singletons in Alberta, Canada. Newborns <10 percentile of expected weight for gestational age and sex were individually matched on sex, maternal smoking and maternal age to referents with weight appropriate to gestational age. Exposure of the fetus to bisphenol-A was estimated from maternal serum collected at 15–16 weeks of gestation. We pooled sera across subjects for exposure assessment, stratified on case-referent status and sex. Individual 1:1 matching was maintained in assembling 69 case and 69 referent pools created from 550 case-referent pairs. Matched pools had an equal number of aliquots from individual women. We used an analytical strategy conditioning on matched set and total pool-level values of covariates to estimate individual-level effects. Pools of cases and referents had identical geometric mean bisphenol-A concentrations (0.5 ng/mL) and similar geometric standard deviations (2.3–2.5). Mean difference in concentration between matched pools was 0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for confounding did not suggest bisphenol-A increased fetal growth restriction. Our analysis does not provide evidence to support the hypothesis that bisphenol-A contributes to fetal growth restriction in full-term singletons. PMID:24336026

  8. Growth hormone and Pit-1 expression in bovine fetal lymphoid cells.

    PubMed

    Chen, H T; Schuler, L A; Schultz, R D

    1997-11-01

    Bovine fetal lymphoid cells were examined for growth hormone (GH) and the transcription factor Pit-1/GHF-1 mRNA. GH and Pit-1/GHF-1 transcripts were detected in thymocytes and splenocytes from fetuses at 60, 90, 120, and 270 d of gestation using reverse transcription-polymerase chain reaction (RT-PCR). Northern analysis indicated that the lymphoid GH mRNA was approximately 350 nucleotides larger than in the pituitary. RT-PCR analysis demonstrated that the coding regions as well as 3' untranslated region of the lymphocyte GH and pituitary transcripts were the same. Analysis of the 5'-untranslated region of the lymphocyte GH mRNA showed that transcription began upstream from the start site in the pituitary gland, suggesting differences in regulation in these tissues. Fetal thymocytes and splenocytes expressed Pit-1/GHF-1 mRNA; however, they contained only the 2.5-kb transcript. The GH and Pit-1/GHF-1 mRNA in fetal lymphoid cells supports the hypothesis that lymphocyte-derived GH may function as an autocrine and/or paracrine factor during the development and maturation of the bovine fetal immune system.

  9. Fetal growth trajectories in pregnancies of European and South Asian mothers with and without gestational diabetes, a population-based cohort study.

    PubMed

    Sletner, Line; Jenum, Anne Karen; Yajnik, Chittaranjan S; Mørkrid, Kjersti; Nakstad, Britt; Rognerud-Jensen, Odd Harald; Birkeland, Kåre I; Vangen, Siri

    2017-01-01

    Our aim was to examine the impact of gestational diabetes (GDM), from before the GDM-diagnosis is made, on fetal growth trajectories, and to compare it in Europeans and South Asians; two ethnic groups with dissimilar fetal growth patterns. We studied European (n = 349) and South Asian (n = 184) pregnant women, from the population-based STORK-Groruddalen cohort in Oslo, Norway. Mothers were enrolled in early pregnancy, screened for GDM in gestational week 28 ±2, and classified as "non-GDM", "mild GDM" or "moderate/severe GDM". We measured fetal head circumference, abdominal circumference and femur length by ultrasound, and estimated fetal weight in gestational week 24, 32 and 37, and performed corresponding measurements at birth. In non-GDM pregnancies, South Asian fetuses (n = 156) had a slower growth from gestational week 24, compared with Europeans (n = 310). More than two thirds of the European mothers later diagnosed with GDM were overweight or obese in early pregnancy, while this was not observed in South Asians. Fetuses of GDM mothers tended to be smaller than fetuses of non-GDM mothers in week 24, but thereafter grew faster until birth. This pattern was especially pronounced in fetuses of South Asian mothers with moderate/severe GDM. In week 24 these fetuses had a -0.95 SD (95% CI: -1.53, -0.36) lower estimated fetal weight than their non-GDM counterparts. In contrast, at birth they were 0.45 SD (0.09, 0.81) larger. Offspring of GDM mothers were smaller in mid pregnancy, but subsequently grew faster until birth, compared with offspring of non-GDM mothers. This pattern was most prominent in South Asian mothers with moderate to severe GDM. However, the most remarkable characteristic of these fetuses was not a large size at birth, but the small size in mid pregnancy, before the GDM diagnosis was set.

  10. Predicting the intrauterine fetal death of fetuses with cystic hygroma in early pregnancy.

    PubMed

    Shimura, Mai; Ishikawa, Hiroshi; Nagase, Hiromi; Mochizuki, Akihiko; Sekiguchi, Futoshi; Koshimizu, Naho; Itai, Toshiyuki; Odagami, Mizuha

    2018-01-11

    We investigated whether it was possible to predict the prognosis of fetuses with cystic hygroma in early pregnancy based on the degree of neck thickening. We retrospectively analyzed 57 singleton pregnancies with fetuses with cystic hygroma who were examined before the 22nd week of pregnancy. The fetuses were categorized according to the outcome, structural abnormalities at birth, and chromosomal abnormalities. Here, we proposed a new sonographic predictor with which we assessed neck thickening by dividing the width of the neck thickening by the biparietal diameter, which is expressed as the cystic hygroma width/biparietal diameter ratio. The median cystic hygroma width/biparietal diameter ratio in the intrauterine fetal death group (0.51) was significantly higher than that in the live birth group (0.27). No significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the structural abnormalities group at birth and the no structural abnormalities group, and no significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the chromosomal abnormality group and the no chromosomal abnormality group. We used receiver operating characteristic analysis to evaluate the cystic hygroma width/biparietal diameter ratio to predict intrauterine fetal death. When the cystic hygroma width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is possible to predict intrauterine fetal death in fetuses with cystic hygroma in early pregnancy if cystic hygroma width/biparietal diameter ratio is measured. However, even if cystic hygroma width/biparietal diameter ratio is measured, predicting the presence or absence of a structural abnormality at birth or a chromosomal abnormality is difficult. © 2018 Japanese Teratology Society.

  11. Improving Metabolic Health in Obese Male Mice via Diet and Exercise Restores Embryo Development and Fetal Growth

    PubMed Central

    McPherson, Nicole O.; Bakos, Hassan W.; Owens, Julie A.; Setchell, Brian P.; Lane, Michelle

    2013-01-01

    Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health. PMID:23977045

  12. Early growth and chronic disease: a public health overview.

    PubMed

    Law, Catherine

    2005-07-01

    Infant and childhood growth result from and reflect a range of influences in pre- and postnatal life. These include nutrition, burden of infection and the psycho-social environment. Nutrition in young children is dependent on individual level factors such as fetal experience, infant feeding and weaning practices, and on societal factors such as education of women and economic conditions. The relationship of early postnatal growth to adult disease may be indicative or causal, and may reveal both biological and sociological processes. Although non-insulin-dependent diabetes mellitus (NIDDM) and obesity are risk factors for ischaemic heart disease, the relationships of these three conditions to infant growth differ. Poor infant growth has been associated with higher levels of NIDDM and ischaemic heart disease, but lower levels of adult obesity. Most research has been of populations living in developed countries at different stages of nutritional transition. However, differences in context are not simply limited to the stage of the nutritional transition. They also need to consider the nature of that transition and its social correlates, which may result in the clustering of aetiological influences such as increased body mass and poverty. The size of effect of the relationship of infant growth to adult disease is important not only to determine its relative aetiological importance but also for its potential for public health policy. Such policy also needs to consider the relationships of infant growth to a range of outcomes, both health and human capital, which are not the subject of this workshop.

  13. Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

    PubMed

    Buklijas, Tatjana

    2014-09-01

    Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome.

    PubMed

    Miller, Suzanne L; Huppi, Petra S; Mallard, Carina

    2016-02-15

    Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  15. Early recognition of growth abnormalities permitting early intervention

    USDA-ARS?s Scientific Manuscript database

    Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children's health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height. This rev...

  16. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  17. Growth in Inuit children exposed to polychlorinated biphenyls and lead during fetal development and childhood.

    PubMed

    Dallaire, Renée; Dewailly, Éric; Ayotte, Pierre; Forget-Dubois, Nadine; Jacobson, Sandra W; Jacobson, Joseph L; Muckle, Gina

    2014-10-01

    Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n=290) were evaluated at birth and at 8-14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood. Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Suggested Mechanisms of Tracheal Occlusion Mediated Accelerated Fetal Lung Growth: A Case for Heterogeneous Topological Zones

    PubMed Central

    Marwan, Ahmed I.; Shabeka, Uladzimir; Dobrinskikh, Evgenia

    2018-01-01

    In this article, we report an up-to-date summary on tracheal occlusion (TO) as an approach to drive accelerated lung growth and strive to review the different maternal- and fetal-derived local and systemic signals and mechanisms that may play a significant biological role in lung growth and formation of heterogeneous topological zones following TO. Pulmonary hypoplasia is a condition whereby branching morphogenesis and embryonic pulmonary vascular development are globally affected and is classically seen in congenital diaphragmatic hernia. TO is an innovative approach aimed at driving accelerated lung growth in the most severe forms of diaphragmatic hernia and has been shown to result in improved neonatal outcomes. Currently, most research on mechanisms of TO-induced lung growth is focused on mechanical forces and is viewed from the perspective of homogeneous changes within the lung. We suggest that the key principle in understanding changes in fetal lungs after TO is taking into account formation of unique variable topological zones. Following TO, fetal lungs might temporarily look like a dynamically changing topologic mosaic with varying proliferation rates, dissimilar scale of vasculogenesis, diverse patterns of lung tissue damage, variable metabolic landscape, and different structures. The reasons for this dynamic topological mosaic pattern may include distinct degree of increased hydrostatic pressure in different parts of the lung, dissimilar degree of tissue stress/damage and responses to this damage, and incomparable patterns of altered lung zones with variable response to systemic maternal and fetal factors, among others. The local interaction between these factors and their accompanying processes in addition to the potential role of other systemic factors might lead to formation of a common vector of biological response unique to each zone. The study of the interaction between various networks formed after TO (action of mechanical forces, activation of

  19. Congenital intrahepatic portosystemic shunt: prenatal diagnosis and possible influence on fetal growth.

    PubMed

    Delle Chiaie, L; Neuberger, P; Von Kalle, T

    2008-08-01

    Congenital intrahepatic portosystemic shunts (IPSS) are abnormal vascular communications within the liver between branches of the portal vein and the hepatic veins. They have been recognized as an important disorder in children and should be differentiated from metabolic diseases, the symptoms of which may be similar. Several cases of prenatal diagnosis of abnormalities of the fetal venous system have been described in the literature, but the significance and prognosis of isolated congenital IPSS in prenatal life have not been reported and have only been derived from children. We present a case of congenital IPSS in which there was severe intrauterine growth restriction with a concomitant atypical fetal Doppler pattern. Findings on Doppler ultrasound indicate that the prenatal diagnosis of congenital IPSS is now feasible. (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.

  20. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    PubMed

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. [Role of ST-analysis of fetal ECG in intrapartal fetus monitoring with presumed growth retardation].

    PubMed

    Hruban, L; Janků, P; Zahradnícková, J; Kurecová, B; Roztocil, A; Kachlík, P; Kucera, M; Jelenek, G

    2006-07-01

    Evaluation of the role of ST analysis of fetus ECG for early detection of developing acute hypoxia in the course of delivery of fetuses with presumed growth retardation. A comparison with present way of intrapartal fetus monitoring. Impact on the number of surgical births for indications of threatening fetus hypoxia. Influence of the method on perinatal results and postnatal adaptation of the newborns. A prospective study. Gynecology-Obstetrics Clinic, Masaryk University and Teaching Hospital Brno. Forty seven women with a growth retardation of the fetus diagnosed before delivery who gave birth in the Teaching Hospital in Brno during 2003-2005 and intrapartal ST analysis of fetus ECG was subsequently used, were enrolled into this prospective study (group A). The control group consisted of 87 deliveries taking place in the same period of time and concerning women with fetuses suffering from growth retardation and monitored by standard methods (group B). The standard methods included cardiotocography (CTG), supplemented with pulse oximetry (IFPO) if needed. The diagnosis of intrauterine fetus growth retardation was established on the basis of the results of repeated prepartal ultrasound fetus biometry with estimation of the mass, which corresponded to a group below 10 percentile for the given gestational age. The numbers of vaginal deliveries and surgically treated delivery due to threatening fetus hypoxia (Cesarean section, forceps delivery) were recorded. The authors evaluated postpartal pH from umbilical artery, independently for the group of values of pH < 7.00, the group of pH 7.00-0.10 and pH 7.10 or more. The values of Apgar score were evaluated for the first, fifth and tenth minute, respectively. The neonatologist followed the duration of stay of the newborn at the Newborn Intensive Care Unit, the Intermediate Care Unit, total duration of hospitalization, the occurrence of sepsis in the early newbotn period, the occurrence of hyperbilirubinemia, and the

  2. Prenatal Air Pollution Exposure and Ultrasound Measures of Fetal Growth in Los Angeles, California

    PubMed Central

    Ritz, Beate; Qiu, Jiaheng; Lee, Pei-Chen; Lurmann, Fred; Penfold, Bryan; Weiss, Robert Erin; McConnell, Rob; Arora, Chander; Hobel, Calvin; Wilhelm, Michelle

    2014-01-01

    Background Few previous studies examined the impact of prenatal air pollution exposures on fetal development based on ultrasound measures during pregnancy. Methods In a prospective birth cohort of more than 500 women followed during 1993-1996 in Los Angeles, California, we examined how air pollution impacts fetal growth during pregnancy. Exposure to traffic related air pollution was estimated using CALINE4 air dispersion modeling for nitrogen oxides (NOx) and a land use regression (LUR) model for nitrogen monoxide (NO), nitrogen dioxide (NO2) and NOx. Exposures to carbon monoxide (CO), NO2, ozone (O3) and particles <10 μm in aerodynamic diameter (PM10) were estimated using government monitoring data. We employed a linear mixed effects model to estimate changes in fetal size at approximately 19, 29 and 37 weeks gestation based on ultrasound. Results Exposure to traffic-derived air pollution during 29 to 37 weeks was negatively associated with biparietal diameter at 37 weeks gestation. For each interquartile range (IQR) increase in LUR-based estimates of NO, NO2 and NOx, or freeway CALINE4 NOx we estimated a reduction in biparietal diameter of 0.2-0.3 mm. For women residing within 5 km of a monitoring station, we estimated biparietal diameter reductions of 0.9-1.0 mm per IQR increase in CO and NO2. Effect estimates were robust to adjustment for a number of potential confounders. We did not observe consistent patterns for other growth endpoints we examined. Conclusions Prenatal exposure to traffic-derived pollution was negatively associated with fetal head size measured as biparietal diameter in late pregnancy. PMID:24517884

  3. Prenatal air pollution exposure and ultrasound measures of fetal growth in Los Angeles, California.

    PubMed

    Ritz, Beate; Qiu, Jiaheng; Lee, Pei-Chen; Lurmann, Fred; Penfold, Bryan; Erin Weiss, Robert; McConnell, Rob; Arora, Chander; Hobel, Calvin; Wilhelm, Michelle

    2014-04-01

    Few previous studies examined the impact of prenatal air pollution exposures on fetal development based on ultrasound measures during pregnancy. In a prospective birth cohort of more than 500 women followed during 1993-1996 in Los Angeles, California, we examined how air pollution impacts fetal growth during pregnancy. Exposure to traffic related air pollution was estimated using CALINE4 air dispersion modeling for nitrogen oxides (NOx) and a land use regression (LUR) model for nitrogen monoxide (NO), nitrogen dioxide (NO2) and NOx. Exposures to carbon monoxide (CO), NO2, ozone (O3) and particles <10μm in aerodynamic diameter (PM10) were estimated using government monitoring data. We employed a linear mixed effects model to estimate changes in fetal size at approximately 19, 29 and 37 weeks gestation based on ultrasound. Exposure to traffic-derived air pollution during 29 to 37 weeks was negatively associated with biparietal diameter at 37 weeks gestation. For each interquartile range (IQR) increase in LUR-based estimates of NO, NO2 and NOx, or freeway CALINE4 NOx we estimated a reduction in biparietal diameter of 0.2-0.3mm. For women residing within 5km of a monitoring station, we estimated biparietal diameter reductions of 0.9-1.0mm per IQR increase in CO and NO2. Effect estimates were robust to adjustment for a number of potential confounders. We did not observe consistent patterns for other growth endpoints we examined. Prenatal exposure to traffic-derived pollution was negatively associated with fetal head size measured as biparietal diameter in late pregnancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Fetal growth and air pollution - A study on ultrasound and birth measures.

    PubMed

    Malmqvist, Ebba; Liew, Zeyan; Källén, Karin; Rignell-Hydbom, Anna; Rittner, Ralf; Rylander, Lars; Ritz, Beate

    2017-01-01

    Air pollution has been suggested to affect fetal growth, but more data is needed to assess the timing of exposure effects by using ultrasound measures. It is also important to study effects in low exposure areas to assess eventual thresholds of effects. The MAPSS (Maternal Air Pollution in Southern Sweden) cohort consists of linked registry data for around 48,000 pregnancies from an ultrasound database, birth registry and exposure data based on residential addresses. Measures of air pollution exposure were obtained through dispersion modelling with input data from an emissions database (NO x ) with high resolution (100-500m grids). Air pollution effects were assessed with linear regressions for the following endpoints; biparietal diameter, femur length, abdominal diameter and estimated fetal weight measured in late pregnancy and birth weight and head circumference measured at birth. We estimated negative effects for NO x ; in the adjusted analyses the decrease of abdominal diameter and femur length were -0.10 (-0.17, -0.03) and -0.13 (-0.17, -0.01)mm, respectively, per 10µg/m 3 increment of NO x . We also estimated an effect of NO x -exposures on birth weight by reducing birth weight by 9g per 10µg/m 3 increment of NO x . We estimated small but statistically significant effects of air pollution on late fetal and birth size and reduced fetal growth late in pregnancy in a geographic area with levels below current WHO air quality guidelines. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  6. Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

    PubMed Central

    Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

    2013-01-01

    Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

  7. Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome.

    PubMed

    Kaminen-Ahola, Nina; Ahola, Arttu; Flatscher-Bader, Traute; Wilkins, Sarah J; Anderson, Greg J; Whitelaw, Emma; Chong, Suyinn

    2010-10-01

    Growth restriction, craniofacial dysmorphology, and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal or postnatal, but the underlying mechanisms remain unknown.We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome (e.g., craniofacial changes and growth restriction in adolescent mice). In this study, we characterize in detail the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and by extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of nonfostered, ethanol-exposed and control mice at postnatal day 28.We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This finding suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiologic result of ethanol exposure in utero. We also find that, despite some catch-up growth after 5 weeks of age, the effect extends into adulthood, which is consistent with longitudinal studies in humans.Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis, and lipid metabolism. © 2010 Wiley-Liss, Inc.

  8. Circulating Soluble Endoglin Levels in Pregnant Women in Cameroon and Malawi—Associations with Placental Malaria and Fetal Growth Restriction

    PubMed Central

    Leke, Rose G. F.; Leke, Robert J. I.; Gwanmesia, Philomina; Molyneux, Malcolm E.; Wallace, Diane Taylor; Rogerson, Stephen J.; Kain, Kevin C.

    2011-01-01

    Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre

  9. Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction.

    PubMed

    Silver, Karlee L; Conroy, Andrea L; Leke, Rose G F; Leke, Robert J I; Gwanmesia, Philomina; Molyneux, Malcolm E; Taylor, Diane Wallace; Wallace, Diane Taylor; Rogerson, Stephen J; Kain, Kevin C

    2011-01-01

    Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0

  10. Soluble CD30 in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women.

    PubMed

    Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

    2010-11-01

    This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. A prospective study of fetal head growth, autistic traits and autism spectrum disorder.

    PubMed

    Blanken, Laura M E; Dass, Alena; Alvares, Gail; van der Ende, Jan; Schoemaker, Nikita K; El Marroun, Hanan; Hickey, Martha; Pennell, Craig; White, Scott; Maybery, Murray T; Dissanayake, Cheryl; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; McIntosh, Will; White, Tonya; Whitehouse, Andrew

    2018-04-01

    Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population-based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism-Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population-based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602-612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences

  12. Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels

    PubMed Central

    Tuersunjiang, Nuermaimaiti; Odhiambo, John F.; Long, Nathan M.; Shasa, Desiree R.; Nathanielsz, Peter W.

    2013-01-01

    Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation (day 75) or late (day 135) gestation. Fetal size and weight, as well as fetal organ weights, were greater (P < 0.05) at midgestation in MO ewes than those of CON and MOI ewes. By late gestation, whereas fetal size and weight did not differ among dietary groups, cardiac ventricular weights and wall thicknesses as well as liver and perirenal fat weights remained elevated in fetuses from MO ewes compared with those from CON and MOI ewes. MO ewes and fetuses exhibited elevated (P < 0.05) plasma concentrations of triglycerides, cholesterol, insulin, glucose, and cortisol at midgestation compared with CON and MOI ewes and fetuses. In late gestation, whereas plasma triglycerides and cholesterol, insulin, and cortisol remained elevated in MO vs. CON and MOI ewes and fetuses, glucose concentrations were elevated in both MO and MOI fetuses compared with CON fetuses, which was associated with elevated placental GLUT3 expression in both groups. These data are consistent with the concept that reducing maternal diet of obese/overfed ewes to requirements from early gestation can prevent subsequent alterations in fetal growth, adiposity, and glucose/insulin dynamics. PMID:23921140

  13. Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels.

    PubMed

    Tuersunjiang, Nuermaimaiti; Odhiambo, John F; Long, Nathan M; Shasa, Desiree R; Nathanielsz, Peter W; Ford, Stephen P

    2013-10-01

    Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation (day 75) or late (day 135) gestation. Fetal size and weight, as well as fetal organ weights, were greater (P < 0.05) at midgestation in MO ewes than those of CON and MOI ewes. By late gestation, whereas fetal size and weight did not differ among dietary groups, cardiac ventricular weights and wall thicknesses as well as liver and perirenal fat weights remained elevated in fetuses from MO ewes compared with those from CON and MOI ewes. MO ewes and fetuses exhibited elevated (P < 0.05) plasma concentrations of triglycerides, cholesterol, insulin, glucose, and cortisol at midgestation compared with CON and MOI ewes and fetuses. In late gestation, whereas plasma triglycerides and cholesterol, insulin, and cortisol remained elevated in MO vs. CON and MOI ewes and fetuses, glucose concentrations were elevated in both MO and MOI fetuses compared with CON fetuses, which was associated with elevated placental GLUT3 expression in both groups. These data are consistent with the concept that reducing maternal diet of obese/overfed ewes to requirements from early gestation can prevent subsequent alterations in fetal growth, adiposity, and glucose/insulin dynamics.

  14. Increased Hepatic Glucose Production in Fetal Sheep With Intrauterine Growth Restriction Is Not Suppressed by Insulin

    PubMed Central

    Thorn, Stephanie R.; Brown, Laura D.; Rozance, Paul J.; Hay, William W.; Friedman, Jacob E.

    2013-01-01

    Intrauterine growth restriction (IUGR) increases the risk for metabolic disease and diabetes, although the developmental origins of this remain unclear. We measured glucose metabolism during basal and insulin clamp periods in a fetal sheep model of placental insufficiency and IUGR. Compared with control fetuses (CON), fetuses with IUGR had increased basal glucose production rates and hepatic PEPCK and glucose-6-phosphatase expression, which were not suppressed by insulin. In contrast, insulin significantly increased peripheral glucose utilization rates in CON and IUGR fetuses. Insulin robustly activated AKT, GSK3β, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers. IUGR livers, however, had increased basal FOXO1 phosphorylation, nuclear FOXO1 expression, and Jun NH2-terminal kinase activation during hyperinsulinemia. Expression of peroxisome proliferator–activated receptor γ coactivator 1α and hepatocyte nuclear factor-4α were increased in IUGR livers during basal and insulin periods. Cortisol and norepinephrine concentrations were positively correlated with glucose production rates. Isolated IUGR hepatocytes maintained increased glucose production in culture. In summary, fetal sheep with IUGR have increased hepatic glucose production, which is not suppressed by insulin despite insulin sensitivity for peripheral glucose utilization. These data are consistent with a novel mechanism involving persistent transcriptional activation in the liver that seems to be unique in the fetus with IUGR. PMID:22933111

  15. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

    PubMed

    Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

    2017-08-14

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

  16. Invited commentary: the incremental value of customization in defining abnormal fetal growth status.

    PubMed

    Zhang, Jun; Sun, Kun

    2013-10-15

    Reference tools based on birth weight percentiles at a given gestational week have long been used to define fetuses or infants that are small or large for their gestational ages. However, important deficiencies of the birth weight reference are being increasingly recognized. Overwhelming evidence indicates that an ultrasonography-based fetal weight reference should be used to classify fetal and newborn sizes during pregnancy and at birth, respectively. Questions have been raised as to whether further adjustments for race/ethnicity, parity, sex, and maternal height and weight are helpful to improve the accuracy of the classification. In this issue of the Journal, Carberry et al. (Am J Epidemiol. 2013;178(8):1301-1308) show that adjustment for race/ethnicity is useful, but that additional fine tuning for other factors (i.e., full customization) in the classification may not further improve the ability to predict infant morbidity, mortality, and other fetal growth indicators. Thus, the theoretical advantage of full customization may have limited incremental value for pediatric outcomes, particularly in term births. Literature on the prediction of short-term maternal outcomes and very long-term outcomes (adult diseases) is too scarce to draw any conclusions. Given that each additional variable being incorporated in the classification scheme increases complexity and costs in practice, the clinical utility of full customization in obstetric practice requires further testing.

  17. Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.

    PubMed

    Valerio, Daria G; Xu, Haiming; Eisold, Meghan E; Woolthuis, Carolien M; Pandita, Tej K; Armstrong, Scott A

    2017-01-05

    K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. © 2017 by The American Society of Hematology.

  18. Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice

    PubMed Central

    Valerio, Daria G.; Xu, Haiming; Eisold, Meghan E.; Woolthuis, Carolien M.; Pandita, Tej K.

    2017-01-01

    K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre–induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage–specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. PMID:27827827

  19. Role of fetal nutrient restriction and postnatal catch-up growth on structural and mechanical alterations of rat aorta.

    PubMed

    Gutiérrez-Arzapalo, Perla Y; Rodríguez-Rodríguez, Pilar; Ramiro-Cortijo, David; López de Pablo, Ángel L; López-Giménez, María Rosario; Condezo-Hoyos, Luis; Greenwald, Stephen E; González, Maria Del Carmen; Arribas, Silvia M

    2017-12-26

    Intrauterine growth restriction (IUGR), induced by maternal undernutrition, leads to impaired aortic development. This is followed by hypertrophic remodelling associated with accelerated growth during lactation. Fetal nutrient restriction is associated with increased aortic compliance at birth and at weaning, but not in adult animals. This mechanical alteration may be related to a decreased perinatal collagen deposition. Aortic elastin scaffolds purified from young male and female IUGR animals also exhibit increased compliance, only maintained in adult IUGR females. These mechanical alterations may be related to differences in elastin deposition and remodelling. Fetal undernutrition induces similar aortic structural and mechanical alterations in young male and female rats. Our data argue against an early mechanical cause for the sex differences in hypertension development induced by maternal undernutrition. However, the larger compliance of elastin in adult IUGR females may contribute to the maintenance of a normal blood pressure level. Fetal undernutrition programmes hypertension development, males being more susceptible. Deficient fetal elastogenesis and vascular growth is a possible mechanism. We investigated the role of aortic mechanical alterations in a rat model of hypertension programming, evaluating changes at birth, weaning and adulthood. Dams were fed ad libitum (Control) or 50% of control intake during the second half of gestation (maternal undernutrition, MUN). Offspring aged 3 days, 21 days and 6 months were studied. Blood pressure was evaluated in vivo. In the thoracic aorta we assessed gross structure, mechanical properties (intact and purified elastin), collagen and elastin content and internal elastic lamina (IEL) organization. Only adult MUN males developed hypertension (systolic blood pressure: MUN males  = 176.6 ± 5.6 mmHg; Control males  = 136.1 ± 4.9 mmHg). At birth MUN rats were lighter, with smaller aortic cross-sectional area

  20. INDIVIDUALIZED FETAL GROWTH ASSESSMENT: CRITICAL EVALUATION OF KEY CONCEPTS IN THE SPECIFICATION OF THIRD TRIMESTER GROWTH TRAJECTORIES

    PubMed Central

    Deter, Russell L.; Lee, Wesley; Yeo, Lami; Romero, Roberto

    2012-01-01

    Objectives To characterize 2nd and 3rd trimester fetal growth using Individualized Growth Assessment in a large cohort of fetuses with normal growth outcomes. Methods A prospective longitudinal study of 119 pregnancies was carried out from 18 weeks, MA, to delivery. Measurements of eleven fetal growth parameters were obtained from 3D scans at 3–4 week intervals. Regression analyses were used to determine Start Points [SP] and Rossavik model [P = c (t) k + st] coefficients c, k and s for each parameter in each fetus. Second trimester growth model specification functions were re-established. These functions were used to generate individual growth models and determine predicted s and s-residual [s = pred s + s-resid] values. Actual measurements were compared to predicted growth trajectories obtained from the growth models and Percent Deviations [% Dev = {{actual − predicted}/predicted} × 100] calculated. Age-specific reference standards for this statistic were defined using 2-level statistical modeling for the nine directly measured parameters and estimated weight. Results Rossavik models fit the data for all parameters very well [R2: 99%], with SP’s and k values similar to those found in a much smaller cohort. The c values were strongly related to the 2nd trimester slope [R2: 97%] as was predicted s to estimated c [R2: 95%]. The latter was negative for skeletal parameters and positive for soft tissue parameters. The s-residuals were unrelated to estimated c’s [R2: 0%], and had mean values of zero. Rossavik models predicted 3rd trimester growth with systematic errors close to 0% and random errors [95% range] of 5.7 – 10.9% and 20.0 – 24.3% for one and three dimensional parameters, respectively. Moderate changes in age-specific variability were seen in the 3rd trimester.. Conclusions IGA procedures for evaluating 2nd and 3rd trimester growth are now established based on a large cohort [4–6 fold larger than those used previously], thus permitting more

  1. Disproportionate Fetal Growth and the Risk for Congenital Cerebral Palsy in Singleton Births

    PubMed Central

    Streja, Elani; Miller, Jessica E.; Wu, Chunsen; Bech, Bodil H.; Pedersen, Lars Henning; Schendel, Diana E.; Uldall, Peter; Olsen, Jørn

    2015-01-01

    Objective To investigate the association between proportionality of fetal and placental growth measured at birth and the risk for congenital cerebral palsy (CP). Study Design We identified all live-born singletons born in Denmark between 1995 and 2003 and followed them from 1 year of age until December 31st, 2008. Information on four indices of fetal growth: ponderal index, head circumference/ abdominal circumference ratio, cephalization index and birth weight/ placenta weight ratio was collected. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). All measurements were evaluated as gestational age and sex specific z-scores and in z-score percentile groups, adjusted for potential confounders, and stratified on gestational age groups (<32, 32-36, 37-38, 39, 40, ≥41 weeks). Results We identified 503,784 singleton births, of which 983 were confirmed cases of CP. Head/ abdominal circumference ratio (aHR:1.12; 95%CI:1.07-1.16) and cephalization index (aHR:1.14; 95%CI:1.11-1.16) were associated with the risk of CP irrespective of gestational age. Birth weight-placental weight ratio was also associated with CP in the entire cohort (aHR:0.90; 95%CI:0.83-0.97). Ponderal index had a u-shaped association with CP, where both children with low and high ponderal index were at higher risk of CP. Conclusions CP is associated with disproportions between birth weight, birth length, placental weight and head circumference suggesting pre and perinatal conditions contribute to fetal growth restriction in children with CP. PMID:25974407

  2. High‐altitude ancestry protects against hypoxia‐associated reductions in fetal growth

    PubMed Central

    Julian, Colleen Glyde; Vargas, Enrique; Armaza, J Fernando; Wilson, Megan J; Niermeyer, Susan; Moore, Lorna G

    2007-01-01

    Objective The chronic hypoxia of high‐altitude (⩾2500 m) residence has been shown to decrease birth weight in all populations studied to date. However, multigenerational high‐altitude populations appear protected relative to newcomer groups. This study aimed to determine whether such protection exists independently of other factors known to influence fetal growth and whether admixed populations (ie, people having both high‐ and low‐altitude ancestry) show an intermediate level of protection. Design 3551 medical records from consecutive deliveries to Andean, European or Mestizo (ie, admixed) women at low, intermediate or high altitudes in Bolivia were evaluated for maternal characteristics influencing fetal growth as measured by birth weight and the frequency of small for gestational age births (SGA or ⩽10th percentile birth weight for gestational age and sex). Two‐way analysis of variance and χ2 tests were used to compare maternal and infant characteristics. The effects of ancestry or altitude on SGA and birth weight were assessed using logistic or linear regression models, respectively. Results Altitude decreased birth weight and increased SGA in all ancestry groups. Andean infants weighed more and were less often SGA than Mestizo or European infants at high altitude (13%, 16% and 33% respectively, p<0.01). After accounting for the influences of maternal hypertensive complications of pregnancy, parity, body weight, and number of prenatal visits, European relative to Andean ancestry increased the frequency of SGA at high altitude nearly fivefold. Conclusions Andean relative to European ancestry protects against altitude‐associated reductions in fetal growth. The intermediate protection seen in the admixed (Mestizo) group is consistent with the influence of genetic or other Andean‐specific protective characteristics. PMID:17329275

  3. Formulae Based on Biomathematics to Estimate the Standard Value of Fetal Growth of Japanese.

    PubMed

    Miyagi, Yasunari; Tada, Katsuhiko; Takayoshi, Riko; Oguni, Nobutsugu; Sato, Yasushi; Shibata, Maki; Kiyokawa, Machiko; Hashimoto, Tadashi; Takada, Tomoyoshi; Oda, Takashi; Miyake, Takahito

    2018-04-01

    We devised biomathematics-based formulae to estimate the standard values of fetal growth of Japanese after 22 weeks' gestation. The growth rates of bi-parietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal body weight (EFBW) at the time of gestation were assumed to be proportional to the product of the value at the time and the rest value of an unknown maximum value, respectively. The EFBW was also assumed to follow a multiple logistic function of BPD, AC and FL to fit the standard values of Japanese fetuses published by the Japan Society of Ultrasonics in Medicine. The Mann-Whitney test was used for statistical analysis. The values as a function of gestational day, t, were as follows: BPD(t)=99.6/(1+exp (2.725-0.01837*t)) (mm); AC(t)=39.7/(1+exp (2.454-0.01379*t)) (cm); FL(t)=79.6/(1+exp (2.851-0.01710*t)) (mm); EFBW(t)=8045.1/(1+exp (6.028-0.06582*BPD(t)-0.1469*AC(t)+ 0.07377*FL(t))) (g). EFBW as a function of BPD, AC and FL was as follows: EFBW=8045.1/(1+exp (4.747+ 0.02584*BPD+0.1010*AC-0.1416*FL)) (g). When the BPD, AC and FL were at -2 standard deviation (SD), -1SD, mean and + 2SD, the EFBW values calculated by the formula were statistically closer to the standard values than conventional formulas with p-values of 4.871×10-7, 4.228×10-7, 9.777×10-7 and 0.028, respectively. The formulae based on biomathematics might be useful to estimate the fetal growth standard values.

  4. Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep.

    PubMed

    Veiga-Lopez, Almudena; Steckler, Teresa L; Abbott, David H; Welch, Kathleen B; MohanKumar, Puliyur S; Phillips, David J; Refsal, Kent; Padmanabhan, Vasantha

    2011-01-01

    Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ~147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64-66, 87-90, and 139-140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep.

  5. Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.

    PubMed

    Di Bernardo, Julie; Maiden, Michael M; Hershenson, Marc B; Kunisaki, Shaun M

    2014-06-01

    Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Pregnant Sprague-Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Intrauterine growth retardation promotes fetal intestinal autophagy in rats via the mechanistic target of rapamycin pathway

    PubMed Central

    WANG, Chao; ZHANG, Ruiming; ZHOU, Le; HE, Jintian; HUANG, Qiang; SIYAL, Farman A; ZHANG, Lili; ZHONG, Xiang; WANG, Tian

    2017-01-01

    Intrauterine growth retardation (IUGR) impairs fetal intestinal development, and is associated with high perinatal morbidity and mortality. However, the mechanism underlying this intestinal injury is largely unknown. We aimed to investigate this mechanism through analysis of intestinal autophagy and related signaling pathways in a rat model of IUGR. Normal weight (NW) and IUGR fetuses were obtained from primiparous rats via ad libitum food intake and 50% food restriction, respectively. Maternal serum parameters, fetal body weight, organ weights, and fetal blood glucose were determined. Intestinal apoptosis, autophagy, and the mechanistic target of rapamycin (mTOR) signaling pathway were analyzed. The results indicated that maternal 50% food restriction reduced maternal serum glucose, bilirubin, and total cholesterol and produced IUGR fetuses, which had decreased body weight; blood glucose; and weights of the small intestine, stomach, spleen, pancreas, and kidney. Decreased Bcl-2 and increased Casp9 mRNA expression was observed in IUGR fetal intestines. Analysis of intestinal autophagy showed that the mRNA expression of WIPI1, MAP1LC3B, Atg5, and Atg14 was also increased, while the protein levels of p62 were decreased in IUGR fetuses. Compared to NW fetuses, IUGR fetuses showed decreased mTOR protein levels and enhanced mRNA expression of ULK1 and Beclin1 in the small intestine. In summary, the results indicated that maternal 50% food restriction on gestational days 10–21 reduced maternal serum glucose, bilirubin, and total cholesterol contents, and produced IUGR fetuses that had low blood glucose and reduced small intestine weight. Intestinal injury of IUGR fetuses caused by maternal food restriction might be due to enhanced apoptosis and autophagy via the mTOR signaling pathway. PMID:28855439

  7. Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth

    PubMed Central

    Julian, Colleen Glyde; Wilson, Megan J.; Lopez, Miriam; Yamashiro, Henry; Tellez, Wilma; Rodriguez, Armando; Bigham, Abigail W.; Shriver, Mark D.; Rodriguez, Carmelo; Vargas, Enrique; Moore, Lorna G.

    2009-01-01

    The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.g., Europeans). Uterine artery (UA) blood flow is greater during pregnancy in Andeans than Europeans at high altitude; however, it is not clear whether such blood flow differences play a causal role in ancestry-associated variations in fetal growth. We tested the hypothesis that greater UA blood flow contributes to the protection of fetal growth afforded by Andean ancestry by comparing UA blood flow and fetal growth throughout pregnancy in 137 Andean or European residents of low (400 m; European n = 28, Andean n = 23) or high (3,100–4,100 m; European n = 51, Andean n = 35) altitude in Bolivia. Blood flow and fetal biometry were assessed by Doppler ultrasound, and maternal ancestry was confirmed, using a panel of 100 ancestry-informative genetic markers (AIMs). At low altitude, there were no ancestry-related differences in the pregnancy-associated rise in UA blood flow, fetal biometry, or birth weight. At high altitude, Andean infants weighed 253 g more than European infants after controlling for gestational age and other known influences. UA blood flow and O2 delivery were twofold greater at 20 wk in Andean than European women at high altitude, and were paralleled by greater fetal size. Moreover, variation in the proportion of Indigenous American ancestry among individual women was positively associated with UA diameter, blood flow, O2 delivery, and fetal head circumference. We concluded that greater UA blood flow protects against hypoxia-associated reductions in fetal growth, consistent with the hypothesis that genetic factors enabled Andeans to achieve a greater pregnancy-associated rise in UA blood flow and O2 delivery than European women at high altitude. PMID:19244584

  8. Differential correlations between maternal hair levels of tobacco and alcohol with fetal growth restriction clinical subtypes.

    PubMed

    Sabra, Sally; Malmqvist, Ebba; Almeida, Laura; Gratacos, Eduard; Gomez Roig, Maria Dolores

    2018-08-01

    Maternal exposure to tobacco and alcohol is a known cause, among others, for fetal growth restriction (FGR). Clinically, FGR can be subclassified into two forms: intrauterine growth restriction (IUGR) and small for gestational age (SGA), based on the severity of the growth retardation, and abnormal uterine artery Doppler or cerebro-placental ratio. This study aimed at investigating any differential correlation between maternal exposures to these toxins with the two clinical forms of FGR. Therefore, a case-control study was conducted in Barcelona, Spain. Sixty-four FGR subjects, who were further subclassified into IUGR (n = 36) and SGA (n = 28), and 89 subjects matched appropriate-for-gestational age (AGA), were included. The levels of nicotine (NIC) and ethyl glucuronide (EtG), biomarkers of tobacco and alcohol exposure, respectively, were assessed in the maternal hair in the third trimester. Our analysis showed 65% of the pregnant women consumed alcohol, 25% smoked, and 19% did both. The odds ratios (ORs) of IUGR were 21 times versus 14 times for being SGA with maternal heavy smoking, while with alcohol consumption the ORs for IUGR were 22 times versus 37 times for the SGA group. The differential correlations between these toxins with the two subtypes of FGR suggest different mechanisms influencing fetal weight. Our alarming data of alcohol consumption during pregnancy should be considered for further confirmation among Spanish women. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

    PubMed Central

    Solano, María Emilia; Kowal, Mirka Katharina; O’Rourke, Greta Eugenia; Horst, Andrea Kristina; Modest, Kathrin; Plösch, Torsten; Barikbin, Roja; Remus, Chressen Catharina; Berger, Robert G.; Jago, Caitlin; Ho, Hoang; Sass, Gabriele; Parker, Victoria J.; Lydon, John P.; DeMayo, Francesco J.; Hecher, Kurt; Karimi, Khalil; Arck, Petra Clara

    2015-01-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor– or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. PMID:25774501

  10. Studies on the growth of the fetal guinea pig. The effects of ligation of the uterine artery on organ growth and development.

    PubMed

    Lafeber, H N; Rolph, T P; Jones, C T

    1984-12-01

    The effects of reduced maternal placental blood flow on the growth and development of the fetal guinea pig have been studied by unilateral ligation of the uterine artery at day 30 of pregnancy. Fetal guinea pigs were investigated about 20 or 30 days later. In about one-third of cases fetal death occurred, in another third fetuses less than 60% of normal weight were observed and in the remainder all fetuses were in the normal weight range. In the growth retarded fetuses prenatal growth occurred at about 50% of the rate in control. There was no postnatal 'catch up' as growth still remained lower than in controls. Restricted fetal growth affected particularly development of the visceral tissues in which case size declined in proportion to body weight. Brain and adrenal by comparison were less affected as their contribution to total body weight increased, but even so in the severely retarded fetuses the mass of both fell. The responses of the liver were in general consistent with a delay in the pattern of development. Thus DNA, RNA, protein and haematopoietic cell content changes occurred later than normal. In contrast an enhanced deposition of glycogen was apparent in the liver of the growth-retarded fetus. The results indicate some of the ways in which nutritional deprivation of the fetuses leads to reprogramming of growth and maturation of selected fetal tissues to allow non-essential changes to await more favourable times.

  11. Falls, sarcopenia and growth in early life

    PubMed Central

    Sayer, Avan Aihie; Syddall, Holly E; Martin, Helen J; Dennison, Elaine M; Anderson, Frazer H; Cooper, Cyrus

    2007-01-01

    Recent studies have shown that people with poor early growth have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls but it is not known whether poor early growth is related to falls. We investigated this in the Hertfordshire Cohort Study where 2148 participants completed a falls history. Grip strength was used as a marker of sarcopenia. Birth weight, weight at one year and conditional infant growth were analysed in relation to falls history. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height and walking speed in men and women as well as to lower conditional infant growth in men (OR 1.27 [95% CI 1.04, 1.56] per SD decrease in conditional infant growth, p=0.02). This association was attenuated after adjustment for grip strength. Our findings support an association between poor early growth and falls in older men which appears to be mediated partly through sarcopenia. The lack of relationship with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important for risk of falls in later life. PMID:16905644

  12. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth

    PubMed Central

    Zamudio, Stacy; Postigo, Lucrecia; Illsley, Nicholas P; Rodriguez, Carmelo; Heredia, Gladys; Brimacombe, Michael; Echalar, Lourdes; Torricos, Tatiana; Tellez, Wilma; Maldonado, Ivan; Balanza, Elfride; Alvarez, Tatiana; Ameller, Julio; Vargas, Enrique

    2007-01-01

    Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O2 delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O2 delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n= 180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphims. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P < 0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O2 delivery regardless of ancestry. But the hypothesis was rejected as O2 delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O2 delivery, regardless of altitude (P < 0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P < 0.01), but admixture was not related to any of the O2 transport variables. Genetically mediated differences in maternal O2 delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O2 and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O2 delivery in these pregnancies was 99 ± 3 ml min−1, ∼5-fold greater than near-term fetal O2 consumption. Deficits in maternal O2 transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth. PMID:17510190

  13. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.

    PubMed

    Vayssière, C; Sentilhes, L; Ego, A; Bernard, C; Cambourieu, D; Flamant, C; Gascoin, G; Gaudineau, A; Grangé, G; Houfflin-Debarge, V; Langer, B; Malan, V; Marcorelles, P; Nizard, J; Perrotin, F; Salomon, L; Senat, M-V; Serry, A; Tessier, V; Truffert, P; Tsatsaris, V; Arnaud, C; Carbonne, B

    2015-10-01

    Small for gestational age (SGA) is defined by weight (in utero estimated fetal weight or birth weight) below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually correspond with SGA associated with evidence indicating abnormal growth (with or without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2). Birthweight curves are not appropriate for the identification of SGA at early gestational ages because of the disorders associated with preterm delivery. In utero curves represent physiological growth more reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent introduction at national level. This choice is based on evidence of feasibility and the absence of any proven benefits for individualized curves for perinatal health in the general population (professional consensus). Children born with FGR or SGA have a higher risk of minor cognitive deficits, school problems and metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked. The measurement of fundal height remains relevant to screening after 22 weeks of gestation (Grade C). The biometric ultrasound indicators recommended are: head circumference (HC), abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening

  14. Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

    PubMed

    Satterfield, M Carey; Bazer, Fuller W; Spencer, Thomas E; Wu, Guoyao

    2010-02-01

    Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

  15. Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth.

    PubMed

    Harmon, Kristin A; Gerard, Lori; Jensen, Dalan R; Kealey, Elizabeth H; Hernandez, Teri L; Reece, Melanie S; Barbour, Linda A; Bessesen, Daniel H

    2011-10-01

    We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates. This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

  16. Birth weight and fetal growth in infants born to female hairdressers and their sisters.

    PubMed

    Axmon, A; Rylander, L

    2009-03-01

    To investigate birth weight and fetal growth in female hairdressers, while controlling for intergenerational effects and effects related to childhood exposures. A cohort of women who had attended vocational schools for hairdressers were compared to their sisters with respect to birth weight and fetal growth (measured as small for gestational age (SGA) or large for gestational age (LGA), respectively) in their infants. In total, 6223 infants born to 3137 hairdressers and 8388 infants born to 3952 hairdressers' sisters were studied. Among the infants born to the hairdressers' sisters, the distribution of birth weights were wider than that among the infants born to the hairdressers. This was also reflected in that hairdresser cohort affiliation tended to be protective against both SGA (odds ratio 0.80; 95% confidence interval 0.49 to 1.31) and LGA (0.77; 0.54 to 1.09). For LGA, this effect was even more pronounced among women who had actually worked as hairdressers during at least one pregnancy (0.60; 0.39 to 0.92). The infants born to these women also had a significantly lower mean birth weight (3387 g vs 3419 g; p = 0.033). The results from the present study suggest that infants born to hairdressers have a decreased risk of being LGA. This is most likely not caused by a shift in birth weight distribution or abnormal glucose metabolism.

  17. Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep.

    PubMed

    Dodson, R Blair; Rozance, Paul J; Petrash, Carson C; Hunter, Kendall S; Ferguson, Virginia L

    2014-02-01

    Intrauterine growth restriction (IUGR) is a fetal complication of pregnancy epidemiologically linked to cardiovascular disease in the newborn later in life. However, the mechanism is poorly understood with very little research on the vascular structure and function during development in healthy and IUGR neonates. Previously, we found vascular remodeling and increased stiffness in the carotid and umbilical arteries, but here we examine the remodeling and biomechanics in the larger vessels more proximal to the heart. To study this question, thoracic and abdominal aortas were collected from a sheep model of placental insufficiency IUGR (PI-IUGR) due to exposure to elevated ambient temperatures. Aortas from control (n = 12) and PI-IUGR fetuses (n = 10) were analyzed for functional biomechanics and structural remodeling. PI-IUGR aortas had a significant increase in stiffness (P < 0.05), increased collagen content (P < 0.05), and decreased sulfated glycosaminoglycan content (P < 0.05). Our derived constitutive model from experimental data related increased stiffness to reorganization changes of increased alignment angle of collagen fibers and increased elastin (P < 0.05) in the thoracic aorta and increased concentration of collagen fibers in the abdominal aorta toward the circumferential direction verified through use of histological techniques. This fetal vascular remodeling in PI-IUGR may set the stage for possible altered growth and development and help to explain the pathophysiology of adult cardiovascular disease in previously IUGR individuals.

  18. Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction.

    PubMed

    Pedroso, Marianna Amaral; Palmer, Kirsten Rebecca; Hodges, Ryan James; Costa, Fabricio da Silva; Rolnik, Daniel Lorber

    2018-05-01

     To perform a comprehensive review of the current evidence on the role of uterine artery Doppler, isolated or in combination with other markers, in screening for preeclampsia (PE) and fetal growth restriction (FGR) in the general population. The review included recently published large cohort studies and randomized trials.  A search of the literature was conducted using Medline, PubMed, MeSH and ScienceDirect. Combinations of the search terms "preeclampsia," "screening," "prediction," "Doppler," "Doppler velocimetry," "fetal growth restriction," "small for gestational age" and "uterine artery" were used. Articles in English (excluding reviews) reporting the use of uterine artery Doppler in screening for PE and FGR were included.  Thirty articles were included. As a single predictor, uterine artery Doppler detects less than 50% of the cases of PE and no more than 40% of the pregnancies affected by FGR. Logistic regression-based models that allow calculation of individual risk based on the combination of multiple markers, in turn, is able to detect ∼ 75% of the cases of preterm PE and 55% of the pregnancies resulting in small for gestational age infants.  The use of uterine artery Doppler as a single predictive test for PE and FGR has poor accuracy. However, its combined use in predictive models is promising, being more accurate in detecting preterm PE than FGR. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

  19. Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison

    PubMed Central

    Class, Quetzal A.; Rickert, Martin E.; Larsson, Henrik; Lichtenstein, Paul; D’Onofrio, Brian M.

    2014-01-01

    Background It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. Aims To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. Method We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. Results In the population, lower birth weight (⩽2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Conclusions Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems. PMID:25257067

  20. Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison.

    PubMed

    Class, Quetzal A; Rickert, Martin E; Larsson, Henrik; Lichtenstein, Paul; D'Onofrio, Brian M

    2014-11-01

    It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. In the population, lower birth weight (⩽ 2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems. Royal College of Psychiatrists.

  1. Social variations in fetal growth in a Russian setting: an analysis of medical records.

    PubMed

    Grjibovski, Andrej M; Bygren, Lars O; Svartbo, Boo; Magnus, Per

    2003-10-01

    The study examines variations in fetal growth by maternal social circumstances in a Russian town. All pregnant women registered at the antenatal clinics in 1999 in Severodvinsk (north-west Russia) and their live born infants comprised the study base (n=1399). Multivariate linear regression analysis was applied to quantify the effect of socio-demographic factors on birthweight and the ponderal index (PI). A clear gradient of birthweight in relation to mothers' education was revealed. Babies of the most educated mothers were 207 g (95% CI, 55, 358) heavier than babies of mothers with basic education. The average weight of those born to mothers with secondary and vocational levels of education was 172 g (95% CI, 91, 253) and 83 g (95% CI, 9, 163) lower compared with infants born to mothers with a university level of education after adjustment for age, parity, pre-pregnancy weight, marital status, maternal occupation, length of gestation, and sex of the baby. Maternal education also influenced the PI. Further studies should focus on the mechanisms of the coherence of maternal education and fetal growth. To ensure that all parts of the society benefit equally from economic and social reforms, social variations in pregnancy outcomes should be monitored during the time of transition.

  2. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: a systematic review.

    PubMed

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Brix, Nis; Nohr, Ellen Aagaard; Bonde, Jens Peter Ellekilde; Henriksen, Tine Brink

    2015-01-01

    Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with reduced fetal growth. However, the results of human studies are inconsistent. To summarize the evidence of an association between exposure to PFASs, particularly PFOS and PFOA, and human fetal growth. Systematic literature searches were performed in MEDLINE and EMBASE. We included original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant articles. Study characteristics and results were extracted to structured tables. The completeness of reporting as well as the risk of bias and confounding were assessed. Fourteen studies were eligible. In utero PFOA exposure was associated with decreased measures of continuous birth weight in all studies, even though the magnitude of the association differed and many results were statistically insignificant. PFOS exposure and birth weight were associated in some studies, while others found no association. Higher PFOS and PFOA concentrations were associated with decreased average birth weight in most studies, but only some results were statistically significant. The impact on public health is unclear, but the global exposure to PFASs warrants further investigation.

  3. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise.

    PubMed

    McQueen, Dana B; Bernardi, Lia A; Stephenson, Mary D

    2014-04-01

    To assess the prevalence of chronic endometritis in women with a history of recurrent early pregnancy loss (REPL) and/or fetal demise (FD). Observational cohort study using prospectively collected data. Recurrent pregnancy loss program in an academic medical center. Three hundred ninety-five women with a history of two or more pregnancy losses of less than 10 weeks' size or a fetal demise of 10 or more weeks' size. All women had an endometrial biopsy. Chronic endometritis was treated with antibiotics, and a second endometrial biopsy was recommended as a "test of cure." Subsequent live-birth rate (LBR). The overall prevalence of chronic endometritis was 9% (35/395) in this cohort; 7% (21/285) in the REPL group, 14% (8/57) in the FD group, and 11% (6/53) in the combined REPL/FD group. The cure rate was 100% after a course(s) of antibiotics. The subsequent cumulative LBR was 88% (21/24) for the treated chronic endometritis group versus 74% (180/244) for the group without chronic endometritis. The per-pregnancy LBR for the treated chronic endometritis group was 7% (7/98) before treatment versus 56% (28/50) after treatment. There was a high prevalence of chronic endometritis in this cohort. The test of cure was 100% with antibiotics. Subsequent LBRs after treatment were encouraging. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Evaluation of early fetal loss induced by gavage with eastern tent caterpillars in pregnant mares.

    PubMed

    Bernard, William V; LeBlanc, Michelle M; Webb, Bruce A; Stromberg, Arnold J

    2004-09-01

    To determine whether gavage of pregnant mares (housed without access to pasture) with starved eastern tent caterpillars (ETCs) or their excreta is associated with early fetal loss (EFL), panophthalmitis, or pericarditis. Randomized clinical trial. 15 mares. 15 mares with fetuses from 40 to 80 days of gestation (dGa) were randomly assigned to 1 of 3 groups and received 2.5 g of ETC excreta, 50 g of starved ETCs, or 500 mL of water, respectively, once daily for 10 days. Mares were housed in box stalls, walked twice daily, and not allowed access to pasture for 12 days before or during the 21-day trial. 4 of 5 mares gavaged with starved ETCs (group 2) aborted on trial days 8 (2 mares), 10, and 13. No control mares or mares that received excreta aborted. Differences between the ETC group and other groups were significant. Abortion occurred on 49, 64, 70, and 96 dGa. Allantoic fluids became hyperechoic the day before or the day of fetal death. Alpha streptococci were recovered from 1 fetus and Serratia marcescens from 3 fetuses. Neither panophthalmitis nor pericarditis was seen. The abortifacient component of the ETCs was not elucidated. These findings suggest that mares with fetuses from 40 to 120 days of gestation should not be exposed to ETCs because they may induce abortion.

  5. Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

    PubMed

    Rozance, Paul J; Zastoupil, Laura; Wesolowski, Stephanie R; Goldstrohm, David A; Strahan, Brittany; Cree-Green, Melanie; Sheffield-Moore, Melinda; Meschia, Giacomo; Hay, William W; Wilkening, Randall B; Brown, Laura D

    2018-01-01

    Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O 2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P < 0.05). Absolute hindlimb blood flow was reduced in IUGR (IUGR: 32.9 ± 5.6 ml min -1 ; CON: 60.9 ± 6.5 ml min -1 ; P < 0.005), although flow normalized to hindlimb weight was similar between groups

  6. Evaluation of Fetal Intestinal Cell Growth and Antimicrobial Biofunctionalities of Donor Human Milk After Preparative Processes.

    PubMed

    Kanaprach, Pasinee; Pongsakul, Nutkridta; Apiwattanakul, Nopporn; Muanprasat, Chatchai; Supapannachart, Sarayut; Nuntnarumit, Pracha; Chutipongtanate, Somchai

    2018-04-01

    Donor human milk is considered the next best nutrition following mother's own milk to prevent neonatal infection and necrotizing enterocolitis in preterm infants who are admitted at neonatal intensive care unit. However, donor milk biofunctionalities after preparative processes have rarely been documented. To evaluate biofunctionalities preserved in donor milk after preparative processes by cell-based assays. Ten pools of donor milk were produced from 40 independent specimens. After preparative processes, including bacterial elimination methods (holder pasteurization and cold-sterilization microfiltration) and storage conditions (-20°C freezing storage and lyophilization) with varied duration of storage (0, 3, and 6, months), donor milk biofunctionalities were examined by fetal intestinal cell growth and antimicrobial assays. At baseline, raw donor milk exhibited 193.1% ± 12.3% of fetal intestinal cell growth and 42.4% ± 11.8% of antimicrobial activities against Escherichia coli. After bacteria eliminating processes, growth promoting activity was better preserved in pasteurized donor milk than microfiltrated donor milk (169.5% ± 14.3% versus 146.0% ± 11.8%, respectively; p < 0.005), whereas antimicrobial activity showed no difference between groups (38.3% ± 14.1% versus 53.7% ± 17.3%, respectively; p = 0.499). The pasteurized donor milk was further examined for the effects of storage conditions at 3 and 6 months. Freezing storage, but not lyophilization, could preserve higher growth-promoting activity during 6 months of storage (163.0% ± 9.4% versus 72.8% ± 6.2%, respectively; p < 0.005). Nonetheless, antimicrobial activity was lost at 6 months, regardless of the storage methods. This study revealed that fetal intestinal cell growth and antimicrobial assays could be applied to measure donor milk biofunctionalities and support the utilization of donor milk within 3 months after preparative processes.

  7. Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: a descriptive study.

    PubMed

    Walraven, M; Beelen, R H J; Ulrich, M M W

    2015-05-01

    TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce. The aim of this study was to compare the canonical TGF-β signaling in unwounded human fetal and adult skin. Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy skin. All components of the canonical TGF-β pathway were present in unwounded fetal skin. Compared to adult skin, fetal skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and adult skin. This descriptive study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and adult skin. The findings of this study can be a starting point for further research into the role of TGF-β signaling in scarless healing. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

  9. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

    PubMed Central

    Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

    2015-01-01

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  10. Fetal exposure to lead during pregnancy and the risk of preterm and early-term deliveries.

    PubMed

    Cheng, Lu; Zhang, Bin; Huo, Wenqian; Cao, Zhongqiang; Liu, Wenyu; Liao, Jiaqiang; Xia, Wei; Xu, Shunqing; Li, Yuanyuan

    2017-08-01

    Studies have reported the association between lead exposure during pregnancy and preterm birth. However, findings are still inconsistent. This prospective birth cohort study evaluated the risks of preterm and early-term births and its association with prenatal lead exposure in Hubei, China. A total of 7299 pregnant women were selected from the Healthy Baby Cohort. Maternal urinary lead levels were measured by the Inductively Coupled Plasma Mass Spectrometry. The associations between tertiles of urinary lead levels and the risks of preterm and early-term deliveries were assessed using multiple logistic regression models. The geometric mean of creatinine-adjusted urinary lead concentrations among all participating mothers, preterm birth, and early-term birth were 3.19, 3.68, and 3.17μg/g creatinine, respectively. A significant increase in the risk of preterm births was associated with the highest urinary lead tertile after adjusting for confounders with odds ratio (OR) of 1.96. The association was more pronounced among 25-36 years old mothers with OR of 2.03. Though significant p trends were observed between lead exposure (medium and high tertiles) and the risk of early-term births, their ORs were not significant. Our findings indicate that the risk of preterm birth might increase with higher fetal lead exposure, particularly among women between the age of 25 and 36 years. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal hypoxia and impaired fetal growth

    PubMed Central

    Julian, Colleen G.; Yang, Ivana V.; Browne, Vaughn A.; Vargas, Enrique; Rodriguez, Carmelo; Pedersen, Brent S.; Moore, Lorna G.; Schwartz, David A.

    2014-01-01

    Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxia-related effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-level residents in the nonpregnant state or during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes apparent between 25 and 29 wk of gestation and continues until delivery. Our sampling strategy was designed to capture changes occurring before (20 wk) and during (36 wk) the time frame of slowed fetal growth. PBMC gene expression profiles were generated using human gene expression microarrays and compared between altitudes. Biological pathways were identified using pathway analysis. Modest transcriptional differences were observed between altitudes in the nonpregnant state. Of the genes that were differentially expressed at high altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36 wk: 985 probes mapped to 700 genes), several are of pathological relevance for fetal growth restriction. In particular, transcriptional changes were consistent with the negative regulation of peroxisome proliferator-activated receptor γ (PPARγ) at high altitude; such effects were accompanied by reduced birth weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level. Our findings indicate that chronic exposure to hypoxia during pregnancy alters maternal gene expression patterns in general and, in particular, expression of key genes involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of fetal growth restriction.—Julian, C. G., Yang, I. V., Browne, V. A., Vargas, E., Rodriguez, C., Pedersen, B. S., Moore, L. G., Schwartz, D. A. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal

  12. Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

    PubMed

    Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

    2018-01-01

    Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

  13. The growth of maternal-fetal emotional attachment in pregnant adolescents: a prospective cohort study.

    PubMed

    Rowe, Heather J; Wynter, Karen H; Steele, Angela; Fisher, Jane R W; Quinlivan, Julie A

    2013-12-01

    To describe self-reported maternal-fetal emotional attachment in adolescent women over the course of pregnancy, compare it with adult pregnant women, and identify risk factors for poor attachment. A prospective cohort study. Young mothers' clinics in 2 public hospitals in metropolitan Melbourne, Australia. English-speaking young women aged 20 years and under attending their first antenatal visit. Self-report questionnaires were completed in each trimester. Validated measures were used to assess anxiety and depression symptoms and maternal-fetal emotional attachment. Data were analyzed with existing data from pregnant adults. Regression analyses were conducted to establish factors independently associated with higher mean first-trimester attachment score and lowest-quartile third trimester score adjusting for confounding variables. Maternal-fetal emotional attachment, assessed by the Quality and Intensity subscales and Global score on Maternal Antenatal Attachment Scale (MAAS). 165/194 (85%) completed the first questionnaire; 130/165 (79%) provided complete data. Mean anxiety but not depression scores were significantly higher in adolescents than adults across pregnancy. Mean (95%CI) first-trimester adolescent Global MAAS was significantly lower than adults (70.3 (68.4, 72.2) vs 76.8 (75.4, 78.2) P < .01), but there were no significant second- or third-trimester between-group differences. Adjusted odds of a lowest-quartile third-trimester MAAS score was significantly associated with lower first-trimester score (P < .001), previous abortion (P = .02) and being born overseas (P = .002). Adolescents report slower development of antenatal emotional attachment than adults. Women with risk factors for poor attachment in late pregnancy are identifiable in early pregnancy and may benefit from additional multidisciplinary care. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  14. A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

    PubMed Central

    Garcia-Canadilla, Patricia; Rudenick, Paula A.; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijens, Bart H.

    2014-01-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  15. Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

    PubMed

    Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

    2016-02-01

    During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia.

    PubMed

    Piairo, Paulina; Moura, Rute S; Baptista, Maria João; Correia-Pinto, Jorge; Nogueira-Silva, Cristina

    2018-01-01

    Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH. © 2018 The Author(s). Published by S. Karger AG, Basel.

  17. Impact of aspirin on fetal growth in diabetic pregnancies according to White classification.

    PubMed

    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

  18. Indoor Exposure and Adverse Birth Outcomes Related to Fetal Growth, Miscarriage and Prematurity—A Systematic Review

    PubMed Central

    Patelarou, Evridiki; Kelly, Frank J.

    2014-01-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in “westernized” countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  19. Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

    PubMed

    Wang, Yan-Ping; Chen, Xu; Zhang, Zhi-Kun; Cui, Hong-Yan; Wang, Peng; Wang, Yue

    2015-12-01

    Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods. © The Author(s) 2014.

  20. Hemodynamic adaptation to suboptimal fetal growth in patients with single ventricle physiology.

    PubMed

    Alsaied, Tarek; Tseng, Stephanie; King, Eileen; Hahn, Eunice; Divanovic, Allison; Habli, Mounira; Cnota, James

    2018-06-10

    In fetuses with structurally normal heart and suboptimal fetal growth (SFG), umbilical artery vascular resistance increases as measured by umbilical artery pulsatility index (UA-PI). The objective of this study is to compare hemodynamic responses to SFG in fetuses with single ventricle (SV) and controls with structurally normal heart. Fetal echocardiograms around 30 weeks of gestation were reviewed. UA-PI and middle cerebral artery pulsatility index (MCA-PI) were calculated. SFG was defined as a birth weight below 25th percentile for gestational age. Studies from 92 fetuses were reviewed-SV (n = 50) and controls (n = 42). The prevalence of SFG was higher in SV compared to controls (46% vs 21%, P = .02). In patients with normal heart and SFG, UAPI was significantly higher than normal controls (P = .003) suggesting increased placental vascular resistance. In SV with SFG there was no difference in UAPI compared to SV without SFG. There was no difference in MCA-PI between the groups. The hemodynamic response to SFG in SV varies from fetuses with structurally normal heart. The mechanism of SFG and the placental pathology may be distinct in SV. © 2018 Wiley Periodicals, Inc.

  1. Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction.

    PubMed

    Erkenekli, K; Keskin, U; Uysal, B; Kurt, Y G; Sadir, S; Çayci, T; Ergün, A; Erkaya, S; Danişman, N; Uygur, D

    2015-04-01

    The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.

  2. Prenatal exposure to polychlorinated biphenyls and fetal growth in British girls.

    PubMed

    Patel, Jill F; Hartman, Terryl J; Sjodin, Andreas; Northstone, Kate; Taylor, Ethel V

    2018-04-17

    Polychlorinated biphenyls (PCBs) are synthetic chemicals that bioaccumulate in the food chain. PCBs were used primarily for industrial applications due to their insulating and fire retardant properties, but were banned in the 1970s in the United States and in the 1980s in the United Kingdom, as adverse health effects following exposure were identified. Previous studies of populations with high PCB exposure have reported inverse associations with birth weight and gestational length. Birth weight is a powerful predictor of infant survival, and low birth weight can predispose infants to chronic conditions in adult life such as diabetes and cardiovascular diseases. Using data from the Avon Longitudinal Study of Parents and Children, we investigated the association between prenatal exposure to PCBs and fetal growth in a sample of 448 mother-daughter dyads. Concentrations of three common PCB analytes, PCB-118, PCB-153 and PCB-187, were measured in maternal serum collected during pregnancy, and fetal growth was measured by birth weight and birth length. Multivariable linear regression was used to examine the associations between PCB analytes and measures of fetal growth, after adjusting for parity, maternal age, pre-pregnancy BMI, educational status, tobacco use and gestational age of infant at sample collection. Birth length, ponderal index and gestational age were not associated with any of the PCB analytes. Mothers' educational status modified associations for PCB analytes with birthweight. We observed significant inverse associations with birth weight only among daughters of mothers with less education. Daughter's birth weight was -138.4 g lower (95% CI: -218.0, -58.9) for each 10 ng/g lipid increase in maternal serum PCB-118. Similarly, every 10 ng/g lipid increase in maternal serum PCB-153 was associated with a -41.9 g (95% CI: -71.6, -12.2) lower birth weight. Every 10 ng/g lipids increase in maternal serum PCB-187, was associated with a -170.4 g (95

  3. [The effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction: a cohort study].

    PubMed

    Shi, M Y; Wang, Y F; Huang, K; Yan, S Q; Ge, X; Chen, M L; Hao, J H; Tong, S L; Tao, F B

    2017-12-06

    Objective: To investigate the effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Methods: From May 2013 to September 2014, a total of 3 474 pregnant women who took their first antenatal care and willing to undergo their prenatal care and delivery in Ma 'anshan Maternity and Child Care Centers were recruited in the cohort study. Excluding subjects without weight data before delivery ( n= 54), pregnancy termination ( n= 162), twins live births ( n= 39), without fetal birth weight data ( n= 7), 3 212 maternal-singleton pairs were enrolled for the final data analysis. Demographic information of pregnant woman, pregnancy history, disease history, height and weight were collected. In the 24(th)-28(th), 32(nd)-36(th) gestational week and childbirth, three follow-up visits were undertaken to collect data of pregnancy weight, pregnancy vomiting, gestational hypertension, gestational diabetes mellitus, newborn gender and birth weight. χ(2) test was used to compare the detection rate of fetal growth restriction in different groups. Multivariate unconditional logistic regression model and spreadsheet were used to analyze the independent and interaction effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Results: The incidence of fetal growth restriction was 9.7%(311/3 212). The incidence of fetal growth restriction in pre-pregnancy underweight group was 14.9% (90/603), higher than that in normal pre-pregnancy weight group (8.7% (194/2 226)) (χ(2)=24.37, P< 0.001). The incidence of fetal growth restriction in inadequate increase of gestational weight group was 17.9% (50/279), higher than the appropriate increase of weight group (11.8% (110/932)) (χ(2)=36.89, P< 0.001). Multivariate unconditional logistic regression analysis showed that compared with normal pre-pregnancy weight group, pre-pregnancy underweightwas a risk factor for fetal growth restriction, with RR (95 %CI ) at 1

  4. Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

    PubMed

    Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

    2015-08-01

    Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

  5. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

    PubMed

    Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

    2015-01-01

    Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

  6. MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH PATTERNS AND NEWBORN SIZE.

    PubMed

    Pölzlberger, Eva; Hartmann, Beda; Hafner, Erich; Stümpflein, Ingrid; Kirchengast, Sylvia

    2017-05-01

    The impact of maternal height, pre-pregnancy weight status and gestational weight gain on fetal growth patterns and newborn size was analysed using a dataset of 4261 singleton term births taking place at the Viennese Danube Hospital between 2005 and 2013. Fetal growth patterns were reconstructed from three ultrasound examinations carried out at the 11th/12th, 20th/21th and 32th/33th weeks of gestation. Crown-rump length, biparietal diameter, fronto-occipital diameter, head circumference, abdominal transverse diameter, abdominal anterior-posterior diameter, abdominal circumference and femur length were determined. Birth weight, birth length and head circumference were measured immediately after birth. The vast majority of newborns were of normal weight, i.e. between 2500 and 4000 g. Maternal height showed a just-significant but weak positive association (r=0.03: p=0.039) with crown-rump length at the first trimester and with the majority of fetal parameters at the second trimester (r>0.06; p0.09; p0.08; p0.17; p0.13; p0.13; p<0.001), were significantly positively associated with newborn size. Some of these associations were quite weak and the statistical significance was mainly due to the large sample size. The association patterns between maternal height and pre-pregnancy weight status with fetal growth patterns (p<0.001), as well as newborn size (p<0.001), were independent of maternal age, nicotine consumption and fetal sex. In general, taller and heavier women gave birth to larger infants. This association between maternal size and fetal growth patterns was detectable from the first trimester onwards.

  7. Prediction of adverse pregnancy outcome in monochorionic- diamniotic twin pregnancies complicated by selective fetal growth restriction.

    PubMed

    Monaghan, Caitriona; Kalafat, Erkan; Binder, Julia; Thilaganathan, Baskaran; Khalil, Asma

    2018-04-28

    To identify key factors implicated in adverse perinatal outcome in monochorionic twin pregnancies complicated by selective fetal growth restriction. This is a retrospective cohort study conducted in a single tertiary referral centre included all monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR). The presence of co-existing twin to twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow (EDF) in the UA of the smaller twin. DV pulsatility indices were converted to z-scores and estimated fetal weight (EFW) values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome. Adverse perinatal outcome was defined according to survival and included both intra-uterine fetal demise and neonatal death of the FGR twin. We analysed 104 pregnancies complicated by sFGR. Sixty-six (63.5%) were diagnosed with type I and 38 (36.5%) with type II at initial presentation. Pregnancies complicated by type II sFGR were diagnosed (median GA 19.6 weeks' vs 21.5 weeks, p=0.012) and delivered (median GA 30.4 weeks' vs 32.57 weeks; p=0.055) earlier and are associated with increased risk of adverse perinatal outcomes (intrauterine demise of the smaller twin 19.7% vs 10.6%, p=0.001), when compared to type I sFGR. Twin pregnancies complicated by sFGR, whether type I or II, resulting in intrauterine demise have a significantly earlier onset of diagnosis (p<0.001), earlier GA at delivery (p<0.05), higher DV pulsatility index (p<0.05), and lower birth weight (BW) centile of the smaller twin (p<0.01) when compared to pregnancies resulting in livebirth. Co-existing TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with

  8. Cognitive outcome in childhood of birth weight discordant monochorionic twins: the long-term effects of fetal growth restriction.

    PubMed

    Swamy, Ravi Shankar; McConachie, Helen; Ng, Jane; Rankin, Judith; Korada, Murthy; Sturgiss, Stephen; Embleton, Nicholas D

    2018-03-02

    Intrauterine growth restriction (IUGR) is associated with poorer outcomes in later life. We used a monochorionic twin model with IUGR in one twin to determine its impact on growth and neurocognitive outcomes. Monochorionic twins with ≥20% birth weight discordance born in the north of England were eligible. Cognitive function was assessed using the British Ability Scales. The Strength and Difficulties Questionnaire was used to identify behavioural problems. Auxological measurements were collected. Generalised estimating equations were used to determine the effects of birth weight on cognition. Fifty-one monochorionic twin pairs were assessed at a mean age of 6.3 years. Mean birth weight difference was 664 g at a mean gestation of 34.7 weeks. The lighter twin had a General Conceptual Ability (GCA) score that was three points lower (Twin L -105.4 vs Twin H -108.4, 95% CI -0.9 to -5.0), and there was a significant positive association (B 0.59) of within-pair birth weight differences and GCA scores. Mathematics and memory skills showed the largest differences. The lighter twin at school age was shorter (mean difference 2.1 cm±0.7) and lighter (mean difference 1.9 kg±0.6). Equal numbers of lighter and heavier twins were reported to have behavioural issues. In a monochorionic twin cohort, fetal growth restriction results in lower neurocognitive scores in early childhood, and there remain significant differences in size. Longer term follow-up will be required to determine whether growth or cognitive differences persist in later child or adulthood, and whether there are any associated longer term metabolic sequelae. © 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.

  9. Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

    PubMed

    Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

    2018-02-20

    The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

  10. Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort

    PubMed Central

    Casas, Maribel; Valvi, Damaskini; Ballesteros-Gomez, Ana; Gascon, Mireia; Fernández, Mariana F.; Garcia-Esteban, Raquel; Iñiguez, Carmen; Martínez, David; Murcia, Mario; Monfort, Nuria; Luque, Noelia; Rubio, Soledad; Ventura, Rosa; Sunyer, Jordi; Vrijheid, Martine

    2015-01-01

    Background: Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies. Objectives: We assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother–child pairs. Methods: We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12–20 and 20–34), and for birth weight, birth length, head circumference at birth, and placental weight. Results: Overall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20–34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (–27 g; 95% CI: –79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12–20 pregnancy weeks [–4.88% of HC average (95% CI: –8.36, –1.36%)]. Conclusions: This study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication. Citation: Casas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernández MF, Garcia-Esteban R, Iñiguez C, Martínez D

  11. Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort.

    PubMed

    Casas, Maribel; Valvi, Damaskini; Ballesteros-Gomez, Ana; Gascon, Mireia; Fernández, Mariana F; Garcia-Esteban, Raquel; Iñiguez, Carmen; Martínez, David; Murcia, Mario; Monfort, Nuria; Luque, Noelia; Rubio, Soledad; Ventura, Rosa; Sunyer, Jordi; Vrijheid, Martine

    2016-04-01

    Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies. We assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother-child pairs. We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12-20 and 20-34), and for birth weight, birth length, head circumference at birth, and placental weight. Overall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20-34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (-27 g; 95% CI: -79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12-20 pregnancy weeks [-4.88% of HC average (95% CI: -8.36, -1.36%)]. This study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication. Casas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernández MF, Garcia-Esteban R, Iñiguez C, Martínez D, Murcia M, Monfort N, Luque N, Rubio S, Ventura R, Sunyer J, Vrijheid M. 2016. Exposure

  12. Amnioinfusion before 26 weeks' gestation for severe fetal growth restriction with oligohydramnios: preliminary pilot study.

    PubMed

    Takahashi, Yuichiro; Iwagaki, Shigenori; Chiaki, Rika; Iwasa, Tomotake; Takenaka, Motoki; Kawabata, Ichiro; Itoh, Mitsuaki

    2014-03-01

    The prognosis for severe fetal growth restriction (FGR) with severe oligohydramnios before 26 weeks' gestation (WG) is currently poor; furthermore, its management is controversial. We report the innovative new management of FGR, such as therapeutic amnioinfusion and tocolysis. For FGR and severe oligohydramnios before 26 WG complicated with absent or reversed umbilical artery end-diastolic flow velocity and/or deceleration by ultrasonography, we performed transabdominal amnioinfusion with tocolysis. Cases with multiple anomalies were excluded. Survival rate and long-term prognosis were analyzed. Among 570 FGR cases, 18 were included in the study. Mean diagnosis and delivery were at 22.6 ± 2.0 and 28.7 ± 3.3 WG. Median birthweight was 625 g (-4.2 standard deviation). Final survival rate was 11/13 (85%). There were five fetal deaths. In seven cases, oligohydramnios improved. Growth was detected in 10/18 fetuses. Furthermore, 8/8 decelerations, 4/12 cases of reversed umbilical artery end-diastolic flow velocity, 7/14 cases of brain-sparing effect, and 6/13 venous Doppler abnormalities were improved. When we detected umbilical cord compression, 8/10 cases were rescued. Eleven infants were followed up for an average of 5 years; one case of cerebral palsy with normal development and 10 cases with intact motor functions without major neurological handicap were confirmed. In cases of extremely severe FGR before 26 WG with oligohydramnios and circulatory failure, amnioinfusion might be a promising, innovative tool. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  13. A Comparative Analysis of Prenatal Care and Fetal Growth in Eight South American Countries

    PubMed Central

    Woodhouse, Cristina; Lopez Camelo, Jorge; Wehby, George L.

    2014-01-01

    There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (<2500 grams; LBW) adjusted for gestational age in eight South American countries using similarly collected data across countries and the same analytical models. OLS and logistic regressions were estimated adjusting for a large set of relevant infant, maternal, and household characteristics and birth year and hospital fixed effects. Birth data were acquired from 140 hospitals that are part of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network. The analytical sample included 56,014 live-born infants (∼69% of total sample) with complete data born without congenital anomalies in the years 1996–2011 in Brazil, Argentina, Chile, Venezuela, Ecuador, Colombia, Bolivia, and Uruguay. Prenatal care visits were significantly (at p<.05) and positively associated with BW and negatively associated with LBW for all countries. The OLS coefficients ranged from 9 grams per visit in Bolivia to 36 grams in Uruguay. The association with LBW was strongest for Chile (OR = 0.87 per visit) and lowest for Argentina and Venezuela (OR = 0.95). The association decreased in the recent decade compared to earlier years. Our findings suggest that estimates of association between prenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country’s healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America. PMID:24625630

  14. Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS.

    PubMed

    Hjorth-Hansen, Anna; Salvesen, Øyvind; Engen Hanem, Liv Guro; Eggebø, Torbjørn; Salvesen, Kjell Å; Vanky, Eszter; Ødegård, Rønnaug

    2018-02-01

    Metformin is used in an attempt to reduce pregnancy complications associated with polycystic ovary syndrome (PCOS). Little is known about the effect of metformin on fetal development and growth. To compare the effect of metformin versus placebo on fetal growth and birth anthropometrics in PCOS offspring compared with a reference population in relation to maternal body mass index (BMI). Post hoc analysis of a randomized controlled trial. Double-blind, placebo-controlled, multicenter study. 258 offspring born to mothers with PCOS. 2000 mg metformin (n = 131) or placebo (n = 121) from first trimester to delivery. Mean abdominal diameter and biparietal diameter (BPD) at gestational weeks 19 and 32. Head circumference (HC), birth length, and weight related to a reference population of healthy offspring, expressed as gestational age- and sex-adjusted z-scores. Metformin- versus placebo-exposed offspring had larger heads at gestational week 32 (BPD, 86.1 mm versus 85.2 mm; P = 0.03) and at birth (HC, 35.6 cm versus 35.1 cm; P < 0.01). Analyses stratified by maternal prepregnancy BMI, larger heads were observed only among offspring of overweight/obese mothers. Among normal-weight mothers, the effect of metformin compared with placebo was reduced length (z-score = -0.96 versus -0.42, P = 0.04) and weight (z-score = -0.44 versus 0.02; P = 0.03). Compared with the reference population, offspring born to PCOS mothers (placebo group) had reduced length (z-score = -0.40; 95% confidence interval, -0.60 to -0.40), but similar birth weight and HC. Metformin exposure resulted in larger head size in offspring of overweight mothers, traceable already in utero. Maternal prepregnancy BMI modified the effect of metformin on offspring anthropometrics. Anthropometrics of offspring born to PCOS mothers differed from those of the reference population. Copyright © 2017 Endocrine Society

  15. Effortful Control Mediates Associations of Fetal Growth with Hyperactivity and Behavioural Problems in 7- to 9-Year-Old Children

    ERIC Educational Resources Information Center

    Schlotz, Wolff; Jones, Alexander; Godfrey, Keith M.; Phillips, David I. W.

    2008-01-01

    Background: Inverse associations of fetal growth with behavioural problems in childhood have been repeatedly reported, suggesting long-term effects of the prenatal developmental environment on behaviour later in life. However, no study so far has examined effects on temperament and potential developmental pathways. Temperamental traits may be…

  16. Polyhydramnios or Excessive Fetal Growth Are Markers for Abnormal Perinatal Outcome in Euglycemic Pregnancies.

    PubMed

    Crimmins, Sarah; Mo, Cecilia; Nassar, Yomna; Kopelman, Jerome N; Turan, Ozhan M

    2018-01-01

     This study aims to investigate the perinatal outcome of fetuses with polyhydramnios and/or accelerated growth among women with a normal oral glucose challenge test (oGCT).  Singleton, nonanomalous pregnancies with an oGCT(< 130 mg/dL) at 24 to 28 weeks, who subsequently demonstrate polyhydramnios (amniotic fluid index > 24 cm or maximum vertical pocket > 8 cm) and/or accelerated growth (abdominal circumference > 95th percentile) on two-third trimester examinations were studied. Maternal demographics, delivery, and neonatal information were recorded. Cases were compared with a reference group (normal oGCT with neither abnormal third-trimester growth nor polyhydramnios).  A total of 282 pregnancies were in the study group, and 663 were in the reference group. Deliveries in the study group were at a higher risk for birth weight (BW)% > 90%, standard deviation, and postpartum hemorrhage when compared with the reference group (adjusted odds ratio: 2.3-5.6). Pregnancies complicated by both polyhydramnios and accelerated fetal growth were significantly more likely to result in a BW% > 90% (odds ratio [OR]: 18.5; 95% confidence interval [CI]: 8.9-38.6) and PPH (OR: 4.2; 95% CI: 2.4-7.6).  Pregnancies with normal oGCT that develop polyhydramnios and accelerated growth are at higher risk for maternal and neonatal complications. Isolated polyhydramnios without accelerated growth increases the risk for delivery complications but not neonatal morbidity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Ultrasonographic measurement of fetal growth parameters over three successive pregnancies in a captive Malayan tapir (Tapirus indicus).

    PubMed

    Hoyer, M J; van Engeldorp Gastelaars, H M D

    2014-01-01

    This study was conducted to establish representative curves that allow evaluation of fetal growth and estimation of gestational age from measurement of fetal structures by ultrasound in Malayan tapirs (Tapirus indicus). Three pregnancies (i.e. 3 fetuses) were examined in one female Malayan tapir. Transabdominal ultrasonographic examination was performed without anesthesia from 79 ± 8 days to 281 ± 48 days (mean ± S.D.) post mating. To assess fetal growth attempts were made to measure biparietal diameter (BPD), head length (HL), thorax diameter A (TDA), thorax height A (THA), thorax diameter B (TDB), thorax height B (THB), abdomen diameter (AD), abdomen height (AH), humerus length (HUL) and Crown rump length (CRL). The value of each parameter as an estimator of gestational age was assessed by ease of observation and the length of time the parameter was measurable throughout gestation. The most precise predictors for gestational age in this study were BPD and CRL (weeks 10-20 of gestation), as well as AD and AH (weeks 14-43 of gestation). The parameters TDB, THB and HUL (weeks 15-41 of gestation) gave almost as good predictions. Fetal viability was assessed by identifying a fetal heartbeat and movement. All pregnancies resulted in normal deliveries and healthy offspring. The ultrasound examination was well tolerated by the female. The gestation lengths (399 ± 3 days) were within reported ranges. The serial transabdominal ultrasound, without the need for anesthesia, was an effective method to evaluate fetal growth, development and well being in a Malayan tapir. © 2014 Wiley Periodicals, Inc.

  18. Reduced angiogenic factor expression in intrauterine fetal growth restriction using semiquantitative immunohistochemistry and digital image analysis.

    PubMed

    Alahakoon, Thushari I; Zhang, Weiyi; Arbuckle, Susan; Zhang, Kewei; Lee, Vincent

    2018-05-01

    To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining. © 2018 Japan Society of Obstetrics and Gynecology.

  19. Fetal and neonatal programming of postnatal growth and feed efficiency in swine.

    PubMed

    Ji, Yun; Wu, Zhenlong; Dai, Zhaolai; Wang, Xiaolong; Li, Ju; Wang, Binggen; Wu, Guoyao

    2017-01-01

    Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences (namely, epigenetics). The mechanisms responsible for the epigenetic regulation of protein expression and functions include chromatin remodeling; DNA methylation (occurring at the 5´-position of cytosine residues within CpG dinucleotides); and histone modifications (acetylation, methylation, phosphorylation, and ubiquitination). Like maternal malnutrition, undernutrition during the neonatal period also reduces growth performance and feed efficiency (weight gain:feed intake; also known as weight-gain efficiency) in postweaning pigs by 5-10%, thereby increasing the days necessary to reach the market body-weight. Supplementing functional amino acids (e.g., arginine and glutamine) and vitamins (e.g., folate) play a key role in activating the mammalian target of rapamycin signaling and regulating the provision of methyl donors for DNA and protein methylation. Therefore, these nutrients are beneficial for the dietary treatment of metabolic disorders in offspring with intrauterine growth restriction or neonatal malnutrition. The mechanism-based strategies hold great promise for the improvement of the efficiency of pork production and the sustainability of the global swine industry.

  20. Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines.

    PubMed

    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

  1. PRETERM BIRTH AND FETAL GROWTH RESTRICTION IN HIV-INFECTED BRAZILIAN PREGNANT WOMEN

    PubMed Central

    dos REIS, Helena Lucia Barroso; ARAUJO, Karina da Silva; RIBEIRO, Lilian Paula; da ROCHA, Daniel Ribeiro; ROSATO, Drielli Petri; PASSOS, Mauro Romero Leal; de VARGAS, Paulo Roberto Merçon

    2015-01-01

    Introduction: Maternal HIV infection and related co-morbidities may have two outstanding consequences to fetal health: mother-to-child transmission (MTCT) and adverse perinatal outcomes. After Brazilian success in reducing MTCT, the attention must now be diverted to the potentially increased risk for preterm birth (PTB) and intrauterine fetal growth restriction (IUGR). Objective: To determine the prevalence of PTB and IUGR in low income, antiretroviral users, publicly assisted, HIV-infected women and to verify its relation to the HIV infection stage. Patients and Methods: Out of 250 deliveries from HIV-infected mothers that delivered at a tertiary public university hospital in the city of Vitória, state of Espírito Santo, Southeastern Brazil, from November 2001 to May 2012, 74 single pregnancies were selected for study, with ultrasound validated gestational age (GA) and data on birth dimensions: fetal weight (FW), birth length (BL), head and abdominal circumferences (HC, AC). The data were extracted from clinical and pathological records, and the outcomes summarized as proportions of preterm birth (PTB, < 37 weeks), low birth weight (LBW, < 2500g) and small (SGA), adequate (AGA) and large (LGA) for GA, defined as having a value below, between or beyond the ±1.28 z/GA score, the usual clinical cut-off to demarcate the 10th and 90th percentiles. Results: PTB was observed in 17.5%, LBW in 20.2% and SGA FW, BL, HC and AC in 16.2%, 19.1%, 13.8%, and 17.4% respectively. The proportions in HIV-only and AIDS cases were: PTB: 5.9 versus 27.5%, LBW: 14.7% versus 25.0%, SGA BW: 17.6% versus 15.0%, BL: 6.0% versus 30.0%, HC: 9.0% versus 17.9%, and AC: 13.3% versus 21.2%; only SGA BL attained a significant difference. Out of 15 cases of LBW, eight (53.3%) were preterm only, four (26.7%) were SGA only, and three (20.0%) were both PTB and SGA cases. A concomitant presence of, at least, two SGA dimensions in the same fetus was frequent. Conclusions: The proportions of preterm

  2. The relationship of newborn adiposity to fetal growth outcome based on birth weight or the modified neonatal growth assessment score

    PubMed Central

    Lee, W; Riggs, T; Koo, W; Deter, RL; Yeo, L; Romero, R

    2013-01-01

    Objectives (1) Develop reference ranges of neonatal adiposity using air displacement plethysmography. (2) Use new reference ranges for neonatal adiposity to compare two different methods of evaluating neonatal nutritional status. Methods Three hundred and twenty-four normal neonates (35–41 weeks post-menstrual age) had body fat (%BF) and total fat mass (FM, g) measured using air displacement plethysmography shortly after delivery. Results were stratified for 92 of these neonates with corresponding fetal biometry using two methods for classifying nutritional status: (1) population-based weight percentiles; and (2) a modified neonatal growth assessment score (m3NGAS51). Results At the 50th percentile, &BF varied from 7.7% (35 weeks) to 11.8% (41 weeks), while the corresponding 50th percentiles for total FM were 186–436g. Among the subset of 92 neonates, no significant differences in adiposity were found between small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA) groups using population-based weight standards. Classification of the same neonates using m3NGAS51 showed significant differences in mean %BF between corresponding groups. Conclusions Population-based weight criteria for neonatal nutritional status can lead to misclassification on the basis of adiposity. A neonatal growth assessment score, that considers the growth potential of several anatomic parameters, appears to more effectively classify under-and over-nourished newborns. PMID:22494346

  3. Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction.

    PubMed

    Gumus, Hatice Gulcin; Illa, Miriam; Pla, Laura; Zamora, Monica; Crispi, Fatima; Gratacos, Eduard

    2018-01-01

    To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). IUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40-50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight. Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups. Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency.

  4. In vivo placental MRI shape and textural features predict fetal growth restriction and postnatal outcome.

    PubMed

    Dahdouh, Sonia; Andescavage, Nickie; Yewale, Sayali; Yarish, Alexa; Lanham, Diane; Bulas, Dorothy; du Plessis, Adre J; Limperopoulos, Catherine

    2018-02-01

    To investigate the ability of three-dimensional (3D) MRI placental shape and textural features to predict fetal growth restriction (FGR) and birth weight (BW) for both healthy and FGR fetuses. We recruited two groups of pregnant volunteers between 18 and 39 weeks of gestation; 46 healthy subjects and 34 FGR. Both groups underwent fetal MR imaging on a 1.5 Tesla GE scanner using an eight-channel receiver coil. We acquired T2-weighted images on either the coronal or the axial plane to obtain MR volumes with a slice thickness of either 4 or 8 mm covering the full placenta. Placental shape features (volume, thickness, elongation) were combined with textural features; first order textural features (mean, variance, kurtosis, and skewness of placental gray levels), as well as, textural features computed on the gray level co-occurrence and run-length matrices characterizing placental homogeneity, symmetry, and coarseness. The features were used in two machine learning frameworks to predict FGR and BW. The proposed machine-learning based method using shape and textural features identified FGR pregnancies with 86% accuracy, 77% precision and 86% recall. BW estimations were 0.3 ± 13.4% (mean percentage error ± standard error) for healthy fetuses and -2.6 ± 15.9% for FGR. The proposed FGR identification and BW estimation methods using in utero placental shape and textural features computed on 3D MR images demonstrated high accuracy in our healthy and high-risk cohorts. Future studies to assess the evolution of each feature with regard to placental development are currently underway. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:449-458. © 2017 International Society for Magnetic Resonance in Medicine.

  5. Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

    PubMed

    Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

    1992-06-01

    To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

  6. Up Front, in Hope: The Value of Early Intervention for Children with Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Harwood, Maureen; Kleinfeld, Judith Smilg

    2002-01-01

    Differentiates fetal alcohol syndrome (FAS) from fetal alcohol effects (FAE) and discusses difficulties in diagnosing these conditions. Describes the effects of FAS/FAE on young children, detailing impact on sensory processing, focusing attention, and cognitive development in infants, toddlers, and preschoolers. Presents suggestions for caregivers…

  7. The role of blood flow distribution in the regulation of cerebral oxygen availability in fetal growth restriction.

    PubMed

    Luria, Oded; Bar, Jacob; Kovo, Michal; Malinger, Gustavo; Golan, Abraham; Barnea, Ofer

    2012-04-01

    Fetal growth restriction (FGR) elicits hemodynamic compensatory mechanisms in the fetal circulation. These mechanisms are complex and their effect on the cerebral oxygen availability is not fully understood. To quantify the contribution of each compensatory mechanism to the fetal cerebral oxygen availability, a mathematical model of the fetal circulation was developed. The model was based on cardiac-output distribution in the fetal circulation. The compensatory mechanisms of FGR were simulated and their effects on cerebral oxygen availability were analyzed. The mathematical analysis included the effects of cerebral vasodilation, placental resistance to blood flow, degree of blood shunting by the ductus venosus and the effect of maternal-originated placental insufficiency. The model indicated a unimodal dependency between placental blood flow and cerebral oxygen availability. Optimal cerebral oxygen availability was achieved when the placental blood flow was mildly reduced compared to the normal flow. This optimal ratio was found to increase as the hypoxic state of FGR worsens. The model indicated that cerebral oxygen availability is increasingly dependent on the cardiac output distribution as the fetus gains weight. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

  8. Maternal dietary omega-3 fatty acid supplementation reduces placental oxidative stress and increases fetal and placental growth in the rat.

    PubMed

    Jones, Megan L; Mark, Peter J; Mori, Trevor A; Keelan, Jeffrey A; Waddell, Brendan J

    2013-02-01

    Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders including intrauterine growth restriction. Oxidative stress occurs when accumulation of reactive oxygen species damages DNA, proteins, and lipids, an outcome normally limited by antioxidant defenses. Dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may limit oxidative stress by increasing antioxidant capacity, but n-3 PUFAs are also highly susceptible to lipid peroxidation; so n-3 PUFA supplementation is potentially harmful. Here we examined the effect of n-3 PUFAs on placental oxidative stress and on placental and fetal growth in the rat. We also investigated whether diet-induced changes in maternal plasma fatty acid profiles are associated with comparable changes in placental and fetal tissues. Rats were fed either standard or high n-3 PUFA diets from Day 1 of pregnancy, and tissues were collected on Day 17 or 22 (term = Day 23). Dietary supplementation with n-3 PUFAs increased fetal (6%) and placental (12%) weights at Day 22, the latter attributable primarily to growth of the labyrinth zone (LZ). Increased LZ weight was accompanied by reduced LZ F(2)-isoprostanes (by 31% and 11% at Days 17 and 22, respectively), a marker of oxidative damage. Maternal plasma PUFA profiles were altered by dietary fatty acid intake and were strongly predictive of corresponding profiles in placental and fetal tissues. Our data indicate that n-3 PUFA supplementation reduces placental oxidative stress and enhances placental and fetal growth. Moreover, fatty acid profiles in the mother, placenta, and fetus are highly dependent on dietary fatty acid intake.

  9. Fetal growth restriction: relation to growth and obesity at the age of 9 years.

    PubMed

    Chakraborty, Supratik; Joseph, Desaline Veronica; Bankart, Michael John Gordon; Petersen, Stewart A; Wailoo, Michael P

    2007-11-01

    To assess growth patterns of 9-year-old children, some of whom had intrauterine growth restriction (IUGR). 75 9-year-old children (41 were IUGR infants) were weighed and measured at birth, at 1 year, at 2 years and at 9 years of age. Using general linear models for continuous data, changes in weight z scores were used to quantify growth rate between birth and 9 years of age. IUGR children were smaller at birth (weight z score -2.1 v 0.2 in normal children; p<0.001) but showed a greater increase in their weight between birth and 9 years (change of weight z score 1.5 v 0.4 in normal children; p = 0.001). At the age of 9 years the weight, height and body mass index (BMI) z scores were lower in IUGR children than the control children (weight z score -0.4 v 0.6, respectively; p<0.001, height z score -0.5 v 0, respectively; p = 0.002, BMI z score -0.2 v 0.7, respectively; p = 0.002). The predictors of these differences were IUGR, birth weight and maternal and paternal heights. IUGR infants grow faster but remain shorter and lighter than their normal counterparts-that is, they fail to fully catch up by 9 years of age.

  10. Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia

    PubMed Central

    Yu, Hong; Shen, Yanting; Ge, Qinyu; He, Youji; Qiao, Dongyan; Ren, Mulan; Zhang, Jianqiong

    2013-01-01

    The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta. PMID:23567271

  11. Fetal Programming and Cardiovascular Pathology

    PubMed Central

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  12. Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

    SciTech Connect

    Leichter, J.

    1991-03-15

    The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitummore » controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.« less

  13. Diagnostic accuracy of fundal height and handheld ultrasound-measured abdominal circumference to screen for fetal growth abnormalities

    PubMed Central

    Haragan, Adriane F.; Hulsey, Thomas C.; Hawk, Angela F.; Newman, Roger B.; Chang, Eugene Y.

    2015-01-01

    OBJECTIVE We sought to compare fundal height and handheld ultrasound–measured fetal abdominal circumference (HHAC) for the prediction of fetal growth restriction (FGR) or large for gestational age. STUDY DESIGN This was a diagnostic accuracy study in nonanomalous singleton pregnancies between 24 and 40 weeks’ gestation. Patients underwent HHAC and fundal height measurement prior to formal growth ultrasound. FGR was defined as estimated fetal weight less than 10%, whereas large for gestational age was defined as estimated fetal weight greater than 90%. Sensitivity and specificity were calculated and compared using methods described elsewhere. RESULTS There were 251 patients included in this study. HHAC had superior sensitivity and specificity for the detection of FGR (sensitivity, 100% vs 42.86%) and (specificity, 92.62% vs 85.24%). HHAC had higher specificity but lower sensitivity when screening for LGA (specificity, 85.66% vs 66.39%) and (sensitivity, 57.14% vs 71.43%). CONCLUSION HHAC could prove to be a valuable screening tool in the detection of FGR. Further studies are needed in a larger population. PMID:25818672

  14. Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

    PubMed

    Murphy, Kellie E; Willan, Andrew R; Hannah, Mary E; Ohlsson, Arne; Kelly, Edmond N; Matthews, Stephen G; Saigal, Saroj; Asztalos, Elizabeth; Ross, Susan; Delisle, Marie-France; Amankwah, Kofi; Guselle, Patricia; Gafni, Amiram; Lee, Shoo K; Armson, B Anthony

    2012-05-01

    To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown

  15. Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies.

    PubMed

    Harley, Kim G; Engel, Stephanie M; Vedar, Michelle G; Eskenazi, Brenda; Whyatt, Robin M; Lanphear, Bruce P; Bradman, Asa; Rauh, Virginia A; Yolton, Kimberly; Hornung, Richard W; Wetmur, James G; Chen, Jia; Holland, Nina T; Barr, Dana Boyd; Perera, Frederica P; Wolff, Mary S

    2016-07-01

    Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.5 cm; 95% CI: -0.9, -0.1). This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and

  16. Maternal, fetal, and placental conditions associated with medically indicated late preterm and early term delivery: a retrospective study.

    PubMed

    Brown, H K; Speechley, K N; Macnab, J; Natale, R; Campbell, M K

    2016-04-01

    Our objectives were: (1) to examine the association between maternal, fetal, and placental phenotypes of preterm delivery and medically indicated early delivery of singletons during the late preterm and early term periods; and (2) to identify the specific maternal, fetal, and placental conditions associated with these early deliveries. Retrospective study. City of London and Middlesex County, Ontario, Canada. Singleton live deliveries, at 34-41 weeks of gestation to women in London and Middlesex. We obtained data from a city-wide perinatal database (2002-2011; n = 25 699). We used multinomial logistic regression for multivariable analyses. The outcome was the occurrence of medically indicated late preterm (34-36 weeks of gestation) and early term (37-38 weeks of gestation) delivery, versus delivery at full term (39-41 weeks of gestation). After controlling for confounding factors, all phenotypes were associated with increased odds of medically indicated late preterm and early term delivery. Within the maternal phenotype, chronic maternal medical conditions were associated with increased odds of medically indicated early term delivery (e.g. for gastrointestinal disease, adjusted odds ratio, aOR 1.72, 95% CI 1.47-2.00; for anaemia, aOR 1.40, 95% CI 1.20-1.63), but not late preterm delivery. The aetiology of medically indicated early delivery close to full term is heterogeneous. Patterns of associations suggest slightly different conditions underlying the late preterm and early term phenotypes, with chronic maternal medical conditions being associated with early term delivery but not with late preterm delivery. These results have implications for the prevention of early delivery as well as the identification of high-risk groups among those born early. The aetiology of medically indicated late preterm and early term delivery is heterogeneous. © 2015 Royal College of Obstetricians and Gynaecologists.

  17. Birth Weight, Intrauterine Growth Retardation and Fetal Susceptibility to Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Ladinig, Andrea; Foxcroft, George; Ashley, Carolyn; Lunney, Joan K.; Plastow, Graham; Harding, John C. S.

    2014-01-01

    The severity of porcine reproductive and respiratory syndrome was compared in pregnant gilts originating from high and low birth weight litters. One-hundred and eleven pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus on gestation day 85 (±1) were necropsied along with their fetuses 21 days later. Ovulation rates and litter size did not differ between groups, but fetuses from low birth weight gilts were shorter, lighter and demonstrated evidence of asymmetric growth with large brain:organ weight ratios (i.e. brain sparing). The number of intrauterine growth retarded fetuses, defined by brain:organ weight ratios greater than 1 standard deviation from the mean, was significantly greater in low, compared to high, birth weight gilts. Although γδ T cells significantly decreased over time in high compared to low birth weight gilts, viral load in serum and tissues, gilt serum cytokine levels, and litter outcome, including the percent dead fetuses per litter, did not differ by birth weight group. Thus, this study provided no substantive evidence that the severity of porcine reproductive and respiratory syndrome is affected by dam birth weight. However, intrauterine growth retarded fetuses had lower viral loads in both fetal thymus and in endometrium adjacent to the umbilical stump. Crown rump length did not significantly differ between fetuses that survived and those that died at least one week prior to termination. Taken together, this study clearly demonstrates that birth weight is a transgenerational trait in pigs, and provides evidence that larger fetuses are more susceptible to transplacental PRRSv infection. PMID:25275491

  18. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    SciTech Connect

    Deng, Yu; Cao, Hong; Cu, Fenglong

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotinemore » exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.« less

  19. EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR).

    PubMed

    Brouillet, S; Murthi, P; Hoffmann, P; Salomon, A; Sergent, F; De Mazancourt, P; Dakouane-Giudicelli, M; Dieudonné, M N; Rozenberg, P; Vaiman, D; Barbaux, S; Benharouga, M; Feige, J-J; Alfaidy, N

    2013-02-01

    Identifiable causes of fetal growth restriction (FGR) account for 30 % of cases, but the remainders are idiopathic and are frequently associated with placental dysfunction. We have shown that the angiogenic factor endocrine gland-derived VEGF (EG-VEGF) and its receptors, prokineticin receptor 1 (PROKR1) and 2, (1) are abundantly expressed in human placenta, (2) are up-regulated by hypoxia, (3) control trophoblast invasion, and that EG-VEGF circulating levels are the highest during the first trimester of pregnancy, the period of important placental growth. These findings suggest that EG-VEGF/PROKR1 and 2 might be involved in normal and FGR placental development. To test this hypothesis, we used placental explants, primary trophoblast cultures, and placental and serum samples collected from FGR and age-matched control women. Our results show that (1) EG-VEGF increases trophoblast proliferation ([(3)H]-thymidine incorporation and Ki67-staining) via the homeobox-gene, HLX (2) the proliferative effect involves PROKR1 but not PROKR2, (3) EG-VEGF does not affect syncytium formation (measurement of syncytin 1 and 2 and β hCG production) (4) EG-VEGF increases the vascularization of the placental villi and insures their survival, (5) EG-VEGF, PROKR1, and PROKR2 mRNA and protein levels are significantly elevated in FGR placentas, and (6) EG-VEGF circulating levels are significantly higher in FGR patients. Altogether, our results identify EG-VEGF as a new placental growth factor acting during the first trimester of pregnancy, established its mechanism of action, and provide evidence for its deregulation in FGR. We propose that EG-VEGF/PROKR1 and 2 increases occur in FGR as a compensatory mechanism to insure proper pregnancy progress.

  20. Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

    PubMed

    Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

    2015-06-01

    Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

    PubMed

    Barrientos, G; Pussetto, M; Rose, M; Staff, A C; Blois, S M; Toblli, J E

    2017-07-01

    What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical

  2. Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide

    EPA Science Inventory

    The present study was performed to determine experimental conditions for thalidomide induction of fetal malformations and to understand the molecular mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys. Cynomolgus monkeys were orally administered (±)-thalidomid...

  3. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

    PubMed

    Cowans, Nicholas J; Spencer, Kevin

    2007-03-01

    PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and

  4. Trophoblastic progranulin expression is upregulated in cases of fetal growth restriction and preeclampsia.

    PubMed

    Stubert, Johannes; Schattenberg, Florian; Richter, Dagmar-Ulrike; Dieterich, Max; Briese, Volker

    2012-05-13

    The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (P<0.05) and FGR (P<0.01). Similar results were shown for HIF-1α expression (P<0.01 for PE and <0.05 for FGR). The increase of the progranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required.

  5. Differences in cortical development assessed by fetal MRI in late-onset intrauterine growth restriction.

    PubMed

    Egaña-Ugrinovic, Gabriela; Sanz-Cortes, Magdalena; Figueras, Francesc; Bargalló, Nuria; Gratacós, Eduard

    2013-08-01

    The objective of the study was to evaluate cortical development parameters by magnetic resonance imaging (MRI) in late-onset intrauterine growth-restricted (IUGR) fetuses and normally grown fetuses. A total of 52 IUGR and 50 control fetuses were imaged using a 3T MRI scanner at 37 weeks of gestational age. T2 half-Fourier acquisition single-shot turbo spin-echo anatomical acquisitions were obtained in 3 planes. Cortical sulcation (fissures depth corrected by biparietal diameter), brain volumetry, and asymmetry indices were assessed by means of manual delineation and compared between cases and controls. Late-onset IUGR fetuses had significantly deeper measurements in the left insula (late-onset IUGR: 0.293 vs control: 0.267; P = .02) and right insula (0.379 vs 0.318; P < .01) and the left cingulate fissure (0.096 vs 0.087; P = .03) and significantly lower intracranial (441.25 cm(3) vs 515.82 cm(3); P < .01), brain (276.47 cm(3) vs 312.07 cm(3); P < .01), and left opercular volumes (2.52 cm(3) vs 3.02 cm(3); P < .01). IUGR fetuses showed significantly higher right insular asymmetry indices. Late-onset IUGR fetuses had a different pattern of cortical development assessed by MRI, supporting the existence of in utero brain reorganization. Cortical development could be useful to define fetal brain imaging-phenotypes characteristic of IUGR. Copyright © 2013 Mosby, Inc. All rights reserved.

  6. Fetal growth restriction but not preterm birth is a risk factor for severe hypospadias.

    PubMed

    Hashimoto, Yukiko; Kawai, Masahiko; Nagai, Sizuyo; Matsukura, Takashi; Niwa, Fusako; Hasegawa, Takeshi; Heike, Toshio

    2016-07-01

    Hypospadias has multifactorial causes and occurs at a high frequency among very low-birthweight infants. Placental insufficiency is hypothesized to be one cause of hypospadias; that is, decreased human chorionic gonadotropin (hCG) secretion caused by placental insufficiency is suspected to result in abnormal male external genitalia, but there is little direct evidence to support this. The aim of this study was therefore to identify the features of hypospadias and to clarify the male genital abnormalities caused by fetal growth restriction (FGR). We reviewed the clinical data of boys who underwent hypospadias repair between 2005 and 2011 at Kyoto University Hospital. Twenty boys were included in this study. Fifteen (75%) of the subjects were preterm or low-birthweight infants. Thirteen (65%) had FGR, 60% of whom had severe hypospadias regardless of gestational age. In addition, 92% of the FGR infants also had other genital anomalies, such as cryptorchidism, bifid scrotum, or micropenis. In contrast, only 14% and 43% of the non-FGR infants had severe hypospadias or genital anomalies other than hypospadias, respectively. Placental histopathology was available in eight FGR infants, in seven of whom it was suggestive of blood flow deficiency such as infarction and single umbilical artery. Infants with FGR have a high incidence of hypospadias. FGR caused by placental dysfunction, but not low birthweight, is a risk factor for severe hypospadias associated with multiple genital anomalies. © 2015 Japan Pediatric Society.

  7. [Intelligence level and structure in school age children with fetal growth restriction].

    PubMed

    Ma, Jian; Ma, Hong-Wei; Tian, Xiao-Bo; Liu, Fang

    2009-10-01

    To study the intelligence level and structure in school age children with fetal growth restriction (FGR). The intelligence levels were tested by the Wechsler Children Scales of Intelligence (C-WISC) in 54 children with FGR and in 84 normal children. The full intelligence quotient (FIQ), verbal IQ (VIQ) and performance IQ (PIQ) in the FGR group were 105.9+/-10.3, 112.4+/-11.2 and 97.1+/-10.6 respectively, and they all were in a normal range. But the PIQ was significantly lower than that in the control group (104.8+/-10.5; p<0.001), and the picture arrangement and the decipher subtest scores were significantly lower than those in the control group (p<0.01). The scores of perception/organization and memory/attention factors in the FGR group were 99.8+/-11.1 and 116.3+/-14.4, respectively, which were inferior to those in the control group (104.6+/-11.5 and 113.4+/-14.5 respectively; p<0.05). The total intelligence level of children with FGR is normal, but there are imbalances in the intelligence structure and dysfunctions in performance ability related to right cerebral hemisphere. Performance trainings should be done from the infancy in children with FGR.

  8. Correlations between Prenatal Exposure to Perfluorinated Chemicals and Reduced Fetal Growth

    PubMed Central

    Washino, Noriaki; Saijo, Yasuaki; Sasaki, Seiko; Kato, Shizue; Ban, Susumu; Konishi, Kanae; Ito, Rie; Nakata, Ayako; Iwasaki, Yusuke; Saito, Koichi; Nakazawa, Hiroyuki; Kishi, Reiko

    2009-01-01

    Background Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, ubiquitous, and persistent contaminants in the environment, wildlife, and humans. Although recent studies have shown that these chemicals interfere with fetal growth in humans, the results are inconsistent. Objectives Our goal was to investigate the correlation between relatively low levels of PFOS and PFOA in maternal serum and birth weight and birth size. Methods We conducted a hospital-based prospective cohort study between July 2002 and October 2005 in Sapporo, Japan. A total of 428 women and their infants were involved in the study. We obtained characteristics of the mothers and infants from self-administered questionnaire surveys and from medical records. We analyzed maternal serum samples for PFOS and PFOA by liquid chromatography–tandem mass spectrometry (LC/MS/MS). Results After adjusting for confounding factors, PFOS levels negatively correlated with birth weight [per log10 unit: β = −148.8 g; 95% confidence interval (CI), −297.0 to −0.5 g]. In addition, analyses stratified by sex revealed that PFOS levels negatively correlated with birth weight only in female infants (per log10 unit: β = −269.4 g; 95% CI, −465.7 to −73.0 g). However, we observed no correlation between PFOA levels and birth weight. Conclusion Our results indicate that in utero exposure to relatively low levels of PFOS was negatively correlated with birth weight. PMID:19440508

  9. Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

    PubMed

    Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang

    2012-07-01

    LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

  10. The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth.

    PubMed

    Salavati, N; Sovio, U; Mayo, R Plitman; Charnock-Jones, D S; Smith, G C S

    2016-02-01

    Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P < 0.001). The lowest decile of placental weight was associated with 0.73 SD higher umbilical artery Doppler PI at 36 weeks (95% CI: 0.54 to 0.93, P < 0.001). The lowest decile of both placental weight and placental area were associated with reduced growth velocity of the fetal abdominal circumference between 20 and 36 weeks (both P < 0.001). Placental area and weight are associated with uterine and umbilical blood flow, respectively, and both are associated with fetal growth rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine.

    PubMed

    Gentile, Salvatore; Bellantuono, Cesario

    2009-03-01

    To analyze all studies reporting primary data on the rate of fetal malformations after early in utero exposure to paroxetine, investigated either specifically or jointly with other antidepressant medications. Medical literature was identified through searches of MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library (1980 through September 2008). Search terms were pregnancy, antidepressants, SSRIs, paroxetine, and fetal malformations. Additional studies were identified from the reference lists of published articles. Twenty-five articles reporting primary data on the rate of fetal structural malformations following exposure to paroxetine or selective serotonin reuptake inhibitors as a group during the first trimester of pregnancy were electronically or manually selected. Studies on the teratogenic risk of paroxetine show a high degree of heterogeneity. Moreover, research studies performed with the same methodology and thus showing the same level of evidence report conflicting results. Given the inconsistency of the findings and limitations of the methodology of the published studies, the teratogenic potential of paroxetine that has been reported in some studies remains unproven. This relevant safety question is likely to remain unanswered until large, prospective studies are conducted. Such studies should be designed to include a control group of untreated mothers with similar psychiatric diagnosis so as to differentiate effects of drug exposure from impact of underlying mental disorder on the fetus. Moreover, further experimental studies are warranted to definitively assess clinical consequences of the impact on fetal development related to physiologic effects of prenatal paroxetine exposure on different maternal and fetal parameters. ©Copyright 2009 Physicians Postgraduate Press, Inc.

  12. Development and morphogenesis of human wrist joint during embryonic and early fetal period

    PubMed Central

    Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Álvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

    2012-01-01

    The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O’Rahilly stages 17–23 and 9–14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology. PMID:22428933

  13. Mediterranean diet adherence during pregnancy and fetal growth: INMA (Spain) and RHEA (Greece) mother-child cohort studies.

    PubMed

    Chatzi, Leda; Mendez, Michelle; Garcia, Raquel; Roumeliotaki, Theano; Ibarluzea, Jesús; Tardón, Adonina; Amiano, Pilar; Lertxundi, Aitana; Iñiguez, Carmen; Vioque, Jesus; Kogevinas, Manolis; Sunyer, Jordi

    2012-01-01

    Dietary intake of specific nutrients or food groups during pregnancy could influence fetal growth, but scant evidence is available on effects of dietary patterns. The aim of this study was to evaluate the impact of Mediterranean diet (MD) adherence during pregnancy on fetal growth in two population-based mother-child cohorts in Spain and Greece. We studied 2461 mother-newborn pairs from the Spanish multi-centre 'INMA' study (Atlantic area: INMA-Atlantic; Mediterranean area: INMA-Mediterranean), and 889 pairs from the 'RHEA' study in Crete, Greece. Maternal diet during pregnancy was assessed by FFQ and MD adherence was evaluated through an a priori score. Fetal growth restriction was based on a customised model, and multivariate log-binomial and linear regression models were used to adjust for several confounders. MD scores differ significantly between the cohorts with women in INMA-Atlantic reporting higher intakes of fish and dairy products, while women in the Mediterranean area reported higher intakes of cereals, vegetables and fruits. Women with high MD adherence had a significantly lower risk of delivering a fetal growth-restricted infant for weight (risk ratios: 0·5; 95 % CI 0·3, 0·9) in the INMA-Mediterranean cohort. Stratified analysis by smoking revealed that higher MD adherence increased birth weight and birth length in smoking mothers, whereas this effect was not apparent in non-smoking mothers. The results of the present study show that several types of MD exist across European Mediterranean regions. High MD adherence may modify the detrimental effect of smoking on birth size, but overall effects of diet were not universal for the studies in this analysis.

  14. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    PubMed Central

    Davis, Melissa A.; Macko, Antoni R.; Steyn, Leah V.; Anderson, Miranda J.; Limesand, Sean W.

    2015-01-01

    Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses. PMID:25584967

  15. Delayed rotation of the cerebellar vermis: a pitfall in early second-trimester fetal magnetic resonance imaging.

    PubMed

    Pinto, J; Paladini, D; Severino, M; Morana, G; Pais, R; Martinetti, C; Rossi, A

    2016-07-01

    We describe two cases in which delayed rotation of the cerebellar vermis simulated a Dandy-Walker malformation (DWM) on early second-trimester magnetic resonance imaging (MRI). Two pregnant women with suspected fetal posterior fossa anomaly on ultrasound examination underwent fetal MRI at 21 (Case 1) and 19 (Case 2) weeks' gestation. In both cases, upward rotation of the cerebellar vermis was noted; on midsagittal imaging, the brainstem-vermis angle was 28° and 43°, respectively, while cerebellar morphometry showed a reduced vermian anteroposterior diameter compared to reference data. The posterior fossa appeared to be mildly enlarged, while all other findings were normal. Follow-up MRI at 28 + 3 weeks' gestation (Case 1) and at 1 postnatal year (Case 2) showed completely normal findings. Both children had normal psychomotor development and neurological examinations at 1 year of age. Incomplete rotation of the cerebellar vermis can be a physiological finding on early second-trimester fetal MRI examination and can simulate DWM or other forms of cerebellar hypoplasia. Embryologically, delayed permeabilization of Blake's pouch could account for the delayed vermian rotation. Follow-up imaging at a later gestational age is crucial to ensure that this condition is not over-reported and to avoid the potential risk of unnecessary pregnancy interruption. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  16. [Air pollutant exposure during pregnancy and fetal and early childhood development. Research protocol of the INMA (Childhood and Environment Project)].

    PubMed

    Esplugues, Ana; Fernández-Patier, Rosalía; Aguilera, Inma; Iñíguez, Carmen; García Dos Santos, Saúl; Aguirre Alfaro, Amelia; Lacasaña, Marina; Estarlich, Marisa; Grimalt, Joan O; Fernández, Marieta; Rebagliato, Marisa; Sala, María; Tardón, Adonina; Torrent, Maties; Martínez, María Dolores; Ribas-Fitó, Núria; Sunyer, Jordi; Ballester, Ferran

    2007-01-01

    The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the study's potential.

  17. Prenatal fasudil exposure alleviates fetal growth but programs hyperphagia and overweight in the adult male rat.

    PubMed

    Butruille, Laura; Mayeur, Sylvain; Duparc, Thibaut; Knauf, Claude; Moitrot, Emmanuelle; Fajardy, Isabelle; Valet, Philippe; Storme, Laurent; Deruelle, Philippe; Lesage, Jean

    2012-08-15

    Numerous data indicate that Rho kinase inhibitors, such as Fasudil, may constitute a novel therapy for cardiovascular and metabolic diseases. We evaluated long-term effects of exposure to Fasudil during late gestation (10 mg/day) in male rat offspring from birth until 9 months. We also analyzed its effects in offspring from hypertensive mothers treated with a nitric oxide synthesis inhibitor (L-NAME; 50 mg/day). Prenatal exposure to Fasudil did not affect birth weight, but increased body weight from postnatal day 7 (P7) to 9 months. In intrauterine growth-restricted (IUGR) fetuses exposed to L-NAME, maternal Fasudil treatment increased birth weight. At P42 and P180, rats exposed to Fasudil and L-NAME showed alterations of their food intake as well as an increased basal glycemia associated with mild glucose intolerance at 6 months which was also observed in Fasudil-exposed rats. In 9 month-old rats, exposure to Fasudil increased the daily food intake as well as hypothalamic mRNA level of the orexigenic NPY peptide without modulation of the anorexigenic POMC gene expression. Altogether, our data suggest that prenatal Fasudil exposure alleviates fetal growth in IUGR rats, but programs long-term metabolic disturbances including transient perturbations of glucose metabolism, a persistent increase of body weight gain, hyperphagia and an augmented expression of hypothalamic NPY orexigenic gene. We postulate that Fasudil treatment during perinatal periods may predispose individuals to the development of metabolic disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. An outcome-based approach for the creation of fetal growth standards: do singletons and twins need separate standards?

    PubMed

    Joseph, K S; Fahey, John; Platt, Robert W; Liston, Robert M; Lee, Shoo K; Sauve, Reg; Liu, Shiliang; Allen, Alexander C; Kramer, Michael S

    2009-03-01

    Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks' gestation in the United States (1995-2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999-2002 vs. 1995-1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards.

  19. Diffusion-weighted magnetic resonance imaging of the fetal brain in intrauterine growth restriction.

    PubMed

    Arthurs, O J; Rega, A; Guimiot, F; Belarbi, N; Rosenblatt, J; Biran, V; Elmaleh, M; Sebag, G; Alison, M

    2017-07-01

    Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive method for assessing brain maturation and detecting brain lesions, providing apparent diffusion coefficient (ADC) values as a measure of water diffusion. Abnormal ADC values are seen in ischemic brain lesions, such as those associated with acute or chronic hypoxia. The aim of this study was to assess whether ADC values in the fetal brain were different in fetuses with severe intrauterine growth restriction (IUGR) compared with normal controls. Brain magnetic resonance imaging (MRI) with single-shot axial DWI (b = 0 and b = 700 s/mm 2 ) was performed in 30 fetuses with severe IUGR (estimated fetal weight < 3 rd centile with absent or reversed umbilical artery Doppler flow) and in 24 normal controls of similar gestational age. Brain morphology and biometry were analyzed. ADC values were measured in frontal and occipital white matter, centrum semiovale, thalami, cerebellar hemisphere and pons. Frontal-occipital and frontal-cerebellar ADC ratios were calculated, and values were compared between IUGR fetuses and controls. There was no difference in gestational age at MRI between IUGR and control fetuses (IUGR, 30.2 ± 1.6 weeks vs controls, 30.7 ± 1.4 weeks). Fetal brain morphology and signals were normal in all fetuses. Brain dimensions (supratentorial ± infratentorial) were decreased (Z-score, < -2) in 20 (66.7%) IUGR fetuses. Compared with controls, IUGR fetuses had significantly lower ADC values in frontal white matter (1.97 ± 0.23 vs 2.17 ± 0.22 × 10 -3 mm 2 /s; P < 0.0001), thalami (1.04 ± 0.15 vs 1.13 ± 0.10 ×10 -3 mm 2 /s; P = 0.0002), centrum semiovale (1.86 ± 0.22 vs 1.97 ± 0.23 ×10 -3 mm 2 /s; P = 0.01) and pons (0.85 ± 0.19 vs 0.94 ± 0.12 ×10 -3 mm 2 /s; P = 0.043). IUGR fetuses had a lower frontal-occipital ADC ratio than did normal fetuses (1.00 ± 0.11 vs 1.08 ± 0.05; P = 0.003). ADC values in IUGR fetuses were significantly lower than in

  20. Effects of hyperthyroidism on expression of vascular endothelial growth factor (VEGF) and apoptosis in fetal adrenal glands.

    PubMed

    Karaca, T; Hulya Uz, Y; Karabacak, R; Karaboga, I; Demirtas, S; Cagatay Cicek, A

    2015-11-26

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis.

  1. Effects of Hyperthyroidism on Expression of Vascular Endothelial Growth Factor (VEGF) and Apoptosis in Fetal Adrenal Glands

    PubMed Central

    Hulya Uz, Y.; Karabacak, R.; Karaboga, I.; Demirtas, S.; Cagatay Cicek, A.

    2015-01-01

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 µg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the ACTH and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis. PMID:26708182

  2. Apoptotic cell death correlates with ROS overproduction and early cytokine expression after hypoxia-ischemia in fetal lambs.

    PubMed

    Alonso-Alconada, Daniel; Hilario, Enrique; Álvarez, Francisco José; Álvarez, Antonia

    2012-07-01

    Despite advances in neonatology, the hypoxic-ischemic injury in the perinatal period remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Using a sheep model of intrauterine asphyxia, we evaluated the correlation between reactive oxygen species (ROS) overproduction, cytokine expression, and apoptotic cell death. Fetal lambs were assigned to sham group, nonasphyctic animals; and hypoxia-ischemia (HI) group, lambs subjected to 60 minutes of HI) by partial cord occlusion and sacrificed 3 hours later. Different brain regions were separated to quantify the number of apoptotic cells and the same territories were dissociated for flow cytometry studies. Our results suggest that the overproduction of ROS and the early increase in cytokine production after HI in fetal lambs correlate in a significant manner with the apoptotic index, as well as with each brain region evaluated.

  3. Prepregnancy and early adulthood body mass index and adult weight change in relation to fetal loss.

    PubMed

    Gaskins, Audrey J; Rich-Edwards, Janet W; Colaci, Daniela S; Afeiche, Myriam C; Toth, Thomas L; Gillman, Matthew W; Missmer, Stacey A; Chavarro, Jorge E

    2014-10-01

    To examine prospectively the relationships of prepregnancy body mass index (BMI), BMI at age 18 years, and weight change since age 18 years with risk of fetal loss. Our prospective cohort study included 25,719 pregnancies reported by 17,027 women in the Nurses' Health Study II between 1990 and 2009. In 1989, height, current weight, and weight at age 18 years were self-reported. Current weight was updated every 2 years thereafter. Pregnancies were self-reported, with case pregnancies lost spontaneously and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. Incident fetal loss was reported in 4,494 (17.5%) pregnancies. Compared with those of normal BMI, the multivariate relative risks of fetal loss were 1.07 (95% CI [confidence interval] 1.00-1.15) for overweight women, 1.10 (95% CI 0.98-1.23) for class I obese women, and 1.27 (95% CI 1.11-1.45) for class II and class III obese women (P trend ≤ .001). Body mass index at age 18 years was not associated with fetal loss (P trend=.59). Compared with women who maintained a stable weight (± 4 kg) between age 18 years and before pregnancy, women who lost weight had a 20% (95% CI 9-29%) lower risk of fetal loss. This association was stronger among women who were overweight at age 18 years. Being overweight or obese before pregnancy was associated with higher risk of fetal loss. In women overweight or obese at age 18 years, losing 4 kg or more was associated with a lower risk of fetal loss. : II.

  4. Air Pollution Exposure During Pregnancy, Ultrasound Measures of Fetal Growth, and Adverse Birth Outcomes: A Prospective Cohort Study

    PubMed Central

    Pierik, Frank H.; de Kluizenaar, Yvonne; Willemsen, Sten P.; Hofman, Albert; van Ratingen, Sjoerd W.; Zandveld, Peter Y.J.; Mackenbach, Johan P.; Steegers, Eric A.P.; Miedema, Henk M.E.; Jaddoe, Vincent W.V.

    2011-01-01

    Background: Air pollution exposure during pregnancy might have trimester-specific effects on fetal growth. Objective: We prospectively evaluated the associations of maternal air pollution exposure with fetal growth characteristics and adverse birth outcomes in 7,772 subjects in the Netherlands. Methods: Particulate matter with an aerodynamic diameter < 10 μm (PM10) and nitrogen dioxide (NO2) levels were estimated using dispersion modeling at the home address. Fetal head circumference, length, and weight were estimated in each trimester by ultrasound. Information on birth outcomes was obtained from medical records. Results: In cross-sectional analyses, NO2 levels were inversely associated with fetal femur length in the second and third trimester, and PM10 and NO2 levels both were associated with smaller fetal head circumference in the third trimester [–0.18 mm, 95% confidence interval (CI): –0.24, –0.12 mm; and –0.12 mm, 95% CI: –0.17, –0.06 mm per 1-μg/m3 increase in PM10 and NO2, respectively]. Average PM10 and NO2 levels during pregnancy were not associated with head circumference and length at birth or neonatally, but were inversely associated with birth weight (–3.6 g, 95% CI: –6.7, –0.4 g; and –3.4 g, 95% CI: –6.2, –0.6 g, respectively). Longitudinal analyses showed similar patterns for head circumference and weight, but no associations with length. The third and fourth quartiles of PM10 exposure were associated with preterm birth [odds ratio (OR) = 1.40, 95% CI: 1.03, 1.89; and OR = 1.32; 95% CI: 0.96, 1.79, relative to the first quartile]. The third quartile of PM10 exposure, but not the fourth, was associated with small size for gestational age at birth (SGA) (OR = 1.38; 95% CI: 1.00, 1.90). No consistent associations were observed for NO2 levels and adverse birth outcomes. Conclusions: Results suggest that maternal air pollution exposure is inversely associated with fetal growth during the second and third trimester and with

  5. Current Recommended Vitamin D Prenatal Supplementation and Fetal Growth: Results From the China-Anhui Birth Cohort Study.

    PubMed

    Tao, Rui-Xue; Meng, Deng-Hon; Li, Jing-Jing; Tong, Shi-Lu; Hao, Jia-Hu; Huang, Kun; Tao, Fang-Biao; Zhu, Peng

    2018-01-01

    Maternal vitamin D insufficiency has been associated with fetal growth restriction. However, the effect of maternal vitamin D supplementation on fetal growth has not been confirmed. To assess the effect of maternal vitamin D supplementation recommended by the Institute of Medicine (IOM) during pregnancy on the neonatal vitamin D status and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort study, maternal sociodemographic characteristics, food intake, lifestyle, information on vitamin D supplementation, and birth outcomes were prospectively collected. For participants, 600 IU/d of vitamin D3 was routinely advised to take during pregnancy. Cord blood levels of 25-hydroxyvitamin D [25(OH)D], calcium, and phosphorus were measured in 1491 neonates who were divided into three groups based on the duration of maternal vitamin D supplementation during pregnancy. Mean cord blood concentrations of 25(OH)D were 3.5 nmol/L higher [95% confidence interval (CI), 0.8, 6.2] in neonates (median, 37.9 nmol/L) whose mother took vitamin D supplementation for >2 months during pregnancy compared with those (median, 34.3 nmol/L) whose mother did not take any supplement. These significant differences on cord blood concentrations of 25(OH)D occurred regardless of the season of birth. The adjusted risk of SGA in pregnant women with vitamin D supplementation for >2 months was significantly decreased than that in women without any vitamin D supplementation (11.8% vs 6.9%; adjusted odds ratio = 0.53; 95% CI, 0.32, 0.87). The findings from China suggest that maternal vitamin D supplementation recommended by the IOM results in a slight but significantly higher fetal level of 25(OH)D and improves fetal growth. Copyright © 2017 Endocrine Society

  6. Transgenerational effects of maternal care interact with fetal growth and influence attention skills at 18 months of age.

    PubMed

    Neuwald, Marla F; Agranonik, Marilyn; Portella, André K; Fleming, Alison; Wazana, Ashley; Steiner, Meir; Levitan, Robert D; Meaney, Michael J; Silveira, Patrícia P

    2014-05-01

    Evidence suggests that there is an association between being born small for gestational age (SGA) and an increased risk of internalizing and externalizing problems, such as ADHD. Additionally, individuals who report having received a lower quality of maternal care show an increased prevalence of depression and anxiety, and they are generally worse caregivers of their offspring. Therefore, an interaction between the birth weight status and the quality of maternal care perceived by the mother could affect behavioral outcomes of the children. Evaluate the influence of being born SGA and parental bonding, as perceived by the mother during her infancy, on the children's behavior at 18 months of age. Nested cross-sectional study within a Canadian prenatal cohort (MAVAN, Maternal Adversity, Vulnerability and Neurodevelopment) recruited from 2003 to 2010. Data from 305 children who were evaluated at 18 months of age. Early Childhood Behavior Questionnaire--ECBQ and Infant-Toddler Social and Emotional Assessment--ITSEA) were included. Children born SGA whose mothers reported low maternal care during her infancy (using the Parental Bonding Instrument--PBI) showed lower scores in the attentional set shifting trait (ECBQ, p=0.002) and attention construct (ITSEA, p=0.05) at 18 months of age. We also found that SGA increases decreases cuddliness (p=0.011) and poor perceived maternal care decreases low intensity pleasure (p=0.016) on the ECBQ. These findings suggest a complex transgenerational transmission whereby mother's own care interacts with the fetal growth of her offspring to predict its attentional skills at 18 months of age. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

    PubMed Central

    2011-01-01

    Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method. Results A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. Conclusions Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia. PMID:21810232

  8. Fetal and Early Post-Natal Mineralization of the Tympanic Bulla in Fin Whales May Reveal a Hitherto Undiscovered Evolutionary Trait

    PubMed Central

    Cozzi, Bruno; Podestà, Michela; Mazzariol, Sandro; Zotti, Alessandro

    2012-01-01

    The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival. PMID:22615912

  9. Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Cañas, Daniel; Herrera, Emilio A.; García-Herrera, Claudio; Celentano, Diego; Krause, Bernardo J.

    2017-01-01

    Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease. PMID:28344561

  10. Impact on fetal growth of prenatal exposure to pesticides due to agricultural activities: a prospective cohort study in Brittany, France

    PubMed Central

    2010-01-01

    Background Pesticide use is widespread in agriculture. Several studies have shown that pesticides used in agricultural fields can contaminate the domestic environment and thus be an important source of pesticide exposure of populations residing nearby. Epidemiological studies that have examined the health effects of in utero pesticide exposure from residence near agricultural activities suggest adverse effects, but the results are inconsistent. Our purpose was to investigate the effect on intrauterine growth of such exposure due to agricultural activities in the residential municipality. Methods A prospective birth cohort recruited 3421 pregnant women in a French agricultural region (Brittany, 2002-2006) through gynecologists, ultrasonographers, and maternity hospitals during routine prenatal care visits before 19 weeks of gestation. The national agricultural census in 2000 provided the percentages of the municipality area devoted to cultivation of corn, wheat, colza, peas, potatoes, and fresh vegetables. Results Birth weight and the risk of fetal growth restriction were not associated with agricultural activities in the municipality of residence in early pregnancy. Children whose mother lived in a municipality where peas were grown had a smaller head circumference at birth than those in municipalities not growing peas (-0.2 cm, p = 0.0002). Head circumference also tended to be lower when wheat was grown, but not to a statistically significant degree (p-trend = 0.10). Risk of an infant with a small head circumference was higher for mothers living in a municipality where peas (OR = 2.2; 95% CI = 1.2-3.6) or potatoes (OR = 1.5; 95% CI = 0.9-2.4) were grown. Conclusions Agricultural activities in the municipality of residence may have negative effects on cranial growth. Cultivation of pea crops and, to a lesser degree, potato and wheat crops, may negatively affect head circumference. Insecticides, including organophosphate insecticides, were applied to most of the

  11. Effects of intrauterine growth restriction during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver.

    PubMed

    Liu, Yingchun; Ma, Chi; Li, Hui; Li, Lingyao; Gao, Feng; Ao, Changjin

    2017-03-01

    This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW -0.75  d -1 , n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW -0.75  d -1 , n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW -0.75  d -1 , n = 6). Fetuses were recovered at slaughter on d 140. Fetal liver weight, DNA content and protein/DNA ratio, proliferation index, cytochrome c, activities of Caspase-3, 8, and 9 were examined, along with relative expression of genes related to apoptosis. Fetuses in both restricted groups exhibited decreased BW, hepatic weight, DNA content, and protein/DNA ratio when compared to CG (P < 0.05), as well as reduced proliferation index (P < 0.05). However, the increased numbers of apoptotic cells in fetal liver were observed in both restricted groups (P < 0.05). Fetuses with severe IUGR (RG1) exhibited increased (P < 0.05) activities of Caspase-3, 8, 9, as higher levels of mitochondrial cytochrome c in fetal liver; intermediate changes were found in RG2 fetuses, but the difference were not significant (P > 0.05). Hepatic expression of gene related to apoptosis showed reduced protein 21 (P21), B-cell lymphoma 2 (Bcl-2) and apoptosis antigen 1 ligand (FasL) expression in RG1 and RG2 (P < 0.05). In contrast, the increased hepatic expression of protein 53 (P53), Bcl-2 associated X protein (Bax) and apoptosis antigen 1 (Fas) in both IUGR fetuses were found (P < 0.05). These results indicate that the fetal hepatocyte proliferation were arrested in G1 cell cycle, and the fetal hepatocyte apoptosis was sensitive to the IUGR resulted from maternal undernutrition. The cell apoptosis in IUGR fetal liver were the potential mechanisms for its retarded proliferation and impaired

  12. Fetal and neonatal outcomes of preterm infants born before 32 weeks of gestation according to antenatal vs postnatal assessments of restricted growth.

    PubMed

    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

  13. Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.

    PubMed

    Pérez-Cruz, M; Cruz-Lemini, M; Fernández, M T; Parra, J A; Bartrons, J; Gómez-Roig, M D; Crispi, F; Gratacós, E

    2015-10-01

    Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001). Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further

  14. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    PubMed

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing; Lin, Shu-Wha; Lin, Shu-Rung

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway.

  15. Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated by lentiviral transgenesis.

    PubMed

    Crispo, M; Vilariño, M; dos Santos-Neto, P C; Núñez-Olivera, R; Cuadro, F; Barrera, N; Mulet, A P; Nguyen, T H; Anegón, I; Menchaca, A

    2015-02-01

    Lentiviral technology has been recently proposed to generate transgenic farm animals more efficiently and easier than traditional techniques. The objective was to evaluate several parameters of lambs obtained by lentiviral transgenesis in comparison with non-transgenic counterparts. In vitro produced embryos were microinjected (TG group) at two-cell stage with a lentiviral construct containing enhanced green fluorescent protein (eGFP) gene, while embryos produced by in vitro fertilization (IVF group) or intrauterine insemination (IUI group) were not microinjected. Microinjection technique efficiently generated eight-cell transgenic embryos (97.4%; 114/117). Development rate on day 5 after fertilization was similar for TG (39.3%, 46/117) and IVF embryos (39.6%, 44/111). Pregnancy rate was detected in 50.0% (6/12) of recipient ewes with TG embryos, in 46.7% (7/15) with IVF embryos, and in 65.0% (13/20) of IUI ewes (P = NS). Nine lambs were born in TG group, six lambs in IVF group, and 16 lambs in IUI group. All TG lambs (9/9) were GFP positive to real-time PCR and eight (88.9%) showed a strong and evident GFP expression in mucosae, eyes and keratin tissues. Fetal growth monitored every 15 day by ultrasonography did not show significant differences. Transgenic lambs neither differ in morphometric variables in comparison with non transgenic IVF lambs within 3 months after birth. Transmission of the transgene to the progeny was observed in green fluorescent embryos produced by IVF using semen from the TG founder lambs. In conclusion, this study demonstrates the high efficiency of lentiviral technology to produce transgenic sheep, with no clinic differences in comparison with non transgenic lambs.

  16. Lifetime racism and blood pressure changes during pregnancy: implications for fetal growth.

    PubMed

    Hilmert, Clayton J; Dominguez, Tyan Parker; Schetter, Christine Dunkel; Srinivas, Sindhu K; Glynn, Laura M; Hobel, Calvin J; Sandman, Curt A

    2014-01-01

    Research suggests that exposure to racism partially explains why African American women are 2 to 3 times more likely to deliver low birth weight and preterm infants. However, the physiological pathways by which racism exerts these effects are unclear. This study examined how lifetime exposure to racism, in combination with maternal blood pressure changes during pregnancy, was associated with fetal growth. African American pregnant women (n = 39) reported exposure to childhood and adulthood racism in several life domains (e.g., at school, at work), which were experienced directly or indirectly, meaning vicariously experienced when someone close to them was treated unfairly. A research nurse measured maternal blood pressure at 18 to 20 and 30 to 32 weeks gestation. Standardized questionnaires and trained interviewers assessed maternal demographics. Neonatal length of gestation and birth weight data were collected from medical charts. Childhood racism interacted with diastolic blood pressure to predict birth weight. Specifically, women with two or more domains of indirect exposure to racism in childhood and increases in diastolic blood pressure between 18 and 32 weeks had lower gestational age adjusted birth weight than the other women. A similar pattern was found for direct exposure to racism in childhood. Increases in diastolic blood pressure between the second and third trimesters predicted lower birth weight, but only when racism exposure in childhood (direct or indirect) was relatively high. Understanding pregnant African American women's lifetime direct and indirect experiences with racism in combination with prenatal blood pressure may improve identification of highest risk subgroups within this population. 2014 APA, all rights reserved

  17. Gestational Weight Gain Trend and Population Attributable Risks of Adverse Fetal Growth Outcomes in Ohio.

    PubMed

    Chen, Aimin; Xu, Fan; Xie, Changchun; Wu, Tianying; Vuong, Ann M; Miao, Maohua; Yuan, Wei; DeFranco, Emily A

    2015-07-01

    The trend of gestational weight gain (GWG) in relation to the Institute of Medicine (IOM) guidelines and the population attributable risks (PARs) of GWG on fetal growth outcomes remain unclear. We analysed Ohio