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: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth. Published by Elsevier Inc.

Association of third-trimester abdominal circumference with provider-initiated preterm delivery

PubMed Central

Hawkins, Leah K.; Schnettler, William T.; Modest, Anna M.; Hacker, Michele R.; Rodriguez, Diana

2016-01-01

Objective Evaluate the association of a small third-trimester abdominal circumference (AC < 10th percentile) in the setting of a normal estimated fetal weight (EFW ≥ 10th percentile) with gestational age at delivery, indication for delivery and neonatal outcomes. Methods Retrospective cohort study at an academic hospital of women with singleton pregnancy seen for ultrasound from 28+0-33+6 weeks of gestation during 2009-2011. Outcomes were compared between two groups: normal AC (AC and EFW ≥ 10th percentile) and small AC (AC < 10th percentile and EFW ≥ 10th percentile). Results Among 592 pregnancies, fetuses in the small AC group (n = 55) experienced a higher incidence of overall preterm delivery (RR: 2.2, 95% Cl: 1.3–3.7) and provider-initiated preterm delivery (RR: 3.7, Cl: 1.8–7.5) compared to those in the normal AC group (n = 537). Neonates in the small AC group had a lower median birth weight whether delivered at term (p < 0.001) or preterm (p = 0.04), but were not more likely to experience intensive care unit admission or respiratory distress syndrome (all p ≥ 0.35). Conclusions Small AC, even in the setting of an EFW ≥ 10th percentile, was associated with a higher incidence of overall and provider-initiated preterm delivery despite similar neonatal outcomes. Further investigation is warranted to determine whether these preterm deliveries could be prevented. PMID:24102316

Prediction of small-for-gestational-age neonate by third-trimester fetal biometry and impact of ultrasound-delivery interval.

PubMed

Reboul, Q; Delabaere, A; Luo, Z C; Nuyt, A-M; Wu, Y; Chauleur, C; Fraser, W; Audibert, F

2017-03-01

To compare third-trimester ultrasound screening methods to predict small-for-gestational age (SGA), and to evaluate the impact of the ultrasound-delivery interval on screening performance. In this prospective study, data were collected from a multicenter singleton cohort study investigating the links between various exposures during pregnancy with birth outcome and later health in children. We included women, recruited in the first trimester, who had complete outcome data and had undergone third-trimester ultrasound examination. Demographic, clinical and biological variables were also collected from both parents. We compared prediction of delivery of a SGA neonate (birth weight < 10 th percentile) by the following methods: abdominal circumference (AC) Z-score based on Hadlock curves (Hadlock AC), on INTERGROWTH-21 st Project curves (Intergrowth AC) and on Salomon curves (Salomon AC); estimated fetal weight (EFW) Z-score based on Hadlock curves (Hadlock EFW) and on customized curves from Gardosi (Gardosi EFW); and fetal growth velocity based on change in AC between second and third trimesters (FGVAC). We also assessed the following ultrasound-delivery intervals: ≤ 4 weeks, ≤ 6 weeks and ≤ 10 weeks. Third-trimester ultrasound was performed in 1805 patients with complete outcome data, of whom 158 (8.8%) delivered a SGA neonate. Ultrasound examination was at a median gestational age of 32 (interquartile range, 31-33) weeks. The ultrasound-delivery interval was ≤ 4 weeks in 17.2% of cases, ≤ 6 weeks in 48.1% of cases and ≤ 10 weeks in 97.3% of cases. Areas under the receiver-operating characteristics curve (AUC) were 0.772 for Salomon AC, 0.768 for Hadlock EFW, 0.766 for Hadlock AC, 0.765 for Intergrowth AC, 0.708 for Gardosi EFW and 0.674 for FGVAC (all P < 0.0001). The screening method with the highest AUC for an ultrasound-delivery interval ≤ 4 weeks was Salomon AC (AUC, 0.856), ≤ 6 weeks was Hadlock AC (AUC, 0.824) and ≤ 10 weeks was Salomon AC (AUC, 0.780). At a fixed 10% false-positive rate, the best detection rates were 60.0%, 54.1% and 42.1% for intervals ≤ 4, ≤ 6 and ≤ 10 weeks, respectively. Third-trimester ultrasound measurements provide poor to moderate prediction of SGA. A shorter ultrasound-delivery interval provides better prediction than does a longer interval. Further studies are needed to test the effect of including maternal or biological characteristics in SGA screening. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

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.

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

National Practice Patterns for Prenatal Monitoring in Gastroschisis: Gastroschisis Outcomes of Delivery (GOOD) Provider Survey.

PubMed

Amin, Ruchi; Domack, Aaron; Bartoletti, Joseph; Peterson, Erika; Rink, Britton; Bruggink, Jennifer; Christensen, Melissa; Johnson, Anthony; Polzin, William; Wagner, Amy J

2018-05-23

Gastroschisis is an abdominal wall defect with increasing incidence. Given the lack of surveillance guidelines among maternal-fetal medicine (MFM) specialists, this study describes current practices in gastroschisis management. An online survey was administered to MFM specialists from institutions affiliated with the North American Fetal Therapy Network (NAFTNet). Questions focused on surveillance timing, testing, findings that changed clinical management, and delivery plan. Responses were obtained from 29/29 (100%) NAFTNet centers, comprising 143/371 (39%) providers. The majority had a regimen for antenatal surveillance in patients with stable gastroschisis (94%; 134/141). Antenatal testing began at 32 weeks for 68% (89/131) of MFM specialists. The nonstress test (55%; 72/129), biophysical profile (50%; 63/126), and amniotic fluid index (64%; 84/131) were used weekly. Estimated fetal weight (EFW) was performed monthly by 79% (103/131) of providers. At 28 weeks, abnormal EFW (77%; 97/126) and Doppler ultrasound (78%; 99/127) most frequently altered management. In stable gastroschisis, 43% (60/140) of providers delivered at 37 weeks, and 29% (40/ 140) at 39 weeks. Gastroschisis management differs among NAFTNet centers, although the majority initiate surveillance at 32 weeks. Timing of delivery still requires consensus. Prospective studies are necessary to further optimize practice guidelines and patient care. © 2018 S. Karger AG, Basel.

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 PCB 153 was observed with noteworthy reductions late in pregnancy in AC and EFW in the group with lower PCB153. Copyright © 2017 Elsevier Inc. All rights reserved.

Fetal biometric parameters: Reference charts for a non-selected risk population from Uberaba, Brazil

PubMed Central

Peixoto, Alberto Borges; da Cunha Caldas, Taciana Mara Rodrigues; Dulgheroff, Fernando Felix; Martins, Wellington P.

2017-01-01

Objective To establish reference charts for fetal biometric parameters in a non-selected risk population from Uberaba, Southeast of Brazil. Methods A retrospective cross-sectional study was performed among 5656 non-selected risk singleton pregnant women between 14 and 41 weeks of gestation. The ultrasound exams were performed during routine visits of second and third trimesters. Biparietal diameter (BPD) was measured at the level of the thalami and cavum septi pellucidi. Head circumference (HC) was calculated by the following formula: HC = 1.62*(BPD + occipital frontal diameter, OFD). Abdominal circumference (AC) was measured using the following formula: AC = (anteroposterior diameter + transverse abdominal diameter) × 1.57. Femur diaphysis length (FDL) was obtained in the longest axis of femur without including the distal femoral epiphysis. The estimated fetal weight (EFW) was obtained by the Hadlock formula. Polynomial regressions were performed to obtain the best-fit model for each fetal biometric parameter as the function of gestational age (GA). Results The mean, standard deviations (SD), minimum and maximum of BPD (cm), HC (cm), AC (cm), FDL (cm) and EFW (g) were 6.9 ± 1.9 (2.3 – 10.5), 24.51 ± 6.61 (9.1 – 36.4), 22.8 ± 7.3 (7.5 – 41.1), 4.9 ± 1.6 (1.2 – 8.1) and 1365 ± 1019 (103 – 4777), respectively. Second-degree polynomial regressions between the evaluated parameters and GA resulted in the following formulas: BPD = –4.044 + 0.540 × GA – 0.0049 × GA2 (R2 = 0.97); HC= –15.420 + 2.024 GA – 0.0199 × GA2 (R2 = 0.98); AC = –9.579 + 1.329 × GA – 0.0055 × GA2 (R2 = 0.97); FDL = –3.778 + 0.416 × GA – 0.0035 × GA2 (R2 = 0.98) and EFW = 916 – 123 × GA + 4.70 × GA2 (R2 = 0.96); respectively. Conclusion Reference charts for the fetal biometric parameters in a non-selected risk population from Uberaba, Southeast of Brazil, were established. PMID:28439425

Fetal biometric parameters: Reference charts for a non-selected risk population from Uberaba, Brazil.

PubMed

Peixoto, Alberto Borges; da Cunha Caldas, Taciana Mara Rodrigues; Dulgheroff, Fernando Felix; Martins, Wellington P; Araujo Júnior, Edward

2017-03-01

To establish reference charts for fetal biometric parameters in a non-selected risk population from Uberaba, Southeast of Brazil. A retrospective cross-sectional study was performed among 5656 non-selected risk singleton pregnant women between 14 and 41 weeks of gestation. The ultrasound exams were performed during routine visits of second and third trimesters. Biparietal diameter (BPD) was measured at the level of the thalami and cavum septi pellucidi. Head circumference (HC) was calculated by the following formula: HC = 1.62*(BPD + occipital frontal diameter, OFD). Abdominal circumference (AC) was measured using the following formula: AC = (anteroposterior diameter + transverse abdominal diameter) × 1.57. Femur diaphysis length (FDL) was obtained in the longest axis of femur without including the distal femoral epiphysis. The estimated fetal weight (EFW) was obtained by the Hadlock formula. Polynomial regressions were performed to obtain the best-fit model for each fetal biometric parameter as the function of gestational age (GA). The mean, standard deviations ( SD ), minimum and maximum of BPD (cm), HC (cm), AC (cm), FDL (cm) and EFW (g) were 6.9 ± 1.9 (2.3 - 10.5), 24.51 ± 6.61 (9.1 - 36.4), 22.8 ± 7.3 (7.5 - 41.1), 4.9 ± 1.6 (1.2 - 8.1) and 1365 ± 1019 (103 - 4777), respectively. Second-degree polynomial regressions between the evaluated parameters and GA resulted in the following formulas: BPD = -4.044 + 0.540 × GA - 0.0049 × GA 2 ( R 2 = 0.97); HC= -15.420 + 2.024 GA - 0.0199 × GA 2 ( R 2 = 0.98); AC = -9.579 + 1.329 × GA - 0.0055 × GA 2 ( R 2 = 0.97); FDL = -3.778 + 0.416 × GA - 0.0035 × GA 2 ( R 2 = 0.98) and EFW = 916 - 123 × GA + 4.70 × GA 2 ( R 2 = 0.96); respectively. Reference charts for the fetal biometric parameters in a non-selected risk population from Uberaba, Southeast of Brazil, were established.

Deficit of vitamin D in pregnancy and growth and overweight in the offspring.

PubMed

Morales, E; Rodriguez, A; Valvi, D; Iñiguez, C; Esplugues, A; Vioque, J; Marina, L S; Jiménez, A; Espada, M; Dehli, C R; Fernández-Somoano, A; Vrijheid, M; Sunyer, J

2015-01-01

Maternal vitamin D status during fetal development may influence offspring growth and risk of obesity; however, evidence in humans is limited. To investigate whether maternal circulating 25-hydroxyvitamin D3 (25(OH)D3) concentration in pregnancy is associated with offspring prenatal and postnatal growth and overweight. Plasma 25(OH)D3 concentration was measured in pregnant women (median weeks of gestation 14.0, range 13.0-15.0) from the INMA (INfancia y Medio Ambiente) cohort (Spain, 2003-2008) (n = 2358). Offspring femur length (FL), biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) were evaluated at 12, 20 and 34 weeks of gestation by ultrasound examinations. Fetal overweight was defined either as AC or as EFW ⩾ 90th percentile. Child's anthropometry was recorded at ages 1 and 4 years. Rapid growth was defined as a weight gain z-score of >0.67 from birth to ages 6 months and 1 year. Age- and sex-specific z-scores for body mass index (BMI) were calculated at ages 1 and 4 years (World Health Organization referent); infant's overweight was defined as a BMI z-score ⩾ 85th percentile. We found no association of maternal 25(OH)D3 concentration with FL and a weak inverse association with BPD at 34 weeks. Maternal deficit of 25(OH)D3 (<20 ng ml(-1)) was associated with increased risk of fetal overweight defined as AC ⩾ 90th percentile (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.01-2.21; P = 0.041) or either as EFW ⩾ 90th percentile (OR = 1.47, 95% CI: 1.00-2.16; P = 0.046). No significant associations were found with rapid growth. Deficit of 25(OH)D3 in pregnancy was associated with an increased risk of overweight in offspring at age 1 year (OR = 1.42, 95% CI: 1.02-1.97; P = 0.039); however, the association was attenuated at age 4 years (OR = 1.19, 95% CI: 0.83-1.72; P = 0.341). Vitamin D deficiency in pregnancy may increase the risk of prenatal and early postnatal overweight in offspring. Clinical trials are warranted to determine the role of vitamin D in the early origins of obesity.

Air pollution exposure during pregnancy and ultrasound and birth measures of fetal growth: A prospective cohort study in Korea.

PubMed

Lamichhane, Dirga Kumar; Ryu, Jia; Leem, Jong-Han; Ha, Mina; Hong, Yun-Chul; Park, Hyesook; Kim, Yangho; Jung, Dal-Young; Lee, Ji-Young; Kim, Hwan-Cheol; Ha, Eun-Hee

2018-04-01

Few studies have examined the effects of air pollution on fetal growth based on ultrasound measures during pregnancy. More data is needed to evaluate the windows of special vulnerability. Our aim was to investigate the association of ambient air pollution during pregnancy with fetal and neonatal characteristics in a cohort of Korean women. Maternal exposure to particulate matter with an aerodynamic diameter<10μm (PM 10 ) and nitrogen dioxide (NO 2 ) was estimated using land-use regression models based on residential address. The biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) were evaluated via ultrasonography, and birth weight (BW), birth length (BL), and head circumference at birth (BHC) were obtained from medical records. The multiple linear regression model was used to adjust for confounders, and the mixed-effect model was used to evaluate longitudinal effect. The negative effects for NO 2 and PM 10 were estimated; in the adjusted analyses the decreases of BPD were -0.26mm (95% confidence interval [CI]=-0.41 to -0.11, with a 10μg/m 3 increase) in the second trimester for NO 2 , and -0.30mm (95% CI=-0.59 to -0.03, with a 10μg/m 3 increase) in the third trimester for PM 10 . Both NO 2 and PM 10 levels (10μg/m 3 ) during third trimester were inversely associated with BHC, and NO 2 level was inversely associated with BL in all exposure windows. No significant associations for AC, FL, and EFW were observed. The longitudinal analyses showed inverse association of NO 2 exposure with head and length growth (P<0.001). Our findings suggest that ambient air pollution is associated with impaired fetal head size from mid-gestation onwards. Copyright © 2017 Elsevier B.V. All rights reserved.

Is there a relationship between the grade of maternal hydronephrosis and birth weight of the babies?

PubMed

Coban, Soner; Biyik, Ismail; Ustunyurt, Emin; Keles, Ibrahim; Guzelsoy, Muhammed; Demirci, Hakan

2015-06-01

Mild hydronephrosis may be present in upto 90% of pregnancies. The degree of hydronephrosis was determined by maximal calyceal diameter (MCD). The aim of this study is to investigate whether there is a relationship between grade of maternal hydronephrosis and birth weight of the babies. Subjects were examined in three groups: group 1 MCD of 5-10 mm (grade I), group 2 10-15 mm (grade II) and group 3 patients >15 mm (grade III). There were 45, 30, 13 patients in the groups, respectively. Estimated fetal weight (EFW) at the time that hydronephrosis was diagnosed, birth weight and duration of pregnancy were compared. The average birth weight of the babies was not statistically different in the three groups (p > 0.05), but there was a statistically significant difference in fetal weights at the time of diagnosis (p = 0.02). The grade of maternal hydronephrosis does not affect the duration of pregnancy.

[Detection of small for gestational age fetuses during third trimester ultrasound. A monocentric observational study].

PubMed

Peyronnet, V; Kayem, G; Mandelbrot, L; Sibiude, J

2016-09-01

Fetus small for gestational age (SGA) screening rate is evaluated around 21,7 % in France. Recommendations were developed to improve the efficiency of ultrasound conducted in the third trimester (T3), because neonatal consequences can be significant. This study aims to evaluate screening of SGA during T3 ultrasound and to describe causes for failure and differences with the recommendations of CNGOF. All children born between 2011 and 2012 with a birth weight below the 3rd percentile were included in this observational, retrospective, monocentric study. We noted that the diagnosis of SGA was placed on file. Then, as recommended by the CNGOF, we calculated estimated fetal weight (EFW) with Hadlock 3 and Hadlock 4, and the corresponding percentiles, using the biometrics from the ultrasound report. We thus could evaluate a new screening rate with SGA fetus identified through this technique. A total of 142 patients were included. By calculating correctly all EFW and checking abdominal circumference percentiles, the screening rate of SGA fetuses with T3 ultrasound increased from 40 % to 50 % and the overall screening rate (clinical and ultrasound) from 54 % to 66 %. By following the recommendations we found a real improvement in fetal SGA screening rates to T3 ultrasound with a potential benefit for their care. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Delivery management for the prevention of shoulder dystocia in case of identified risk factors].

PubMed

Schmitz, T

2015-12-01

To determine the impact of (i) computed tomographic (CT) pelvimetry for the choice of the mode of delivery, (ii) cesarean, (iii) induction of labor, and of (iv) various delivery managements on the risk of shoulder dystocia in case of fetal macrosomia, with or without maternal diabetes, and in women with previous history of shoulder dystocia. The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. In case of clinically suspected macrosomia, a sonography should be performed to increase diagnostic performances and to assist in decision-making (Professional consensus). Because CT pelvimetry is associated with high false positive rates and increases cesarean deliveries, its use is not recommended to prevent shoulder dystocia in case of fetal macrosomia (Professional consensus). To avoid the neonatal complications of shoulder dystocia, mainly permanent brachial plexus palsy, cesarean delivery is recommended in case of estimated fetal weight (EFW) greater than 4500 g if associated with maternal diabetes (grade C), and greater than 5000 g in the absence of maternal diabetes (grade C). The published data do not provide definitive evidences to recommend systematic labor induction in case of impending fetal macrosomia (Professional consensus). In case of favourable cervix and gestational age greater than 39 weeks of gestation, labor induction should be promoted (Professional consensus). Prophylactic McRoberts maneuver is not recommended to prevent shoulder dystocia in case of fetal macrosomia (grade C). Because data are lacking, no recommendation is possible regarding the use of episiotomy. In case of fetal macrosomia and failure to progress in the second stage of labor, midpelvic and higher instrumental deliveries are not recommended and a cesarean delivery should be preferred (grade C), if the fetal head is at or lower than a +2 station, cesarean delivery is not recommended and an instrumental delivery should be preferred (grade C). Finally, cesarean delivery should be discussed when history of shoulder dystocia has been associated with severe neonatal or maternal complications (Professional consensus). To avoid shoulder dystocia and its complications, only two measures are proposed. Induction of labor is recommended in case of impending macrosomia if the cervix is favourable and gestational age greater than 39 weeks of gestation (Professional consensus). Cesarean delivery is recommended before labor in case of (i) EFW greater than 4500 g if associated with maternal diabetes (grade C), (ii) EFW greater than 5000 g in the absence of maternal diabetes (grade C), and finally (iii) during labor, in case of fetal macrosomia and failure to progress in the second stage, when the fetal head is above a +2 station (grade C). Finally, cesarean delivery should be discussed when history of shoulder dystocia has been associated with severe neonatal or maternal complications (Professional consensus). Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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. Hadlock's EFW formula with three indicators (HC, AC and FL) should ideally be used (Grade B). The ultrasound report must specify the percentile of the EFW (Grade C). Verification of the date of conception is essential. It is based on the crown-rump length between 11 and 14 weeks of gestation (Grade A). The HC, AC and FL measurements must be related to the appropriate reference curves (professional consensus); those modelled from College Francais d'Echographie Fetale data are recommended because they are multicentere French curves (professional consensus). Whether or not a work-up should be performed and its content depend on the context (gestational age, severity of biometric abnormalities, other ultrasound data, parents' wishes, etc.) (professional consensus). Such a work-up only makes sense if it might modify pregnancy management and, in particular, if it has the potential to reduce perinatal and long-term morbidity and mortality (professional consensus). The use of umbilical artery Doppler velocimetry is associated with better newborn health status in populations at risk, especially in those with FGR (Grade A). This Doppler examination must be the first-line tool for surveillance of fetuses with SGA and FGR (professional consensus). A course of corticosteroids is recommended for women with an FGR fetus, and for whom delivery before 34 weeks of gestation is envisaged (Grade C). Magnesium sulphate should be prescribed for preterm deliveries before 32-33 weeks of gestation (Grade A). The same management should apply for preterm FGR deliveries (Grade C). In cases of FGR, fetal growth must be monitored at intervals of no less than 2 weeks, and ideally 3 weeks (professional consensus). Referral to a Level IIb or III maternity ward must be proposed in cases of EFW <1500g, potential birth before 32-34 weeks of gestation (absent or reversed umbilical end-diastolic flow, abnormal venous Doppler) or a fetal disease associated with any of these (professional consensus). Systematic caesarean deliveries for FGR are not recommended (Grade C). In cases of vaginal delivery, fetal heart rate must be monitored continuously during labour, and any delay before intervention must be faster than in low-risk situations (professional consensus). Regional anaesthesia is preferred in trials of vaginal delivery, as in planned caesareans. Morbidity and mortality are higher in SGA newborns than in normal-weight newborns of the same gestational age (LE3). The risk of neonatal mortality is two to four times higher in SGA newborns than in non-SGA preterm and full-term infants (LE2). Initial management of an SGA newborn includes combatting hypothermia by maintaining the heat chain (survival blanket), ventilation with a pressure-controlled insufflator, if necessary, and close monitoring of capillary blood glucose (professional consensus). Testing for antiphospholipids (anticardiolipin, circulating anticoagulant, anti-beta2-GP1) is recommended in women with previous severe FGR (below third percentile) that led to birth before 34 weeks of gestation (professional consensus). It is recommended that aspirin should be prescribed to women with a history of pre-eclampsia before 34 weeks of gestation, and/or FGR below the fifth percentile with a probable vascular origin (professional consensus). Aspirin must be taken in the evening or at least 8h after awakening (Grade B), before 16 weeks of gestation, at a dose of 100-160mg/day (Grade A). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Performance of third-trimester combined screening model for prediction of adverse perinatal outcome.

PubMed

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

2017-09-01

To explore the potential value of third-trimester combined screening for the prediction of adverse perinatal outcome (APO) in the general population and among small-for-gestational-age (SGA) fetuses. This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester evaluation (32 + 0 to 36 + 6 weeks' gestation). Maternal baseline characteristics, mean arterial blood 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 had an APO (n = 148) and in a control group without perinatal complications (n = 902). APO was defined as the occurrence of stillbirth, umbilical artery cord blood pH < 7.15, 5-min Apgar score < 7 or emergency operative delivery for fetal distress. Logistic regression models were developed for the prediction of APO in the general population and among SGA cases (defined as customized birth weight < 10 th centile). The prevalence of APO was 9.3% in the general population and 27.4% among SGA cases. In the general population, a combined screening model including a-priori risk (maternal characteristics), estimated fetal weight (EFW) centile, umbilical artery pulsatility index (UA-PI), estriol and PlGF achieved a detection rate for APO of 26% (area under receiver-operating characteristics curve (AUC), 0.59 (95% CI, 0.54-0.65)), at a 10% false-positive rate (FPR). Among SGA cases, a model including a-priori risk, EFW centile, UA-PI, cerebroplacental ratio, estriol and PlGF predicted 62% of APO (AUC, 0.86 (95% CI, 0.80-0.92)) at a FPR of 10%. The use of fetal ultrasound and maternal biochemical markers at 32-36 weeks provides a poor prediction of APO in the general population. Although it remains limited, the performance of the screening model is improved when applied to fetuses with suboptimal fetal growth. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

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.

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, Murcia M, Monfort N, Luque N, Rubio S, Ventura R, Sunyer J, Vrijheid M. 2016. Exposure to bisphenol A and phthalates during pregnancy and ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health Perspect 124:521–528; http://dx.doi.org/10.1289/ehp.1409190 PMID:26196298

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 to bisphenol A and phthalates during pregnancy and ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health Perspect 124:521-528; http://dx.doi.org/10.1289/ehp.1409190.

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 therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. NCT02097667 registered 31 st October 2013.

Ultrasonographic Fetal Weight Estimation: Should Macrosomia-Specific Formulas Be Utilized?

PubMed

Porter, Blake; Neely, Cherry; Szychowski, Jeff; Owen, John

2015-08-01

This study aims to derive an estimated fetal weight (EFW) formula in macrosomic fetuses, compare its accuracy to the 1986 Hadlock IV formula, and assess whether including maternal diabetes (MDM) improves estimation. Retrospective review of nonanomalous live-born singletons with birth weight (BWT) ≥ 4 kg and biometry within 14 days of birth. Formula accuracy included: (1) mean error (ME = EFW - BWT), (2) absolute mean error (AME = absolute value of [1]), and (3) mean percent error (MPE, [1]/BWT × 100%). Using loge BWT as the dependent variable, multivariable linear regression produced a macrosomic-specific formula in a "training" dataset which was verified by "validation" data. Formulas specific for MDM were also developed. Out of the 403 pregnancies, birth gestational age was 39.5 ± 1.4 weeks, and median BWT was 4,240 g. The macrosomic formula from the training data (n = 201) had associated ME = 54 ± 284 g, AME = 234 ± 167 g, and MPE = 1.6 ± 6.2%; evaluation in the validation dataset (n = 202) showed similar errors. The Hadlock formula had associated ME = -369 ± 422 g, AME = 451 ± 332 g, MPE = -8.3 ± 9.3% (all p < 0.0001). Diabetes-specific formula errors were similar to the macrosomic formula errors (all p = NS). With BWT ≥ 4 kg, the macrosomic formula was significantly more accurate than Hadlock IV, which systematically underestimates fetal/BWT. Diabetes-specific formulas did not improve accuracy. A specific formula should be considered when macrosomia is suspected. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Shoulder dystocia: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF).

PubMed

Sentilhes, Loïc; Sénat, Marie-Victoire; Boulogne, Anne-Isabelle; Deneux-Tharaux, Catherine; Fuchs, Florent; Legendre, Guillaume; Le Ray, Camille; Lopez, Emmanuel; Schmitz, Thomas; Lejeune-Saada, Véronique

2016-08-01

Shoulder dystocia (SD) is defined as a vaginal delivery in cephalic presentation that requires additional obstetric maneuvers to deliver the fetus after the head has delivered and gentle traction has failed. It complicates 0.5-1% of vaginal deliveries. Risks of brachial plexus birth injury (level of evidence [LE]3), clavicle and humeral fracture (LE3), perinatal asphyxia (LE2), hypoxic-ischemic encephalopathy (LE3) and perinatal mortality (LE2) increase with SD. Its main risk factors are previous SD and macrosomia, but both are poorly predictive; 50-70% of SD cases occur in their absence, and most deliveries when they are present do not result in SD. No study has proven that the correction of these risk factors (except gestational diabetes) would reduce the risk of SD. Physical activity is recommended before and during pregnancy to reduce the occurrence of some risk factors for SD (Grade C). In obese women, physical activity should be coupled with dietary measures to reduce fetal macrosomia and weight gain during pregnancy (Grade A). Women with gestational diabetes require diabetes care (diabetic diet, glucose monitoring, insulin if needed) (Grade A) because it reduces the risk of macrosomia and SD (LE1). Only two measures are proposed for avoiding SD and its complications. First, induction of labor is recommended in cases of impending macrosomia if the cervix is favorable at a gestational age of 39 weeks or more (professional consensus). Second, cesarean delivery is recommended before labor in three situations and during labor in one: (i) estimated fetal weight (EFW) >4500g if associated with maternal diabetes (Grade C), (ii) EFW >5000g in women without diabetes (Grade C), (iii) history of SD associated with severe neonatal or maternal complications (professional consensus), and finally during labor, (iv) in case of fetal macrosomia and failure to progress in the second stage, when the fetal head station is above +2 (Grade C). In cases of SD, it is recommended to avoid the following actions: excessive traction on the fetal head (Grade C), fundal pressure (Grade C), and inverse rotation of the fetal head (professional consensus). The McRoberts maneuver, with or without suprapubic pressure, is recommended first (Grade C). If it fails and the posterior shoulder is engaged, Wood's maneuver should be performed preferentially; if the posterior shoulder is not engaged, it is preferable to attempt to deliver the posterior arm next (professional consensus). It appears necessary to know at least two maneuvers to perform should the McRoberts maneuver fail (professional consensus). A pediatrician should be immediately informed of SD. The initial clinical examination should check for complications, such as brachial plexus injury or clavicle fracture (professional consensus). If no complications are observed, neonatal monitoring need not be modified (professional consensus). The implementation of practical training with simulation for all care providers in the delivery room is associated with a significant reduction in neonatal (LE3) but not maternal (LE3) injury. SD remains an unpredictable obstetric emergency. All physicians and midwives should know and perform obstetric maneuvers if needed, quickly but calmly. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Performance of third-trimester ultrasound for prediction of small-for-gestational-age neonates and evaluation of contingency screening policies.

PubMed

Souka, A P; Papastefanou, I; Pilalis, A; Michalitsi, V; Kassanos, D

2012-05-01

To assess the performance of third-trimester fetal biometry and fetal Doppler studies for the prediction of small-for-gestational-age (SGA) neonates, and to explore contingency strategies using a first-trimester prediction model based on maternal and fetal parameters and third-trimester ultrasound. This was an observational cross-sectional study of uncomplicated singleton pregnancies. Risk assessment for chromosomal abnormality was carried out in 4702 pregnancies using a combination of ultrasound markers (fetal nuchal translucency thickness (NT) and nasal bone assessment) and biochemistry (free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A)) at 11 to 13 + 6 weeks. Maternal demographic characteristics and method of conception were recorded. Third-trimester (30-34 weeks) fetal biometry (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL)) and umbilical artery (UA) and middle cerebral artery Doppler studies were performed routinely in a subgroup (n = 2310). Reference ranges for birth weight were constructed using the cohort of 4702 women, and neonates were classified as small (SGA, ≤ 5th centile) or appropriate (AGA) for gestational age. First-trimester, third-trimester and integrated first- and third-trimester prediction models for SGA were constructed using regression analysis and three different contingency strategies of rescanning in the third trimester were investigated. According to the areas under the receiver-operating characteristics curves (AUCs), AC (AUC = 0.85) and ultrasound-estimated fetal weight (EFW, AUC = 0.87) were equally good predictors of SGA. The model was marginally improved by the addition of UA Doppler, smoking status and first-trimester indices (free β-hCG and PAPP-A multiples of the median) (combined model, AUC = 0.88), but the difference was not statistically significant. A contingency strategy of rescanning 50% of the population in the third trimester according to the risk estimated by a first-trimester prediction model yielded a detection rate of 79% for a 25% screen-positive rate. Third-trimester ultrasound is effective in screening for SGA in uncomplicated pregnancies. The use of a contingency screening policy can reduce the need for unnecessary examinations. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Management of small-for-gestational-age twins with absent/reversed end diastolic flow in the umbilical artery: outcome of a policy of daily biophysical profile (BPP).

PubMed

Kennelly, Máiréad M; Sturgiss, Stephen N

2007-01-01

To evaluate a strategy of daily biophysical profile (BPP) for pregnancies with small-for-gestational-age twins and with absent or reversed end diastolic flow (AREDF) in the umbilical artery of one twin and to assess the latency interval between detection and delivery in monochorionic (MC) and dichorionic (DC) twin pregnancy. A search of the Fetal Medicine Database was carried out between 2000 and 2005 at a single tertiary centre to identify all cases with AREDF in the umbilical artery with one small-for-gestational-age twin. Active monitoring with daily BPP was undertaken, once the estimated fetal weights (EFW) was >or= 500 g and at a gestational age of >or= 24 weeks in both twins. Delivery was timed on the basis of an abnormal BPP, two equivocal BPP within 12 h or gestational age of >or= 32(+0) weeks. Twenty-two MC and 17 DC twin pregnancies were identified. There were no fetal losses in the viable actively monitored MC (19) and DC (13) twins. There was a longer latency interval in the MC group at 21.7 days versus 14.4 days in the DC group (p = 0.13). Delivery was indicated for an abnormal BPP (57.8% MC vs 30.8% DC). A strategy of daily BPP can be used to monitor preterm twin fetuses with AREDF, prolonging pregnancy with an acceptable perinatal outcome. Copyright 2007 John Wiley & Sons, Ltd.

Global energy consumption for direct water use

NASA Astrophysics Data System (ADS)

Liu, Y.; Hejazi, M. I.; Kim, S. H.; Kyle, P.; Davies, E. G.; Miralles, D. G.; Teuling, R.; He, Y.; Niyogi, D.

2015-12-01

Despite significant efforts to quantify the mutual inter-dependence of the water and energy sectors, global energy for water (EFW) remains poorly understood, resulting in biases in energy accounting that directly affect water and energy management and policy. We firstly evaluate the global energy consumption for direct water use from 1973 to 2012 with sectoral, regional and process-level details. Over the 40-year period, we detected multiple shifts in EFW by county and region. For example, we find that India, the Middle East and China have surpassed the United States as the three largest consumers of EFW since 2003, mostly because of rapid growth in groundwater-based irrigation, desalination, and industrial and municipal water use, respectively. Globally, EFW accounts for 1-3% of total primary energy consumption in 2010, of which 52% is surface water, 36% is groundwater, and 12% is non-fresh water. The sectoral allocation of EFW includes municipal (45%), industrial (29%), and agricultural use (26%), and process-level contributions are from source/conveyance (41%), water purification (19%), water distribution (13%) and wastewater treatment (22%). Our evaluation suggests that the EFW may increase in importance in the future due to growth in population and income, and depletion of surface and shallow aquifer water resources in water-scarce regions. We are incorporating this element into an integrated assessment model (IAM) and linking it back to energy balance within that IAM. By doing this, we will then explore the impacts of EFW on the global energy market (e.g., changes in the share of groundwater use and desalination), and the uncertainty of future EFW under different shared social pathway (SSP) and representative concentration pathway (RCP) scenarios, and consequences on the emission of greenhouse gases as well. We expect these EFW induced impacts will be considerable, and will then have significant implications for adaptive management and policy making.

[Shoulder dystocia: Guidelines for clinical practice--Short text].

PubMed

Sentilhes, L; Sénat, M-V; Boulogne, A-I; Deneux-Tharaux, C; Fuchs, F; Legendre, G; Le Ray, C; Lopez, E; Schmitz, T; Lejeune-Saada, V

2015-12-01

To determine the available evidence to prevent and treat shoulder dystocia to attempt to decrease its related neonatal and maternal morbidity. The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. Shoulder dystocia, defined as a vaginal delivery that requires additional obstetric maneuvers to deliver the fetus after the head has delivered and gentle traction has failed, complicates 0.5-1 % of vaginal deliveries. Risks of brachial plexus birth injury (LE3), clavicle and humeral fracture (LE3), perinatal asphyxia (LE2), hypoxic-ischemic encephalopathy (LE3) and perinatal mortality (LE2) are increased after shoulder dystocia. Its main risk factors are previous shoulder dystocia and macrosomia, but they are poorly predictive; 50 % to 70 % of shoulder dystocia cases occur in their absence, and the great majority of deliveries when they are present are not associated with shoulder dystocia. No study has proven that the correction of these risk factors (except gestational diabetes) would reduce the risk of shoulder dystocia (SD). Physical activity is recommended before and during pregnancy to reduce the occurrence of some risk factors for shoulder dystocia (grade C). In obese patients, physical activity should be coupled with dietary measures to reduce fetal macrosomia and weight gain during pregnancy (grade A). In case of gestational diabetes, diabetes care is recommended (diabetic diet, glucose monitoring, insulin if needed) (grade A) as it reduces the risk of macrosomia and shoulder dystocia (LE1). In order to avoid shoulder dystocia and its complications, only two measures are proposed. Induction of labor is recommended in case of impending macrosomia if the cervix is favourable and gestational age greater than 39 weeks of gestation (professional consensus). Cesarean delivery is recommended before labor in case of EFW greater than 4500g if associated with maternal diabetes (grade C), EFW greater than 5000g in the absence of maternal diabetes (grade C), history of shoulder dystocia associated with severe neonatal or maternal complications (Professional consensus), and finally during labor, in case of fetal macrosomia and failure to progress in the second stage, when the fetal head is above a +2 station (grade C). In case of shoulder dystocia, it is recommended not to pull excessively on the fetal head (grade C), do not perform uterine expression (grade C) and do not realize inverse rotation of the fetal head (professional consensus). McRoberts' maneuver, with or without a suprapubic pressure, is recommended in the first line (grade C). In case of failure, if the posterior shoulder is engaged, Wood's maneuver should be performed preferentially; if the posterior shoulder is not engaged, delivery of the posterior arm should be performed preferentially (professional consensus). It seems necessary to know at least two maneuvers to perform in case of shoulder dystocia unresolved by the maneuver of McRoberts (professional consensus). Pediatrician should be immediately informed in case of shoulder dystocia. The initial clinical examination should search complications such as brachial plexus birth injury or clavicle fracture (professional consensus). In absence of neonatal complication, monitoring of the neonate is not modified (professional consensus). The implementation of a practical training using simulation and concerning all caregivers of the delivery room is associated with a significant reduction in neonatal (LE3) but not maternal (LE3) injury. Shoulder dystocia remains a non-predictable obstetrics emergency. All physicians and midwives should know and perform obstetric maneuvers if needed quickly but without precipitation. A training program using simulation for the management of shoulder dystocia is encouraged for the initial and continuing formation of different actors in the delivery room (professional consensus). Copyright © 2015. Published by Elsevier Masson SAS.

Mechanical design of EFW Exo II: A hybrid exoskeleton for elbow-forearm-wrist rehabilitation.

PubMed

Bian, Hui; Chen, Ziye; Wang, Hao; Zhao, Tieshi

2017-07-01

The use of rehabilitation exoskeleton has become an important means for the treatment of stroke patients. A hybrid exoskeleton named EFW Exo II is developed for the motor function rehabilitation of elbow, forearm and wrist. The EFW Exo II is based on a parallel 2-URR/RRS mechanism and a serial R mechanism. It could fit both left and right arms for the symmetrical and open structure, and the distance between the elbow and wrist could automatically adjust for different forearm length. Details of the mechanical design are introduced. Brushless DC servo motors with planetary gear reducer are used as the actuators of the exoskeleton. Gear drive and belt drive are used for power transmission. A three dimensional force sensor is mounted in the handle to regulate the interaction between the exoskeleton and patient. The EFW Exo II can realize rehabilitation exercise for each joint and the ranges of motion meet the rehabilitation demands of daily living.

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 either type I or type II sFGR (p>0.05 for both). Earlier GA at diagnosis (HR 0.70, 95% CI 0.56-0.88; p=0.002), type II sFGR (HR 3.53, 95% CI 1.37-9.07; p=0.008) and higher DV PI z scores (HR 1.36, 95% CI 1.12-1.65; p=0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin. Pregnancies complicated by type II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcomes when compared to type I. Co-existing TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either type I or type II sFGR. Earlier GA at diagnosis, type II sFGR and higher DV PI z scores are significantly associated with increased risk of adverse perinatal outcome for the smaller twin. This article is protected by copyright. All rights reserved.

Comparison of conventional 2D ultrasound to magnetic resonance imaging for prenatal estimation of birthweight in twin pregnancy.

PubMed

Kadji, Caroline; Bevilacqua, Elisa; Hurtado, Ivan; Carlin, Andrew; Cannie, Mieke M; Jani, Jacques C

2018-01-01

During prenatal follow-up of twin pregnancies, accurate identification of birthweight and birthweight discordance is important to identify the high-risk group and plan perinatal care. Unfortunately, prenatal evaluation of birthweight discordance by 2-dimensional ultrasound has been far from optimal. The objective of the study was to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound (ultrasound-estimated fetal weight) and magnetic resonance imaging (magnetic resonance-estimated fetal weight) with actual birthweight in women carrying twin pregnancies. Written informed consent was obtained for this ethics committee-approved study. Between September 2011 and December 2015 and within 48 hours before delivery, ultrasound-estimated fetal weight and magnetic resonance-estimated fetal weight were conducted in 66 fetuses deriving from twin pregnancies at 34.3-39.0 weeks; gestation. Magnetic resonance-estimated fetal weight derived from manual measurement of fetal body volume. Comparison of magnetic resonance-estimated fetal weight and ultrasound-estimated fetal weight measurements vs birthweight was performed by calculating parameters as described by Bland and Altman. Receiver-operating characteristic curves were constructed for the prediction of small-for-gestational-age neonates using magnetic resonance-estimated fetal weight and ultrasound-estimated fetal weight. For twins 1 and 2 separately, the relative error or percentage error was calculated as follows: (birthweight - ultrasound-estimated fetal weight (or magnetic resonance-estimated fetal weight)/birthweight) × 100 (percentage). Furthermore, ultrasound-estimated fetal weight, magnetic resonance-estimated fetal weight, and birthweight discordance were calculated as 100 × (larger estimated fetal weight-smaller estimated fetal weight)/larger estimated fetal weight. The ultrasound-estimated fetal weight discordance and the birthweight discordance were correlated using linear regression analysis and Pearson's correlation coefficient. The same was done between the magnetic resonance-estimated fetal weight and birthweight discordance. To compare data, the χ 2 , McNemar test, Student t test, and Wilcoxon signed rank test were used as appropriate. We used the Fisher r-to-z transformation to compare correlation coefficients. The bias and the 95% limits of agreement of ultrasound-estimated fetal weight are 2.99 (-19.17% to 25.15%) and magnetic resonance-estimated fetal weight 0.63 (-9.41% to 10.67%). Limits of agreement were better between magnetic resonance-estimated fetal weight and actual birthweight as compared with the ultrasound-estimated fetal weight. Of the 66 newborns, 27 (40.9%) were of weight of the 10th centile or less and 21 (31.8%) of the fifth centile or less. The area under the receiver-operating characteristic curve for prediction of birthweight the 10th centile or less by prenatal ultrasound was 0.895 (P < .001; SE, 0.049), and by magnetic resonance imaging it was 0.946 (P < .001; SE, 0.024). Pairwise comparison of receiver-operating characteristic curves showed a significant difference between the areas under the receiver-operating characteristic curves (difference, 0.087, P = .049; SE, 0.044). The relative error for ultrasound-estimated fetal weight was 6.8% and by magnetic resonance-estimated fetal weight, 3.2% (P < .001). When using ultrasound-estimated fetal weight, 37.9% of fetuses (25 of 66) were estimated outside the range of ±10% of the actual birthweight, whereas this dropped to 6.1% (4 of 66) with magnetic resonance-estimated fetal weight (P < .001). The ultrasound-estimated fetal weight discordance and the birthweight discordance correlated significantly following the linear equation: ultrasound-estimated fetal weight discordance = 0.03 + 0.91 × birthweight (r = 0.75; P < .001); however, the correlation was better with magnetic resonance imaging: magnetic resonance-estimated fetal weight discordance = 0.02 + 0.81 × birthweight (r = 0.87; P < .001). In twin pregnancies, magnetic resonance-estimated fetal weight performed immediately prior to delivery is more accurate and predicts small-for-gestational-age neonates significantly better than ultrasound-estimated fetal weight. Prediction of birthweight discordance is better with magnetic resonance imaging as compared with ultrasound. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultrasonic prediction of term birth weight in Hispanic women. Accuracy in an outpatient clinic.

PubMed

Nahum, Gerard G; Pham, Krystle Q; McHugh, John P

2003-01-01

To investigate the accuracy of ultrasonic fetal biometric algorithms for estimating term fetal weight. Ultrasonographic fetal biometric assessments were made in 74 Hispanic women who delivered at 37-42 weeks of gestation. Measurements were taken of the fetal biparietal diameter, head circumference, abdominal circumference and femur length. Twenty-seven standard fetal biometric algorithms were assessed for their accuracy in predicting fetal weight. Results were compared to those obtained by merely guessing the mean term birth weight in each case. The correlation between ultrasonically predicted and actual birth weights ranged from 0.52 to 0.79. The different ultrasonic algorithms estimated fetal weight to within +/- 8.6-15.0% (+/- 295-520 g) of actual birth weight as compared with +/- 13.6% (+/- 449 g) for guessing the mean birth weight in each case (mean +/- SD). The mean absolute prediction errors for 17 of the ultrasonic equations (63%) were superior to those obtained by guessing the mean birth weight by 3.2-5.0% (96-154 g) (P < .05). Fourteen algorithms (52%) were more accurate for predicting fetal weight to within +/- 15%, and 20 algorithms (74%) were more accurate for predicting fetal weight to within +/- 10% of actual birth weight than simply guessing the mean birth weight (P < .05). Ten ultrasonic equations (37%) showed significant utility for predicting fetal weight > 4,000 g (likelihood ratio > 5.0). Term fetal weight predictions using the majority of sonographic fetal biometric equations are more accurate, by up to 154 g and 5%, than simply guessing the population-specific mean birth weight.

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

PubMed

Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M

2007-03-15

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

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.

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.

[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 1.76 (1.34-2.32); Compared with the appropriate increase of gestational weight group, inadequate weight increase during pregnancy was a risk factor for fetal growth restriction, with the RR (95 %CI ) at 1.70 (1.17-2.48). No additive model interaction [relative excess risk of interaction, attributable proportions of interaction, the synergy index and their 95 %CI were 0.75 (-2.14-3.63), 0.21 (-0.43-0.86) and 1.43 (0.45-4.53), respectively] or multiplication model interaction ( RR (95 %CI ): 1.00 (0.44-2.29)) existed between pre-pregnancy underweight and inadequate increase of gestational weight on fetal growth restriction. Conclusion: Pre-pregnancy underweight and inadequate increase of gestational weight would increase the risk of fetal growth restriction without interaction.

Predictors of successful external cephalic version in an Australian maternity hospital.

PubMed

Mowat, Alex; Gardener, Glenn

2014-02-01

There are minimal data involving predictors of success of external cephalic version (ECV) in an Australian healthcare setting. To determine the predictors of successful ECV as well as the success rate of ECV and the mode of, and presentation at, delivery for women undergoing ECV for breech presentation from 36-weeks gestation. A prospective review was carried out on all women who had undergone ECV from 36-weeks gestation at the Mater Mothers Hospital over an 8-year period from 2001 to 2008. Data were collected prospectively and were collated in conjunction with database review, chart review and telephonic patient interviews. A total of 355 women underwent ECV for breech presentation. The overall success rate was 66% (57% for nulliparous, 76% for multiparous). A woman who underwent ECV had a 46% chance of a vaginal birth. If the ECV was successful, she had a 70% chance of vaginal birth. From bivariate analysis, parity, amniotic fluid index (AFI) and estimated fetal weight (EFW) were determined to be possible predictors of success of ECV and were included in the logistic regression modelling. In the regression analysis, multiparity increased the odds of successful ECV by 2.18. For every one unit increase in AFI, the odds of successful ECV increased by 1.18. Multiparity and amniotic fluid volume as assessed by AFI were the significant predictors of immediate success of ECV. Conversely, lower AFI and nulliparity are factors that are likely to reduce the likelihood of successful ECV. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Estimation of Fetal Weight during Labor: Still a Challenge.

PubMed

Barros, Joana Goulão; Reis, Inês; Pereira, Isabel; Clode, Nuno; Graça, Luís M

2016-01-01

To evaluate the accuracy of fetal weight prediction by ultrasonography labor employing a formula including the linear measurements of femur length (FL) and mid-thigh soft-tissue thickness (STT). We conducted a prospective study involving singleton uncomplicated term pregnancies within 48 hours of delivery. Only pregnancies with a cephalic fetus admitted in the labor ward for elective cesarean section, induction of labor or spontaneous labor were included. We excluded all non-Caucasian women, the ones previously diagnosed with gestational diabetes and the ones with evidence of ruptured membranes. Fetal weight estimates were calculated using a previously proposed formula [estimated fetal weight = 1687.47 + (54.1 x FL) + (76.68 x STT). The relationship between actual birth weight and estimated fetal weight was analyzed using Pearson's correlation. The formula's performance was assessed by calculating the signed and absolute errors. Mean weight difference and signed percentage error were calculated for birth weight divided into three subgroups: < 3000 g; 3000-4000 g; and > 4000 g. We included for analysis 145 cases and found a significant, yet low, linear relationship between birth weight and estimated fetal weight (p < 0.001; R2 = 0.197) with an absolute mean error of 10.6%. The lowest mean percentage error (0.3%) corresponded to the subgroup with birth weight between 3000 g and 4000 g. This study demonstrates a poor correlation between actual birth weight and the estimated fetal weight using a formula based on femur length and mid-thigh soft-tissue thickness, both linear parameters. Although avoidance of circumferential ultrasound measurements might prove to be beneficial, it is still yet to be found a fetal estimation formula that can be both accurate and simple to perform.

Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study.

PubMed

Ay, L; Kruithof, C J; Bakker, R; Steegers, E A P; Witteman, J C M; Moll, H A; Hofman, A; Mackenbach, J P; Hokken-Koelega, A C S; Jaddoe, V W V

2009-06-01

We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. Population-based birth cohort study. Data of pregnant women and their children in Rotterdam, the Netherlands. In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.

Optimizing hidden layer node number of BP network to estimate fetal weight

NASA Astrophysics Data System (ADS)

Su, Juan; Zou, Yuanwen; Lin, Jiangli; Wang, Tianfu; Li, Deyu; Xie, Tao

2007-12-01

The ultrasonic estimation of fetal weigh before delivery is of most significance for obstetrical clinic. Estimating fetal weight more accurately is crucial for prenatal care, obstetrical treatment, choosing appropriate delivery methods, monitoring fetal growth and reducing the risk of newborn complications. In this paper, we introduce a method which combines golden section and artificial neural network (ANN) to estimate the fetal weight. The golden section is employed to optimize the hidden layer node number of the back propagation (BP) neural network. The method greatly improves the accuracy of fetal weight estimation, and simultaneously avoids choosing the hidden layer node number with subjective experience. The estimation coincidence rate achieves 74.19%, and the mean absolute error is 185.83g.

Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

PubMed

Hughes, Alice E; Nodzenski, Michael; Beaumont, Robin N; Talbot, Octavious; Shields, Beverley M; Scholtens, Denise M; Knight, Bridget A; Lowe, William L; Hattersley, Andrew T; Freathy, Rachel M

2018-05-01

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry ( n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms. © 2018 by the American Diabetes Association.

How to find non-dependent opiate users: a comparison of sampling methods in a field study of opium and heroin users.

PubMed

Korf, Dirk J; van Ginkel, Patrick; Benschop, Annemieke

2010-05-01

The first aim is to better understand the potentials and limitations of different sampling methods for reaching a specific, rarely studied population of drug users and for persuading them to take part in a multidisciplinary study. The second is to determine the extent to which these different methods reach similar or dissimilar segments of the non-dependent opiate-using population. Using ethnographic fieldwork (EFW) and targeted canvassing (TARC; small newspaper advertisements and website announcements), supplemented by snowball referrals, we recruited and interviewed 127 non-dependent opiate users (lifetime prevalence of use 5-100 times; 86.6% had used heroin and 56.7% opium). Average age was 39.0; 66.1% were male and 33.9% female. In addition to opiates, many respondents had wide experience with other illicit drugs. The majority had non-conventional lifestyles. Both EFW and TARC yielded only limited numbers of snowball referrals. EFW requires specific skills, is labour-intensive, thus expensive, but allows unsuitable candidates to be excluded faster. Respondents recruited through EFW were significantly more likely to have experience with opium and various drugs other than opiates. TARC resulted in larger percentages of women and respondents with conventional lifestyles. TARC is less labour-intensive but requires more time for screening candidates; its cost-effectiveness depends on the price of advertising for the recruitment. Different methods reach different segments of the population of non-dependent opiate users. It is useful to employ a multi-method approach to reduce selectivity. Copyright 2009 Elsevier B.V. All rights reserved.

Applicability of fetal thoracic aortic diameter measurement in the prediction of birth weight in Holstein-Friesian cows - Short communication.

PubMed

Vincze, Boglárka; Gáspárdy, András; Kovács, Levente; Albert, Ervin; Kézér, Luca; Baska, Ferenc; Szenci, Ottó

2017-03-01

Transabdominal ultrasonography has been shown to be a useful and reliable method for assessing fetal well-being in horses and cattle. To test the applicability of fetal aortic diameter measurement in cattle, 44 late-term pregnant cows and heifers were examined 21 to 0 days prior to calving. Mean fetal aortic diameter was 2.07 ± 0.14 cm and mean fetal heart rate (FHR) was 109 ± 17 bpm. Three dead calves were dissected and their aortic diameter was measured in a water bath. The mean birth weight (n = 44) was 39.9 ± 5.8 kg. There was a significant negative correlation between FHR and fetal aortic diameter. However, although some studies have shown that fetal aortic diameter strongly correlates with birth weight in near-term horses and cattle, in this study there was no correlation between fetal aortic diameter and birth weight in Holstein-Friesian cows and heifers irrespective of whether the fetus was born alive or dead.

[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.

Sonographic estimation of fetal weight: comparison of bias, precision and consistency using 12 different formulae.

PubMed

Anderson, N G; Jolley, I J; Wells, J E

2007-08-01

To determine the major sources of error in ultrasonographic assessment of fetal weight and whether they have changed over the last decade. We performed a prospective observational study in 1991 and again in 2000 of a mixed-risk pregnancy population, estimating fetal weight within 7 days of delivery. In 1991, the Rose and McCallum formula was used for 72 deliveries. Inter- and intraobserver agreement was assessed within this group. Bland-Altman measures of agreement from log data were calculated as ratios. We repeated the study in 2000 in 208 consecutive deliveries, comparing predicted and actual weights for 12 published equations using Bland-Altman and percentage error methods. We compared bias (mean percentage error), precision (SD percentage error), and their consistency across the weight ranges. 95% limits of agreement ranged from - 4.4% to + 3.3% for inter- and intraobserver estimates, but were - 18.0% to 24.0% for estimated and actual birth weight. There was no improvement in accuracy between 1991 and 2000. In 2000 only six of the 12 published formulae had overall bias within 7% and precision within 15%. There was greater bias and poorer precision in nearly all equations if the birth weight was < 1,000 g. Observer error is a relatively minor component of the error in estimating fetal weight; error due to the equation is a larger source of error. Improvements in ultrasound technology have not improved the accuracy of estimating fetal weight. Comparison of methods of estimating fetal weight requires statistical methods that can separate out bias, precision and consistency. Estimating fetal weight in the very low birth weight infant is subject to much greater error than it is in larger babies. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Sonographic large fetal head circumference and risk of cesarean delivery.

PubMed

Lipschuetz, Michal; Cohen, Sarah M; Israel, Ariel; Baron, Joel; Porat, Shay; Valsky, Dan V; Yagel, Oren; Amsalem, Hagai; Kabiri, Doron; Gilboa, Yinon; Sivan, Eyal; Unger, Ron; Schiff, Eyal; Hershkovitz, Reli; Yagel, Simcha

2018-03-01

Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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.

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

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

PubMed

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

1996-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, Robert A., III (Inventor)

1994-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate is presented. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Sonography in Fetal Birth Weight Estimation

ERIC Educational Resources Information Center

Akinola, R. A.; Akinola, O. I.; Oyekan, O. O.

2009-01-01

The estimation of fetal birth weight is an important factor in the management of high risk pregnancies. The information and knowledge gained through this study, comparing a combination of various fetal parameters using computer assisted analysis, will help the obstetrician to screen the high risk pregnancies, monitor the growth and development,…

Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study.

PubMed

Kondo, Tomohiro; Kitano-Amahori, Yoko; Nagai, Hiroaki; Mino, Masaki; Takeshita, Ai; Kusakabe, Ken Takeshi; Okada, Toshiya

2015-11-01

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth. © 2015 Japanese Teratology Society.

Fetal MRI: A Technical Update with Educational Aspirations

PubMed Central

Gholipour, Ali; Estroff, Judith A.; Barnewolt, Carol E.; Robertson, Richard L.; Grant, P. Ellen; Gagoski, Borjan; Warfield, Simon K.; Afacan, Onur; Connolly, Susan A.; Neil, Jeffrey J.; Wolfberg, Adam; Mulkern, Robert V.

2015-01-01

Fetal magnetic resonance imaging (MRI) examinations have become well-established procedures at many institutions and can serve as useful adjuncts to ultrasound (US) exams when diagnostic doubts remain after US. Due to fetal motion, however, fetal MRI exams are challenging and require the MR scanner to be used in a somewhat different mode than that employed for more routine clinical studies. Herein we review the techniques most commonly used, and those that are available, for fetal MRI with an emphasis on the physics of the techniques and how to deploy them to improve success rates for fetal MRI exams. By far the most common technique employed is single-shot T2-weighted imaging due to its excellent tissue contrast and relative immunity to fetal motion. Despite the significant challenges involved, however, many of the other techniques commonly employed in conventional neuro- and body MRI such as T1 and T2*-weighted imaging, diffusion and perfusion weighted imaging, as well as spectroscopic methods remain of interest for fetal MR applications. An effort to understand the strengths and limitations of these basic methods within the context of fetal MRI is made in order to optimize their use and facilitate implementation of technical improvements for the further development of fetal MR imaging, both in acquisition and post-processing strategies. PMID:26225129

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

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.

The effect of Ramadan fasting on fetal development.

PubMed

Karateke, Atilla; Kaplanoglu, Mustafa; Avci, Fazil; Kurt, Raziye Keskin; Baloglu, Ali

2015-01-01

To evaluate the effects of Ramadan fasting on fetal development and outcomes of pregnancy. We performed this study in Antakya State Hospital of Obstetrics and Child Care, between 28 June 2014 and 27 July 2014 (during the month of Ramadan). A total of two hundred forty healthy pregnant women who were fasting during Ramadan, were included in the groups. The three groups were divided according to the trimesters. The each group was consisted of 40 healthy pregnant women with fasting and 40 healthy pregnant women without fasting. For evaluating the effects of Ramadan on fetus, ultrasonography was performed on all pregnant women in the beginning and the end of Ramadan. We used the essential parameters for the following measurements: increase of fetal biparietal diameter (BPD), increase of fetal femur length (FL), increase of estimated fetal body weight (EFBW), fetal biophysical profile (BPP), amniotic fluid index (AFI), and umbilical artery systole/diastole (S/D) ratio. No significant difference was found between the two groups for the fetal age, maternal weight gain (kilogram), estimated fetal weight gain (EFWG), fetal BPP, AFI, and umbilical artery S/D ratio. On the other hand, a statistically significant increase was observed in maternal weight in the second and third trimesters and a significant increase was observed in the amniotic fluid index in second trimester. In Ramadan there was no bad fetal outcome between pregnant women with fasting and pregnant women without fasting. Pregnant women who want to be with fast, should be examined by doctors, adequately get breakfast before starting to fast and after the fasting take essential calori and hydration. More comprehensive randomized studies are needed to explain the effects of fasting on the pregnancy and fetal outcomes.

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.

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

Modeling Fetal Weight for Gestational Age: A Comparison of a Flexible Multi-level Spline-based Model with Other Approaches

PubMed Central

Villandré, Luc; Hutcheon, Jennifer A; Perez Trejo, Maria Esther; Abenhaim, Haim; Jacobsen, Geir; Platt, Robert W

2011-01-01

We present a model for longitudinal measures of fetal weight as a function of gestational age. We use a linear mixed model, with a Box-Cox transformation of fetal weight values, and restricted cubic splines, in order to flexibly but parsimoniously model median fetal weight. We systematically compare our model to other proposed approaches. All proposed methods are shown to yield similar median estimates, as evidenced by overlapping pointwise confidence bands, except after 40 completed weeks, where our method seems to produce estimates more consistent with observed data. Sex-based stratification affects the estimates of the random effects variance-covariance structure, without significantly changing sex-specific fitted median values. We illustrate the benefits of including sex-gestational age interaction terms in the model over stratification. The comparison leads to the conclusion that the selection of a model for fetal weight for gestational age can be based on the specific goals and configuration of a given study without affecting the precision or value of median estimates for most gestational ages of interest. PMID:21931571

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 (1-4.5% each), their effect was graded across the percentiles. For example, the positive effect of maternal height on fetal weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Anthropometric measurements as predictors of cephalopelvic disproportion: Can the diagnostic accuracy be improved?

PubMed

Benjamin, Santosh J; Daniel, Anjali B; Kamath, Asha; Ramkumar, Vani

2012-01-01

We assessed the efficacy of maternal anthropometric measurements and clinical estimates of fetal weight in isolation and in combination as predictors of cephalopelvic disproportion (CPD). Prospective cohort study. Tertiary care teaching hospital, two affiliated hospitals with facilities for conducting cesarean delivery and seven affiliated primary care facilities with no operation theaters. Primigravidae over 37 weeks' gestation attending these facilities during a 20-month period with a singleton pregnancy in vertex presentation. Several anthropometric measurements were taken in 249 primigravidae. Fetal weight was estimated. Differences in these measurements between the vaginal delivery and CPD groups were analyzed. The validity of these measurements in predicting CPD was analyzed by plotting receiver operating characteristic curves and by logistic regression analysis. Mode of delivery. Maternal height, foot size, inter-trochanteric diameter and bis-acromial diameter showed the highest positive predictive values for CPD. Combining some maternal measurements with estimates of fetal weight increased predictive values modestly, which are likely to be greater if the estimates of fetal weight are close to the actual birth weight. Based on multivariate analysis the risk factors for CPD in our population were foot length ≤23cm, inter-trochanteric diameter ≤30cm and estimated fetal weight ≥3 000g. Maternal anthropometric measurements can predict CPD to some extent. Combining maternal measurements with clinical estimates of fetal weight only enhances the predictive value to a relatively modest degree (positive predictive value 24%). © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Standard curves of placental weight and fetal/placental weight ratio in Japanese population: difference according to the delivery mode, fetal sex, or maternal parity.

PubMed

Ogawa, Masaki; Matsuda, Yoshio; Nakai, Akihito; Hayashi, Masako; Sato, Shoji; Matsubara, Shigeki

2016-11-01

Placental weight (PW) and fetal/placental weight ratio (F/P) have been considered to be useful parameters for understanding the pathophysiology of fetal growth. However, there have been no standard data on PW and F/P in Asian populations. This study was conducted to establish nomograms of PW and F/P in the Japanese population and to clarify characteristics of PW and F/P in this population. Included in the study were 79,590 Japanese cases: 58,871 vaginal and 20,719 cesarean deliveries at obstetrical facilities (2001-2002) and registered to the Japan Society of Obstetrics and Gynecology Database. Multiple pregnancies, stillbirths, and fetal anomalies were excluded. Nomograms of PW and F/P were created by spline methods in groups categorized by fetal sex (male or female) and maternal parity (primipara or multipara). Standard curves of PW and F/P were established, which indicated that PW and F/P were lower in cesarean deliveries than vaginal deliveries, especially during preterm period. PW differed depending on fetal sex and maternal parity. F/P differed according to fetal sex. We for the first time established standard curves of PW and F/P in the Japanese population with statistically sufficient data, which showed that PW and F/P were lower in cesarean deliveries. PW and F/P were also affected by fetal sex. These data might be useful to understand the pathophysiology between the fetus and placenta in utero. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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 confirm these findings and to assess post-natal consequences. PMID:22215632

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.

Birth weight and mortality: causality or confounding?

PubMed

Basso, Olga; Wilcox, Allen J; Weinberg, Clarice R

2006-08-15

The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality.

Effects of sire and dam on late-pregnancy conceptus and hormone traits in beef cattle.

PubMed

Bellows, R A; Staigmiller, R B; Orme, L E; Short, R E; Knapp, B W

1993-03-01

Forty-six primiparous F1 heifers produced from mating Brahman (B), Charolais (C), Jersey (J), Longhorn (L), or Shorthorn (S) sires to crossbred cows were bred by AI to one of two Angus sires selected to produce high (H) or moderate (M) fetal growth. Dams were slaughtered at an average of 231 d of gestation. Daily blood samples were obtained from the dam on d 228 to 231 to determine serum estradiol, progesterone, and testosterone concentrations. Pelvic height was greatest (P < .05) in B, C, and L and pelvic width was greatest (P < .05) in S, C, and J dams, but pelvic areas did not differ (P > .10). Dams with greater hip height had larger pelvic areas (r = .45; P < .01). Intact fetuses from C and S dams were heaviest (P < .05), those from S dams had the greatest (P < .05) head width, and heart girth was greatest (P < .05) in fetuses from L dams. Fetuses from H sires were greater in weight (P < .01), body length (P < .01), and cannon circumference (P < .01). Dam differences were found in fetal heart weight (P < .01), trimmed placental membrane weight (P < .01), and average placentome weight (P < .05). Weights of eviscerated fetuses were greatest from C dams (P < .05). Placentome number was lowest (P < .05) in J dams, but J dams had the highest (P < .05) average placentome weight. Interactions between fetal genotype and breed of maternal environment were found for weight of eviscerated fetus (P < .05), body length, and heart weight (P < .01) and resulted from both magnitude and direction of change in the sire effect. The H sire increase in fetal weight was greatest in J dams, whereas B dams allowed expression of the fetal growth potential but at a lower level. Fetal trait interactions were also found for breed x sex and sex x sire (P < .05 to P < .01) and were due to the magnitude of differences expressed between the M and H sires. Serum testosterone concentrations were highest (P < .05) in B and L dams, dams gestating fetuses sired by the H sire (P = .08), and those with male fetuses (P < .01). We interpret these results to indicate that some maternal environments can suppress fetal growth, whereas others seem to complement the growth and allow maximum expression of the fetal genetic growth potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Fetal Cardiac Responding: A Correlate of Birth Weight and Neonatal Behavior.

ERIC Educational Resources Information Center

Emory, Eugene K.; Noonan, John R.

1984-01-01

Explores whether an empirical classification of healthy fetuses as fetal heart rate accelerators or decelerators would predict birth weight and neonatal behavior scored with the Brazelton Neonatal Behavior Assessment Scale. (Author/RH)

[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.

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…

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.

Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

PubMed

Bleker, O P; Buimer, M; van der Post, J A M; van der Veen, F

2006-01-01

In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

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.

Widespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation.

PubMed

Xiang, Ruidong; Lee, Alice M C; Eindorf, Tanja; Javadmanesh, Ali; Ghanipoor-Samami, Mani; Gugger, Madeleine; Fitzsimmons, Carolyn J; Kruk, Zbigniew A; Pitchford, Wayne S; Leviton, Alison J; Thomsen, Dana A; Beckman, Ian; Anderson, Gail I; Burns, Brian M; Rutley, David L; Xian, Cory J; Hiendleder, Stefan

2014-11-01

Parent-of-origin-dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1-6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = -0.34 and -0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle-bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration.

PubMed

D'Souza, Stephen W; Solanky, Nita; Guarino, Jane; Moat, Stuart; Sibley, Colin P; Taggart, Michael; Glazier, Jocelyn D

2017-07-01

Methionine demethylation during metabolism generates homocysteine (Hcy) and its remethylation requires folate and cobalamin. Elevated Hcy concentrations are associated with vascular-related complications of pregnancy, including increased vascular stiffness, predictive of clinical vascular disease. Maternal and fetal total Hcy (tHcy) concentrations are positively related, yet the influence of Hcy on fetoplacental vascular function in normal pregnancy has not been examined. We hypothesized that Hcy alters fetoplacental vascular characteristics with influences on fetal growth outcomes. We investigated (1) placental chorionic plate artery distensibility and neonatal blood pressure in relation to umbilical plasma tHcy; (2) relationships between cord venous (CV) and cord arterial (CA) plasma tHcy, folate, and cobalamin concentrations; and (3) tHcy associations with birth weight and anthropometric measurements of body size as indices of fetal growth in normal pregnancies with appropriate weight-for-gestational age newborns. Maternal plasma tHcy, folate, and cobalamin concentrations were consistent with published data. Placental chorionic plate artery distensibility index (β; measure of vessel stiffness) was inversely related to CA tHcy, yet neonatal blood pressure was not significantly affected. CV and CA tHcy concentrations were positively related and CV tHcy negatively related to CV cobalamin but not folate. CV tHcy concentration positively related to birth weight, corrected birth weight percentile, length, head circumference, and mid-arm circumference of newborns. CV cobalamin was inversely related to fetal growth indices but not to folate concentration. Our study demonstrates a potential relationship between fetal tHcy and placental artery distensibility, placing clinical relevance to cobalamin in influencing Hcy concentration and maintaining low vascular resistance to facilitate nutrient exchange favorable to fetal growth.

Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing.

PubMed

Kinnings, Sarah L; Geis, Jennifer A; Almasri, Eyad; Wang, Huiquan; Guan, Xiaojun; McCullough, Ron M; Bombard, Allan T; Saldivar, Juan-Sebastian; Oeth, Paul; Deciu, Cosmin

2015-08-01

Sufficient fetal DNA in a maternal plasma sample is required for accurate aneuploidy detection via noninvasive prenatal testing, thus highlighting a need to understand the factors affecting fetal fraction. The MaterniT21™ PLUS test uses massively parallel sequencing to analyze cell-free fetal DNA in maternal plasma and detect chromosomal abnormalities. We assess the impact of a variety of factors, both maternal and fetal, on the fetal fraction across a large number of samples processed by Sequenom Laboratories. The rate of increase in fetal fraction with increasing gestational age varies across the duration of the testing period and is also influenced by fetal aneuploidy status. Maternal weight trends inversely with fetal fraction, and we find no added benefit from analyzing body mass index or blood volume instead of weight. Strong correlations exist between fetal fractions from aliquots taken from the same patient at the same blood draw and also at different blood draws. While a number of factors trend with fetal fraction across the cohort as a whole, they are not the sole determinants of fetal fraction. In this study, the variability for any one patient does not appear large enough to justify postponing testing to a later gestational age. © 2015 John Wiley & Sons, Ltd.

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.

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.

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

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

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.

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.

Influence of fetal birth weight on perinatal outcome in planned vaginal births.

PubMed

Temerinac, Dunja; Chen, Xi; Sütterlin, Marc; Kehl, Sven

2014-02-01

The aim of this study was to provide information for better obstetric counseling by analyzing the impact of fetal birth weight (BW) on fetal and maternal outcome when vaginal birth is planned in a university hospital. In this retrospective study from January 1st 2006 to December 31st 2011, 5,177 singleton, alive deliveries at or >37 gestational weeks were assessed with regard to the fetal BW when vaginal birth was attempted. The normal BW group was defined as ≥2,500 <4,500 g. For comparison, further BW groups were defined as: group 1 <2,500 g, group 2 ≥4,000 <4,250 g, group 3 ≥4,250 <4,500 g and group 4 ≥4,500 g. Outcome criteria were mode of delivery and perineal lacerations as well as the pH and base excess of the umbilical cord artery, the Apgar score after 5 min and occurrence of shoulder dystocia. The set of controlling variables included maternal height, maternal weight, maternal age, gestational age, neonatal sex and parity. Second stage caesarean section is significantly more likely when fetal BW is under 2,500 g (30.7 vs. 15.5 % in the normal BW group, odds ratio 3.01, 95 % confidence interval 2.03-4.46, p value < 0.001). Shoulder dystocia occurred significantly more often when fetal BW was over 4,250 g (group 3: odds ratio 4.95, 95 % confidence interval 1.74-14.10, p value 0.003, group 4: odds ratio 19.96, 95 % confidence interval 7.61-52.38, p value < 0.001). The risk of an Apgar score after 5 min below 7 increased, when fetal BW was below 2,500 g (odds ratio 9.28, 95 % confidence interval 3.15-27.35, p value < 0.001) or above 4,500 g (odds ratio 5.65, 95 % confidence interval 1.22-26.24, p value 0.027). All groups were comparable to the normal group regarding pH and base excess of the umbilical cord artery as well as the risk for severe (third and fourth degree) perineal lacerations. Although a fetal birth weight under 2,500 g and a birth weight over 4,250 g are associated with some risks, there is no general contraindication for an attempt to deliver vaginally in a university hospital with regard to fetal birth weight.

Fetal intracranial hemorrhage. Imaging by ultrasound and magnetic resonance imaging.

PubMed

Kirkinen, P; Partanen, K; Ryynänen, M; Ordén, M R

1997-08-01

To describe the magnetic resonance imaging (MRI) findings associated with fetal intracranial hemorrhage and to compare them with ultrasound findings. In four pregnancies complicated by fetal intracranial hemorrhage, fetal imaging was carried out using T2-weighted fast spin echo sequences and T1-weighted fast low angle shot imaging sequences and by transabdominal ultrasonography. An antepartum diagnosis of hemorrhage was made by ultrasound in one case and by MRI in two. Retrospectively, the hemorrhagic area could be identified from the MRI images in an additional two cases and from the ultrasound images in one case. In the cases of intraventricular hemorrhage, the MRI signal intensity in the T1-weighted images was increased in the hemorrhagic area as compared to the contralateral ventricle and brain parenchyma. In a case with subdural hemorrhage, T2-weighted MRI signals from the hemorrhagic area changed from low-to high-intensity signals during four weeks of follow-up. Better imaging of the intracranial anatomy was possible by MRI than by transabdominal ultrasonography. MRI can be used for imaging and dating fetal intracranial hemorrhages. Variable ultrasound and MRI findings are associated with this complication, depending on the age and location of the hemorrhage.

Developmental co-expression of small molecular weight apolipoprotein B synthesis and triacylglycerol secretion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coleman, R.A.; Haynes, E.B.; Sand, T.M.

1987-05-01

The development of the liver's ability to coordinately express the synthesis and secretion of the two major components of very low density lipoproteins (VLDL): triacylglycerol (TG) and apolipoprotein B (apo B) was examined in cultured hepatocytes obtained from fetal, suckling and adult rats. Hepatocytes from fetal and suckling rats synthesized and secreted TG at rates lower than that displayed by adult cells. When TG synthesis was equalized by adding oleic acid to the culture medium, fetal cells still secreted only 39% as much TG as did adult cells. To determine the basis for the apparent defect in VLDL assembly/secretion displayedmore » by fetal cells, the synthesis and secretion of (TVS)methionine-labeled apo B was quantified by immunoprecipitation. Although adult and fetal cells synthesized and secreted large molecular weight apo B at similar rates, the synthesis and secretion of small molecular weight apo B was 2-fold greater in adult cells. These data suggest that the ability to assemble/secrete VLDL triacylglycerol varies in parallel with the developmental expression of small molecular weight apo B. Furthermore, these studies show the usefulness of the cultured rat hepatocyte model for examining the ontogeny and regulation of VLDL assembly/secretion.« less

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.

A comparative assessment of waste incinerators in the UK.

PubMed

Nixon, J D; Wright, D G; Dey, P K; Ghosh, S K; Davies, P A

2013-11-01

The uptake in Europe of Energy from Waste (EfW) incinerator plants has increased rapidly in recent years. In the UK, 25 municipal waste incinerators with energy recovery are now in operation; however, their waste supply chains and business practices vary significantly. With over a hundred more plant developments being considered it is important to establish best business practices for ensuring efficient environmental and operational performance. By reviewing the 25 plants we identify four suitable case study plants to compare technologies (moving grate, fluidised bed and rotary kiln), plant economics and operations. Using data collected from annual reports and through interviews and site visits we provide recommendations for improving the supply chain for waste incinerators and highlight the current issues and challenges faced by the industry. We find that plants using moving grate have a high availability of 87-92%. However, compared to the fluidised bed and rotary kiln, quantities of bottom ash and emissions of hydrogen chloride and carbon monoxide are high. The uptake of integrated recycling practices, combined heat and power, and post incineration non-ferrous metal collections needs to be increased among EfW incinerators in the UK. We conclude that one of the major difficulties encountered by waste facilities is the appropriate selection of technology, capacity, site, waste suppliers and heat consumers. This study will be of particular value to EfW plant developers, government authorities and researchers working within the sector of waste management. Copyright © 2013 Elsevier Ltd. All rights reserved.

ACR Appropriateness Criteria® growth disturbances - risk of intrauterine growth restriction.

PubMed

Zelop, Carolyn M; Javitt, Marcia C; Glanc, Phyllis; Dubinsky, Theodore; Harisinghani, Mukesh G; Harris, Robert D; Khati, Nadia J; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Wong-You-Cheong, Jade J

2013-09-01

Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

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.

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

Reference charts of fetal biometric parameters in 31,476 Brazilian singleton pregnancies.

PubMed

Araujo Júnior, Edward; Martins Santana, Eduardo Félix; Martins, Wellington P; Júnior, Julio Elito; Ruano, Rodrigo; Pires, Claudio Rodrigues; Filho, Sebastião Marques Zanforlin

2014-07-01

The purpose of this study was to establish reference charts of fetal biometric parameters measured by 2-dimensional sonography in a large Brazilian population. A cross-sectional retrospective study was conducted including 31,476 low-risk singleton pregnancies between 18 and 38 weeks' gestation. The following fetal parameters were measured: biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. To assess the correlation between the fetal biometric parameters and gestational age, polynomial regression models were created, with adjustments made by the determination coefficient (R(2)). The means ± SDs of the biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight measurements at 18 and 38 weeks were 4.2 ± 2.34 and 9.1 ± 4.0 cm, 15.3 ± 7.56 and 32.3 ± 11.75 cm, 13.3 ± 10.42 and 33.4 ± 20.06 cm, 2.8 ± 2.17 and 7.2 ± 3.58 cm, and 256.34 ± 34.03 and 3169.55 ± 416.93 g, respectively. Strong correlations were observed between all fetal biometric parameters and gestational age, best represented by second-degree equations, with R(2) values of 0.95, 0.96, 0.95, 0.95, and 0.95 for biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. Fetal biometric parameters were determined for a large Brazilian population, and they may serve as reference values in cases with a high risk of intrauterine growth disorders. © 2014 by the American Institute of Ultrasound in Medicine.

Effects of intrauterine retention and postmortem interval on body weight following intrauterine death: implications for assessment of fetal growth restriction at autopsy.

PubMed

Man, J; Hutchinson, J C; Ashworth, M; Heazell, A E; Levine, S; Sebire, N J

2016-11-01

According to the classification system used, 15-60% of stillbirths remain unexplained, despite undergoing recommended autopsy examination, with variable attribution of fetal growth restriction (FGR) as a cause of death. Distinguishing small-for-gestational age (SGA) from pathological FGR is a challenge at postmortem examination. This study uses data from a large, well-characterized series of intrauterine death autopsies to investigate the effects of secondary changes such as fetal maceration, intrauterine retention and postmortem interval on body weight. Autopsy findings from intrauterine death investigations (2005-2013 inclusive, from Great Ormond Street Hospital and St George's Hospital, London) were collated into a research database. Growth charts published by the World Health Organization were used to determine normal expected weight centiles for fetuses born ≥ 24 weeks' gestation, and the effects of intrauterine retention (maceration) and postmortem interval were calculated. There were 1064 intrauterine deaths, including 533 stillbirths ≥ 24 weeks' gestation with a recorded birth weight. Of these, 192 (36%) had an unadjusted birth weight below the 10 th centile and were defined as SGA. The majority (86%) of stillborn SGA fetuses demonstrated some degree of maceration, indicating a significant period of intrauterine retention after death. A significantly greater proportion of macerated fetuses were present in the SGA population compared with the non-SGA population (P = 0.01). There was a significant relationship between increasing intrauterine retention interval and both more severe maceration and reduction in birth weight (P < 0.0001 for both), with an average artifactual reduction in birth weight of around -0.8 SD of expected weight. There was an average 12% reduction in fetal weight between delivery and autopsy and, as postmortem interval increased, fetal weight loss increased (P = 0.0001). Based on birth weight alone, 36% of stillbirths are classified as SGA. However, fetuses lose weight in utero with increasing intrauterine retention and continue to lose weight between delivery and autopsy, resulting in erroneous overestimation of FGR. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Macrosomia Predictors in Infants Born to Cuban Mothers with Gestational Diabetes.

PubMed

Cruz, Jeddú; Grandía, Raiden; Padilla, Liset; Rodríguez, Suilbert; Hernández García, Pilar; Lang Prieto, Jacinto; Márquez-Guillén, Antonio

2015-07-01

INTRODUCTION Fetal macrosomia is the most important complication in infants of women with diabetes, whether preconceptional or gestational. Its occurrence is related to certain maternal and fetal conditions and negatively affects maternal and perinatal outcomes. The definitive diagnosis is made at birth if a newborn weighs >4000 g. OBJECTIVE Identify which maternal and fetal conditions could be macrosomia predictors in infants born to Cuban mothers with gestational diabetes. METHODS A case-control study comprising 236 women with gestational diabetes who bore live infants (118 with macrosomia and 118 without) was conducted in the América Arias University Maternity Hospital, Havana, Cuba, during 2002-2012. The dependent variable was macrosomia (birth weight >4000 g). Independent maternal variables included body mass index at pregnancy onset, overweight or obesity at pregnancy onset, gestational age at diabetes diagnosis, pregnancy weight gain, glycemic control, triglycerides and cholesterol. Fetal variables examined included third-semester fetal abdominal circumference, estimated fetal weight at ≥28 weeks (absolute and percentilized by Campbell and Wilkin, and Usher and McLean curves). Chi square was used to compare continuous variables (proportions) and the student t test (X ± SD) for categorical variables, with significance threshold set at p <0.05. ORs and their 95% CIs were calculated. RESULTS Significant differences between cases and controls were found in most variables studied, with the exception of late gestational diabetes diagnosis, total fasting cholesterol and hypercholesterolemia. The highest OR for macrosomia were for maternal hypertriglyceridemia (OR 4.80, CI 2.34-9.84), third-trimester fetal abdominal circumference >75th percentile (OR 7.54, CI 4.04-14.06), and estimated fetal weight >90th percentile by Campbell and Wilkin curves (OR 4.75, CI 1.42-15.84) and by Usher and McLean curves (OR 8.81, CI 4.25-18.26). CONCLUSIONS Most variables assessed were predictors of macrosomia in infants of mothers with gestational diabetes. They should therefore be taken into account for future studies and for patient management. Wide confidence intervals indicate uncertainty about the magnitude of predictive power. KEYWORDS Fetal macrosomia, fetal diseases, gestational diabetes, risk factors, risk prediction, Cuba.

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.

Evaluation of the effectiveness of low-dose aspirin and omega 3 in treatment of asymmetrically intrauterine growth restriction: A randomized clinical trial.

PubMed

Ali, Mohammed K; Amin, Maggy E; Amin, Ahmed F; Abd El Aal, Diaa Eldeen M

2017-03-01

To test the effect of aspirin and omega 3 on fetal weight as well as feto-maternal blood flow in asymmetrical intrauterine growth restriction (IUGR). This study is a clinically registered (NCT02696577), open, parallel, randomized controlled trial, conducted at Assiut Woman's Health Hospital, Egypt including 80 pregnant women (28-30 weeks) with IUGR. They were randomized either to group I: aspirin or group II: aspirin plus omega 3. The primary outcome was the fetal weight after 6 weeks of treatment. Secondary outcomes included Doppler blood flow changes in both uterine and umbilical arteries, birth weight, time and method of delivery and admission to NICU. The outcome variables were analyzed using paired and unpaired t-test. The estimated fetal weight increased significant in group II more than group I (p=0.00). The uterine and umbilical arteries blood flow increased significantly in group II (p<0.05). The birth weight in group II was higher than that observed in group I (p<0.05). The using of aspirin with omega 3 is more effective than using aspirin only in increasing fetal weight and improving utero-placental blood flow in IUGR. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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.

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.

Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

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.

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.

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

Maternal KIR in combination with paternal HLA-C2 regulate human birth weight.

PubMed

Hiby, Susan E; Apps, Richard; Chazara, Olympe; Farrell, Lydia E; Magnus, Per; Trogstad, Lill; Gjessing, Håkon K; Carrington, Mary; Moffett, Ashley

2014-06-01

Human birth weight is subject to stabilizing selection; babies born too small or too large are less likely to survive. Particular combinations of maternal/fetal immune system genes are associated with pregnancies where the babies are ≤ 5th birth weight centile, specifically an inhibitory maternal KIR AA genotype with a paternally derived fetal HLA-C2 ligand. We have now analyzed maternal KIR and fetal HLA-C combinations at the opposite end of the birth weight spectrum. Mother/baby pairs (n = 1316) were genotyped for maternal KIR as well as fetal and maternal HLA-C. Presence of a maternal-activating KIR2DS1 gene was associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p = 0.005, n = 1316). Effect of KIR2DS1 was most significant in pregnancies where its ligand, HLA-C2, was paternally but not maternally inherited by a fetus (p = 0.005, odds ratio = 2.65). Thus, maternal KIR are more frequently inhibitory with small babies but activating with big babies. At both extremes of birth weight, the KIR associations occur when their HLA-C2 ligand is paternally inherited by a fetus. We conclude that the two polymorphic immune gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birth weight between two extremes with a clear role for paternal HLA.

Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice.

PubMed

Panchenko, Polina E; Voisin, Sarah; Jouin, Mélanie; Jouneau, Luc; Prézelin, Audrey; Lecoutre, Simon; Breton, Christophe; Jammes, Hélène; Junien, Claudine; Gabory, Anne

2016-01-01

Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects. Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; -13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized. This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype.

High Tumor Volume to Fetal Weight Ratio Is Associated with Worse Fetal Outcomes and Increased Maternal Risk in Fetuses with Sacrococcygeal Teratoma.

PubMed

Gebb, Juliana S; Khalek, Nahla; Qamar, Huma; Johnson, Mark P; Oliver, Edward R; Coleman, Beverly G; Peranteau, William H; Hedrick, Holly L; Flake, Alan W; Adzick, N Scott; Moldenhauer, Julie S

2018-03-01

Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor outcome in fetuses with sacrococcygeal teratoma (SCT). We evaluated TFR in predicting poor fetal outcome and increased maternal operative risk in our cohort of SCT pregnancies. This is a retrospective, single-center review of fetuses seen with SCT from 1997 to 2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had initial evaluation at > 24 weeks were excluded. Receiver operating characteristic (ROC) analysis determined the optimal TFR to predict poor fetal outcome and increased maternal operative risk. Poor fetal outcome included fetal demise, neonatal demise, or fetal deterioration warranting open fetal surgery or delivery < 32 weeks. Increased maternal operative risk included cases necessitating open fetal surgery, classical cesarean delivery, or ex utero intrapartum treatment (EXIT). Of 139 pregnancies with SCT, 27 chose TOP, 14 delivered elsewhere, and 40 had initial evaluation at > 24 weeks. Thus, 58 fetuses were reviewed. ROC analysis revealed that at ≤24 weeks, TFR > 0.095 was predictive of poor fetal outcome and TFR > 0.12 was predictive of increased maternal operative risk. This study supports the use of TFR at ≤24 weeks for risk stratification of pregnancies with SCT. © 2018 S. Karger AG, Basel.

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.

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.

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

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.

Effect of mild pressure applied by the ultrasound transducer on fetal cephalic measurements at 20-24 weeks' gestation.

PubMed

Kliper, Yael; Ben-Ami, Moshe; Perlitz, Yuri

2014-01-01

The aim of this study was to assess the effect of mild pressure applied on the abdominal wall by the ultrasound transducer on fetal cephalic indices. We examined by ultrasound 60 fetuses of healthy women, at 20-24 weeks of pregnancy, during routine prenatal evaluation. For every fetus biparietal diameter and head circumference were measured, with and without applying mild pressure by the ultrasound transducer. The weight and gestational age (GA) were calculated. The pressure applied by the transducer had a significant effect on the cephalic indices and on the weight and GA evaluations (p < 0.001). Fetal positioning significantly affected the impact that applied pressure had on head circumference and on the weight evaluation derived from it (p < 0.05). Applied pressure by an abdominal ultrasound probe affects cephalic indices and the derived weight and GA estimations. This may lead to incorrect diagnoses or hide pathological findings. The effect of applied pressure depends on fetal positioning. The examiner must be aware of this effect when evaluating the results of the measurements.

Finding the most accurate method to measure head circumference for fetal weight estimation.

PubMed

Schmidt, Ulrike; Temerinac, Dunja; Bildstein, Katharina; Tuschy, Benjamin; Mayer, Jade; Sütterlin, Marc; Siemer, Jörn; Kehl, Sven

2014-07-01

Accurate measurement of fetal head biometry is important for fetal weight estimation (FWE) and is therefore an important prognostic parameter for neonatal morbidity and mortality and a valuable tool for determining the further obstetric management. Measurement of the head circumference (HC) in particular is employed in many commonly used weight equations. The aim of the present study was to find the most accurate method to measure head circumference for fetal weight estimation. This prospective study included 481 term pregnancies. Inclusion criteria were a singleton pregnancy and ultrasound examination with complete fetal biometric parameters within 3 days of delivery, and an absence of structural or chromosomal malformations. Different methods were used for ultrasound measurement of the HC (ellipse-traced, ellipse-calculated, and circle-calculated). As a reference method, HC was also determined using a measuring tape immediately after birth. FWE was carried out with Hadlock formulas, including either HC or biparietal diameter (BPD), and differences were compared using percentage error (PE), absolute percentage error (APE), limits of agreement (LOA), and cumulative distribution. The ellipse-traced method showed the best results for FWE among all of the ultrasound methods assessed. It had the lowest median APE and the narrowest LOA. With regard to the cumulative distribution, it included the largest number of cases at a discrepancy level of ±10%. The accuracy of BPD was similar to that of the ellipse-traced method when it was used instead of HC for weight estimation. Differences between the three techniques for calculating HC were small but significant. For clinical use, the ellipse-traced method should be recommended. However, when BPD is used instead of HC for FWE, the accuracy is similar to that of the ellipse-traced method. The BPD might therefore be a good alternative to head measurements in estimating fetal weight. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Uterine and placenta characteristics during early vascular development in the pig from day 22 to 42 of gestation.

PubMed

Wright, Elane C; Miles, Jeremy R; Lents, Clay A; Rempel, Lea A

2016-01-01

Insufficient placenta development is one of the primary causes of fetal death and reduced fetal growth after 35 days of gestation. Between day 22 and 42 the placenta consists of a central highly vascular placenta (HVP), adjacent to the fetus, a less vascular placenta (LVP), on either side of the fetus, and necrotic tips (NT). The objective of this study was to comprehensively evaluate uterine-placenta characteristics during early gestation in the gilt and determine time points and physiological changes. Gilts (n=25) were artificially inseminated at first detection of estrus (day 0) and 24h later, and harvested at 22, 27, 32, 37 or 42 days of gestation. Litter size, 12.1±3.4, was similar for all days of gestation. Fetal and placenta weight increased with day of gestation. The greatest increase in placenta weight occurred between 37 and 42 days of gestation. The LVP zones had no measurable fold formation until day 27. Necrotic tips became apparent after 27 days of gestation. Unoccupied areas of the uterus developed folds with changes in endometrial cell size and morphology from day 32 to 42 of gestation. Limited changes occurred in either fetal growth or placenta weight from day 27 through 32 of gestation; however, significant morphological changes occur at the maternal-fetal interface, demonstrating the dynamic architecture of the developing porcine placenta during early gestation. This work establishes fundamental time points in placenta development corresponding to fetal growth and microfold formation that may influence fetal growth and impact fetal survival. Published by Elsevier B.V.

Determinants and outcome of fetal macrosomia in a Nigerian tertiary hospital.

PubMed

Olokor, Oghenefegor Edwin; Onakewhor, Joseph Ubini; Aderoba, Adeniyi Kolade

2015-01-01

To determine the incidence and risk factors of fetal macrosomia and maternal and perinatal outcome. This was a 1-year prospective case-control study of singleton pregnancies in a Nigerian tertiary hospital. Only women who gave consent were recruited for the study. The maternal and perinatal outcomes in women who delivered macrosomic infants (birth weight ≥ 4000 g) were compared with the next consecutive delivery of normal birth weight (2500-3999 g) infants. The total deliveries for the study period were 2437, of which 135 were macrosomic babies. The incidence of fetal macrosomia was 5.5%. The mean birth weights of macrosomic and nonmacrosomic babies were 4.26 ± 0.29 kg and 3.20 ± 0.38 kg, respectively, P = 0.000. Mothers with macrosomic babies were more likely to be older (P = 0.047), of higher parity (0.001), taller (P = 0.007), and weighed more at delivery (P = 0.000). Previous history of fetal macrosomia (P = 0.000) and maternal diabetes (P = 0.007) were factors strongly associated with the delivery of macrosomic infants. Pregnancies associated with fetal macrosomia had increased duration of labor (P = 0.007), interventional deliveries (P = 0.000), shoulder dystocia, and genital laceration (P = 0.000). There was no significant difference in the incidence of primary postpartum hemorrhage (P = 0.790), birth asphyxia, and perinatal mortality (P = 0.197). Fetal macrosomia is associated with maternal and fetal morbidities. The presence of the observed risk factors should elicit the suspicion of a macrosomic fetus and the need for appropriate management to reduce maternal and fetal morbidities.

Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

PubMed

Evans, I M; Pickard, M R; Sinha, A K; Leonard, A J; Sampson, D C; Ekins, R P

2002-12-01

Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

Maternal Obesity and Occurrence of Fetal Macrosomia: A Systematic Review and Meta-Analysis

PubMed Central

Gaudet, Laura; Ferraro, Zachary M.; Walker, Mark

2014-01-01

Objective. To determine a precise estimate for the contribution of maternal obesity to macrosomia. Data Sources. The search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950–2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced. Methods of Study Selection. All studies that examined the relationship between maternal obesity (BMI ≥30 kg/m2) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion. Tabulation, Integration, and Results. Data regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72). Conclusion. Maternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain. PMID:25544943

A Program Aimed at Reducing Anxiety in Pregnant Women Diagnosed With a Small-for-Gestational-Age Fetus: Evaluative Findings From a Spanish Study.

PubMed

Arranz Betegón, Ángela; García, Marta; Parés, Sandra; Montenegro, Gala; Feixas, Georgina; Padilla, Nelly; Camacho, Alba; Goberna, Josefina; Botet, Francesc; Gratacós, Eduard

The objective of this study was to evaluate the effect of anxiety-reducing techniques including music therapy, sophrology, and creative visualization in pregnant women with a fetus diagnosed as small for gestational age and improved fetal and neonatal weight. This was a quasi-experimental study with a nonrandomized clinical trial design. We compared 2 groups of pregnant women with a fetus diagnosed as small for gestational age with no abnormalities on Doppler studies. The control group (n = 93) received standard care, and the intervention group (n = 65), in addition to standard care, underwent a program of 6 sessions led by a midwife or nurse who taught anxiety-reduction techniques. The State-Trait Anxiety Inventory (STAI) including trait and state subscales were completed by both groups at the start of the study, and only the STAI-State subscale was completed again at the end of the study. Comparisons between the 2 groups regarding fetal weight and centile and maternal STAI scores were performed using the t test and the χ test. There were no significant differences in the STAI-Trait scores between the 2 groups. There were statistically significant differences in the intervention group's STAI-State score percentiles between the start and the end of the study, being lower at the end of the study (P < .001). There were significant differences between the 2 groups in fetal weight trajectory on the basis of fetal weight: the intervention group had a larger weight gain (P < .005). The program designed to reduce anxiety in pregnant women was effective at reducing anxiety in the women in the intervention group, leading to a favorable fetal weight trajectory in this group.

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

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

PubMed Central

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

PubMed

Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

2014-08-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

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.

MR imaging of the fetal musculoskeletal system.

PubMed

Nemec, Stefan Franz; Nemec, Ursula; Brugger, Peter C; Bettelheim, Dieter; Rotmensch, Siegfried; Graham, John M; Rimoin, David L; Prayer, Daniela

2012-03-01

Magnetic resonance imaging (MRI) appears to be increasingly used, in addition to standard ultrasonography for the diagnosis of abnormalities in utero. Previous studies have recently drawn attention to the technical refinement of MRI to visualize the fetal bones and muscles. Beyond commonly used T2-weighted MRI, echoplanar, thick-slab T2-weighted and dynamic sequences, and three-dimensional MRI techniques, are about to provide new imaging insights into the normal and the pathological musculoskeletal system of the fetus. This review emphasizes the potential significance of MRI in the visualization of the fetal musculoskeletal system. © 2012 John Wiley & Sons, Ltd.

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity.

PubMed

Nam, Juha; Greenwald, Esther; Jack-Roberts, Chauntelle; Ajeeb, Tamara T; Malysheva, Olga V; Caudill, Marie A; Axen, Kathleen; Saxena, Anjana; Semernina, Ekaterina; Nanobashvili, Khatia; Jiang, Xinyin

2017-11-01

Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites and gene expression were measured. HF feeding significantly (P<.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P<.05) glucose transporter 1 and fatty acid transport protein 1 expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P<.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at midgestation and improved biomarkers of placental macronutrient homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Customized Fetal Growth Charts for Parents' Characteristics, Race, and Parity by Quantile Regression Analysis: A Cross-sectional Multicenter Italian Study.

PubMed

Ghi, Tullio; Cariello, Luisa; Rizzo, Ludovica; Ferrazzi, Enrico; Periti, Enrico; Prefumo, Federico; Stampalija, Tamara; Viora, Elsa; Verrotti, Carla; Rizzo, Giuseppe

2016-01-01

The purpose of this study was to construct fetal biometric charts between 16 and 40 weeks' gestation that were customized for parental characteristics, race, and parity, using quantile regression analysis. In a multicenter cross-sectional study, 8070 sonographic examinations from low-risk pregnancies between 16 and 40 weeks' gestation were analyzed. The fetal measurements obtained were biparietal diameter, head circumference, abdominal circumference, and femur diaphysis length. Quantile regression was used to examine the impact of parental height and weight, parity, and race across biometric percentiles for the fetal measurements considered. Paternal and maternal height were significant covariates for all of the measurements considered (P < .05). Maternal weight significantly influenced head circumference, abdominal circumference, and femur diaphysis length. Parity was significantly associated with biparietal diameter and head circumference. Central African race was associated with head circumference and femur diaphysis length, whereas North African race was only associated with femur diaphysis length. In this study we constructed customized biometric growth charts using quantile regression in a large cohort of low-risk pregnancies. These charts offer the advantage of defining individualized normal ranges of fetal biometric parameters at each specific percentile corrected for parental height and weight, parity, and race. This study supports the importance of including these variables in routine sonographic screening for fetal growth abnormalities.

Diagnosis of intrauterine growth restriction: comparison of ultrasound parameters.

PubMed

Ott, William J

2002-04-01

The objective of this study is an attempt to evaluate the best ultrasonic method of diagnosing intrauterine growth restriction (IUGR); a retrospective study of patients with singleton pregnancies who had been scanned at the author's institution within 2 weeks of their delivery was undertaken. Estimated fetal weight, abdominal circumference, head circumference/abdominal circumference ratio, abdominal circumference/femur length ratio, and umbilical artery S/D ratio were compared for accuracy in prediction IUGR in the neonate using both univariant and multivariant statistical analysis. Five hundred one (501) patients were analyzed. One hundred fourteen (114) neonates were classified as IUGR (22.8%). Doppler evaluation of the umbilical artery showed the best sensitivity while both abdominal circumference alone and estimated fetal weight showed similar specificity, positive and negative predictive value, and lowest false-positive and -negative results. Logistic regression analysis confirmed the univariant results and showed that, when used in combination, abdominal circumference and Doppler, or estimated fetal weight and Doppler resulted in the best predictive values. Either estimated fetal weight or abdominal circumference (alone) are accurate predictors of IUGR. Combined with Doppler studies of the umbilical artery either method will provide accurate evaluation of suspected IUGR.

Intrauterine position affects fetal weight and crown-rump length throughout gestation.

PubMed

Jang, Y D; Ma, Y L; Lindemann, M D

2014-10-01

To investigate the effect of intrauterine positions on fetal growth throughout gestation, data from a total of 65 gilts (n = 784 fetuses) that were slaughtered at assigned days of gestation (d 43, 58, 73, 91, 101, and 108) on a project to evaluate fetal mineral deposition were used. Placenta units were removed from the uterus, and position, sex, weight, and crown-rump length (CRL) of each fetus were recorded. Fetuses were classified into 5 categories within a uterine horn for the absolute intrauterine position: the ovarian end (OE) of the uterine horn, next to the ovarian end (NOE), the middle (MD), next to the cervical end (NCE), and the cervical end (CE), and also classified for the relative fetal position with respect to the sex of adjacent fetuses. Fetuses at the OE and NOE of the uterine horn tended to be heavier (P = 0.06) and longer (P < 0.05) than those at the MD of the uterine horn at d 58 of gestation. Fetuses at the OE of the uterine horn were also heavier and longer than those at the MD and NCE of the uterine horn at d 101 and 108 of gestation (P < 0.05). Fetuses at the CE of the uterine horn were intermediate in weight and length. There were no major effects of adjacent fetal sex (fetuses surrounded by the opposite sexes) in weight or length. Male fetuses were heavier than female fetuses at d 43, 58, 73, and 108 of gestation (P < 0.05) and longer than female fetuses at d 58 (P = 0.06), 73 (P < 0.05), 101 (P = 0.07), and 108 (P < 0.05) of gestation. Fetal weight was highly correlated with CRL at all gestational ages (P < 0.01). These results indicate that 1) the absolute intrauterine position affects fetal growth more than the sex of the adjacent fetus in the uterine horn, 2) each end of the uterine horn (OE and CE) has heavier fetuses than the MD, and 3) male pigs grow faster than female pigs even before birth.

Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size.

PubMed

Ahlsson, Fredrik; Diderholm, Barbro; Ewald, Uwe; Jonsson, Björn; Forslund, Anders; Stridsberg, Mats; Gustafsson, Jan

2013-05-01

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation. Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique. Median (range) rate of glucose production was 805 (653-1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5mg/L and median level of leptin was 47.1 (9.9-58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure. The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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 fewer nephrons than those from non-smoking mothers. Previous studies have shown that glomerular filtration rate is not related to birth weight, thus infants with smaller kidney volumes are hyperfiltering from birth and therefore are likely to be more susceptible to early onset renal disease in later life.

Assessing the perception and reality of arguments against thermal waste treatment plants in terms of property prices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, K.J.O.; Longhurst, P.J.; Wagland, S.T., E-mail: s.t.wagland@cranfield.ac.uk

Highlights: • Previous research studies have shown that EfW facilities negatively impact the local house prices. • In this study property prices surrounding 3 operational EfW plants were analysed. • No significant negative effect on property prices due to an incinerator was found. - Abstract: The thermal processing of waste materials, although considered to be an essential part of waste management, is often sharply contested in the UK. Arguments such as health, depletion of resources, cost, noise, odours, traffic movement and house prices are often cited as reasons against the development of such facilities. This study aims to review themore » arguments and identify any effect on property prices due to the public perception of the plant. A selection of existing energy from waste (EfW) facilities in the UK, operational for at least 7 years, was selected and property sales data, within 5 km of the sites, was acquired and analysed in detail. The locations of the properties were calculated in relation to the plant using GIS software (ArcGIS) and the distances split into 5 zones ranging from 0 to 5 km from the site. The local property sale prices, normalised against the local house price index, were compared in two time periods, before and after the facility became operational, across each of the 5 zones. In all cases analysed no significant negative effect was observed on property prices at any distance within 5 km from a modern operational incinerator. This indicated that the perceived negative effect of the thermal processing of waste on local property values is negligible.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nixon, J.D., E-mail: j.nixon@kingston.ac.uk; Wright, D.G.; Dey, P.K.

Highlights: • We evaluate operational municipal solid waste incinerators in the UK. • The supply chain of four case study plants are examined and compared in detail. • Technical, financial and operational data has been gathered for the four plants. • We suggest the best business practices for waste incinerators. • Appropriate strategy choices are the major difficulties for waste to energy plants. - Abstract: The uptake in Europe of Energy from Waste (EfW) incinerator plants has increased rapidly in recent years. In the UK, 25 municipal waste incinerators with energy recovery are now in operation; however, their waste supplymore » chains and business practices vary significantly. With over a hundred more plant developments being considered it is important to establish best business practices for ensuring efficient environmental and operational performance. By reviewing the 25 plants we identify four suitable case study plants to compare technologies (moving grate, fluidised bed and rotary kiln), plant economics and operations. Using data collected from annual reports and through interviews and site visits we provide recommendations for improving the supply chain for waste incinerators and highlight the current issues and challenges faced by the industry. We find that plants using moving grate have a high availability of 87–92%. However, compared to the fluidised bed and rotary kiln, quantities of bottom ash and emissions of hydrogen chloride and carbon monoxide are high. The uptake of integrated recycling practices, combined heat and power, and post incineration non-ferrous metal collections needs to be increased among EfW incinerators in the UK. We conclude that one of the major difficulties encountered by waste facilities is the appropriate selection of technology, capacity, site, waste suppliers and heat consumers. This study will be of particular value to EfW plant developers, government authorities and researchers working within the sector of waste management.« less

Co-expression analysis of fetal weight-related genes in ovine skeletal muscle during mid and late fetal development stages

USDA-ARS?s Scientific Manuscript database

Muscle development and lipid metabolism play important roles during fetal development stages. The commercial Texel sheep are more muscular than the indigenous Ujumqin sheep which are fatter. We performed serial transcriptomics assays and systems biology analyses to investigate the dynamics of gene e...

Fetal DNA does not induce preeclampsia-like symptoms when delivered in late pregnancy in the mouse.

PubMed

Čonka, Jozef; Konečná, Barbora; Lauková, Lucia; Vlková, Barbora; Celec, Peter

2017-04-01

The etiology of preeclampsia is unclear. Fetal DNA is present in higher concentrations in the plasma of pregnant women suffering from preeclampsia than in the plasma of healthy pregnant women. A previously published study has shown that human fetal DNA injected into pregnant mice induces preeclampsia-like symptoms when administered between gestation days 10-14. The aim of our experiment was to determine whether or not similar effects would be induced by administration of human and mouse fetal DNA, as well as mouse adult DNA and lipopolysaccharide during late pregnancy in the mouse. Experimental animals were injected daily intraperitoneally during gestation days 14-18 with either saline - negative control, lipopolysaccharide - positive control, or various types of DNA. On gestation day 19, blood pressure and proteinuria were measured, and placental and fetal weights were recorded. Fetal and placental hypotrophy were induced only by lipopolysaccharide (p < 0.001). Neither fetal nor adult DNA induced changes in fetal/placental weight. None of the experimental groups had higher blood pressure or urinary protein in comparison to saline treated animals. In our experiment, we found that there was no effect from intraperitoneally injected human fetal DNA, mouse fetal DNA, or mouse adult DNA on pregnant mice. Additionally, relatively high doses of various types of DNA did not induce preeclampsia-like symptoms in mice when administered in late pregnancy. Our negative results support the hypothesis that the increase of fetal DNA circulating in maternal circulation during the third trimester is rather a consequence than a cause of preeclampsia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

PubMed

Beaumont, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke; Freathy, Rachel M

2018-02-15

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. © The Author(s) 2018. Published by Oxford University Press.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

PubMed Central

Beaumont, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke

2018-01-01

Abstract Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10−8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. PMID:29309628

Influence of Maternal Undernutrition and Overfeeding on Cardiac Ciliary Neurotrophic Factor Receptor and Ventricular Size in Fetal Sheep

PubMed Central

Dong, Feng; Ford, Stephen P.; Nijland, Mark J.; Nathanielsz, Peter W.; Ren, Jun

2008-01-01

Intrauterine nutrition status is reported to correlate with risk of cardiovascular diseases in adulthood. Either under- or over-nutrition during early to mid gestation contributes to altered fetal growth and ventricular geometry. This study was designed to examine myocardial expression of ciliary neurotrophic factor receptor α (CTNFRα) and its down-stream mediator signal transducer and activator of transcription 3 (STAT3) on maternal under- or over-nutrition-induced changes in fetal heart weight. Multiparous ewes were fed with 50% (nutrient-restricted, NR), 100% (control) or 150% (overfed, OF) of NRC requirements from 28 to 78 days of gestation (dG; Term 148 dG). Ewes were euthanized on day 78, and the gravid uteri and fetuses recovered. Ventricular protein expression of CTNFRα, STAT3, phosphorylated STAT3, insulin-like growth factor I receptor (IGF-1R) and IGF binding protein 3 (IGFBP3) were quantitated using western blot. Plasma cortisol levels were higher in both NR and OF fetuses whereas plasma IGF-1 levels were lower and higher, in NR and OF fetuses. Fetal weights were reduced by 29.9% in NR ewes and were increased by 22.2% in fetuses from OF ewes compared to control group. Nutrient restriction did not affect fetal heart or ventricular weights whereas overfeeding increased heart and ventricular weights. Protein expression of CTNFRα in fetal ventricular tissue was reduced in OF group whereas STAT3 and pSTAT3 levels were reduced in both NR and OF groups. Expression of IGF-1R and IGFBP3 was unaffected in either NR or OF group. These data suggested that compared with maternal undernutrition, intrauterine overfeeding during early to mid gestation is associated with increases fetal blood concentrations of cortisol and IGF-1 in association with ventricular hypertrophy where reduced expression of CNTFRα and STAT3 may play a role. PMID:17869083

Intrauterine insulin resistance in fetuses of overweight mothers.

PubMed

Liu, Bin; Xu, Yun; Liang, Jian-Ming; Voss, Courtney; Xiao, Huan-Yu; Sheng, Wei-Yang; Sun, Yan-Hong; Wang, Zi-Lian

2013-01-01

To investigate the relationship between maternal overweight and fetal insulin resistance. Nineteen overweight and 30 lean pregnant women were recruited in the present study. Maternal and fetal insulin resistance were determined by measuring sex hormone binding globulin (SHBG) concentrations in maternal venous or umbilical cord serum, respectively. Maternal age, gestational age, height, pre-gravidity weight, pre-partum weight, as well as fetal gender, birth weight, birth height, and head circumference were collected as clinical data. Fetuses of overweight mothers had larger birth weight (3.58±0.55kg vs 3.32±0.42, adjusted P=0.006) and lower SHBG concentrations (26.64±3.65 vs 34.36±7.84, adjusted P=0.007) than those of lean mothers after values were adjusted for potential cofactors. Fetal SHBG level was negatively correlated with pre-gravidity body mass index (R=-0.392, adjusted P=0.025) and weight gain during pregnancy (R=-0.332, adjusted P=0.026) even with adjustment for potential cofactors. Among the 29 pregnant women with gestational diabetes mellitus, the overweight mothers had higher H1AC levels than their lean counterparts (6.47±0.44 vs 5.74±0.52, adjusted P=0.004). Intrauterine insulin resistance is more prominent in fetuses of overweight mothers, an effect that is decreased by weight gain control during pregnancy. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Are gestational age, birth weight, and birth length indicators of favorable fetal growth conditions? A structural equation analysis of Filipino infants.

PubMed

Bollen, Kenneth A; Noble, Mark D; Adair, Linda S

2013-07-30

The fetal origins hypothesis emphasizes the life-long health impacts of prenatal conditions. Birth weight, birth length, and gestational age are indicators of the fetal environment. However, these variables often have missing data and are subject to random and systematic errors caused by delays in measurement, differences in measurement instruments, and human error. With data from the Cebu (Philippines) Longitudinal Health and Nutrition Survey, we use structural equation models, to explore random and systematic errors in these birth outcome measures, to analyze how maternal characteristics relate to birth outcomes, and to take account of missing data. We assess whether birth weight, birth length, and gestational age are influenced by a single latent variable that we call favorable fetal growth conditions (FFGC) and if so, which variable is most closely related to FFGC. We find that a model with FFGC as a latent variable fits as well as a less parsimonious model that has birth weight, birth length, and gestational age as distinct individual variables. We also demonstrate that birth weight is more reliably measured than is gestational age. FFGCs were significantly influenced by taller maternal stature, better nutritional stores indexed by maternal arm fat and muscle area during pregnancy, higher birth order, avoidance of smoking, and maternal age 20-35 years. Effects of maternal characteristics on newborn weight, length, and gestational age were largely indirect, operating through FFGC. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of individualised dietary education at medical check-ups on maternal and fetal outcomes in pregnant Japanese women.

PubMed

Tajirika-Shirai, Reiko; Takimoto, Hidemi; Yokoyama, Tetsuji; Kaneko, Hitoshi; Kubota, Toshiro; Miyasaka, Naoyuki

2018-01-01

An increased prevalence of low maternal weight and insufficient pregnancy weight gain may be responsible for an increase in low birthweight infants in Japan. We aimed to examine the effects of individualised dietary education at medical check-ups on maternal/fetal outcomes in Japanese women. Four hundred and six underweight and normal weight singleton pregnant women, who attended check-ups at an obstetric facility until ≥30 weeks gestation and delivered at 36-41 weeks gestation, were selected for analyses. Weight gain was assessed at each check-up based on the official "Dietary Guidelines for Pregnant and Lactating Women". Individual dietary advice was provided by dieticians to those with insufficient or excess weight gain status around 28 weeks gestation. The medical records from uncomplicated singleton deliveries (36-41 weeks gestation) at the same facility from 2008-2010 were used (n=792) to examine the effect of dietary education on maternal/fetal outcomes. Pre-pregnancy underweight was present in >24% of women in both the intervention and non-intervention groups. Adequate weight gain occurred more frequently in the intervention group (p<0.01). There were no significant differences in mean birthweight or the proportion of low birthweight infants. However, the proportion of extremely small for gestational age infants (birthweight <3rd percentile) was lower in the intervention group (p=0.011). There were no differences in the frequency of caesarean delivery, pregnancy induced hypertension, or infant Apgar scores <7. Dietary education during pregnancy check-ups promotes adequate maternal weight gain and helps prevent extreme fetal growth restraint.

Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant

PubMed Central

2013-01-01

Background Current fetal-infant growth references have an obvious growth disjuncture around 40 week gestation overlapping where the fetal and infant growth references are combined. Graphical smoothening of the disjuncture to connect the matching percentile curves has never been validated. This study was designed to compare weight gain patterns of contemporary preterm infants with a fetal-infant growth reference (derived from a meta-analysis) to validate the previous smoothening assumptions and inform the revision of the Fenton chart. Methods Growth and descriptive data of preterm infants (23 to 31 weeks) from birth through 10 weeks post term age were collected in three cities in Canada and the USA between 2001 and 2010 (n = 977). Preterm infants were grouped by gestational age into 23–25, 26–28, and 29–31 weeks. Comparisons were made between the weight data of the preterm cohort and the fetal-infant growth reference. Results Median weight gain curves of the three preterm gestational age groups were almost identical and remained between the 3rd and the 50th percentiles of the fetal-infant-growth-reference from birth through 10 weeks post term. The growth velocity of the preterm infants decreased in a pattern similar to the decreased velocity of the fetus and term infant estimates, from a high of 17–18 g/kg/day between 31–34 weeks to rates of 4–5 g/kg/day by 50 weeks in each gestational age group. The greatest discrepancy in weight gain velocity between the preterm infants and the fetal estimate was between 37 and 40 weeks; preterm infants grew more rapidly than the fetus. The infants in this study regained their birthweight earlier compared to those in the 1999 National Institute of Child Health and Human Development report. Conclusion The weight gain velocity of preterm infants through the period of growth data disjuncture between 37 and 50 weeks gestation is consistent with and thus validates the smoothening assumptions made between preterm and post-term growth references. PMID:23758808

Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant.

PubMed

Fenton, Tanis R; Nasser, Roseann; Eliasziw, Misha; Kim, Jae H; Bilan, Denise; Sauve, Reg

2013-06-11

Current fetal-infant growth references have an obvious growth disjuncture around 40 week gestation overlapping where the fetal and infant growth references are combined. Graphical smoothening of the disjuncture to connect the matching percentile curves has never been validated. This study was designed to compare weight gain patterns of contemporary preterm infants with a fetal-infant growth reference (derived from a meta-analysis) to validate the previous smoothening assumptions and inform the revision of the Fenton chart. Growth and descriptive data of preterm infants (23 to 31 weeks) from birth through 10 weeks post term age were collected in three cities in Canada and the USA between 2001 and 2010 (n = 977). Preterm infants were grouped by gestational age into 23-25, 26-28, and 29-31 weeks. Comparisons were made between the weight data of the preterm cohort and the fetal-infant growth reference. Median weight gain curves of the three preterm gestational age groups were almost identical and remained between the 3rd and the 50th percentiles of the fetal-infant-growth-reference from birth through 10 weeks post term. The growth velocity of the preterm infants decreased in a pattern similar to the decreased velocity of the fetus and term infant estimates, from a high of 17-18 g/kg/day between 31-34 weeks to rates of 4-5 g/kg/day by 50 weeks in each gestational age group. The greatest discrepancy in weight gain velocity between the preterm infants and the fetal estimate was between 37 and 40 weeks; preterm infants grew more rapidly than the fetus. The infants in this study regained their birthweight earlier compared to those in the 1999 National Institute of Child Health and Human Development report. The weight gain velocity of preterm infants through the period of growth data disjuncture between 37 and 50 weeks gestation is consistent with and thus validates the smoothening assumptions made between preterm and post-term growth references.

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.

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

Effect of zinc oxide nanoparticles on dams and embryo–fetal development in rats

PubMed Central

Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

2014-01-01

This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnOSM20[−] NPs; negatively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague Dawley rats. ZnOSM20(−) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnOSM20(−) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day. PMID:25565833

Pregnancy rates and gravid uterine parameters in single, twin and triplet pregnancies in naturally bred ewes and ewes after transfer of in vitro produced embryos.

PubMed

Grazul-Bilska, Anna T; Pant, Disha; Luther, Justin S; Borowicz, Pawel P; Navanukraw, Chainarong; Caton, Joel S; Ward, Marcy A; Redmer, Dale A; Reynolds, Lawrence P

2006-05-01

The objectives of this study were to: (1) evaluate the pregnancy rates after transfer of embryos produced in the presence or absence of epidermal growth factor (EGF) during in vitro maturation, and (2) compare several variables of the gravid uterus on day 140 after fertilization in single, twin and triplet pregnancies in ewes (n = 12) bred naturally and in ewes (n = 18) after transfer of embryos produced in vitro. Oocytes collected from FSH-treated ewes (n = 18) were collected from all visible follicles and cultured in maturation medium with or without EGF. Oocytes were then fertilized in vitro by frozen-thawed semen. On day 5 after fertilization, embryos with > or = 16 cells were transferred to recipient ewes (n = 39). In addition 12 ewes were bred naturally. Pregnancy was verified by real-time ultrasonography on day 45 or later after embryo transfer (ET) or breeding. On day 140 of pregnancy, the reproductive tract was collected from all ewes and the following parameters were determined: the number, sex, weight and crown to rump length (CRL) of fetuses, weights of gravid uterus and fetal membranes, and weight and number of placentomes. Presence of EGF in maturation medium increased (P < 0.04) cleavage rates (78% versus 59%) and percentage of > or = 16 cell embryos on day 5 after fertilization (62% versus 40%). Pregnancy rates tended to be greater (P < 0.1) after transfer of embryos matured in the presence of EGF (52%) than in the absence of EGF (39%). EGF presence in maturation medium did not affect any variables of gravid uterus or fetal weight. For single pregnancies in naturally bred ewes and ewes after ET all uterine variables were similar. For twin pregnancies, weight of gravid uterus, weight of uterus plus fetal membranes, total weight of placentomes/ewe, mean weight of individual placentome, mean weight of fetus, total fetal weight/ewe and CRL were greater (P < 0.0001-0.04) for ewes after ET than for ewes bred naturally. The weights of gravid uterus, fluid, uterus plus fetal membranes, fetal membranes, total placentomes/ewe, mean weight of individual placentome and total fetal weight/ewe were greater (P < 0.0001-0.08) for triplet pregnancies in ewes after ET than single and twin pregnancies in ewes naturally bred or after ET. The number of placentomes/fetus was greatest (P < 0.0001-0.06) in single pregnancies in ewes bred naturally and after ET fewer in twin pregnancies in ewes bred naturally and after ET and fewest in triplet pregnancies in ewes after ET. The total number of placentomes/ewe was greatest (P < 0.0001-0.06) for twin pregnancies in ewes naturally bred, fewer in single pregnancies in ewes naturally bred and twin and triplet pregnancies after ET, and fewest in single pregnancies in ewes after ET. The mean weight of fetus was greater (P < 0.0001-0.07) in single pregnancies in ewes naturally bred or after ET than in twin or triplet pregnancies in ewes naturally bred or after ET. The CRL was the lowest (P < 0.01) in twin pregnancies in ewes bred naturally. For pregnancies after natural breeding and after ET, the number of fetuses/ewe was negatively correlated (P < 0.03-0.0001) with the weight of placentomes/fetus, the number of placentomes/fetus, the mean weight of the fetus and CRL, and was positively correlated (P < 0.0001-0.05) with weight of gravid uterus, the total number of placentomes/ewe and total fetal weight/ewe. These data demonstrate that the presence of EGF in maturation medium increases the rates of cleavage and early embryonic development, and has a tendency to enhance rates of pregnancy but does not affect variables of the gravid uteri in ewes after transfer of in vitro produced embryos. Transfer of embryos produced in vitro affected some uterine variables in twin but not single pregnancies to compare with pregnancies after natural breeding. In addition, culture conditions in the present experiment did not create large offspring syndrome. The low number of placentomes/fetus seen in triple pregnancies appears to be compensated for by the increase in the weight of each individual placentome.

Management of hyperthyroidism in pregnancy

PubMed Central

Cezar, C; Grigoras, M; Horhoianu, I; Parau, C; Virtej, P; Lungu, A; Horhoianu, V; Poiana, C

2008-01-01

Maternal hypertiroidism is a relative rare disorder, which can seriously complicate pregnancy in each of its periods. There are several maternal and fetal complications during pregnancy, delivery and postpartum period. Correct management includes an accurate diagnosis, rigorous individualized treatment and minutious follow–up. We are presenting a retrospective study of 38 pregnant women who delivered in the Obstetric Unit of the University Emergency Bucharest Hospital in the past five years. We established a follow–up protocol in collaboration with endocrinologists. Precocious diagnosis of pregnancy is, in our opinion, mandatory. Accurate diagnosis of hormonal status beginning from the first week of pregnancy is of great importance. Maternal (weight, BP, TSH, thyroid hormones, ECG, etc.) and fetal (ultrasound, non–stress test, Doppler study) evaluation during pregnancy were rigorous performed. Results: abortion rate was 5%; 15% of pregnant women delivered prematurely; cesarean section rate was 22%; fetal outcome was excellent. Treatment adjustment during pregnancy was frequent, 28% of pregnant women had no hormonal treatment in the last trimester of pregnancy. Maternal complications were rare (poor weight gain, tachycardia). Fetal complications included low birth weight (24%), fetal respiratory distress (10%). Conclusions: team work with experienced endocrinologists and understanding of versatility of disease leads to good prognosis of mother and fetus in presence of hypertiroidism. PMID:20108518

Brain glucose content in fetuses of ethanol-fed rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pullen, G.; Singh, S.P.; Snyder, A.K.

1986-03-01

The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4more » and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.« less

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...

A Pilot Study: The importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome

PubMed Central

Gelmann, Elyssa R; Gurzau, Eugen; Gurzau, Anca; Goessler, Walter; Kunrath, Julie

2013-01-01

Inorganic arsenic (iAs) exposure is detrimental to birth outcome. We lack information regarding the potential for iAs metabolism to affect fetal growth. Our pilot study evaluated postpartum Romanian women with known birth weight outcome for differences in iAs metabolism. Subjects were chronically exposed to low-to-moderate drinking water iAs. We analyzed well water, arsenic metabolites in urine, and toenail arsenic. Urine iAs and metabolites, toenail iAs, and secondary methylation efficiency increased as an effect of exposure (p<0.001). Urine iAs and metabolites showed a significant interaction effect between exposure and birth weight. Moderately exposed women with low compared to normal birth weight outcome had greater metabolite excretion (p<0.03); 67% with low compared to 10% with normal birth weight outcome presented urine iAs >9μg/L (p=0.019). Metabolic partitioning of iAs toward excretion may impair fetal growth. Prospective studies on iAs excretion before and during pregnancy may provide a biomarker for poor fetal growth risk. PMID:24211595

Prenatal diagnosis of fetal respiratory function: evaluation of fetal lung maturity using lung-to-liver signal intensity ratio at magnetic resonance imaging.

PubMed

Oka, Yasuko; Rahman, Mosfequr; Sasakura, Chihaya; Waseda, Tomoo; Watanabe, Yukio; Fujii, Ryota; Makinoda, Satoru

2014-12-01

The purpose of this retrospective study is to determine the fetal lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images for the prediction of neonatal respiratory outcome. One hundred ten fetuses who underwent magnetic resonance imaging (MRI) examination for various indications after 22 weeks of gestation participated in this study. LLSIR was measured as the ratio of signal intensities of the fetal lung and liver on T2-weighted images at MRI. We examined the changes of the ratio with advancing gestation and the relations between LLSIR and the presence of the severe respiratory disorder (SRD) after birth. The best cut-off value of the LLSIR to predict respiratory outcome after birth was calculated using receiver operating characteristic (ROC) curve analysis. Lung-to-liver signal intensity ratio correlated significantly with advancing gestational age (R = 0.35, p < 0.001). The non-SRD group had higher LLSIR compared with the SRD group (2.15 ± 0.30 vs. 1.53 ± 0.40, p < 0.001). ROC curve analysis showed that fetuses with an LLSIR < 2.00 were more likely to develop SRD [sensitivity: 100%, 95% confidence interval (CI): 52-100%; specificity: 73%, 95% CI 54-88%]. The fetal LLSIR on T2-weighted images is an accurate marker to diagnose the fetal lung maturity. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

[Morphologic study of the intestine in an experimental model of amnioinfusion in fetal rabbits with gastroschisis].

PubMed

Muñoz, M E; Albert, A; Juliá, V; Sancho, M A; Grande, C; Martínez, A; Morales, L

2002-10-01

An experimental model of serial amnioinfusion has been developed in fetal rabbits with gastroschisis, using an intraamniotic catheter connected to a subcutaneous port. Fetuses of 4 groups were compared 7 days after surgery: group A: gastroschisis and daily amnioinfusion through an implanted catheter; group C: gastroschisis and blind amniotic catheter; group G: gastroschisis without catheter; group O: nonoperated fetuses. Survival rate, fetal body weight, lung weight, intestinal weight and length were determined. Computer aided morphometric analysis was performed, in which intestinal diameter, thickness and villi length were measured. Amniotic fluid samples were recovered along the experimental period. Intestinal length was significantly shorter and had a significantly thicker wall than nonoperated fetuses; we found no other morphometric differences between gastroschisis treated with amnioinfusion (group A) and the other gastroschisis groups (C and G). Amnioinfusion did not affect fetal survival rate; the amniotic catheter alone did not cause pulmonary hypoplasia due to significant amniotic leak. The physiological decrease in amniotic volume towards the end of gestation has not been modified by this regime of amnioinfusion.

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.

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

PubMed

Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

2013-07-01

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogush, Anna; Stegemann, Julia A., E-mail: j.stegemann@ucl.ac.uk; Wood, Ian

Highlights: • 66 elements, including “critical strategic elements” were determined in UK EfW APC residues. • Metal pollutants (Zn, Pb, As, Cd, Cu, Mo, Sb, Sn, Se, Ag and In) are enriched in APC residues. • Metal pollutants were widely associated with fine deposits of highly soluble CaCl{sub x}OH{sub 2−x}. • Specific metal (Zn, Pb, Cu)-bearing minerals were also detected in APC residues. - Abstract: Air pollution control (APC) residues from energy-from-waste (EfW) are alkaline (corrosive) and contain high concentrations of metals, such as zinc and lead, and soluble salts, such as chlorides and sulphates. The EPA 3050B-extractable concentrations ofmore » 66 elements, including critical elements of strategic importance for advanced electronics and energy technologies, were determined in eight APC residues from six UK EfW facilities. The concentrations of Ag (6–15 mg/kg) and In (1–13 mg/kg), as well as potential pollutants, especially Zn (0.26–0.73 wt.%), Pb (0.05–0.2 wt.%), As, Cd, Cu, Mo, Sb, Sn and Se were found to be enriched in all APC residues compared to average crustal abundances. Results from a combination of scanning electron microscopy with energy dispersive X-ray spectroscopy and also powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy give an exceptionally full understanding of the mineralogy of these residues, which is discussed in the context of other results in the literature. The present work has shown that the bulk of the crystalline phases present in the investigated APC residues include Ca-based phases, such as CaCl{sub x}OH{sub 2−x}, CaCO{sub 3}, Ca(OH){sub 2}, CaSO{sub 4}, and CaO, as well as soluble salts, such as NaCl and KCl. Poorly-crystalline aragonite was identified by FTIR. Sulphur appears to have complex redox speciation, presenting as both anhydrite and hannebachite in some UK EfW APC residues. Hazardous elements (Zn and Pb) were widely associated with soluble Ca- and Cl-bearing phases (e.g. CaCl{sub x}OH{sub 2−x} and sylvite), as well as unburnt organic matter and aluminosilicates. Specific metal-bearing minerals were also detected in some samples: e.g., Pb present as cerussite; Zn in gahnite, zincowoodwardite and copper nickel zinc oxide; Cu in tenorite, copper nickel zinc oxide and fedotovite. Aluminium foil pieces were present and abundantly covered by fine phases, particularly in any cracks, probably in the form of Friedel’s salt.« less

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

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.

Combined effects of radiation and caffeine on embryonic development in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusama, T.; Sugiura, N.; Kai, M.

1989-02-01

The combined effect of radiation and caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on Day 11 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Doses of whole-body gamma irradiation were 0.5 to 2.5 Gy and those of caffeine were 100 and 250 mg/kg maternal body wt. Intrauterine mortality increased with increasing radiation dose; this trend was more remarkable in combination with caffeine. Gross malformations such as cleft palate and defects of forelegs and hindlegs appeared frequently in the fetuses treated with both radiation andmore » caffeine. Decreased fetal weight was observed even in mice treated with 0.5 Gy of radiation or 100 mg/kg caffeine. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was a sensitive, precise, and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of cleft palate and defects of forelegs and hindlegs were higher than the sum of those induced by radiation and by caffeine separately. The results indicated that the combined action of radiation and caffeine on intrauterine death and malformations was synergistic.« less

Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

PubMed

Ahmed, R G

2016-09-01

Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Invited commentary: Timing and types of cardiovascular risk factors in relation to offspring birth weight.

PubMed

Ness, Roberta B; Catov, Janet

2007-12-15

Birth weight is associated with later-life cardiovascular risk. A new study by Romundstad et al. (Am J Epidemiol 2007;166:1359-1364) challenges us to consider influences on birth weight with respect to timing and type. Timing of effects on birth weight, according to the "fetal origins hypothesis," is in utero. Alternatively, familial aggregation--genetics or shared environment--may explain birth weight and suggests prepregnancy influences. The Romundstad et al. findings support familial effects: maternal metabolic factors predicted birth weight for gestational age. However, because maternal physiology sets the fetal environment, these data do not necessarily counter the fetal origins hypothesis. Types of maternal metabolic influences demonstrated by Romundstad et al. include elevations in blood pressure being associated with lower birth weight for gestational age, whereas unfavorable glucose and lipid levels were associated with higher birth weight. These findings are consistent with the authors prior hypothesis that vascular dysfunction and metabolic profile (glucose and lipids) have divergent effects during pregnancy. Moreover, these new data underscore that both extremes of birth weight may be related to cardiovascular risk. Few data sets contain prepregnancy, pregnancy, and childhood information. Without all such time points, life course effects will remain only partially understood. It is hoped that studies such as the forthcoming National Children's Study will generate critical understanding of this issue.

Intraplacental Gene Therapy with Ad-IGF-1 Corrects Naturally Occurring Rabbit Model of Intrauterine Growth Restriction

PubMed Central

Keswani, Sundeep G.; Balaji, Swathi; Katz, Anna B.; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles

2015-01-01

Abstract Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal–fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of this novel therapy. PMID:25738403

Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy.

PubMed

Kim, J C; Shin, H C; Cha, S W; Koh, W S; Chung, M K; Han, S S

2001-10-19

Bisphenol A (BPA) is an essential component of epoxy resins used in the lacquer lining of metal food cans, as a component of polycarbonates, and in dental sealants. The present study was conducted in an attempt to evaluate the adverse effects of the environmental estrogen BPA on initiation and maintenance of pregnancy and embryofetal development after maternal exposure during the entire period of pregnancy in Sprague-Dawley rats. The test chemical was administered by gavage to mated females from days 1 to 20 of gestation (sperm in varginal lavage = day 0) at dose levels of 0, 100, 300, and 1000 mg/kg. All females were subjected to caesarean section on day 21 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, significant toxic effects including abnormal clinical signs, decreased maternal body weight and body weight gain, and reduced food consumption were observed in pregnant rats. An increase in pregnancy failure was also found in the successfully mated females. In addition, increased number of embryonal deaths, increased postimplantation loss, reduced litter size and fetal body weight, and decreased number of fetal ossification centers of several skeletal districts were seen. On the contrary, no significant changes induced by BPA were detected in the number of corpora lutea and implantation sites and by fetal morphological examinations. In the 300 mg/kg group, suppressed maternal body weight and body weight gain, decreased food intake and reduced body weight of male fetuses were seen. There were no adverse signs of either maternal toxicity or developmental toxicity in the 100 mg/kg group. It was concluded that BPA administration during the entire period of pregnancy in rats produced pregnancy failure, pre- and postimplantation loss, fetal developmental delay and severe maternal toxicity, but no embryo-fetal dysmorphogenesis at an oral exposure level of 1000 mg/kg.

Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction.

PubMed

Keswani, Sundeep G; Balaji, Swathi; Katz, Anna B; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles; Crombleholme, Timothy M

2015-03-01

Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal-fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of this novel therapy.

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

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

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.

Magnetic resonance imaging of the fetal brain.

PubMed

Tee, L Mf; Kan, E Yl; Cheung, J Cy; Leung, W C

2016-06-01

This review covers the recent literature on fetal brain magnetic resonance imaging, with emphasis on techniques, advances, common indications, and safety. We conducted a search of MEDLINE for articles published after 2010. The search terms used were "(fetal OR foetal OR fetus OR foetus) AND (MR OR MRI OR [magnetic resonance]) AND (brain OR cerebral)". Consensus statements from major authorities were also included. As a result, 44 relevant articles were included and formed the basis of this review. One major challenge is fetal motion that is largely overcome by ultra-fast sequences. Currently, single-shot fast spin-echo T2-weighted imaging remains the mainstay for motion resistance and anatomical delineation. Recently, a snap-shot inversion recovery sequence has enabled robust T1-weighted images to be obtained, which is previously a challenge for standard gradient-echo acquisitions. Fetal diffusion-weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopy are also being developed. With multiplanar capabilities, superior contrast resolution and field of view, magnetic resonance imaging does not have the limitations of sonography, and can provide additional important information. Common indications include ventriculomegaly, callosum and posterior fossa abnormalities, and twin complications. There are safety concerns about magnetic resonance-induced heating and acoustic damage but current literature showed no conclusive evidence of deleterious fetal effects. The American College of Radiology guideline states that pregnant patients can be accepted to undergo magnetic resonance imaging at any stage of pregnancy if risk-benefit ratio to patients warrants that the study be performed. Magnetic resonance imaging of the fetal brain is a safe and powerful adjunct to sonography in prenatal diagnosis. It can provide additional information that aids clinical management, prognostication, and counselling.

Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.

PubMed

Sovio, Ulla; White, Ian R; Dacey, Alison; Pasupathy, Dharmintra; Smith, Gordon C S

2015-11-21

Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15-24; 69 of 352 fetuses) for selective ultrasonography and 57% (51-62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2·9, 95% CI 2·4-3·5, p<0·0001). Of the 3977 fetuses, 562 (14·1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk [RR] 1·60, 95% CI 1·22-2·09, p=0·0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction=0·005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3·9, 95% CI 1·9-8·1, p=0·0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17·6 (9·2-34·0, p<0·0001). Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare. Copyright © 2015 Sovio et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

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

Bendectin and fetal development. A study of Boston City Hospital.

PubMed

Morelock, S; Hingson, R; Kayne, H; Dooling, E; Zuckerman, B; Day, N; Alpert, J J; Flowerdew, G

1982-01-15

As part of a prospective study investigating maternal characteristics and habits during pregnancy and their impact on fetal development, 1,690 mother/infant pairs were studied. Of the mothers, 375 reported using Bendectin during pregnancy. Multivariate analyses examining birth weight, length, head circumference, gestational age, and congenital malformations as dependent variables demonstrated no associations between Bendectin exposure and adverse fetal outcome.

The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsang, Verne; Fry, Rebecca C.; Niculescu, Mihai D.

Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous studies have demonstrated that in utero exposure to iAs promotes cancer in adult mouse offspring, possibly acting through epigenetic mechanisms. Humans and rodents enzymatically convert iAs to its methylated metabolites. This reaction requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required for DNA methylation. Supplementation with folate, a major dietary source of methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the adverse effects of iAs exposure. However, effects of gestational folate supplementation on iAs metabolism and fetal DNA methylation have never beenmore » thoroughly examined. In the present study, pregnant CD1 mice were fed control (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite) from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18 fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in fetal livers. High folate intake lowered the burden of total arsenic in maternal livers but did not prevent the effects of iAs exposure on fetal weight or hepatic SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further significant body weight reduction. Notably, iAs exposure alone had little effect on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure changed the CpG island methylation in 2,931 genes, including genes known to be imprinted. Most of these genes were associated with neurodevelopment, cancer, cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which regulates fetal development, was among the most affected biological pathways. Taken together, our results suggest that a combined in utero exposure to iAs and a high folate intake may adversely influence DNA methylation profiles and weight of fetuses, compromising fetal development and possibly increasing the risk for early-onset of disease in offspring. Highlights: ► We used transplacental CD1 mice model for inorganic arsenic (iAs) carcinogenesis. ► We examined the effects of gestational iAs and high folate exposure on DNA methylation. ► iAs–folate interaction resulted in low fetal weights and changes in DNA methylation. ► Epigenetically altered genes were associated with cancer and neurodevelopment. ► We showed that in utero iAs–folate interaction negatively affects fetal development.« less

Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants.

PubMed

Bottoms, S F; Paul, R H; Mercer, B M; MacPherson, C A; Caritis, S N; Moawad, A H; Van Dorsten, J P; Hauth, J C; Thurnau, G R; Miodovnik, M; Meis, P M; Roberts, J M; McNellis, D; Iams, J D

1999-03-01

The aim of the study was to compare clinical and ultrasonographic variables obtained before delivery as predictors of neonatal survival and morbidity in infants weighing

Maternal obesity accelerates fetal pancreatic beta-cell but not alpha-cell development in sheep: prenatal consequences.

PubMed

Ford, Stephen P; Zhang, Liren; Zhu, Meijun; Miller, Myrna M; Smith, Derek T; Hess, Bret W; Moss, Gary E; Nathanielsz, Peter W; Nijland, Mark J

2009-09-01

Maternal obesity affects offspring weight, body composition, and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high-energy diet on fetal pancreatic development. Sixty days prior to breeding, ewes were assigned to control [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by approximately 43% and approximately 6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased beta-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and/or cortisol-induced accelerated fetal beta-cell maturation and may contribute to premature beta-cell function loss and predisposition to obesity and metabolic disease in offspring.

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.

Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep: prenatal consequences

PubMed Central

Ford, Stephen P.; Zhang, Liren; Zhu, Meijun; Miller, Myrna M.; Smith, Derek T.; Hess, Bret W.; Moss, Gary E.; Nathanielsz, Peter W.; Nijland, Mark J.

2009-01-01

Maternal obesity affects offspring weight, body composition, and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high-energy diet on fetal pancreatic development. Sixty days prior to breeding, ewes were assigned to control [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by ∼43% and ∼6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased β-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and/or cortisol-induced accelerated fetal β-cell maturation and may contribute to premature β-cell function loss and predisposition to obesity and metabolic disease in offspring. PMID:19605766

Vitrified-warmed embryo transfer is associated with mean higher singleton birth weight compared to fresh embryo transfer.

PubMed

Beyer, Daniel Alexander; Griesinger, Georg

2016-08-01

To test for differences in birth weight between singletons born after IVF with fresh embryo transfer vs. vitrified-warmed 2PN embryo transfer (vitrification protocol). Retrospective analysis of 464 singleton live births after IVF or ICSI during a 12 year period. University hospital. Fresh embryo transfer, vitrified-warmed 2PN embryo transfer (vitrification protocol). Birth weight standardized as a z-score, adjusting for gestational week at delivery and fetal sex. As a reference, birth weight means from regular deliveries from the same hospital were used. Multivariate regression analysis was used to investigate the relationship between the dependent variable z-score (fetal birth weight) and the independent predictor variables maternal age, weight, height, body mass index, RDS prophylaxis, transfer protocol, number of embryos transferred, indication for IVF treatment and sperm quality. The mean z-score was significantly lower after fresh transfer (-0.11±92) as compared to vitrification transfer (0.72±83) (p<0.001). Multivariate regression analysis indicated that only maternal height and maternal body mass index, but not type of cryopreservation protocol, was a significant predictor of birth weight. In this analysis focusing on 2PN oocytes, vitrified-warmed embryo transfer is associated with mean higher birth weight compared to fresh embryo transfer. Maternal height and body mass index are significant confounders of fetal birth weight and need to be taken into account when studying birth weight differences between ART protocols. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Correlation of maternal-fetal attachment and health practices during pregnancy with neonatal outcomes.

PubMed

Maddahi, Maryam Sadat; Dolatian, Mahrokh; Khoramabadi, Monirsadat; Talebi, Atefeh

2016-07-01

Low birth weight due to preterm delivery or intrauterine growth restriction (IUGR) is the strongest factor contributing to prenatal, neonatal, and postnatal mortality. Maternal-fetal attachment plays a significant role in maternal and fetal health. Health practices performed by the mother during pregnancy constitute one of the factors that may affect neonatal outcomes. The present study was conducted to identify the relationship between maternal-fetal attachment and health practices during pregnancy with neonatal outcomes. This cross-sectional study was conducted on 315 pregnant women with a gestational age of 33-41 weeks who presented to hospitals in Sirjan (Iran) between December 2014 and February 2015. The data collection tools used included the Health Practices in Pregnancy Questionnaire and the Maternal Fetal Attachment Scale. Data were analyzed using IBM-SPSS version 20, focusing on the Pearson product-moment correlation and the logistic regression model. Statistical significance was set to p<0.05. The mean score of maternal-fetal attachment was 60.34, and the mean score of health practices was 123.57. The mean birth weight of the neonates was 3052.38 g. Health practices (p<0.05, r=0.11) and maternal-fetal attachment (p<0.01, r=0.23) were positively and significantly correlated with neonatal outcomes. A significant positive relationship was also observed between maternal-fetal attachment and neonatal outcomes. No significant relationships were observed between health practices during pregnancy and neonatal outcomes. Maternal-fetal attachment and health practices during pregnancy are positively and significantly correlated with neonatal outcomes.

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

PubMed

Orlandini, Cinzia; Torricelli, Michela; Spirito, Nicoletta; Alaimo, Lucia; Di Tommaso, Mariarosaria; Severi, Filiberto Maria; Ragusa, Antonio; Petraglia, Felice

2017-07-01

Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

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.

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.

Early biometric lag in the prediction of small for gestational age neonates and preeclampsia.

PubMed

Schwartz, Nadav; Pessel, Cara; Coletta, Jaclyn; Krieger, Abba M; Timor-Tritsch, Ilan E

2011-01-01

An early fetal growth lag may be a marker of future complications. We sought to determine the utility of early biometric variables in predicting adverse pregnancy outcomes. In this retrospective cohort study, the crown-rump length at 11 to 14 weeks and the head circumference, biparietal diameter, abdominal circumference, femur length, humerus length, transverse cerebellar diameter, and estimated fetal weight at 18 to 24 weeks were converted to an estimated gestational age using published regression formulas. Sonographic fetal growth (difference between each biometric gestational age and the crown-rump length gestational age) minus expected fetal growth (number of days elapsed between the two scans) yielded the biometric growth lag. These lags were tested as predictors of small for gestational age (SGA) neonates (≤10th percentile) and preeclampsia. A total of 245 patients were included. Thirty-two (13.1%) delivered an SGA neonate, and 43 (17.6%) had the composite outcome. The head circumference, biparietal diameter, abdominal circumference, and estimated fetal weight lags were identified as significant predictors of SGA neonates after adjusted analyses (P < .05). The addition of either the estimated fetal weight or abdominal circumference lag to maternal characteristics alone significantly improved the performance of the predictive model, achieving areas under the curve of 0.72 and 0.74, respectively. No significant association was found between the biometric lag variables and the development of preeclampsia. Routinely available biometric data can be used to improve the prediction of adverse outcomes such as SGA. These biometric lags should be considered in efforts to develop screening algorithms for adverse outcomes.

Does early second-trimester sonography predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies?

PubMed

Allaf, M Baraa; Campbell, Winston A; Vintzileos, Anthony M; Haeri, Sina; Javadian, Pouya; Shamshirsaz, Amir A; Ogburn, Paul; Figueroa, Reinaldo; Wax, Joseph; Markenson, Glenn; Chavez, Martin R; Ravangard, Samadh F; Ruano, Rodrigo; Sangi-Haghpeykar, Haleh; Salmanian, Bahram; Meyer, Marjorie; Johnson, Jeffery; Ozhand, Ali; Davis, Sarah; Borgida, Adam; Belfort, Michael A; Shamshirsaz, Alireza A

2014-09-01

To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second-trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes. We conducted a multicenter retrospective cohort study involving 9 regional perinatal centers in the United States. We examined the records of all monochorionic diamniotic twin pregnancies with two live fetuses at the 16- to 18-week sonographic examination who had serial follow-up sonography until delivery. The intertwin discordance in abdominal circumference, femur length, head circumference, and estimated fetal weight was calculated as the difference between the two fetuses, expressed as a percentage of the larger using the 16- to 18-week sonographic measurements. An adverse composite obstetric outcome was defined as the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction, twin-twin transfusion syndrome, intrauterine fetal death, abnormal growth discordance (≥20% difference), and very preterm birth at or before 28 weeks. An adverse composite neonatal outcome was defined as the occurrence of 1 or more of the following: respiratory distress syndrome, any stage of intraventricular hemorrhage, 5-minute Apgar score less than 7, necrotizing enterocolitis, culture-proven early-onset sepsis, and neonatal death. Receiver operating characteristic and logistic regression-with-generalized estimating equation analyses were constructed. Among the 177 monochorionic diamniotic twin pregnancies analyzed, intertwin abdominal circumference and estimated fetal weight discordances were only predictive of adverse composite obstetric outcomes (areas under the curve, 79% and 80%, respectively). Receiver operating characteristic curves showed that intertwin discordances in abdominal circumference, femur length, head circumference, and estimated fetal weight were not acceptable predictors of twin-twin transfusion syndrome or adverse neonatal outcomes. In our cohort, only second-trimester abdominal circumference and estimated fetal weight discordances in monochorionic diamniotic twin pregnancies were predictive of adverse composite obstetric outcomes. Twin-twin transfusion syndrome and adverse neonatal outcomes were not predicted by any of the intertwin discordances measured. © 2014 by the American Institute of Ultrasound in Medicine.

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.

Triplet ultrasound growth parameters.

PubMed

Vora, Neeta L; Ruthazer, Robin; House, Michael; Chelmow, David

2006-03-01

To create ultrasound growth curves for normal growth of fetal triplets using statistical methodology that properly accounts for similarities of growth of fetuses within a mother as well as repeated measurements over time for each fetus. In this longitudinal study, all triplet pregnancies managed at a single tertiary center from 1992-2004 were reviewed. Fetuses with major anomalies, prior selective reduction, or fetal demise were excluded. Data from early and late gestation in which there were fewer than 30 fetal measurements available for analysis were excluded. We used multilevel models to account for variation in growth within a single fetus over time, variations in growth between multiple fetuses within a single mother, and variations in fetal growth between mothers. Medians (50th), 10th, and 90th percentiles were estimated by the creation of multiple quadratic growth models from bootstrap samples adapting a previously published method to compute prediction intervals. Estimated fetal weight was derived from Hadlock's formula. One hundred fifty triplet pregnancies were identified. Twenty-seven pregnancies were excluded for the following reasons: missing records (23), fetal demise (3), and fetal anomaly (1). The study group consisted of 123 pregnancies. The gestational age range was restricted to 14-34 weeks. Figures and tables were developed showing medians, 10th and 90th percentiles for estimated fetal weight, femur length, biparietal diameter, abdominal circumference, and head circumference. Growth curves for triplet pregnancies were derived. These may be useful for identification of abnormal growth in triplet fetuses. III.

[Maternal and fetal outcome in Mexican women with rheumatoid arthritis].

PubMed

Saavedra, Miguel A; Sánchez, Antonio; Bustamante, Reyna; Miranda-Hernández, Dafhne; Soliz-Antezana, Jimena; Cruz-Domínguez, Pilar; Morales, Sara; Jara, Luis J

2015-01-01

To report our experience in maternal-fetal outcome in women with RA in a national medical referral center. A retrospective analysis of the records of pregnant women with rheumatoid arthritis attending at a Pregnancy and Autoimmune Rheumatic Diseases Clinic was performed. Maternal-fetal outcomes such as disease activity, preclampsia/eclampsia, rate of live births, abortions, stillbirths, preterm birth, weeks of gestation, birth weight, congenital malformations and use of anti-rheumatic drugs were studied. We included 73 pregnancies in 72 patients. Disease activity was documented in 47.2% of patients during pregnancy and/or postpartum and 87.7% of patients received some antirheumatic drug. Preclampsia developed in 8.2% of cases. The live birth rate was 98.6%, with preterm delivery in 15.9% and low weight at term in 17.6% of cases. Cesarean section was performed in 77.1% of cases. The disease activity was not associated with a higher percentage of maternal-fetal complications. Our study showed that most patients do not experience significant activity of RA during pregnancy, fetal outcome is satisfactory and disease activity did not appear to influence significantly the obstetric outcome.

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

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

PubMed

Hiersch, Liran; Melamed, Nir

2018-02-01

Fetal growth restriction implies failure of a fetus to meet its growth potential and is associated with increased perinatal mortality and morbidity. Therefore, antenatal detection of fetal growth restriction is of major importance in an attempt to deliver improved clinical outcomes. The most commonly used approach towards screening for fetal growth restriction is by means of sonographic fetal weight estimation, to detect fetuses small for gestational age, defined by an estimated fetal weight <10th percentile for gestational age. However, the predictive accuracy of this approach is limited both by suboptimal detection rate (as it may overlook non-small-for-gestational-age growth-restricted fetuses) and by a high false-positive rate (as most small-for-gestational-age fetuses are not growth restricted). Here, we review 2 strategies that may improve the diagnostic accuracy of sonographic fetal biometry for fetal growth restriction. The first strategy involves serial ultrasound evaluations of fetal biometry. The information obtained through these serial assessments can be interpreted using several different approaches including fetal growth velocity, conditional percentiles, projection-based methods, and individualized growth assessment that can be viewed as mathematical techniques to quantify any decrease in estimated fetal weight percentile, a phenomenon that many care providers assess and monitor routinely in a qualitative manner. This strategy appears promising in high-risk pregnancies where it seems to improve the detection of growth-restricted fetuses at increased risk of adverse perinatal outcomes and, at the same time, decrease the risk of falsely diagnosing healthy constitutionally small-for-gestational-age fetuses as growth restricted. Further studies are needed to determine the utility of this strategy in low-risk pregnancies as well as to optimize its performance by determining the optimal timing and interval between exams. The second strategy refers to the 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.

Fetal lung apparent diffusion coefficient measurement using diffusion-weighted MRI at 3 Tesla: Correlation with gestational age.

PubMed

Afacan, Onur; Gholipour, Ali; Mulkern, Robert V; Barnewolt, Carol E; Estroff, Judy A; Connolly, Susan A; Parad, Richard B; Bairdain, Sigrid; Warfield, Simon K

2016-12-01

To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T). Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated. When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks. We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655. © 2016 International Society for Magnetic Resonance in Medicine.

Effect of Bauhinia forficata aqueous extract on the maternal-fetal outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats.

PubMed

Volpato, G T; Damasceno, D C; Rudge, M V C; Padovani, C R; Calderon, I M P

2008-02-28

Bauhinia forficata Link, commonly known as "paw-of-cow", is widely used in Brazilian folk medicine for the treatment of diabetes. To evaluate the effect of Bauhinia forficata treatment on maternal-fetal outcome and antioxidant systems of streptozotocin-induced diabetic rats. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats at increasing doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. At day 21 of pregnancy the rats were anaesthetized with ether and a maternal blood sample was collected for the determination superoxide dismutase (SOD) and reduced glutathione (GSH). The gravid uterus was weighed with its contents and fetuses were analyzed. The data showed that the diabetic dams presented an increased glycemic level, resorption, placental weight, placental index, and fetal anomalies, and reduced GSH and SOD determinations, live fetuses, maternal weight gain, gravid uterine weight, and fetal weight. It was also verified that Bauhinia forficata treatment had no hypoglycemic effect, did not improve maternal outcomes in diabetic rats, but it contributed to maintain GSH concentration similarly to non-diabetic groups, suggesting relation with the decreased incidence of visceral anomalies.

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.

Fetal Thyroid Function, Birth Weight, and in Utero Exposure to Fine Particle Air Pollution: A Birth Cohort Study

PubMed Central

Janssen, Bram G.; Saenen, Nelly D.; Roels, Harry A.; Madhloum, Narjes; Gyselaers, Wilfried; Lefebvre, Wouter; Penders, Joris; Vanpoucke, Charlotte; Vrijens, Karen; Nawrot, Tim S.

2016-01-01

Background: Thyroid hormones are critical for fetal development and growth. Whether prenatal exposure to fine particle air pollution (≤ 2.5 μm; PM2.5) affects fetal thyroid function and what the impact is on birth weight in normal healthy pregnancies have not been studied yet. Objectives: We studied the impact of third-trimester PM2.5 exposure on fetal and maternal thyroid hormones and their mediating role on birth weight. Methods: We measured the levels of free thyroid hormones (FT3, FT4) and thyroid-stimulating hormone (TSH) in cord blood (n = 499) and maternal blood (n = 431) collected after delivery from mother–child pairs enrolled between February 2010 and June 2014 in the ENVIRONAGE birth cohort with catchment area in the province of Limburg, Belgium. Results: An interquartile range (IQR) increment (8.2 μg/m3) in third-trimester PM2.5 exposure was inversely associated with cord blood TSH levels (–11.6%; 95% CI: –21.8, –0.1) and the FT4/FT3 ratio (–62.7%; 95% CI: –91.6, –33.8). A 10th–90th percentile decrease in cord blood FT4 levels was associated with a 56 g decrease in mean birth weight (95% CI: –90, –23). Assuming causality, we estimated that cord blood FT4 mediated 21% (–19 g; 95% CI: –37, –1) of the estimated effect of an IQR increment in third-trimester PM2.5 exposure on birth weight. Third-trimester PM2.5 exposure was inversely but not significantly associated with maternal blood FT4 levels collected 1 day after delivery (–4.0%, 95% CI: –8.0, 0.2 for an IQR increment in third-trimester PM2.5). Conclusions: In our study population of normal healthy pregnancies, third-trimester exposure to PM2.5 air pollution was associated with differences in fetal thyroid hormone levels that may contribute to reduced birth weight. Additional research is needed to confirm our findings in other populations and to evaluate potential consequences later in life. Citation: Janssen BG, Saenen ND, Roels HA, Madhloum N, Gyselaers W, Lefebvre W, Penders J, Vanpoucke C, Vrijens K, Nawrot TS. 2017. Fetal thyroid function, birth weight, and in utero exposure to fine particle air pollution: a birth cohort study. Environ Health Perspect 125:699–705; http://dx.doi.org/10.1289/EHP508 PMID:27623605

Does rat fetal DNA induce preeclampsia in pregnant rats?

PubMed

Konečná, B; Borbélyová, V; Celec, P; Vlková, B

2015-02-01

Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is unclear whether it is the cause or the consequence of the disease. The aim of this study was to prove whether injected rat fetal DNA induces preeclampsia-like symptoms in pregnant Wistar rats. They received daily i.p. injections of water or rat fetal DNA (400 μg) from gestation day 14 to 18. Blood pressure, proteinuria, placental and fetal weight were measured at gestation day 19. Plasma DNase activity, proteinuria and creatinine clearance were assessed. There was no significant difference in any of the measured parameters. The results of this study do not confirm the hypothesis that fetal DNA might induce preeclampsia. This is in contrast to others using human fetal DNA in mice. Further studies should be focused on the effects of fetal DNA from the same species protected from DNase activity.

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

Acidic electrolyzed water efficiently improves the flavour of persimmon (Diospyros kaki L. cv. Mopan) wine.

PubMed

Zhu, Wanqi; Zhu, Baoqing; Li, Yao; Zhang, Yanyan; Zhang, Bolin; Fan, Junfeng

2016-04-15

The ability of acidic (AcW) and alkaline electrolyzed waters (AlW) to improve the flavour of persimmon (Diospyros kaki L.) wine was evaluated. Wines made with AcW (WAcW) were significantly better than wines made with AlW or pure water (PW) in aroma, taste, and colour. Volatile analysis showed that WAcW has high alcohol and ester contents, including 2-phenylethanol, isopentanol, isobutanol, ethyl dodecanoate, phenethyl acetate, and butanedioic acid diethyl ester. The total amino acid content of persimmon slurry soaked with AcW reached 531.2 mg/l, which was much higher than those of the slurries soaked in AlW (381.3 mg/l) and PW (182.7 mg/l). The composition of major amino acids in the AcW-soaked slurry may contribute to the strong ester flavour of WAcW. This is the first report to suggest that electrolyzed functional water (EFW) can be used to improve wine flavour, leading to the possible use of EFW in food processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Magnesium sulfate versus esomeprazole impact on the neonates of preeclamptic rats.

PubMed

Shafik, Amani N; Khattab, Mahmoud A; Osman, Ahmed H

2018-06-01

Preeclampsia represents a major complication of pregnancy, associated with greater maternal and fetal complications. We compared the effects of esomeprazole (a proton pump inhibitor) and magnesium sulfate (MgSO4) on the deleterious effects observed on the mother and neonates in experimentally induced preeclampsia in rats. Preeclampsia was induced in pregnant rats with NG-nitro-l-arginine methyl ester (L-NAME) starting from day 10-till end of pregnancy. Pregnant rats were divided into four groups: control pregnant; untreated preeclampsia; preeclamptic rats treated with MgSO4 and preeclamptic treated with esomeprazole. Treatment was started on day 14 and continued until end of pregnancy. Systolic blood pressure, gestation duration, the total number of pups/fetal resorption, pups birth weight, and histopathology examination of the pup's organs were recorded. In comparison with the L-NAME group, the MgSO4 and esomeprazole treatment reduced the values of systolic blood pressure; MgSO4 normalized gestational duration while esomeprazole prolonged it (post-term pregnancy); both restored number of delivered pups; with no statistical differences between the numbers of died pups between the four groups studied while with esomeprazole, out of 10 pregnant females, 2 of them had complete intrauterine fetal resorption; esomeprazole normalized birth weight and histological structure of fetal liver, kidney, and brain. On the other side, MgSO4 treatment gave rise to lower than normal birth weight and minimal tissue damage. Esomeprazole and MgSO4 improved systolic blood pressure, prevented preterm labor and restored numbers of pups delivered and fetal weight. Esomeprazole prolonged gestational period post-term with subsequent improving reproductive outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

[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 with fetal weight, respectively. The isomers of phosphorylated IGFBP-1 in cord sera are separated by anion ion exchange chromatography in which one nonphosphorylated and four phosphorylated IGFBP-1 are detected. In pared blood samples from mid-term delivery, percentage of nonphosphorylated IGFBP-1 is higher in fetal blood compared to those in mother. Similarly, percentage of nonphosphorylated IGFBP-1 is elevated in AFD infants than is SFD infants from term delivery. Thus, the proportion of nonphosphorylated and phosphorylated isomers of IGFBP-1 varies corresponding to fetal growth.(ABSTRACT TRUNCATED AT 400 WORDS)

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women.

PubMed

Ardawi, Mohammed-Salleh M; Nasrat, Hasan A; Rouzi, Abdulrahim A; Qari, Mohammed H; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2007-04-01

To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined. Copyright (c) 2007 John Wiley & Sons, Ltd.

77 FR 75561 - Quinclorac; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

..., subgroup 13- 07 H and rhubarb. Interregional Research Project Number 4 (IR-4) requested these tolerances.... There was no increased qualitative or quantitative fetal or offspring susceptibility in the prenatal... resorptions, post-implantation loss, decreased number of live fetuses, and reduced fetal body weight. These...

In utero exposure to venlafaxine, a serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat.

PubMed

Laurent, Laetitia; Huang, Chunwei; Ernest, Sheila R; Berard, Anick; Vaillancourt, Cathy; Hales, Barbara F

2016-12-01

Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT 2B /Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044-1055, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neo-liberal economic practices and population health: a cross-national analysis, 1980-2004.

PubMed

Tracy, Melissa; Kruk, Margaret E; Harper, Christine; Galea, Sandro

2010-04-01

Although there has been substantial debate and research concerning the economic impact of neo-liberal practices, there is a paucity of research about the potential relation between neo-liberal economic practices and population health. We assessed the extent to which neo-liberal policies and practices are associated with population health at the national level. We collected data on 119 countries between 1980 and 2004. We measured neo-liberalism using the Fraser Institute's Economic Freedom of the World (EFW) Index, which gives an overall score as well as a score for each of five different aspects of neo-liberal economic practices: (1) size of government, (2) legal structure and security of property rights, (3) access to sound money, (4) freedom to exchange with foreigners and (5) regulation of credit, labor and business. Our measure of population health was under-five mortality. We controlled for potential mediators (income distribution, social capital and openness of political institutions) and confounders (female literacy, total population, rural population, fertility, gross domestic product per capita and time period). In longitudinal multivariable analyses, we found that the EFW index did not have an effect on child mortality but that two of its components: improved security of property rights and access to sound money were associated with lower under-five mortality (p = 0.017 and p = 0.024, respectively). When stratifying the countries by level of income, less regulation of credit, labor and business was associated with lower under-five mortality in high-income countries (p = 0.001). None of the EFW components were significantly associated with under-five mortality in low-income countries. This analysis suggests that the concept of 'neo-liberalism' is not a monolithic entity in its relation to health and that some 'neo-liberal' policies are consistent with improved population health. Further work is needed to corroborate or refute these findings.

Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

PubMed

Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

2014-11-01

Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

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

Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice.

PubMed

Hong, Fashui; Zhou, Yingjun; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling

2017-01-01

Although nanoscale titanium dioxide (nano-TiO 2 ) has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO 2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO 2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO 2 -exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown-rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO 2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO 2 can cross the blood-fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in both calcium and zinc in maternal serum and the fetus, and both the placenta and embryos may be major targets of developmental toxicity following maternal exposure to nano-TiO 2 during the prenatal period. Therefore, the application of nano-TiO 2 should be carried out with caution.

Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice

PubMed Central

Hong, Fashui; Zhou, Yingjun; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling

2017-01-01

Although nanoscale titanium dioxide (nano-TiO2) has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO2-exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown–rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO2 can cross the blood–fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in both calcium and zinc in maternal serum and the fetus, and both the placenta and embryos may be major targets of developmental toxicity following maternal exposure to nano-TiO2 during the prenatal period. Therefore, the application of nano-TiO2 should be carried out with caution. PMID:28883729

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.

Maternal and paternal genomes differentially affect myofibre characteristics and muscle weights of bovine fetuses at midgestation.

PubMed

Xiang, Ruidong; Ghanipoor-Samami, Mani; Johns, William H; Eindorf, Tanja; Rutley, David L; Kruk, Zbigniew A; Fitzsimmons, Carolyn J; Thomsen, Dana A; Roberts, Claire T; Burns, Brian M; Anderson, Gail I; Greenwood, Paul L; Hiendleder, Stefan

2013-01-01

Postnatal myofibre characteristics and muscle mass are largely determined during fetal development and may be significantly affected by epigenetic parent-of-origin effects. However, data on such effects in prenatal muscle development that could help understand unexplained variation in postnatal muscle traits are lacking. In a bovine model we studied effects of distinct maternal and paternal genomes, fetal sex, and non-genetic maternal effects on fetal myofibre characteristics and muscle mass. Data from 73 fetuses (Day153, 54% term) of four genetic groups with purebred and reciprocal cross Angus and Brahman genetics were analyzed using general linear models. Parental genomes explained the greatest proportion of variation in myofibre size of Musculus semitendinosus (80-96%) and in absolute and relative weights of M. supraspinatus, M. longissimus dorsi, M. quadriceps femoris and M. semimembranosus (82-89% and 56-93%, respectively). Paternal genome in interaction with maternal genome (P<0.05) explained most genetic variation in cross sectional area (CSA) of fast myotubes (68%), while maternal genome alone explained most genetic variation in CSA of fast myofibres (93%, P<0.01). Furthermore, maternal genome independently (M. semimembranosus, 88%, P<0.0001) or in combination (M. supraspinatus, 82%; M. longissimus dorsi, 93%; M. quadriceps femoris, 86%) with nested maternal weight effect (5-6%, P<0.05), was the predominant source of variation for absolute muscle weights. Effects of paternal genome on muscle mass decreased from thoracic to pelvic limb and accounted for all (M. supraspinatus, 97%, P<0.0001) or most (M. longissimus dorsi, 69%, P<0.0001; M. quadriceps femoris, 54%, P<0.001) genetic variation in relative weights. An interaction between maternal and paternal genomes (P<0.01) and effects of maternal weight (P<0.05) on expression of H19, a master regulator of an imprinted gene network, and negative correlations between H19 expression and fetal muscle mass (P<0.001), suggested imprinted genes and miRNA interference as mechanisms for differential effects of maternal and paternal genomes on fetal muscle.

Maternal and Paternal Genomes Differentially Affect Myofibre Characteristics and Muscle Weights of Bovine Fetuses at Midgestation

PubMed Central

Xiang, Ruidong; Ghanipoor-Samami, Mani; Johns, William H.; Eindorf, Tanja; Rutley, David L.; Kruk, Zbigniew A.; Fitzsimmons, Carolyn J.; Thomsen, Dana A.; Roberts, Claire T.; Burns, Brian M.; Anderson, Gail I.; Greenwood, Paul L.; Hiendleder, Stefan

2013-01-01

Postnatal myofibre characteristics and muscle mass are largely determined during fetal development and may be significantly affected by epigenetic parent-of-origin effects. However, data on such effects in prenatal muscle development that could help understand unexplained variation in postnatal muscle traits are lacking. In a bovine model we studied effects of distinct maternal and paternal genomes, fetal sex, and non-genetic maternal effects on fetal myofibre characteristics and muscle mass. Data from 73 fetuses (Day153, 54% term) of four genetic groups with purebred and reciprocal cross Angus and Brahman genetics were analyzed using general linear models. Parental genomes explained the greatest proportion of variation in myofibre size of Musculus semitendinosus (80–96%) and in absolute and relative weights of M. supraspinatus, M. longissimus dorsi, M. quadriceps femoris and M. semimembranosus (82–89% and 56–93%, respectively). Paternal genome in interaction with maternal genome (P<0.05) explained most genetic variation in cross sectional area (CSA) of fast myotubes (68%), while maternal genome alone explained most genetic variation in CSA of fast myofibres (93%, P<0.01). Furthermore, maternal genome independently (M. semimembranosus, 88%, P<0.0001) or in combination (M. supraspinatus, 82%; M. longissimus dorsi, 93%; M. quadriceps femoris, 86%) with nested maternal weight effect (5–6%, P<0.05), was the predominant source of variation for absolute muscle weights. Effects of paternal genome on muscle mass decreased from thoracic to pelvic limb and accounted for all (M. supraspinatus, 97%, P<0.0001) or most (M. longissimus dorsi, 69%, P<0.0001; M. quadriceps femoris, 54%, P<0.001) genetic variation in relative weights. An interaction between maternal and paternal genomes (P<0.01) and effects of maternal weight (P<0.05) on expression of H19, a master regulator of an imprinted gene network, and negative correlations between H19 expression and fetal muscle mass (P<0.001), suggested imprinted genes and miRNA interference as mechanisms for differential effects of maternal and paternal genomes on fetal muscle. PMID:23341941

Fetal Thyroid Function, Birth Weight, and in Utero Exposure to Fine Particle Air Pollution: A Birth Cohort Study.

PubMed

Janssen, Bram G; Saenen, Nelly D; Roels, Harry A; Madhloum, Narjes; Gyselaers, Wilfried; Lefebvre, Wouter; Penders, Joris; Vanpoucke, Charlotte; Vrijens, Karen; Nawrot, Tim S

2017-04-01

Thyroid hormones are critical for fetal development and growth. Whether prenatal exposure to fine particle air pollution (≤ 2.5 μm; PM 2.5 ) affects fetal thyroid function and what the impact is on birth weight in normal healthy pregnancies have not been studied yet. We studied the impact of third-trimester PM 2.5 exposure on fetal and maternal thyroid hormones and their mediating role on birth weight. We measured the levels of free thyroid hormones (FT 3 , FT 4 ) and thyroid-stimulating hormone (TSH) in cord blood ( n = 499) and maternal blood ( n = 431) collected after delivery from mother-child pairs enrolled between February 2010 and June 2014 in the ENVIR ON AGE birth cohort with catchment area in the province of Limburg, Belgium. An interquartile range (IQR) increment (8.2 μg/m 3 ) in third-trimester PM 2.5 exposure was inversely associated with cord blood TSH levels (-11.6%; 95% CI: -21.8, -0.1) and the FT 4 /FT 3 ratio (-62.7%; 95% CI: -91.6, -33.8). A 10th-90th percentile decrease in cord blood FT 4 levels was associated with a 56 g decrease in mean birth weight (95% CI: -90, -23). Assuming causality, we estimated that cord blood FT 4 mediated 21% (-19 g; 95% CI: -37, -1) of the estimated effect of an IQR increment in third-trimester PM 2.5 exposure on birth weight. Third-trimester PM 2.5 exposure was inversely but not significantly associated with maternal blood FT 4 levels collected 1 day after delivery (-4.0%, 95% CI: -8.0, 0.2 for an IQR increment in third-trimester PM 2.5 ). In our study population of normal healthy pregnancies, third-trimester exposure to PM 2.5 air pollution was associated with differences in fetal thyroid hormone levels that may contribute to reduced birth weight. Additional research is needed to confirm our findings in other populations and to evaluate potential consequences later in life.

Fetal heart rate abnormalities during and after external cephalic version: Which fetuses are at risk and how are they delivered?

PubMed

Kuppens, Simone M; Smailbegovic, Ida; Houterman, Saskia; de Leeuw, Ingrid; Hasaart, Tom H

2017-10-17

Fetal heart rate abnormalities (FHR) during and after external cephalic version (ECV) are relatively frequent. They may raise concern about fetal wellbeing. Only occasionally they may lead to an emergency cesarean section. Prospective cohort study in 980 women (> 34 weeks gestation) with a singleton fetus in breech presentation. During and after external cephalic version (ECV) FHR abnormalities were recorded. Obstetric variables and delivery outcome were evaluated. Primary outcome was to identify which fetuses are at risk for FHR abnormalities. Secondary outcome was to identify a possible relationship between FHR abnormalities during and after ECV and mode of delivery and fetal distress during subsequent labor. The overall success rate of ECV was 60% and in 9% of the attempts there was an abnormal FHR pattern. In two cases FHR abnormalities after ECV led to an emergency CS. Estimated fetal weight per 100 g (OR 0.90, CI: 0.87-0.94) and longer duration of the ECV-procedure (OR 1.13, CI: 1.05-1.21) were factors significantly associated with the occurrence of FHR abnormalities. FHR abnormalities were not associated with the mode of delivery or the occurrence of fetal distress during subsequent labor. FHR abnormalities during and after ECV are more frequent with lower estimated fetal weight and longer duration of the procedure. FHR abnormalities during and after ECV have no consequences for subsequent mode of delivery. They do not predict whether fetal distress will occur during labor. The Eindhoven Breech Intervention Study, NCT00516555 . Date of registration: August 13, 2007.

External cephalic version for singleton breech presentation: proposal of a practical check-list for obstetricians.

PubMed

Indraccolo, U; Graziani, C; Di Iorio, R; Corona, G; Bonito, M; Indraccolo, S R

2015-07-01

External cephalic version (ECV) for breech presentation is not routinely performed by obstetricians in many clinical settings. The aim of this work is to assess to what extent the factors involved in performing ECV are relevant for the success and safety of ECV, in order to propose a practical check-list for assessing the feasibility of ECV. Review of 214 references. Factors involved in the success and risks of ECV (feasibility of ECV) were extracted and were scored in a semi-quantitative way according to textual information, type of publication, year of publication, number of cases. Simple conjoint analysis was used to describe the relevance found for each factor. Parity has the pivotal role in ECV feasibility (relevance 16.6%), followed by tocolysis (10.8%), gestational age (10.6%), amniotic fluid volume (4.7%), breech variety (1.9%), and placenta location (1.7%). Other factors with estimated relevance around 0 (regional anesthesia, station, estimated fetal weight, fetal position, obesity/BMI, fetal birth weight, duration of manoeuvre/number of attempts) have some role in the feasibility of ECV. Yet other factors, with negative values of estimated relevance, have even less importance. From a logical interpretation of the relevance of each factor assessed, ECV should be proposed with utmost prudence if a stringent check-list is followed. Such a check-list should take into account: parity, tocolytic therapy, gestational age, amniotic fluid volume, breech variety, placenta location, regional anesthesia, breech engagement, fetal well-being, uterine relaxation, fetal size, fetal position, fetal head grasping capability and fetal turning capability.

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

Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots.

PubMed

Long, N M; Rule, D C; Zhu, M J; Nathanielsz, P W; Ford, S P

2012-07-01

Maternal nutrient restriction leads to alteration in fetal adipose tissue, and offspring from obese mothers have an increased risk of developing obesity. We hypothesized that maternal obesity increases fetal adipogenesis. Multiparous ewes (Columbia/Rambouillet cross 3 to 5 yr of age) carrying twins were assigned to a diet of 100% (Control; CON; n = 4) or 150% (Obese; OB, n = 7) of NRC maintenance requirements from 60 d before conception until necropsy on d 135 of gestation. Maternal and fetal plasma were collected and stored at -80°C for glucose and hormone analyses. Fetal measurements were made at necropsy, and perirenal, pericardial, and subcutaneous adipose tissues were collected from 7 male twin fetuses per group and snap frozen at -80°C. Protein and mRNA expression of fatty acid translocase [cluster of differentiation (CD) 36], fatty acid transport proteins (FATP) 1 and 4, insulin-sensitive glucose transporter (GLUT-4), fatty acid synthase (FASN), and acetyl-coA carboxylase (ACC) was evaluated. Fetal weight was similar, but fetal carcass weight (FCW) was reduced (P < 0.05) in OB versus CON fetuses. Pericardial and perirenal adipose tissue weights were increased (P < 0.05) as a percentage of FCW in OB versus CON fetuses, as was subcutaneous fat thickness (P < 0.001). Average adipocyte diameter was greater (P < 0.01) in the perirenal fat and the pericardial fat (P = 0.06) in OB fetuses compared with CON fetuses. Maternal plasma showed no difference (P > 0.05) in glucose or other hormones, fetal plasma glucose was similar (P = 0.42), and cortisol, IGF-1, and thyroxine were reduced (P ≤ 0.05) in OB fetuses compared with CON fetuses. Protein and mRNA expression of CD 36, FATP 1 and 4, and GLUT-4 were increased (P ≤ 0.05) in all fetal adipose depots in OB versus CON fetuses. The mRNA expression of FASN and ACC was increased (P < 0.05) in OB vs. CON fetuses in all 3 fetal adipose tissue depots. Fatty acid concentrations were increased (P = 0.01) in the perirenal depot of OB versus CON fetuses, and specific fatty acid concentrations were altered (P < 0.05) in subcutaneous and pericardial adipose tissue because of maternal obesity. In conclusion, maternal obesity was associated with increased fetal adiposity, increased fatty acid and glucose transporters, and increased expression of enzymes mediating fatty acid biosynthesis in adipose depots. These alterations, if maintained into the postnatal period, could predispose the offspring to later obesity and metabolic disease.

Adverse perinatal outcomes in borderline amniotic fluid index.

PubMed

Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

2016-11-01

Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10 th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10 th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.

Leptin Promotes Fetal Lung Maturity and Upregulates SP-A Expression in Pulmonary Alveoli Type-II Epithelial Cells Involving TTF-1 Activation

PubMed Central

Huang, Hui; Wang, Zhen-Hua; Cheng, Rui; Cai, Wei-Bin

2013-01-01

The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR). Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP) A in type-II alveolar epithelial cells (AECs) in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1), a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent. PMID:23894445

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.

Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses.

PubMed

Songstad, Nils Thomas; Kaspersen, Knut-Helge Frostmo; Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

2015-01-01

To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85-90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.

Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

PubMed Central

Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

2015-01-01

Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

PubMed Central

Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

2015-01-01

Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

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

Di-isoheptyl Phthalate (DIHP) in utero exposure reduces testicular testosterone (T) production in fetal Sprague Dawley (SD) rats

EPA Science Inventory

Exposure to DIHP, a commercial phthalate ester plasticizer used in flooring manufacturing, during the fetal period of sexual differentiation disrupts male reproductive development resulting in reproductive malformations and reduced androgen-dependent reproductive tissue weights i...

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

Maternal high-fat diet is associated with impaired fetal lung development

PubMed Central

Mayor, Reina S.; Finch, Katelyn E.; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D.; Frank, Aaron P.; Hahner, Lisa D.; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F.; Rosenfeld, Charles R.; Savani, Rashmin C.

2015-01-01

Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development. PMID:26092997

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

Donor catch-up growth after laser surgery for twin-twin transfusion syndrome.

PubMed

Chmait, Ramen H; Chon, Andrew H; Schrager, Sheree M; Kontopoulos, Eftichia V; Quintero, Rubén A; Vanderbilt, Douglas L

2015-12-01

To assess fetal growth after laser surgery for TTTS at the time of prenatal diagnosis, birth, and at 2years of age. Growth data were collected from surviving children treated between 2007 and 2010 as part of a study to assess neurodevelopment at 24months (±6weeks) corrected age. Fetal weights were obtained via ultrasound using Hadlock's formula at the time of preoperative assessment for laser surgery. Birth weights were recorded by the staff at the delivering institutions. Weights at 2years corrected age were recorded at the time of neurodevelopmental testing. Weights were converted into percentiles according to standard growth curves. Growth restriction was defined as <10th percentile for given age. Multilevel latent growth curve models in Mplus (twins nested in families) examined weight change over time as a function of donor status, and repeated measures ANOVA was utilized to assess in donor-recipient weight discordance over time for twin pairs. 99 of 206 children (56 of 130 families) were studied. There were no differences between enrolled and non-enrolled patients in donor/recipient status and survival rates, fetal demise, intrauterine growth restriction, Quintero stage, and gestational age of surgery or delivery. 48.5% were donors. The median fetal, birth, and 2-year weights for all twins were 288g, 1.9kg, and 11.8kg, respectively, and the overall prevalence of growth restriction was 28%, 22%, and 3%, respectively. Growth restriction rates at prenatal diagnosis were 56% in donors vs. 2% in recipients (OR=64.3, p<0.001); at birth, 35% vs. 10% (OR=5.0, p<0.01); and at 2years, 6% vs. 0%. Donors showed significant gains in weight percentile (B=13.1, p<0.001) and a significant decrease in growth restriction rates over time (B=-1.6, p<0.001). Weight discordance between donor and recipient pairs also significantly decreased over time (linear F(1,42)=54.34, p<0.001). After laser surgery for TTTS, donor twins exhibit significant catch-up growth by two years of age. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Sibutramine effects on the reproductive performance of pregnant overweight and non-overweight rats.

PubMed

Francia-Farje, Luis Alberto Domingo; Silva, Denise Salioni; Volpato, Gustavo Tadeu; Fernandes, Glaura Scantamburlo Alves; Carnietto, Nilson; Cicogna, Antonio Carlos; Kempinas, Wilma De Grava

2010-01-01

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. On d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

Di(n)butyl phthalate reduces testicular weight, testosterone and associated gene expression in fetal Harlan Sprague Dawley rats.

EPA Science Inventory

Certain phthalate esters (PE) cause reproductive malformations in male rats when exposure occurs during sexual differentiation in utero. Reductions in fetal testosterone levels are causally linked to the induction of these malformations. While reproductive development studies on ...

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 weight at birth. PM10 exposure was positively associated with preterm birth and SGA. PMID:22222601

Body weight lower limits of fetal postmortem MRI at 1.5 T.

PubMed

Jawad, N; Sebire, N J; Wade, A; Taylor, A M; Chitty, L S; Arthurs, O J

2016-07-01

To evaluate the diagnostic yield of postmortem magnetic resonance imaging (PM-MRI) compared with conventional autopsy in fetuses of early gestational age and low body weight. Fetuses of < 31 weeks' gestation that underwent 1.5-T PM-MRI and conventional autopsy were included. The findings of PM-MRI and conventional autopsy were reported blinded to each other. The reports of conventional autopsy and PM-MRI for each organ system (cardiovascular, neurological, abdominal, non-cardiac thoracic and musculoskeletal) were classified as either diagnostic or non-diagnostic. The likelihood of a non-diagnostic examination by PM-MRI was calculated according to fetal gestational age and body weight. Full datasets were examined of 204 fetuses, with mean gestational age of 20.95 ± 3.82 weeks (range, 12.0-30.7 weeks) and body-weight range of 15.9-1872 g. Body weight was the most significant predictor of diagnostic yield of PM-MRI. There was 95% confidence that 90% of fetuses will show diagnostic images by PM-MRI for all five organ systems when fetal body weight is ≥ 535 g, but < 50% of fetuses will have all five systems diagnostic on PM-MRI when body weight is < 122 g. PM-MRI is highly likely to provide adequate diagnostic images for fetuses with a body weight > 500 g. Below this weight, the diagnostic yield of standard 1.5-T PM-MRI decreases significantly. These data should help inform parents and clinicians on the suitability of performing PM-MRI in fetuses with low body weight. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

PubMed Central

Saal, Frederick S. vom; Timms, Barry G.; Montano, Monica M.; Palanza, Paola; Thayer, Kristina A.; Nagel, Susan C.; Dhar, Minati D.; Ganjam, V. K.; Parmigiani, Stefano; Welshons, Wade V.

1997-01-01

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship. PMID:9050904

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.

Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA’s ToxRefDB

EPA Science Inventory

As the primary source for regulatory developmental toxicity information, prenatal studies characterize maternal effects and fetal endpoints including malformations, resorptions, and fetal weight reduction. Results from 383 rat and 368 rabbit prenatal studies on 387 chemicals, mo...

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.

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

The Epigenetic Effects of a High Prenatal Folate Intake in Male Mouse Fetuses Exposed In Utero to Arsenic

PubMed Central

Tsang, Verne; Fry, Rebecca C.; Niculescu, Mihai D.; Rager, Julia E.; Saunders, Jesse; Paul, David S.; Zeisel, Steven H.; Waalkes, Michael P.; Stýblo, Miroslav; Drobná, Zuzana

2012-01-01

Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous studies have demonstrated that in utero exposure to iAs promotes cancer in adult mouse offspring, possibly acting through epigenetic mechanisms. Humans and rodents enzymatically convert iAs to its methylated metabolites. This reaction requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required for DNA methylation. Supplementation with folate, a major dietary source of methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the adverse effects of iAs exposure. However, effects of gestational folate supplementation on iAs metabolism and fetal DNA methylation have never been thoroughly examined. In the present study, pregnant CD1 mice were fed control (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite) from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18 fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in fetal livers. High folate intake lowered the burden of total arsenic in maternal livers but did not prevent the effects of iAs exposure on fetal weight or hepatic SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further significant body weight reduction. Notably, iAs exposure alone had little effect on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure changed the CpG island methylation in 2,931 genes, including genes known to be imprinted. Most of these genes were associated with neurodevelopment, cancer, cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which regulates fetal development, was among the most affected biological pathways. Taken together, our results suggest that a combined in utero exposure to iAs and a high folate intake may adversely influence DNA methylation profiles and weight of fetuses, compromising fetal development and possibly increasing the risk for early-onset of disease in offspring. PMID:22959928

Dynamic energy-balance model predicting gestational weight gain

USDA-ARS?s Scientific Manuscript database

Gestational weight gains (GWGs) that exceed the 2009 Institute of Medicine recommended ranges increase risk of long-term postpartum weight retention; conversely, GWGs within the recommended ranges are more likely to result in positive maternal and fetal outcomes. Despite this evidence, recent epide...

Placental Weight Mediates the Effects of Prenatal Factors on Fetal Growth: the Extent Differs by Preterm Status

PubMed Central

Ouyang, Fengxiu; Parker, Margaret; Cerda, Sandra; Pearson, Colleen; Fu, Lingling; Gillman, Matthew W.; Zuckerman, Barry; Wang, Xiaobin

2012-01-01

Elevated pre-pregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre-pregnancy BMI, GWG, and GDM with birthweight-for-gestational age, and whether the relationships differ by preterm status. We examined 1035 mother-infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status. We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. 41% were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking and stress during pregnancy, birthweight-for-gestational age z-score was 0.55 (0.30, 0.80) units higher for pre-pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre-pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre-pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birthweight-for-gestational age z-score, but pre-pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM. These results suggest that placental weight partially mediates the effects of pre-pregnancy obesity, GDM and excessive GWG on fetal growth among term infants. PMID:23592670

Deleterious effects of polynuclear aromatic hydrocarbon on blood vascular system of the rat fetus.

PubMed

Sanyal, Mrinal K; Li, You-Lan

2007-10-01

Polynuclear aromatic hydrocarbons (PAH), benzo[alpha]pyrene (B[alpha]P) and 7,12-dimethylbenz[alpha]anthracene (DMBA) are toxic environmental agents distributed widely. The relative deleterious effects of these agents on growth and blood vasculature of fetus and placental tissues of the rat were studied. Pregnant rats (Day 1 sperm positive) with implantation sites confirmed by laparotomy were treated intraperitoneally (i.p.) on Pregnancy Days 10, 12, and 14 with these agents dissolved in corn oil at cumulated total doses 50, 100, and 200 mg/kg/rat, and control with corn oil only (3-20 dams/group). Fetal growth, tissue hemorrhage, and placental pathology were evaluated by different parameters on Pregnancy Day (PD) 20 in treated and control rats. DMBA was relatively more deleterious compared to B[alpha]P indicated by increased lethality and progressive reduction of body weight of the mother with increasing doses. At 200 mg/kg/rat doses of these agents, maternal survival was 45% and 100% and body weight reduced 24% and 52% of controls, respectively. The fetal survival rates in live mothers were similar to that of controls. They induced marked fetal growth retardation and necrosis of placental tissues. B[alpha]P and DMBA produced significant toxicity to differentiating fetal blood vascular system as exhibited by rupture of blood vessels and hemorrhage, especially in the skin, cranial, and brain tissues. Maternal PAH exposure induced placental toxicity and associated adverse fetal development and hemorrhage in different parts of the fetal body, in particular, marked intradermal and cranial hemorrhage, showing that developing fetal blood vasculature is a target of PAH toxicity.

Transplacental Passage of Acetaminophen in Term Pregnancy.

PubMed

Nitsche, Joshua F; Patil, Avinash S; Langman, Loralie J; Penn, Hannah J; Derleth, Douglas; Watson, William J; Brost, Brian C

2017-05-01

Objective  The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose. Study Design  After obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated. Results  In this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal ( T 1/2 , 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [V d /F], 57.5 L) and fetal compartments ( T 1/2 , 82 minutes; Cl/F, 31.2 L/h; V d /F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated ( p  < 0.0001). Conclusion  Fetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

PubMed Central

Feng, Xiaodi; Wood, Charles E.; Richards, Elaine; Anthony, Russell V.; Dahl, Geoffrey E.; Tao, Sha

2014-01-01

In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg−1·day−1) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes. PMID:24920731

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 response to pressure overload.

Bilateral periventricular nodular heterotopia (BPNH) detected on fetal and maternal MRI, caused by a novel Filamin A mutation.

PubMed

Stoecklein, S; Haberler, C; Gruber, G; Diogo, M; Ulm, B; Laccone, F A; Prayer, D

2017-12-20

We present the case of a 31-year-old, neurologically unremarkable woman who underwent fetal MRI for evaluation of suspected corpus callosum agenesis at 23+0 gestational weeks (GW). On fetal MRI, the corpus callosum appeared thin, but all portions could be clearly delineated (Fig. 1A). However, T2-weighted images revealed subependymal heterotopia and a megacisterna magna (Fig. 1B). This article is protected by copyright. All rights reserved.

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

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% CI: -306.1, -34.7) lower birth weight, among girls with mothers in the lowest education group. Our findings suggest that prenatal exposure to PCBs is inversely associated with daughters' birth weight and that mothers' education, which is a possible marker for socioeconomic status, significantly modified the association between maternal PCB concentrations and birth weight in female newborns. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spacecraft surface charging within geosynchronous orbit observed by the Van Allen Probes

DOE PAGES

Sarno-Smith, Lois K.; Larsen, Brian A.; Skoug, Ruth M.; ...

2016-02-27

Using the Helium Oxygen Proton Electron (HOPE) and Electric Field and Waves (EFW) instruments from the Van Allen Probes, we explored the relationship between electron energy fluxes in the eV and keV ranges and spacecraft surface charging. We present statistical results on spacecraft charging within geosynchronous orbit by L and MLT. An algorithm to extract the H+ charging line in the HOPE instrument data was developed to better explore intense charging events. Also, this study explored how spacecraft potential relates to electron number density, electron pressure, electron temperature, thermal electron current, and low-energy ion density between 1 and 210 eV.more » It is demonstrated that it is imperative to use both EFW potential measurements and the HOPE instrument ion charging line for examining times of extreme spacecraft charging of the Van Allen Probes. The results of this study show that elevated electron energy fluxes and high-electron pressures are present during times of spacecraft charging but these same conditions may also occur during noncharging times. Furthermore, we also show noneclipse significant negative charging events on the Van Allen Probes.« less

EFFECTS ON BIRTH WEIGHT AND ADULT HEALTH IN RATS PRENATALLY EXPOSED TO TOXICANTS OR UNDERNUTRITION

EPA Science Inventory

Low fetal weight is a sensitive indicator of developmental toxicity in animal studies. While low birth weight may be permanent or transitory, the long-term effects of low birth weight on adult health have not been elucidated. Previous research has shown in humans an inverse rela...

Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wlodarczyk, Bogdan J., E-mail: bwlodarczyk@austin.utexas.edu; Zhu, Huiping; Finnell, Richard H.

Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr{sup +/−} × Mthfr{sup +/−} matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from amore » background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr{sup +/+} × Mthfr{sup +/−}, Mthfr{sup +/−} × Mthfr{sup +/−} and Mthfr{sup −/−} × {sup Mthfr+/−}) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype contributes to the sensitivity of As embryotoxicity. • Fetal Mthfr genotype does not affect the reproductive outcome after As exposure.« less

Periconceptional undernutrition and being a twin each alter kidney development in the sheep fetus during early gestation.

PubMed

MacLaughlin, Severence M; Walker, Simon K; Kleemann, David O; Tosh, Darran N; McMillen, I Caroline

2010-03-01

Adaptive growth responses of the embryo and fetus to nutritional restraint are important in ensuring early survival, but they are implicated in the programming of hypertension. It has been demonstrated that kidney growth and nephrogenesis are each regulated by intrarenal factors, including the insulin-like growth factors, glucocorticoids, and the renin-angiotensin system. Therefore, we have investigated the impact of periconceptional undernutrition (PCUN; from approximately 6 wk before to 7 days after conception) in singleton (control, n = 18; PCUN, n = 16) and twin pregnancies (control, n = 6; PCUN, n = 5) on the renal mRNA expression of 11beta- hydroxysteroid dehydrogensase type 1 and type 2 (11beta-HSD-1 and -2), the glucocorticoid (GR), and mineralocorticoid receptors, angiotensinogen, angiotensin receptor type 1 (AT1R) and 2 (AT2R), IGF-1 and IGF-2, and IGF1R and IGF2R at approximately 55 days gestation. There was no effect of PCUN or fetal number on fetal weight on relative kidney weight at approximately day 55 of gestation. There was an inverse relationship between the relative weight of the fetal kidney at approximately day 55 and maternal weight loss during the periconceptional period in fetuses exposed to PCUN. Exposure to PCUN resulted in a higher expression of IGF1 in the fetal kidney in singleton and twin pregnancies. Being a twin resulted in higher intrarenal expression of IGF-1 and IGF-2, GR, angiotensinogen, AT1R, and AT2R mRNA at 55 days gestation. Renal 11beta-HSD-2 mRNA expression was higher in PCUN singletons, but not PCUN twins, compared with controls. Thus, there may be an adaptive response in the kidney to the early environment of a twin pregnancy, which precedes the fetal growth restriction that occurs later in pregnancy. The kidney of the twin fetus exposed to periconceptional undernutrition may also be less protected from the consequences of glucocorticoid exposure.

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

PubMed Central

Sari, Youssef; Chiba, Tomohiro; Yamada, Marina; Rebec, George V.; Aiso, Sadakazu

2009-01-01

Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ALC combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TUNEL staining, caspase-3 colorimetric assay, ELISA, and MSD electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c. Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies. PMID:19782727

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

An Evidence-Based Approach to Defining Fetal Macrosomia.

PubMed

Froehlich, Rosemary; Simhan, Hyagriv N; Larkin, Jacob C

2016-04-01

This study aims to determine the risk of adverse outcomes associated with the current diagnostic criteria for fetal macrosomia. Study We evaluated three techniques for characterizing birth weight as a predictor of shoulder dystocia or third- or fourth-degree laceration in 79,879 vaginal deliveries. First, we compared deliveries with birth weights above or below 4,500 g. We then performed logistic regression using birth weight as a continuous predictor, both with and without fractional polynomial transformation. Finally, we calculated the number of cesarean sections required to prevent one incident of the interrogated outcomes (number needed to treat [NNT]). Rates of adverse intrapartum outcomes increase incrementally with increasing birth weight and are predicted most accurately with logistic regression following fractional polynomial transformation. The NNT for third- or fourth-degree laceration dropped from 14.3 (95% confidence interval [CI], 13.9-14.7) at a birth weight of 3,500 g to 6.4 (95% CI, 6.1-6.8) at 4,500 g and, for shoulder dystocia, from 54.9 (95% CI, 51.5-58.6) at 3,500 g to 5.6 (95% CI, 5.2-6.0) at 4,500 g. The conventional distinction between "normal" and "macrosomic" does not reflect the incremental effect of increasing birth weight on the risk of obstetric morbidity. Outcomes analysis can inform fetal growth standards to better reflect relevant thresholds of risk. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Transplacental effects of bemithyl].

PubMed

Bugaeva, L I; Denisova, T D; Spasov, A A

2007-01-01

The daily administration of bemithyl (20 mg/kg) from 6 th to 16 th day of pregnancy in female rats led to the decrease in fetal death after the implantation and increased fetal body weight. The treatment of pregnant rats also led to acceleration of the development of physical condition and sensomotor reflexes of progeny in the postnatal period.

Fetal programming of infant neuromotor development: the generation R study.

PubMed

van Batenburg-Eddes, Tamara; de Groot, Laila; Steegers, Eric A P; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning

2010-02-01

The objective of the study was to examine whether infant neuromotor development is determined by fetal size and body symmetry in the general population. This study was embedded within the Generation R Study, a population-based cohort in Rotterdam. In 2965 fetuses, growth parameters were measured in mid-pregnancy and late pregnancy. After birth, at age 9 to 15 wks, neuromotor development was assessed with an adapted version of Touwen's Neurodevelopmental Examination. Less optimal neuromotor development was defined as a score in the highest tertile. We found that higher fetal weight was beneficial to infant neurodevelopment. A fetus with a 1-SD score higher weight in mid-pregnancy had an 11% lower risk of less optimal neuromotor development (OR: 0.89; 95% CI: 0.82-0.97). Similarly, a fetus with a 1-SD score larger abdominal-to-head circumference (AC/HC) ratio had a 13% lower risk of less optimal neuromotor development (OR: 0.87; 95% CI: 0.79-0.96). These associations were also present in late pregnancy. Our findings show that fetal size and body symmetry in pregnancy are associated with infant neuromotor development. These results suggest that differences in infant neuromotor development, a marker of behavioral and cognitive problems, are at least partly caused by processes occurring early in fetal life.

Tumor-homing peptides as tools for targeted delivery of payloads to the placenta

PubMed Central

King, Anna; Ndifon, Cornelia; Lui, Sylvia; Widdows, Kate; Kotamraju, Venkata R.; Agemy, Lilach; Teesalu, Tambet; Glazier, Jocelyn D.; Cellesi, Francesco; Tirelli, Nicola; Aplin, John D.; Ruoslahti, Erkki; Harris, Lynda K.

2016-01-01

The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics. PMID:27386551

Maternal di-(2-ethylhexyl) phthalate exposure during pregnancy causes fetal growth restriction in a stage-specific but gender-independent manner.

PubMed

Shen, Ru; Zhao, Ling-Li; Yu, Zhen; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang

2017-01-01

Di (2-ethylhexyl) phthalate (DEHP) is male developmental toxicant that impairs testis development with reduced anogenital distance. The present study aimed to investigate whether maternal DEHP exposure during pregnancy causes intrauterine growth restriction (IUGR) in a gender-specific manner and to identify the critical window of DEHP-induced fetal IUGR. Pregnant mice were administered with DEHP (0, 50 or 200mg/kg) by gavage. Fetal IUGR was observed not only in males but also in females when litters were exposed to DEHP on gestational day (GD)0-GD17. Interestingly, fetal weight and crown-rump length were reduced, markedly in dams with DEHP on GD13-GD17, slightly in dams with on GD7-GD12, but not in dams with on GD0-GD6. Further analysis showed that maternal DEHP exposure on GD7-GD12 inhibited cell proliferation, lowered placental weight, and reduced blood sinusoid area in placental labyrinth layer. These results suggest that maternal DEHP exposure induces IUGR in a stage-specific but gender-independent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Fetal size in mid- and late pregnancy is related to infant alertness: the generation R study.

PubMed

Henrichs, Jens; Schenk, Jacqueline J; Schmidt, Henk G; Arends, Lidia R; Steegers, Eric A P; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning

2009-03-01

The vulnerability for behavioral problems is partly shaped in fetal life. Numerous studies have related indicators of intrauterine growth, for example, birth weight and body size, to behavioral development. We investigated whether fetal size in mid- and late pregnancy is related to infant irritability and alertness. In a population-based birth cohort of 4,255 singleton full-term infants ultrasound measurements of fetal head and abdominal circumference in mid- and late pregnancy were performed. Infant irritability and alertness scores were obtained by the Mother and Baby Scales at 3 months and z-standardized. Multiple linear regression analyses revealed curvilinear associations (inverted J-shape) of measures of fetal size in both mid- and late pregnancy with infant alertness. Fetal size characteristics were not associated with infant irritability. These results suggest that alterations of intrauterine growth affecting infant alertness are already detectable from mid-pregnancy onwards.

Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.

PubMed

Zhang, Qianqian; Ye, Xiangfeng; Wang, Lingzhi; Peng, Bangjie; Zhang, Yingxue; Bao, Jie; Li, Wanfang; Wei, Jinfeng; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

2016-02-01

The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex-specific differences in fetal growth in newborns exposed prenatally to traffic-related air pollution in the PELAGIE mother-child cohort (Brittany, France).

PubMed

Bertin, Mélanie; Chevrier, Cécile; Serrano, Tania; Monfort, Christine; Cordier, Sylvaine; Viel, Jean-François

2015-10-01

Numerous studies have linked prenatal traffic-related air pollution exposure to fetal growth. Recently, several studies have suggested exploring this association independently among boys and girls because of potential sex-specific biological vulnerability to air pollution. Residence-based factors can also influence fetal growth by enhancing susceptibility to the toxic effects of air pollution and must also be considered in these relations. We examined sex-specific associations between prenatal air pollution exposure and fetal growth and explored whether they differed by the urban-rural status of maternal residence. This study relied on the PELAGIE mother-child cohort (2521 women, Brittany, France, 2002-2006). Fetal growth was assessed through birth weight, head circumference and small weight (SGA) and small head circumference (SHC) for gestational age. Nitrogen dioxide (NO2) concentrations at mothers' homes were estimated by using a land use regression model taking into account temporal variation during pregnancy. Associations between estimated NO2 concentrations and fetal growth were assessed with linear regression or logistic regression models, depending on the outcome investigated. An interquartile range (8.8 µg m(-3)) increase in NO2 exposure estimates was associated with a 27.4 g (95% CI 0.8 to 55.6) increase in birth weight and a 0.09 cm (95% CI 0.00-0.17) significant increase in head circumference, among newborn boys only. Their risks of SGA and SHC were reduced (OR 0.70, 95% CI 0.53-0.92, OR 0.76, 95% CI 0.56-1.03, respectively, for an increase of 8.8 µg m(-3)). No statistically significant trends were observed among girls. Urban-rural status modified the effect of air pollution only for SHC and again only for newborn boys. Findings from this study confirm the need to consider sex-specific associations between air pollution and fetal growth and to investigate possible mechanisms by which traffic-related air pollution may increase anthropometric parameters at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

Management of Pregnant Women with Type 2 Diabetes Mellitus and the Consequences of Fetal Programming in Their Offspring.

PubMed

Berry, Diane C; Boggess, Kim; Johnson, Quinetta B

2016-05-01

The obesity epidemic has fueled an epidemic of prediabetes and type 2 diabetes mellitus in women of childbearing age. This paper examines the state of the science on preconception and pregnancy management of women with type 2 diabetes to optimize outcomes for the women and their infants. In addition, the consequence of fetal programming as a result of suboptimal maternal glycemic control is discussed. The paper focuses on type 2 diabetes, not type 1 diabetes or gestational diabetes. Management of women with type 2 diabetes includes preconception counseling, preconception weight management and weight loss, proper weight gain during pregnancy, self-monitoring of blood glucose levels, medication, medical nutrition therapy, and exercise.

ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR.

PubMed

Wu, Yanming; Chen, Xiao; Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

2014-01-01

Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in intrauterine fetal death.

Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping.

PubMed

Yarnykh, V L; Prihod'ko, I Y; Savelov, A A; Korostyshevskaya, A M

2018-05-10

Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination. This prospective study included 41 pregnant women (gestational age range, 18-38 weeks) without abnormal findings on fetal brain MR imaging performed for clinical indications. A fast fetal brain macromolecular proton fraction mapping protocol was implemented on a clinical 1.5T MR imaging scanner without software modifications and was performed after a clinical examination with an additional scan time of <5 minutes. 3D macromolecular proton fraction maps were reconstructed from magnetization transfer-weighted, T1-weighted, and proton density-weighted images by the single-point method. Mean macromolecular proton fraction in the brain stem, cerebellum, and thalamus and frontal, temporal, and occipital WM was compared between structures and pregnancy trimesters using analysis of variance. Gestational age dependence of the macromolecular proton fraction was assessed using the Pearson correlation coefficient ( r ). The mean macromolecular proton fraction in the fetal brain structures varied between 2.3% and 4.3%, being 5-fold lower than macromolecular proton fraction in adult WM. The macromolecular proton fraction in the third trimester was higher compared with the second trimester in the brain stem, cerebellum, and thalamus. The highest macromolecular proton fraction was observed in the brain stem, followed by the thalamus, cerebellum, and cerebral WM. The macromolecular proton fraction in the brain stem, cerebellum, and thalamus strongly correlated with gestational age ( r = 0.88, 0.80, and 0.73; P < .001). No significant correlations were found for cerebral WM regions. Myelin is the main factor determining macromolecular proton fraction in brain tissues. Macromolecular proton fraction mapping is sensitive to the earliest stages of the fetal brain myelination and can be implemented in a clinical setting. © 2018 by American Journal of Neuroradiology.

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

The effect of customization and use of a fetal growth standard on the association between birthweight percentile and adverse perinatal outcome.

PubMed

Sovio, Ulla; Smith, Gordon C S

2018-02-01

It has been proposed that correction of offspring weight percentiles (customization) might improve the prediction of adverse pregnancy outcome; however, the approach is not accepted universally. A complication in the interpretation of the data is that the main method for calculation of customized percentiles uses a fetal growth standard, and multiple analyses have compared the results with birthweight-based standards. First, we aimed to determine whether women who deliver small-for-gestational-age infants using a customized standard differed from other women. Second, we aimed to compare the association between birthweight percentile and adverse outcome using 3 different methods for percentile calculation: (1) a noncustomized actual birthweight standard, (2) a noncustomized fetal growth standard, and (3) a fully customized fetal growth standard. We analyzed data from the Pregnancy Outcome Prediction study, a prospective cohort study of nulliparous women who delivered in Cambridge, UK, between 2008 and 2013. We used a composite adverse outcome, namely, perinatal morbidity or preeclampsia. Receiver operating characteristic curve analysis was used to compare the 3 methods of calculating birthweight percentiles in relation to the composite adverse outcome. We confirmed previous observations that delivering an infant who was small for gestational age (<10th percentile) with the use of a fully customized fetal growth standard but who was appropriate for gestational age with the use of a noncustomized actual birthweight standard was associated with higher rates of adverse outcomes. However, we also observed that the mothers of these infants were 3-4 times more likely to be obese and to deliver preterm. When we compared the risk of adverse outcome from logistic regression models that were fitted to the birthweight percentiles that were derived by each of the 3 predefined methods, the areas under the receiver operating characteristic curves were similar for all 3 methods: 0.56 (95% confidence interval, 0.54-0.59) fully customized, 0.56 (95% confidence interval, 0.53-0.59) noncustomized fetal weight standard, and 0.55 (95% confidence interval, 0.53-0.58) noncustomized actual birthweight standard. When we classified the top 5% of predicted risk as high risk, the methods that used a fetal growth standard showed attenuation after adjustment for gestational age, whereas the birthweight standard did not. Further adjustment for the maternal characteristics, which included weight, attenuated the association with the customized standard, but not the other 2 methods. The associations after full adjustment were similar when we compared the 3 approaches. The independent association between birthweight percentile and adverse outcome was similar when we compared actual birthweight standards and fetal growth standards and compared customized and noncustomized standards. Use of fetal weight standards and customized percentiles for maternal characteristics could lead to stronger associations with adverse outcome through confounding by preterm birth and maternal obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Growth curves for twins in Slovenia.

PubMed

Bricelj, Katja; Blickstein, Isaac; Bržan-Šimenc, Gabrijela; Janša, Vid; Lučovnik, Miha; Verdenik, Ivan; Trojner-Bregar, Andreja; Tul, Nataša

2017-02-01

Abnormalities of fetal growth are more common in twins. We introduce the growth curves for monitoring fetal growth in twin pregnancies in Slovenia. Slovenian National Perinatal Information System for the period between 2002 and 2010 was used to calculate birth weight percentiles for all live born twins for each week from 22nd to 40th week. The calculated percentiles of birth weight for all live-born twins in Slovenia served as the basis for drawing 'growth' curves. The calculated growth curves for twins will help accurately diagnose small or large twin fetuses for their gestational age in the native central European population.

Perinatal outcomes in a South Asian setting with high rates of low birth weight.

PubMed

George, Kuryan; Prasad, Jasmin; Singh, Daisy; Minz, Shanthidani; Albert, David S; Muliyil, Jayaprakash; Joseph, K S; Jayaraman, Jyothi; Kramer, Michael S

2009-02-09

It is unclear whether the high rates of low birth weight in South Asia are due to poor fetal growth or short pregnancy duration. Also, it is not known whether the traditional focus on preventing low birth weight has been successful. We addressed these and related issues by studying births in Kaniyambadi, South India, with births from Nova Scotia, Canada serving as a reference. Population-based data for 1986 to 2005 were obtained from the birth database of the Community Health and Development program in Kaniyambadi and from the Nova Scotia Atlee Perinatal Database. Menstrual dates were used to obtain comparable information on gestational age. Small-for-gestational age (SGA) live births were identified using both a recent Canadian and an older Indian fetal growth standard. The low birth weight and preterm birth rates were 17.0% versus 5.5% and 12.3% versus 6.9% in Kaniyambadi and Nova Scotia, respectively. SGA rates were 46.9% in Kaniyambadi and 7.5% in Nova Scotia when the Canadian fetal growth standard was used to define SGA and 6.7% in Kaniyambadi and < 1% in Nova Scotia when the Indian standard was used. In Kaniyambadi, low birth weight, preterm birth and perinatal mortality rates did not decrease between 1990 and 2005. SGA rates in Kaniyambadi declined significantly when SGA was based on the Indian standard but not when it was based on the Canadian standard. Maternal mortality rates fell by 85% (95% confidence interval 57% to 95%) in Kaniyambadi between 1986-90 and 2001-05. Perinatal mortality rates were 11.7 and 2.6 per 1,000 total births and cesarean delivery rates were 6.0% and 20.9% among live births >or= 2,500 g in Kaniyambadi and Nova Scotia, respectively. High rates of fetal growth restriction and relatively high rates of preterm birth are responsible for the high rates of low birth weight in South Asia. Increased emphasis is required on health services that address the morbidity and mortality in all birth weight categories.

Low birth weight and fetal anaemia as risk factors for infant morbidity in rural Malawi.

PubMed

Kalanda, Boniface; Verhoeff, Francine; le Cessie, Saskia; Brabin, John

2009-06-01

Low birth weight (LBW) and fetal anaemia (FA) are common in malaria endemic areas. To investigate the incidence of infectious morbidity in infants in rural Malawi in relation to birth weight and fetal anaemia, a cohort of babies was followed for a year on the basis of LBW (<2500) and FA (cord haemoglobin < 12.5 g/dl). A matched group of normal birth weight (NBW), non-anaemic (NFA) new-borns were enrolled as controls. Morbidity episodes were recorded at 4-weekly intervals and at each extra visit made to a health centre with any illness. Infants in the NBW NFA group experienced an average of 1.15 (95% C.I. 0.99, 1.31), 1.04 (0.89, 1.19), 0.92 (0.73, 1.11) episodes per year of malaria, respiratory infection and diarrhoea respectively. Corresponding values for the LBW FA group were 0.83 (0.5, 1.16), 0.82 (0.5, 1.16) and 0.76 (0.33, 1.19). FA was not associated with a higher incidence of morbidity, but was significantly associated with a shorter time to first illness episode (p = 0.014). LBW was not a significant risk factor for higher morbidity incidence. LBW and FA were not significant risk factors for incidence of illness episodes in infants.

Climate Change and Fetal Health: The Impacts of Exposure to Extreme Temperatures in New York City

NASA Technical Reports Server (NTRS)

Ngo, Nicole S.; Horton, Radley M.

2015-01-01

Background: Climate change is projected to increase the frequency, intensity, and duration of heat waves while reducing cold extremes, yet few studies have examined the relationship between temperature and fetal health. Objectives: We estimate the impacts of extreme temperatures on birth weight and gestational age in Manhattan, a borough in New York City, and explore differences by socioeconomic status (SES). Methods: We combine average daily temperature from 1985 to 2010 with birth certificate data in Manhattan for the same time period. We then generate 33 downscaled climate model time series to project impacts on fetal health. Results: We find exposure to an extra day where average temperature 25 F and 85 F during pregnancy is associated with a 1.8 and 1.7 g (respectively) reduction in birth weight, but the impact varies by SES, particularly for extreme heat, where teen mothers seem most vulnerable. We find no meaningful, significant effect on gestational age. Using projections of temperature from these climate models, we project average net reductions in birth weight in the 2070- 2099 period of 4.6 g in the business-as-usual scenario. Conclusions: Results suggest that increasing heat events from climate change could adversely impact birth weight and vary by SES.

Telomere length in the two extremes of abnormal fetal growth and the programming effect of maternal arterial hypertension.

PubMed

Tellechea, Mariana; Gianotti, Tomas Fernandéz; Alvariñas, Jorge; González, Claudio D; Sookoian, Silvia; Pirola, Carlos J

2015-01-19

We tested the hypothesis that leukocyte telomere length (LTL) is associated with birth weight in both extremes of abnormal fetal growth: small (SGA) and large for gestational age newborns (LGA). Clinical and laboratory variables of the mothers and the neonates were explored; 45 newborns with appropriate weight for gestational age (AGA), 12 SGA and 12 LGA were included. Whether the differences might be explained by variation in OBFC1 (rs9419958) and CTC1 (rs3027234) genes associated with LTL was determined. A significant association between birth weight and LTL was observed; LTL was significantly shorter in LGA newborns (1.01 ± 0.12) compared with SGA (1.73 ± 0.19) p < 0.005, mean ± SE. Maternal (Spearman R = -0.6, p = 0.03) and neonatal LTL (R = -0.25, p = 0.03) were significantly and inversely correlated with maternal history of arterial hypertension in previous gestations. Neonatal LTL was not significantly associated with either rs9419950 or rs3027234, suggesting that the association between neonatal LTL and birth weight is not influenced by genetic variation in genes that modify the interindividual LTL. In conclusion, telomere biology seems to be modulated by abnormal fetal growth; modifications in telomere length might be programmed by an adverse environment in utero.

Incidence of fetal bradycardia and effect of placental injury on fetal heart rate during second-trimester genetic amniocentesis.

PubMed

Hanprasertpong, T; Petpichetchian, C; Ponglopisit, S; Suksai, M; Kor-Anantakul, O; Geater, A; Pruksanusak, N; Hanprasertpong, J

2016-05-01

A prospective study was conducted for comparing the incidence of fetal bradycardia and level of fetal heart rate change following a second-trimester genetic amniocentesis with and without placental injury. A total of 257 and 495 participants in injured and non-injured groups were analysed. The incidence of fetal bradycardia following amniocentesis was not statistically different between the two groups (1.17%, [95% CI 0.24, 3.37] and 0.20%, [95% CI 0.005, 1.12]) in injured and non-injured placenta groups, respectively; p = 0.118). The mean change in baseline fetal heart rate before and after amniocentesis was also not significantly different between the two groups (p = 0.844). No fetal death or pregnancy loss occurred within 4 weeks after the procedure. All 4 bradycardia participants were normal and healthy and had an appropriate weight for their gestational age. We conclude that placental injury during a second-trimester genetic amniocentesis due to advanced maternal age poses only a low risk of fetal bradycardia, and there is no evidence of differences between subjects with injured and non-injured placenta in the changes in fetal heart rate.

A method for the automatic reconstruction of fetal cardiac signals from magnetocardiographic recordings

NASA Astrophysics Data System (ADS)

Mantini, D.; Alleva, G.; Comani, S.

2005-10-01

Fetal magnetocardiography (fMCG) allows monitoring the fetal heart function through algorithms able to retrieve the fetal cardiac signal, but no standardized automatic model has become available so far. In this paper, we describe an automatic method that restores the fetal cardiac trace from fMCG recordings by means of a weighted summation of fetal components separated with independent component analysis (ICA) and identified through dedicated algorithms that analyse the frequency content and temporal structure of each source signal. Multichannel fMCG datasets of 66 healthy and 4 arrhythmic fetuses were used to validate the automatic method with respect to a classical procedure requiring the manual classification of fetal components by an expert investigator. ICA was run with input clusters of different dimensions to simulate various MCG systems. Detection rates, true negative and false positive component categorization, QRS amplitude, standard deviation and signal-to-noise ratio of reconstructed fetal signals, and real and per cent QRS differences between paired fetal traces retrieved automatically and manually were calculated to quantify the performances of the automatic method. Its robustness and reliability, particularly evident with the use of large input clusters, might increase the diagnostic role of fMCG during the prenatal period.

Fetal and maternal outcomes in pregnancies complicated with fetal macrosomia.

PubMed

Alsammani, Mohamed Alkahatim; Ahmed, Salah Roshdy

2012-06-01

Fetal macrosomia remains a considerable challenge in current obstetrics due to the fetal and maternal complications associated with this condition. This study was designed to determine the prevalence of fetal macrosomia and associated fetal and maternal morbidity and mortality in the Al Qassim Region of Saudi Arabia. This register-based study was conducted from January 1, 2011 through December 30, 2011 at the Maternity and Child Hospital, Qassim, Saudi Arabia. Macrosomia was defined as birth weight of 4 kg or greater. Malformed babies and those born dead were excluded. The total number of babies delivered was 9241; of these, 418 were macrosomic. Thus, the prevalence of fetal macrosomia was 4.5%. The most common maternal complications were postpartum hemorrhage (5 cases, 1.2%), perineal tear (7 cases, 1.7%), cervical lacerations (3 cases, 0.7%), and shoulder dystocia (40 cases, 9.6%) that resulted in 4 cases of Erb's palsy (0.96%), and 6 cases of bone fractures (1.4%). The rate of cesarean section among women delivering macrosomic babies was 47.6% (199), while 52.4% (219) delivered vaginally. Despite extensive efforts to reduce fetal and maternal complications associated with macrosomia, considerable fetal and maternal morbidity remain associated with this condition.

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis.

PubMed

Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Øyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njølstad, Pål Rasmus; Jacobsson, Bo; Muglia, Louis

2015-08-01

Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10-9), birth weight (p = 2.19 × 10-15), and gestational age (p = 1.51 × 10-7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis

PubMed Central

Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Øyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njølstad, Pål Rasmus; Jacobsson, Bo; Muglia, Louis

2015-01-01

Background Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. Methods and Findings We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Conclusions Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring. PMID:26284790

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus.

PubMed

Stanirowski, Paweł Jan; Szukiewicz, Dariusz; Pyzlak, Michał; Abdalla, Nabil; Sawicki, Włodzimierz; Cendrowski, Krzysztof

2017-10-16

The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM). Placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pregestational DM (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements. In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p < .05). Similarly in the GDMG2 patients positive correlations between GLUT-4 expression, FBW and SSFM were observed (p < .05). In the multivariate regression analysis, only the type of diabetes and FBW were significantly associated with GLUTs expression (p < .001). In addition, maternal prepregnancy BMI significantly contributed to GLUT-1 expression (p < .001). The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.

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.

Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

PubMed

Harris, E K; Berg, E P; Berg, E L; Vonnahme, K A

2013-02-01

Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known.

Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight.

PubMed

Hellgren, Charlotte; Edvinsson, Åsa; Olivier, Jocelien D; Fornes, Romina; Stener-Victorin, Elisabet; Ubhayasekera, S J Kumari A; Skalkidou, Alkistis; Bergquist, Jonas; Sundström-Poromaa, Inger

2016-07-01

Maternal serum cortisol has been suggested to be influenced by psychiatric morbidity, and may also influence fetal growth. However, several studies found equal cortisol levels in depressed and healthy pregnant women. Placental 11-β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus from maternal cortisol by conversion to cortisone, a function that may be compromised by maternal stress. We aimed to compare the serum ratio of cortisone to cortisol, in women with and without psychiatric morbidity during pregnancy. A secondary aim was to investigate whether fetal growth, approximated by infant birth weight, was associated with the cortisone to cortisol ratio. We performed tandem mass spectrometry analysis of serum cortisol and cortisone in late pregnancy in 94 women with antenatal psychiatric morbidity and 122 controls (cohort 1). We also compared the placental gene expression of HSD11B1 and 2 in another group of 69 women with psychiatric morbidity and 47 controls (cohort 2). There were no group differences in cortisol to cortisone ratio, absolute levels of cortisone and cortisol (cohort 1), or expression of HSD11B1 or 2 (cohort 2). However, cortisone to cortisol ratio was positively associated with birth weight in women with psychiatric morbidity, also after adjustment for gestational length, fetal sex, maternal height, smoking, SSRI use, and time of blood sampling (standardized β=0.35, p<0.001), with no association in the healthy controls Thus, the maternal serum cortisone to cortisol ratio does not seem to be affected by psychiatric morbidity, but psychiatric morbidity may increase fetal exposure to cortisol or other metabolic factors influencing fetal growth. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The association between a low cerebro-umbilical ratio at 30-34 weeks gestation, increased intrapartum operative intervention and adverse perinatal outcomes.

PubMed

Twomey, Sarah; Flatley, Christopher; Kumar, Sailesh

2016-08-01

The aim of this study was to investigate the relationship between the cerebro-umbilical ratio (CUR), measured at 30-34 weeks, and adverse intrapartum and perinatal outcomes. This was a retrospective cross-sectional cohort study of women delivering at the Mater Mothers' Hospital in Brisbane, Australia. Fetal Doppler indices for 1224 singleton pregnancies were correlated with maternal demographics and intrapartum and perinatal outcomes. Only women who attempted vaginal delivery were included in the study. Infants delivered by emergency cesarean section for fetal compromise had the lowest median CUR, 1.65 (IQR 1.17-2.12), compared to any other delivery group. The proportion of infants with a CUR ≤1 who required emergency cesarean section for fetal compromise was 33.3% compared to 9.3% of infants with a CUR >1 (adjusted OR 6.92 (95% CI 2.04-25.75), p<0.001). However, the detection rate of CUR ≤1 as a predictor for emergency cesarean delivery for fetal compromise was poor (18.9%). Detection rates increased in cohorts of infants born within two weeks of the scan or with birth weights <10th centile or <5th centile. Additionally, a CUR ≤1 was associated with lower median birth weight, higher rates of admission to the neonatal critical care unit and increased neonatal mortality. This study suggests that a CUR ≤1, measured at 30-34 weeks, is associated with a greater risk of emergency cesarean delivery for fetal compromise and a number of other adverse perinatal outcomes. The association was strongest in low birth weight babies. Copyright © 2016. Published by Elsevier Ireland Ltd.

Intrauterine growth restriction in infants of less than thirty-two weeks' gestation: associated placental pathologic features.

PubMed

Salafia, C M; Minior, V K; Pezzullo, J C; Popek, E J; Rosenkrantz, T S; Vintzileos, A M

1995-10-01

Our purpose was to describe placental lesions associated with normal and abnormal fetal growth in infants delivered for obstetric indications at < 32 weeks' gestation. Maternal and neonatal charts and placental tissues from 420 consecutive nonanomalous live-born singleton infants delivered at < 32 weeks' gestation with accurate gestational dates were retrospectively studied. Excluded were cases with maternal diabetes, chronic hypertension, hydrops fetalis, diagnosed congenital viral infection, and placenta previa, leaving four primary indications for delivery: preeclampsia, preterm labor, premature rupture of membranes, and nonhypertensive abruptio placentae. The presence and severity of placental lesions was scored by a pathologist blinded to clinical data. Birth weight and length percentiles were calculated from published nomograms. Asymmetric intrauterine growth retardation (n = 32) was defined as birth weight < 10th percentile with length > 10th percentile and symmetric intrauterine growth retardation (n = 48) as both weight and length < 10th percentile for gestational age. A "growth restriction index" was developed to express a continuum of growth in both length and weight. Contingency tables, analyses of variance, and multiple regression analysis defined significance as p < 0.05 (with corrections for multiple comparisons). A greater proportion of cases with intrauterine growth retardation had lesions of uteroplacental insufficiency (p < 0.001) or chronic villitis (p < 0.02) than did appropriately grown preterm infants. Cases with asymmetric intrauterine growth retardation tended to have more lesions than did cases with appropriate-for-gestational-age infants. Four multiple regression analyses used the growth restriction index as outcome and the histologic lesion that had significant relationships to fetal growth as independent predictors in univariate analyses. Overall, uteroplacental fibrinoid necrosis, circulating nucleated erythrocytes, avascular terminal villi, and villous infarct were significant independent predictors of fetal growth (adjusted R2 = 0.312). With addition of preeclampsia as a variable, villous fibrosis, avascular villi, infarct, and preeclampsia were independent predictors of fetal growth (adjusted R2 = 0.341). In the 65 preeclampsia cases no histologic lesion was an independent predictor of fetal growth, whereas in the nonpreeclampsia cases, villous fibrosis and avascular villi were independent predictors of fetal growth (adjusted R2 = 0.075). In nonanomalous preterm infants intrauterine growth retardation is most commonly symmetric and is primarily related to the cumulative number and severity of lesions reflecting abnormal uteroplacental or fetoplacental blood flow. The growth restriction index may contribute to the study of the biologic range of fetal growth. The statistical relationship of most placental lesions to intrauterine growth retardation depends on the presence or absence of preeclampsia.

Nonhuman primate models of polycystic ovary syndrome

PubMed Central

Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

2013-01-01

With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

Diagnosis and Management of IUGR in Pregnancy Complicated by Type 1 Diabetes Mellitus.

PubMed

Gutaj, Paweł; Wender-Ozegowska, Ewa

2016-05-01

This review discusses available literature on the diagnosis and management of intrauterine growth restriction (IUGR) in women with type 1 diabetes. IUGR is diagnosed when ultrasound-estimated fetal weight is below the 10th percentile for gestational age. IUGR diagnosis implies a pathologic process behind low fetal weight. IUGR in pregnancy complicated by type 1 diabetes is usually caused by placental dysfunction related to maternal vasculopathy. Prevention of IUGR should ideally start before pregnancy. Strict glycemic control and intensive treatment of nephropathy and hypertension are essential. Low-dose aspirin initiated before 16 gestational weeks can also reduce IUGR risk in women with vasculopathy. Umbilical and uterine artery Doppler studies can guide diagnosis and surveillance of fetuses with IUGR. Decisions regarding the timing of delivery should be based on assessment of umbilical artery Doppler. The risk of prematurity and impaired fetal lung maturation should always be considered, especially in fetuses younger than 32 weeks.

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.

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.

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.

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

Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination in normal and pathological fetal kidneys.

PubMed

Chaumoitre, K; Colavolpe, N; Shojai, R; Sarran, A; D' Ercole, C; Panuel, M

2007-01-01

To assess the use of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of the fetal kidney and to estimate age-dependent changes in the apparent diffusion coefficient (ADC) of normal and pathological fetal kidneys. DW-MRI was performed on a 1.5-T machine at 23-38 gestational weeks in 51 pregnant women in whom the fetal kidneys were normal and in 10 whose fetuses had renal pathology (three with suspected nephropathy, three with renal tract dilatation, one with unilateral renal venous thrombosis, and three with twin-twin transfusion syndrome (TTTS)). The ADC was measured in an approximately 1-cm2 region of interest within the renal parenchyma. ADC values in normal renal parenchyma ranged from 1.1 to 1.8 10(-3) mm2 s-1. There was no significant age-dependent change in the ADC of normal kidneys. In cases of nephropathy, the ADC value was not always pathological but an ADC map could show abnormal findings. In cases of dilatation, the ADC value was difficult to determine when the dilatation was huge. In cases of TTTS, the ADC of the donor twin was higher than that of the recipient twin and the difference seemed to be related to the severity of the syndrome. Evaluation of the ADC for fetal kidneys is feasible. Fetal measurement of the ADC value and ADC maps may be useful tools with which to explore the fetal kidney when used in conjunction with current methods. DW-MR images, ADC value and ADC map seem to be useful in cases of suspected nephropathy (hyperechoic kidneys), dilated kidney and vascular pathology (renal venous thrombosis, TTTS). Copyright (c) 2006 ISUOG.

Co-infection with Zika and Chikungunya Viruses Associated with Fetal Death.

PubMed

Prata-Barbosa, Arnaldo; Cleto-Yamane, Thaís Lira; Rodrigues Robaina, Jaqueline; Guastavino, Andrea Bittencourt; de Magalhães-Barbosa, Maria Clara; de Moraes Brindeiro, Rodrigo; Medronho, Roberto Andrade; da Cunha, Antonio José Ledo Alves

2018-05-05

We describe a case of fetal death associated with a recent infection by Chikungunya virus (CHIKV) in a Brazilian pregnant woman (positive RT-PCR in blood and placenta). Zika virus (ZIKV) infection during pregnancy was also identified, based on a positive RT-PCR in a fetal kidney specimen. The maternal infection caused by the ZIKV was asymptomatic and the CHIKV infection had a classical clinical presentation. The fetus had no apparent anomalies, but her weight was between the 3rd and 10th percentile for the gestational age. This is the is the second case report of congenital arboviral co-infection and the first followed by antepartum fetal death. Copyright © 2018. Published by Elsevier Ltd.

Maternal Obesity Accelerates Fetal Pancreatic Beta Cell but not Alpha Cell Development in the Sheep: Prenatal and Postnatal Consequences

USDA-ARS?s Scientific Manuscript database

Maternal obesity affects offspring weight, body composition and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high energy diet on fetal pancreatic development. Sixty days prior to breeding. ewes were assigned to control (C, 100% of N...

Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM THE LE GRAY RESEARCH TEAM FOR NCEA June 15 2016

EPA Science Inventory

this file contains the raw data on the effects of in utero administration of di-iso-butyl phthalate on maternal weight gain during dosing and the numbers of fetuses and fetal resorptions. The data have all been previously published, as described on the file metadata sheet.

Element composition and mineralogical characterisation of air pollution control residue from UK energy-from-waste facilities.

PubMed

Bogush, Anna; Stegemann, Julia A; Wood, Ian; Roy, Amitava

2015-02-01

Air pollution control (APC) residues from energy-from-waste (EfW) are alkaline (corrosive) and contain high concentrations of metals, such as zinc and lead, and soluble salts, such as chlorides and sulphates. The EPA 3050B-extractable concentrations of 66 elements, including critical elements of strategic importance for advanced electronics and energy technologies, were determined in eight APC residues from six UK EfW facilities. The concentrations of Ag (6-15 mg/kg) and In (1-13 mg/kg), as well as potential pollutants, especially Zn (0.26-0.73 wt.%), Pb (0.05-0.2 wt.%), As, Cd, Cu, Mo, Sb, Sn and Se were found to be enriched in all APC residues compared to average crustal abundances. Results from a combination of scanning electron microscopy with energy dispersive X-ray spectroscopy and also powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy give an exceptionally full understanding of the mineralogy of these residues, which is discussed in the context of other results in the literature. The present work has shown that the bulk of the crystalline phases present in the investigated APC residues include Ca-based phases, such as CaCl(x)OH(2-x), CaCO3, Ca(OH)2, CaSO4, and CaO, as well as soluble salts, such as NaCl and KCl. Poorly-crystalline aragonite was identified by FTIR. Sulphur appears to have complex redox speciation, presenting as both anhydrite and hannebachite in some UK EfW APC residues. Hazardous elements (Zn and Pb) were widely associated with soluble Ca- and Cl-bearing phases (e.g. CaCl(x)OH(2-x) and sylvite), as well as unburnt organic matter and aluminosilicates. Specific metal-bearing minerals were also detected in some samples: e.g., Pb present as cerussite; Zn in gahnite, zincowoodwardite and copper nickel zinc oxide; Cu in tenorite, copper nickel zinc oxide and fedotovite. Aluminium foil pieces were present and abundantly covered by fine phases, particularly in any cracks, probably in the form of Friedel's salt. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Maternal undernutrition during the pre- and post-conception periods in twin-bearing hairsheep ewes: effects on fetal and placental development at mid-gestation.

PubMed

Macías-Cruz, Ulises; Vicente-Pérez, Ricardo; Mellado, Miguel; Correa-Calderón, Abelardo; Meza-Herrera, Cesar A; Avendaño-Reyes, Leonel

2017-10-01

To evaluate the effects of pre- and post-conception undernutrition (UN) on fetal and placental development at mid-gestation, 28 Katahdin × Pelibuey multiparous ewes were blocked by weight and assigned to the following four dietary treatments (n = 7 each): ewes fed 100% (control) or 60% of their nutritional requirements 30 days before mating (UNPre), 50 days after mating (UNPost) or during both periods (UNB). Four twin-bearing ewes were selected per treatment at day 50 post-conception and then slaughtered at day 75 of gestation to analyze their fetuses. Control fetuses were heavier (P < 0.05) than UNPost and UNB fetuses in 14.6 and 9.4%, respectively. Organ weights as percentage of the fetal weight (except for liver) and morphometric measurements (except for abdominal girth) were similar between control and UN fetuses (UNPre, UNPost, and UNB). Placental mass was heavier (P < 0.05) in control ewes than UNB ewes, but not relative to ewes of other treatments. The number of placentomes per ewe and placental efficiency were unaffected by UN treatments. Compared to control, only UNB ewes exhibited variations (P < 0.05) in the proportion of placentomes, specifically for type A (+13.8%) and B (-12.6%). Placentomes of type A and B had lower weight, length, and width of placentas in UNPost and UNB ewes than placentas of control ewes (P < 0.05). Overall results indicate that fetal and placental development of ewes carrying twins is mainly altered when nutritional restriction occurs simultaneously before conception and during the first third of pregnancy.

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

Small Size at Birth or Abnormal Intrauterine Growth Trajectory: Which Matters More for Child Growth?

PubMed Central

Hutcheon, Jennifer A.; Jacobsen, Geir W.; Kramer, Michael S.; Martinussen, Marit; Platt, Robert W.

2016-01-01

Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986–1988). Size at birth was classified using birth weight-for-gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks’ gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (β = 0.24 (95% confidence interval (CI): 0.18, 0.31), β = 0.16 (95% CI: 0.09, 0.23), β = 0.08 (95% CI: 0.01, 0.16), and β = 0.37 (95% CI: 0.22, 0.52), respectively). However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R2 increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional insight into child growth beyond that obtained from absolute size at birth. PMID:27257112

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Zhengqi

Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showedmore » a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. - Highlights: • Glucocorticoid but not ethanol enhanced the expression of OPG in chondrocytes. • PEE reduced osteoclast differentiation relative with over-expression of OPG. • PEE inhibited endochondral ossification in fetal long bones of rats. • Endochondral ossification delay is regarded as the thrifty phenotype induced by PEE.« less

Treatment of Sleep Disordered Breathing Reverses Low Fetal Activity Levels in Preeclampsia

PubMed Central

Blyton, Diane M.; Skilton, Michael R.; Edwards, Natalie; Hennessy, Annemarie; Celermajer, David S.; Sullivan, Colin E.

2013-01-01

Study Objectives: Preeclampsia affects 5% to 7% of pregnancies, is strongly associated with low birth weight and fetal death, and is accompanied by sleep disordered breathing. We hypothesized that sleep disordered breathing may link preeclampsia with reduced fetal movements (a marker of fetal health), and that treatment of sleep disordered breathing might improve fetal activity during sleep. Design, Setting, and Participants: First, a method of fetal movement recording was validated against ultrasound in 20 normal third trimester pregnancies. Second, fetal movement was measured overnight with concurrent polysomnography in 20 patients with preeclampsia and 20 control subjects during third trimester. Third, simultaneous polysomnography and fetal monitoring was done in 10 additional patients with preeclampsia during a control night and during a night of nasal CPAP. Intervention: Overnight continuous positive airway pressure. Measurements and Results: Women with preeclampsia had inspiratory flow limitation and an increased number of oxygen desaturations during sleep (P = 0.008), particularly during REM sleep. Preeclampsia was associated with reduced total fetal movements overnight (319 [SD 32]) versus controls (689 [SD 160], P < 0.0001) and a change in fetal movement patterns. The number of fetal hiccups was also substantially reduced in preeclampsia subjects (P < 0.0001). Continuous positive airway pressure treatment increased the number of fetal movements and hiccups (P < 0.0001 and P = 0.0002, respectively). Conclusions: The effectiveness of continuous positive airway pressure in improving fetal movements suggests a pathogenetic role for sleep disordered breathing in the reduced fetal activity and possibly in the poorer fetal outcomes associated with preeclampsia. Citation: Blyton DM; Skilton MR; Edwards N; Hennessy A; Celermajer DS; Sullivan CE. Treatment of sleep disordered breathing reverses low fetal activity levels in preeclampsia. SLEEP 2013;36(1):15–21. PMID:23288967

Effect of maternal metabolism on fetal supply: Glucose, non-esterified fatty acids and beta-hydroxybutyrate concentrations in canine maternal serum and fetal fluids at term pregnancy.

PubMed

Balogh, Orsolya; Bruckmaier, Rupert; Keller, Stefanie; Reichler, Iris Margaret

2018-06-01

The progressive adaptations in carbohydrate and lipid metabolism during canine pregnancy are reflected in the concentrations of glucose, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). The levels of these metabolites in the bitch likely affect fetal concentrations and the composition of amniotic and allantoic fluids (AMF and ALF, respectively). We studied 31 canine parturitions (Cesarean sections) and found that glucose, NEFA and BHB concentrations were significantly higher in maternal serum than in AMF or ALF. Glucose levels in maternal serum, AMF and ALF were closely related (R 2  ≥ 0.821, P < 0.0001) as well as serum and AMF BHB levels (R 2  = 0.661, P < 0.0001). In maternal serum, increases in NEFA were associated with increased BHB, and both were negatively related to glucose (P ≤ 0.010). To estimate the effect of the metabolic burden of pregnancy, we evaluated these variables in relation to the dam's body weight and to the ratio of litter weight to the dam's body weight (LW/BW). Maternal serum glucose was not influenced by LW/BW, but it was lower in small than in large/giant bitches. Small breed dogs and those with >10% LW/BW had significantly higher serum NEFA and BHB concentrations. Glucose in AMF and ALF was independent of LW/BW (P ≥ 0.399). AMF NEFA was lower and BHB higher, if LW/BW was >10% (P ≤ 0.048). In conclusion, the extent of the metabolic load of pregnancy in bitches depends on breed size and on the ratio of litter weight to dam's body weight. Maternal concentrations of glucose, BHB and NEFA determine the concentrations of these metabolites in fetal fluids. Copyright © 2018 Elsevier B.V. All rights reserved.

Transplacental transfer of 2-naphthol in human placenta.

PubMed

Mirghani, Hisham; Osman, Nawal; Dhanasekaran, Subramanian; Elbiss, Hassan M; Bekdache, Gharid

2015-01-01

To determine the transfer of 2-naphthol (2-NPH) in fullterm human placental tissues. Six placentas were studied. The ex-vivo dual closed-loop human placental cotyledon perfusion model was used. 2-NPH was added to the perfusate in the maternal compartment. Samples were obtained from the maternal and fetal up to 360 min measuring. The mean fetal weight was 2880 ± 304.2 g. Mean perfused cotyledon weight was 26.3 (±5.5) g. All unperfused placental tissue samples contained NPH with a mean level of 7.98 (±1.73) μg\\g compared to a mean of 15.58 (±4.53) μg\\g after 360 min perfusion. A rapid drop in maternal 2-NPH concentration was observed; from 5.54 μg\\g in the first 15 min and 13.8 μg\\g in 360 min. The fetal side increased from 0.65 μg\\g in the initial 15 min to 1.5 μg\\g in 360 min. The transfer rate of NPH was much lower than that of antipyrine. 2-NPH has the ability to rapidly across the placenta from the maternal to the fetal compartment within 15 min. The placenta seems to play a role in limiting the passage of 2-NPH in the fetal compartment.

Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth.

PubMed

Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

2015-08-01

To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5. HF/HS diet increased maternal fat mass by 2.2-fold (P < 0.01) and resulted in glucose intolerance with normal fasting glucose. Maternal circulating insulin, leptin, and cholesterol were increased (P < 0.05) whereas total and high-molecular-weight adiponectin was decreased (P < 0.05). HF/HS diet increased fetal weight (+18%, P = 0.0005). In trophoblast plasma membranes (TPM) isolated from placentas of HF/HS-fed animals, protein expression of glucose transporter (GLUT) 1 and 3, sodium-coupled neutral amino acid transporter (SNAT) 2, and large neutral amino acid transporter 1 (LAT1) was increased. TPM System A and L amino acid transporter activity was increased in the HF/HS group. Up-regulation of specific placental nutrient transporter isoforms may constitute a mechanism underlying fetal overgrowth in maternal obesity. © 2015 The Obesity Society.

The Gini coefficient: a methodological pilot study to assess fetal brain development employing postmortem diffusion MRI.

PubMed

Viehweger, Adrian; Riffert, Till; Dhital, Bibek; Knösche, Thomas R; Anwander, Alfred; Stepan, Holger; Sorge, Ina; Hirsch, Wolfgang

2014-10-01

Diffusion-weighted imaging (DWI) is important in the assessment of fetal brain development. However, it is clinically challenging and time-consuming to prepare neuromorphological examinations to assess real brain age and to detect abnormalities. To demonstrate that the Gini coefficient can be a simple, intuitive parameter for modelling fetal brain development. Postmortem fetal specimens(n = 28) were evaluated by diffusion-weighted imaging (DWI) on a 3-T MRI scanner using 60 directions, 0.7-mm isotropic voxels and b-values of 0, 150, 1,600 s/mm(2). Constrained spherical deconvolution (CSD) was used as the local diffusion model. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and complexity (CX) maps were generated. CX was defined as a novel diffusion metric. On the basis of those three parameters, the Gini coefficient was calculated. Study of fetal brain development in postmortem specimens was feasible using DWI. The Gini coefficient could be calculated for the combination of the three diffusion parameters. This multidimensional Gini coefficient correlated well with age (Adjusted R(2) = 0.59) between the ages of 17 and 26 gestational weeks. We propose a new method that uses an economics concept, the Gini coefficient, to describe the whole brain with one simple and intuitive measure, which can be used to assess the brain's developmental state.

The Impact of Gender on Anthropometric Measures of Twins.

PubMed

Jahanfar, Shayesteh; Lim, Kenneth

2016-12-01

Literature suggests that male hormones influence fetal growth in singleton pregnancies. We hypothesized that the same phenomenon is seen in twin gestations. (1) to identify the impact of gender associated with fetal birth weight, head circumference, and birth length for twins; (2) to examine the effect of gender on standardized fetal growth at birth, according to gestational age and birth order; (3) to examine the effect of gender on placenta weight and dimensions. This was a population-based retrospective cohort study of twins (4,368 twins, 2,184 pairs) born in British Columbia, Canada from 2000-2010. We excluded twins with stillbirth, congenital anomalies, and those delivered with cesarean section. We also controlled for confounding factors, including birth order, gestational age, maternal anthropometric measures, maternal smoking habits, and obstetric history. A subsample of this population was analyzed from Children and Women Hospital to obtain chorionicity information. Male-male twins were heavier than male-females and female-female twin pairs (p=.01). Within sex-discordant twin pairs, males were also heavier than females (p=.01). Regression analysis suggested that gender affects birth weight independent of birth order and gestational age. Other newborn anthropometric measures were not found to be dependent on gender. In analyzing a subsample with chorionicity data, birth weight was the only anthropometric measure that was both statistically and clinically affected by sex, even after adjustment for gestational age, chorionicity, birth order, and maternal age. Birth weight was affected by gender while head circumference and birth length were not.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

PubMed

Roberts, Linda G; Gray, Thomas M; Trimmer, Gary W; Parker, Robert M; Murray, F Jay; Schreiner, Ceinwen A; Clark, Charles R

2014-11-01

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption. No significant malformations were seen in any study. Developmental effects occurred at 20,000mg/m(3) of G/TAME (reduced fetal body weight, increased incidence of stunted fetuses), G/TBA (reduced fetal body weight, increased skeletal variants) and G/DIPE (reduced fetal weight) resulting in developmental NOAEL of 10,000mg/m(3) for these materials. Developmental NOAELs for other materials were 20,000mg/m(3) as no developmental toxicity was induced in those studies. Developmental NOAELs were equal to or greater than the concurrent maternal NOAELs which ranged from 2000 to 20,000mg/m(3). There were no clear cut differences in developmental toxicity between vapors of gasoline and gasoline blended with the ether or alcohol oxygenates. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

PubMed Central

Oz, Helieh S.

2014-01-01

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams Conclusions This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis. PMID:25210646

Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

PubMed

Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio

2008-09-03

A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of angiotensins I and II were lower in the HS group than in the NS and LS groups. Placental angiotensin receptor type 1 (AT(1)) gene expression and levels of thiobarbituric acid reactive substances (TBARS) were higher in HS dams, as were uterine blood flow and cardiac output. The degree of salt intake did not influence plasma sodium, potassium or creatinine. Although fractional sodium excretion was higher in HS dams than in NS and LS dams, fractional potassium excretion was unchanged. In conclusion, findings from this study indicate that the reduction in fetal weight in response to salt restriction during pregnancy does not involve alterations in uterine-placental perfusion or the RAS. Moreover, no change in fetal weight is observed in response to salt overload during pregnancy. However, salt overload did lead to an increase in placental weight and uterine blood flow associated with alterations in maternal plasma and placental RAS. Therefore, these findings indicate that changes in salt intake during pregnancy lead to alterations in uterine-placental perfusion and fetal growth.

2,3-diphosphoglycerate in normal and pathologic pregnancy: relationship to neonatal weight.

PubMed

Paparella, P; Francesconi, R; Zullo, M; Giorgino, R; Riccardi, P; Ferrazzani, S; Mancuso, S

1989-03-01

2,3-Diphosphoglycerate levels were assayed in 154 pregnant women in third trimester (61 normal, 52 diabetic, 19 with gestational hypertension, 7 with fetal macrosomia, and 15 with idiopathic fetal underdevelopment). A correlation was found between 2,3-diphosphoglycerate levels and birth weight (absolute and relative birth weight or birth weight expressed as percentile), which was negative in normal patients evaluated in the last 7 days before delivery (r = 0.38; p = 0.04) and positive in diabetic patients (evaluated in the third trimester and in the last 7 days before delivery) and in patients with gestational hypertension (evaluated in the third trimester) (r and p values differ according to whether birth weight is expressed as absolute, relative, or a percentile). No correlation was found between 2,3-diphosphoglycerate levels and birth weight in patients with neonatal underdevelopment or macrosomia of unknown origin. On the basis of these results we hypothesize that in some conditions the fetus can influence maternal 2,3-diphosphoglycerate levels and hence its own oxygen supply and growth in utero.

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

Assessing the value of customized birth weight percentiles.

PubMed

Hutcheon, Jennifer A; Walker, Mark; Platt, Robert W

2011-02-15

Customized birth weight percentiles are weight-for-gestational-age percentiles that account for the influence of maternal characteristics on fetal growth. Although intuitively appealing, the incremental value they provide in the identification of intrauterine growth restriction (IUGR) over conventional birth weight percentiles is controversial. The objective of this study was to assess the value of customized birth weight percentiles in a simulated cohort of 100,000 infants aged 37 weeks whose IUGR status was known. A cohort of infants with a range of healthy birth weights was first simulated on the basis of the distributions of maternal/fetal characteristics observed in births at the Royal Victoria Hospital in Montreal, Canada, between 2000 and 2006. The occurrence of IUGR was re-created by reducing the observed birth weights of a small percentage of these infants. The value of customized percentiles was assessed by calculating true and false positive rates. Customizing birth weight percentiles for maternal characteristics added very little information to the identification of IUGR beyond that obtained from conventional weight-for-gestational-age percentiles (true positive rates of 61.8% and 61.1%, respectively, and false positive rates of 7.9% and 8.5%, respectively). For the process of customization to be worthwhile, maternal characteristics in the customization model were shown through simulation to require an unrealistically strong association with birth weight.

A Mobile Multi-Agent Information System for Ubiquitous Fetal Monitoring

PubMed Central

Su, Chuan-Jun; Chu, Ta-Wei

2014-01-01

Electronic fetal monitoring (EFM) systems integrate many previously separate clinical activities related to fetal monitoring. Promoting the use of ubiquitous fetal monitoring services with real time status assessments requires a robust information platform equipped with an automatic diagnosis engine. This paper presents the design and development of a mobile multi-agent platform-based open information systems (IMAIS) with an automated diagnosis engine to support intensive and distributed ubiquitous fetal monitoring. The automatic diagnosis engine that we developed is capable of analyzing data in both traditional paper-based and digital formats. Issues related to interoperability, scalability, and openness in heterogeneous e-health environments are addressed through the adoption of a FIPA2000 standard compliant agent development platform—the Java Agent Development Environment (JADE). Integrating the IMAIS with light-weight, portable fetal monitor devices allows for continuous long-term monitoring without interfering with a patient’s everyday activities and without restricting her mobility. The system architecture can be also applied to vast monitoring scenarios such as elder care and vital sign monitoring. PMID:24452256

Enzyme markers of maternal malnutrition in fetal rat brain.

PubMed

Shambaugh, G E; Mankad, B; Derecho, M L; Koehler, R R

1987-01-01

The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.

Correlation between pre-pregnancy body mass index and maternal visceral adiposity with fetal biometry during the second trimester.

PubMed

Lopes, Karina R M; Souza, Alex Sandro R; Figueiroa, José N; Alves, João Guilherme B

2017-08-01

To determine the correlation between pre-pregnancy body mass index (BMI) and maternal visceral adiposity with fetal biometry during the second trimester. A cross-sectional observational study was conducted among pregnant women who received prenatal care at a center in Recife, Brazil, between October 3, 2011, and September 27, 2013. Pre-pregnancy BMI was determined at the first prenatal care visit. Maternal visceral adiposity and fetal biometry were measured at the same ultrasonography session. The associations between maternal and fetal variables were evaluated using the Pearson correlation coefficient (R). The Student t test was used to test the null hypothesis of adjusted correlation coefficients. Overall, 740 women were included. No correlation was found between pre-pregnancy BMI and any of the fetal biometric variables assessed. By contrast, maternal visceral adiposity positively correlated with fetal abdominal circumference (R=0.529), estimated fetal weight (R=0.524), head circumference (R=0.521), femur length (R=0.521), and biparietal diameter (R=0.524; P<0.001 for all fetal variables). These findings remained statistically significant after controlling for pregnancy length. Maternal visceral adiposity, but not pre-pregnancy BMI, positively correlated with fetal biometry during the second trimester. © 2017 International Federation of Gynecology and Obstetrics.

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 intrauterine death is high is iatrogenic preterm birth, with the use of peripartum maternal administration of magnesium sulphate for neuroprotection and corticosteroids for fetal lung maturity, to prevent adverse neonatal outcomes. The pipeline of potential therapies use different strategies, many aiming to increase fetal growth by improving poor placentation and uterine blood flow. Phosphodiesterase type 5 inhibitors that potentiate nitric oxide availability such as sildenafil citrate have been extensively researched both in preclinical and clinical studies; results from the Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction consortium of randomized control clinical trials are keenly awaited. Targeting the uteroplacental circulation with novel therapeutics is another approach, the most advanced being maternal vascular endothelial growth factor gene therapy, which is being translated into the clinic via the doEs Vascular endothelial growth factor gene therapy safEly impRove outcome in seveRe Early-onset fetal growth reSTriction consortium. Other targeting approaches include nanoparticles and microRNAs to deliver drugs locally to the uterine arterial endothelium or trophoblast. In vitro and in vivo studies and animal models have demonstrated effects of nitric oxide donors, dietary nitrate, hydrogen sulphide donors, statins, and proton pump inhibitors on maternal blood pressure, uteroplacental resistance indices, and angiogenic/antiangiogenic factors. Data from human pregnancies and, in particular, pregnancies with fetal growth restriction remain very limited. Early research into melatonin, creatine, and N-acetyl cysteine supplementation in pregnancy suggests they may have potential as neuro- and cardioprotective agents in fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of biochemical markers combined with uterine artery Doppler parameters in fetuses with growth restriction: a case-control study.

PubMed

Zamarian, Ana Cristina Perez; Araujo Júnior, Edward; Daher, Sílvia; Rolo, Liliam Cristine; Moron, Antonio Fernandes; Nardozza, Luciano Marcondes Machado

2016-10-01

Assessing the biochemical markers levels and the uterine artery Doppler (UtA) parameters in fetuses with growth restriction (FGR). Prospective case-control study included 66 patients with diagnosis of FGR and 64 healthy pregnancies at 24-41 weeks of gestation. For both groups, maternal circulating concentrations of biochemical factors of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin(sEng), adiponectin, A disintegrin and metalloproteinases (ADAM-12), pregnancy-associated plasma protein-A (PAPP-A), angiopoietin-2 (ANGI-2), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were assayed by ELISA and UtA by Doppler were performed. ANOVA, Mann-Whitney tests and Pearson correlation coefficient were applied to compare the biochemical factors, UtA Doppler and EFW Z-score between the groups. Concentrations of sFlt-1, sEng, PAPP-A were significantly higher in FGR than controls (p < 0.0001, p = 0.02 and p = 0.03, respectively), but concentration of ANGI-2 (p < 0.0001) was significantly lower in FGR than controls and ADAM-12 levels had a tendency to be lower in the FGR, though not statistically significant (p = 0.059). Increased sEng concentrations were correlated with abnormal UtA Doppler in FGR. Fetal growth restriction fetuses showed increased serum levels of sFlt-1, sEng and PAPP-A with levels of ANGI-2 decreased and a positive association between elevated concentrations of sEng and changing impedance of UtA Doppler were observed.

Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China.

PubMed

Su, Pu-Yu; Huang, Kun; Hao, Jia-Hu; Xu, Ye-Qin; Yan, Shuang-Qin; Li, Tao; Xu, Yuan-Hong; Tao, Fang-Biao

2011-10-01

There are a few prospective population-based cohort studies evaluating the effects of maternal thyroid dysfunctions on fetal and infant developments, but they are inconsistent. The objective of the study was to investigate the effects of maternal thyroid dysfunction on fetal and infant development. The study was nested within a prospective population-based China-Anhui Birth Defects and Child Development study. A total of 1017 women with singleton pregnancies participated in this study. Maternal serum samples in the first 20 wk of pregnancy were tested for thyroid hormones (TSH and free T(4)). Pregnant women were classified by hormone status into percentile categories based on laboratory assay and were compared accordingly. Outcomes included fetal loss, malformation, birth weight, preterm delivery, fetal stress, neonatal death, and infant development. Clinical hypothyroidism was associated with increased fetal loss, low birth weight, and congenital circulation system malformations; the adjusted odds ratios [95% confidence interval (CI)] were 13.45 (2.54-71.20), 9.05 (1.01-80.90), and 10.44 (1.15-94.62), respectively. Subclinical hypothyroidism was associated with increased fetal distress, preterm delivery, poor vision development, and neurodevelopmental delay; the adjusted odds ratios (95% CI) were 3.65 (1.44-9.26), 3.32 (1.22-9.05), 5.34 (1.09-26.16), and 10.49 (1.01-119.19), respectively. Isolated hypothyroxinemia was related to fetal distress, small for gestational age, and musculoskeletal malformations; the adjusted odds ratios (95% CI) were 2.95 (1.08-8.05), 3.55 (1.01-12.83), and 9.12 (1.67-49.70), respectively. Isolated hyperthyroxinemia was associated with spontaneous abortion; the adjusted odds ratio (95% CI) was 6.02 (1.25-28.96). Clinical hyperthyroidism was associated with hearing dysplasia; the adjusted odds ratio (95% CI) was 12.14 (1.22-120.70). Thyroid dysfunction in the first 20 wk of pregnancy may result in fetal loss and dysplasia and some congenital malformations.

[Clinical analysis of pregnancy outcomes and fetal loss after fetal reduction of triplets to twins or singleton pregnancy].

PubMed

Li, Shanling; Wang, Xietong; Li, Hongyan; Wang, Yanyun; Hou, Haiyan

2015-04-01

To investigate and evaluate the pregnancy outcomes and fetal loss after fetal reduction of triplets to twins or singleton pregnancy. 282 cases of triplets who received multi-fetal pregnancy reduction (MFPR) at Shandong Provincial Hospital affiliated to Shandong University were recruited from Sep 2001 to Mar 2014. According to the remaining fetal number after MFPR, 231 cases were opted to reduce to twins (twins group) while 51 cases were opted to singleton pregnancy (singleton group). The indication of the former group was fetal abnormalities under ultrasound or on patients' demand; while the indication for the later group included dichorionic triamniotic (DCTA) triplets or patients' aspiration. Potassium chloride was injected into the targeted fetal heart until cardiac standstill was obtained. The pregnancy outcomes, gestational age at delivery, birth weight of newborns of the two groups were recorded. Successful pregnancy was defined as take-home at least one baby. (1) The overall rate of successful pregnancy was 91.5% (258/282). There were 413 neonates in the twins group, including 4 neonatal deaths and 409 live babies, with the successful rate of 90.5% (209/231). There were 49 neonates in the singleton group, including 2 cases of fetal loss. Thus the successful rate was 96.1% (49/51). There was no difference of successful pregnancy rate between the two groups (P>0.05). (2) The mean gestational age at operation for the twins group and singleton group were (16.5±3.5) weeks and (14.2±2.0) weeks, respectively. Each group was divided into three periods, 11-13(+6) weeks, 14-16(+6) weeks and ≥17 weeks. In the twins group, the cases in each time period were 129 (55.8%, 129/231), 50 (21.6%, 50/231) and 52 (22.5%, 52/231), respectively. While in the singleton group, the cases in each time period were 27 (53%, 27/51), 16 (31%, 16/51) and 8 (16%, 8/51). There was no difference between the two groups at each time period (P>0.05). (3) The fetal loss rate in the twins group were 7% (9/129), 12% (6/50), 10% (5/52) at each time period, respectively. While for the singleton group they were 4% (1/27), 0 (0/16) and 1/8, respectively. There was no significant difference between the two groups at each time period (P>0.05). (4) The mean birth weight of the twins group was lower than the singleton group [(2,555±447) g vs (3,084±550) g, respectively, P<0.05]. The rates of low birth weight infants (<2,499 g) in the twins group and the singleton group were 45.5% (188/413) and 8% (4/49), respectively (P<0.05). The rate of very low birth weight infants (≤1,499 g) was 3.9% (16/413) in the twins group compared with 0 (0/49) in the singleton group (P>0.05). (5) The gestational age at delivery of the twins group was earlier than the singleton group [(36.2±2.4) weeks vs (38.3±2.2) weeks, respectively, P<0.05]. The labor rate of the two groups was significantly different for both 34-36(+6) weeks and ≥ 37 weeks (P<0.05). The full-term delivery rate in the twins group was 47.6% (110/231), and was 88.2% (45/51) in the singleton group (P < 0.05). The fetal loss rate before 28 weeks did not differ between the two groups [8.7% (20/231) vs 3.9% (2/51), P>0.05]. Reduction to one fetus led to significantly better outcome than two fetuses, with no significant difference in fetal loss rate. It is better to advise patients with triplets reduce to singleton pregnancy.

Can Thrifty Gene(s) or Predictive Fetal Programming for Thriftiness Lead to Obesity?

PubMed Central

Baig, Ulfat; Belsare, Prajakta; Watve, Milind; Jog, Maithili

2011-01-01

Obesity and related disorders are thought to have their roots in metabolic “thriftiness” that evolved to combat periodic starvation. The association of low birth weight with obesity in later life caused a shift in the concept from thrifty gene to thrifty phenotype or anticipatory fetal programming. The assumption of thriftiness is implicit in obesity research. We examine here, with the help of a mathematical model, the conditions for evolution of thrifty genes or fetal programming for thriftiness. The model suggests that a thrifty gene cannot exist in a stable polymorphic state in a population. The conditions for evolution of thrifty fetal programming are restricted if the correlation between intrauterine and lifetime conditions is poor. Such a correlation is not observed in natural courses of famine. If there is fetal programming for thriftiness, it could have evolved in anticipation of social factors affecting nutrition that can result in a positive correlation. PMID:21773010

A Systematic Review of Fetal Genes as Biomarkers of Cardiac Hypertrophy in Rodent Models of Diabetes

PubMed Central

2014-01-01

Pathological cardiac hypertrophy activates a suite of genes called the fetal gene program (FGP). Pathological hypertrophy occurs in diabetic cardiomyopathy (DCM); therefore, the FGP is widely used as a biomarker of DCM in animal studies. However, it is unknown whether the FGP is a consistent marker of hypertrophy in rodent models of diabetes. Therefore, we analyzed this relationship in 94 systematically selected studies. Results showed that diabetes induced with cytotoxic glucose analogs such as streptozotocin was associated with decreased cardiac weight, but genetic or diet-induced models of diabetes were significantly more likely to show cardiac hypertrophy (P<0.05). Animal strain, sex, age, and duration of diabetes did not moderate this effect. There were no correlations between the heart weight:body weight index and mRNA or protein levels of the fetal genes α-myosin heavy chain (α-MHC) or β-MHC, sarco/endoplasmic reticulum Ca2+-ATPase, atrial natriuretic peptide (ANP), or brain natriuretic peptide. The only correlates of non-indexed heart weight were the protein levels of α-MHC (Spearman's ρ = 1, P<0.05) and ANP (ρ = −0.73, P<0.05). These results indicate that most commonly measured genes in the FGP are confounded by diabetogenic methods, and are not associated with cardiac hypertrophy in rodent models of diabetes. PMID:24663494

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.

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 ± 1.1 μmol/d; P < 0.001) and increased in response to l-citrulline or l-arginine (12.1 ± 2.2 and 10.6 ± 0.9 μmol/d; P < 0.05), whereas they did not in the LP + NEAA group. l-Citrulline increases fetal growth in a model of IUGR, and the effect may be mediated by enhanced fetal muscle protein synthesis and/or increased NO production. © 2016 American Society for Nutrition.

Dosimetric factors for diagnostic nuclear medicine procedures in a non-reference pregnant phantom.

PubMed

Rafat-Motavalli, Laleh; Miri Hakimabad, Hashem; Hoseinian Azghadi, Elie

2018-05-01

This study was evaluated the impact of using non-reference fetal models on the fetal radiation dose from diagnostic radionuclide administration. The 6 month pregnant phantoms including fetal models at 10th and 90th growth percentiles were constructed at either end of the normal range around the 50th percentile and implemented in the Monte Carlo N-Particle code version MCNPX 2.6. The code have been used then to evaluate the 99mTc S factors of interested target organs as the most common used radionuclide in nuclear medicine procedures. Substantial variations were observed in the S factors between the 10th/90th percentile phantoms from the 50th percentile phantom, with the greatest difference being 38.6 %. When the source organs were in close proximity to, or inside the fetal body, the 99mTc S factors presented strong statistical correlations with fetal body habitus. The trends observed in the S factors and the differences between various percentiles were justified by the source organs' masses, and chord length distributions (CLDs). The results of this study showed that fetal body habitus had a considerable effect on fetal dose (on average up to 8.4%) if constant fetal biokinetic data was considered for all fetal weight percentiles. However, an almost smaller variation on fetal dose (up to 5.3%) was obtained if the available biokinetic data for the reference fetus was scaled by fetal mass. © 2018 IOP Publishing Ltd.

Neighborhood factors associated with physical activity and adequacy of weight gain during pregnancy

EPA Science Inventory

Healthy diet, physical activity, smoking, and adequate weight gain are all associated with maternal health and fetal growth during pregnancy. Neighborhood characteristics have been associated with poor maternal and child health outcomes, yet conceptualization of potential mechani...

ITE and TCDD Differentially Regulate the Vascular Remodeling of Rat Placenta via the Activation of AhR

PubMed Central

Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

2014-01-01

Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in intrauterine fetal death. PMID:24475139

Analysis of MicroRNA Expression in Newborns with Differential Birth Weight Using Newborn Screening Cards

PubMed Central

Rodil-Garcia, Patricia; Arellanes-Licea, Elvira del Carmen; Montoya-Contreras, Angélica; Salazar-Olivo, Luis A.

2017-01-01

Birth weight is an early predictor for metabolic diseases and microRNAs (miRNAs) are proposed as fetal programming participants. To evaluate the use of dried blood spots (DBS) on newborn screening cards (NSC) as a source of analyzable miRNAs, we optimized a commercial protocol to recover total miRNA from normal birth weight (NBW, n = 17–20), low birth weight (LBW, n = 17–20) and high birth weight (macrosomia, n = 17–20) newborns and analyzed the relative expression of selected miRNAs by stem-loop RT-qPCR. The possible role of miRNAs on the fetal programming of metabolic diseases was explored by bioinformatic tools. The optimized extraction of RNA resulted in a 1.2-fold enrichment of miRNAs respect to the commercial kit. miR-33b and miR-375 were overexpressed in macrosomia 9.8-fold (p < 0.001) and 1.7-fold, (p < 0.05), respectively and miR-454-3p was overexpressed in both LBW and macrosomia (19.7-fold, p < 0.001 and 10.8-fold, p < 0.001, respectively), as compared to NBW. Potential target genes for these miRNAs are associated to cyclic-guanosine monophosphate (cGMP)-dependent protein kinase (PKG), mitogen-activated protein kinase (MAPK), type 2 diabetes, transforming growth factor-β (TGF-β)and Forkhead box O protein (FoxO) pathways. In summary, we improved a protocol for analyzing miRNAs from NSC and provide the first evidence that birth weight modifies the expression of miRNAs associated to adult metabolic dysfunctions. Our work suggests archived NSC are an invaluable resource in the search for fetal programming biomarkers. PMID:29182561

Paternally Expressed, Imprinted Insulin-Like Growth Factor-2 in Chorionic Villi Correlates Significantly with Birth Weight

PubMed Central

Demetriou, Charalambos; Abu-Amero, Sayeda; Thomas, Anna C.; Ishida, Miho; Aggarwal, Reena; Al-Olabi, Lara; Leon, Lydia J.; Stafford, Jaime L.; Syngelaki, Argyro; Peebles, Donald; Nicolaides, Kypros H.; Regan, Lesley; Stanier, Philip; Moore, Gudrun E.

2014-01-01

Context Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. Objective The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Design Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11–13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Results Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3·6×10−7). Interpretation Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth. PMID:24454871

Leptin does not influence surfactant synthesis in fetal sheep and mice lungs

PubMed Central

Sato, Atsuyasu; Schehr, Angelica

2011-01-01

In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122–124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment. PMID:21216976

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.

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.

Gestational 3,3',4,4',5-pentachlorobiphenyl (PCB 126) exposure disrupts fetoplacental unit: Fetal thyroid-cytokines dysfunction.

PubMed

Ahmed, R G; El-Gareib, A W; Shaker, H M

2018-01-01

Exposure to polychlorinated biphenyls (PCBs) is related to several endocrine disorders. This study examined the effect of maternal exposure of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on the fetoplacental unit and fetal thyroid-cytokine axis during the pregnancy. Pregnant albino rats received PCB 126 (20 or 40μg/kgb.wt.) by oral gavage from gestation day (GD) 1 to 20. Potential effects of PCB 126 were evaluated by following the histopathological changes in the placenta by Haematoxylin and Eosin (H&E) stain and measuring the maternofetal thyroid axis (ELIZA), maternofetal body weight, and fetal growth markers (ELIZA), and cytokines (ELIZA) at embryonic day (ED) 20. Placental tissues of both treated groups showed hyperemia, hemorrhage, degeneration and apoptosis in labyrinth layer and spiral artery at GD 20. Both administrations of PCB 126 elevated serum thyrotropin (TSH) concentration, and decreased free thyroxine (FT4) and free triiodothyronine (FT3) concentrations, resulting in a maternofetal hypothyroidism. The presence of hypothyroidism increased fetal serum concentration of transforming growth factor-β (TGF-β), leptin (LEP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and decreased the fetal serum insulin growth factor-I (IGF-I), IGF-II, insulin, adiponectin (ADP), and growth hormone (GH) in both treated groups at ED 20. However, the increase in resistin (RETN) and interferon-γ (IFN-γ) was non-significant in low-dose group and highly significant in high-dose group. Simultaneously, the reduction in body weight of the dams and fetuses was observed in both PCB 126 groups of examined day with respect to the control group. The maternal PCB 126 distorted the fetoplacental unit might disrupt the fetal thyroid-cytokines axis and prenatal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Gay Male Only-Children: Evidence for Low Birth Weight and High Maternal Miscarriage Rates.

PubMed

Skorska, Malvina N; Blanchard, Ray; VanderLaan, Doug P; Zucker, Kenneth J; Bogaert, Anthony F

2017-01-01

Recent findings suggest that there may be a maternal immune response underpinning the etiology of sexual orientation of gay male only-children. This maternal immune response appears to be distinct from that which is purported to explain the classic fraternal birth order effect found in studies of male sexual orientation. We tested two predictions related to the hypothesized maternal immune response in mothers of gay male only-children: (1) elevated fetal loss among mothers who have had gay male only-children and (2) lower birth weight in gay male only-children. Mothers of at least one gay son (n = 54) and mothers of heterosexual son(s) (n = 72) self-reported their pregnancy histories, including the birth weights of newborns and number of fetal losses (e.g., miscarriages). Mothers of gay male only-children (n = 8) reported significantly greater fetal loss compared with mothers of males with four other sibship compositions (gay with no older brothers, gay with older brothers, heterosexual only-children, heterosexual with siblings) (n = 118). Also, firstborn gay male only-children (n = 4) had a significantly lower birth weight than firstborn children in the four other sibship compositions (n = 59). Duration of pregnancy was not significantly different among the groups of firstborn children in the birth weight analyses. Thus, this study found further support for a distinct pattern of maternal immune response implicated in the etiology of male sexual orientation. Mechanisms that may underlie this potential second type of maternal immune response are discussed.

A Maternal High-Energy Diet Promotes Intestinal Development and Intrauterine Growth of Offspring

PubMed Central

Liu, Peilin; Che, Long; Yang, Zhenguo; Feng, Bin; Che, Lianqiang; Xu, Shengyu; Lin, Yan; Fang, Zhengfeng; Li, Jian; Wu, De

2016-01-01

It has been suggested that maternal nutrition during gestation is involved in an offspring’s intestinal development. The aim of this study was therefore to evaluate the effects of maternal energy on the growth and small intestine development of offspring. After mating, twenty gilts (Large White (LW) breeding, body weight (BW) at 135.54 ± 0.66 kg) were randomly allocated to two dietary treatments: a control diet (CON) group and a high-energy diet (HED) group, respectively. The nutrient levels of the CON were referred to meet the nutrient recommendations by the National Research Council (NRC, 2012), while the HED was designed by adding an amount of soybean oil that was 4.6% of the total diet weight to the CON. The dietary treatments were introduced from day 1 of gestation to farrowing. At day 90 of gestation, day 1 post-birth, and day 28 post-birth, the weights of fetuses and piglets, intestinal morphology, enzyme activities, and gene and protein expressions of intestinal growth factors were determined. The results indicated that the maternal HED markedly increased the BW, small intestinal weight, and villus height of fetuses and piglets. Moreover, the activities of lactase in fetal intestine, sucrase in piglet intestine were markedly increased by the maternal HED. In addition, the maternal HED tended to increase the protein expression of insulin-like growth factor 1 receptor (IGF-1R) in fetal intestine, associated with significantly increased the gene expression of IGF-1R. In conclusion, increasing energy intake could promote fetal growth and birth weight, with greater intestinal morphology and enzyme activities. PMID:27164130

[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.

[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.

Developmental origins of chronic inflammation: a review of the relationship between birth weight and C-reactive protein.

PubMed

deRosset, Leslie; Strutz, Kelly L

2015-07-01

The developmental origins of adult disease hypothesis suggests that the intrauterine environment may program postnatal health outcomes through mechanisms such as chronic inflammation. The purpose of this article was to review the literature on the association between infant birth weight and C-reactive protein (CRP), markers of the fetal environment and inflammation, respectively. We used PubMed, Google Scholar, Web of Science, ScienceDirect, the citation lists of the reviewed literature, and recommendations from experts in the field to identify potential articles. Inclusion criteria for the studies, regardless of study design, included human subjects, documented or self-reported infant birth weight, and a minimum of one measurement of CRP (during childhood, adolescence, or adulthood). Several studies demonstrated a statistically significant inverse association between birth weight and CRP in adulthood, although in many cases only after controlling for markers of current adiposity. No studies significantly linked birth weight to CRP in childhood or adolescence. Longitudinal studies, including multigenerational studies, are needed to further understand whether adult CRP has origins in the fetal environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Paternal Body Mass Index (BMI) Is Associated with Offspring Intrauterine Growth in a Gender Dependent Manner

PubMed Central

Chen, You-Peng; Xiao, Xiao-Min; Li, Jian; Reichetzeder, Christoph; Wang, Zi-Neng; Hocher, Berthold

2012-01-01

Background Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. Conclusions Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion. PMID:22570703

Differential nongenetic impact of birth weight versus third-trimester growth velocity on glucose metabolism and magnetic resonance imaging abdominal obesity in young healthy twins.

PubMed

Pilgaard, Kasper; Hammershaimb Mosbech, Thomas; Grunnet, Louise; Eiberg, Hans; Van Hall, Gerrit; Fallentin, Eva; Larsen, Torben; Larsen, Rasmus; Poulsen, Pernille; Vaag, Allan

2011-09-01

Low birth weight is associated with type 2 diabetes, which to some extent may be mediated via abdominal adiposity and insulin resistance. Fetal growth velocity is high during the third trimester, constituting a potential critical window for organ programming. Intra-pair differences among monozygotic twins are instrumental in determining nongenetic associations between early environment and adult metabolic phenotype. Our objective was to investigate the relationship between size at birth and third-trimester growth velocity on adult body composition and glucose metabolism using intra-pair differences in young healthy twins. Fifty-eight healthy twins (42 monozygotic/16 dizygotic) aged 18-24 yr participated. Insulin sensitivity was assessed using hyperinsulinemic-euglycemic clamps. Whole-body fat was assessed by dual-energy x-ray absorptiometry scan, whereas abdominal visceral and sc fat (L1-L4) were assessed by magnetic resonance imaging. Third-trimester growth velocity was determined by repeated ultrasound examinations. Size at birth was nongenetically inversely associated with adult visceral and sc fat accumulation but unrelated to adult insulin action. In contrast, fetal growth velocity during third trimester was not associated with adult visceral or sc fat accumulation. Interestingly, third-trimester growth was associated with insulin action in a paradoxical inverse manner. Abdominal adiposity including accumulation of both sc and visceral fat may constitute primary nongenetic factors associated with low birth weight and reduced fetal growth before the third trimester. Reduced fetal growth during vs. before the third trimester may define distinct adult trajectories of metabolic and anthropometric characteristics influencing risk of developing type 2 diabetes.

Intra-amniotic pharmacological blockade of inflammatory signalling pathways in an ovine chorioamnionitis model.

PubMed

Ireland, D J; Kemp, M W; Miura, Y; Saito, M; Newnham, J P; Keelan, J A

2015-05-01

Intrauterine inflammation (IUI) associated with infection is the major cause of preterm birth (PTB) at <32 weeks' gestation and accounts for ∼40% of all spontaneous PTBs. Pharmacological strategies to prevent PTB and improve fetal outcomes will likely require both antimicrobial and anti-inflammatory therapies. Here we investigated the effects of two cytokine-suppressive anti-inflammatory drugs (CSAIDs), compounds that specifically target inflammatory signalling pathways, in an ovine model of lipopolysaccharide (LPS)-induced chorioamnionitis. Chronically catheterized ewes at 116 days gestation (n = 7/group) received an intra-amniotic (IA) bolus of LPS (10 mg) plus vehicle or CSAIDS: TPCA-1 (1.2 mg/kg fetal weight) or 5z-7-oxozeaenol (OxZnl; 0.4 mg/kg fetal weight); controls received vehicle (dimethylsulphoxide). Amniotic fluid (AF), fetal and maternal blood samples were taken 0, 2, 6, 12, 24 and 48 h later; tissues were taken at autopsy (48 h). Administration of TPCA-1 or OxZnl abrogated the stimulatory effects of LPS (P < 0.01 versus vehicle control) on production of PGE2 in AF, with lesser (non-significant) effects on IL-6 production. Fetal membrane polymorphonuclear cell infiltration score was significantly higher in LPS versus vehicle control animals (P < 0.01), and this difference was absent with TPCA-1 and OxZnl treatment. LPS-induced systemic fetal inflammation was highly variable, with no significant effects of CSAIDs observed. Lung inflammation was evident with LPS exposure, but unaffected by CSAID treatment. We have shown in a large animal model that IA administration of a single dose of CSAIDs can suppress LPS-induced IA inflammatory responses, while fetal effects were minimal. Further development and investigation of these compounds in infectious models is warranted. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

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.

Effect of metformin treatment during pregnancy on women with PCOS: a systematic review and meta-analysis.

PubMed

Tan, Xingrong; Li, Shengbing; Chang, Ying; Fang, Chao; Liu, Hua; Zhang, Xingping; Wang, Yi

2016-09-11

Some previous studies have found that continued metformin use is beneficial in the management of polycystic ovary syndrome (PCOS) in pregnant women. A systemic review and meta-analysis were needed to more fully assess the effects of metformin on pregnant PCOS patients. The literature was fully searched using MEDLINE, EMBASE, SCOPUS, and COCHRANE for continued metformin use during pregnancy in women with PCOS. A systematic review and meta-analysis were performed to evaluate the comprehensive effects of continued metformin treatment on pregnancy-related outcomes in these women. Eleven eligible studies out of 127 relevant publications were included in meta-analysis. The rates of early pregnancy loss and preterm delivery were found to be significantly decreased in metformin-treated PCOS women. A non-significant difference was found in fetal abnormality and fetal birth weight between the metformin-treated and the non-treated groups. The incidence of gestational diabetes mellitus (GDM) and hypertension/preeclampsia were not significantly different in the two groups, probably because of inconsistent results in the subgroup analysis. Our results showed that continued use during of metformin, during pregnancy in women with PCOS, had no effect on incidence of fetal abnormalities or fetal birth weight. The effects of metformin on GDM and hypertension/preeclampsia should be determined through high-quality randomized controlled trials.

Prognostic usefulness of derived T2-weighted fetal magnetic resonance imaging measurements in congenital diaphragmatic hernia.

PubMed

Sebastià, C; Gomez, O; Salvador, R; Buñesch, L; Garcia, R; Nicolau, C

2015-01-01

To determine the usefulness of various parameters based on T2-weighted fetal magnetic resonance (MR) imaging measurements of the uninvolved lung for the neonatal prognosis of congenital diaphragmatic hernia (CDH). We used ultrasonography and MR imaging to study 28 fetuses with CDH. We retrospectively analyzed a) on fetal ultrasonography, the observed-to-expected lung to head ratio (O/E LHR) and the position of the liver, and b) on fetal MR imaging, the lung-liver signal ratio (LLSR) and the lungcerebrospinal fluid ratio (L/CSF SR). To determine the prognostic value of these parameters, we compared them with the following postnatal parameters: survival, pulmonary hypertension, need for oxygen supplementation, and need for extracorporeal membrane oxygenation. We found significant differences between O/E LHR and the need for postnatal extracorporeal membrane oxygenation (P=.033) and postnatal survival (P=.01). We also found significant differences in LLSR between fetuses that survived more than 45 days and those that died within 45 days (1.91 vs. 2.56; P=.039). In fetuses with CDH, the LLSR correlates with postnatal survival and can potentially be used as a prognostic parameter in CDH. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Low birth weight of contemporary African Americans: an intergenerational effect of slavery?

PubMed

Jasienska, Grazyna

2009-01-01

The average birth weight in the contemporary African-American population is about 250 g lower than the average birth weight of European Americans. Differences in genetic and socioeconomic factors present between these two groups can explain only part of birth weight variation. I propose a hypothesis that the low birth weight of contemporary African Americans not only results from the difference in present exposure to lifestyle factors known to affect fetal development but also from conditions experienced during the period of slavery. Slaves had poor nutritional status during all stages of life because of the inadequate dietary intake accompanied by high energetic costs of physical work and infectious diseases. The concept of "fetal programming" suggests that physiology and metabolism including growth and fat accumulation of the developing fetus, and, thus its birth weight, depend on intergenerational signal of environmental quality passed through generations of matrilinear ancestors. I suggest that several generations that have passed since the abolition of slavery in the United States (1865) has not been enough to obliterate the impact of slavery on the current biological and health condition of the African-American population. (c) 2008 Wiley-Liss, Inc.

Medical, nutritional, and dental considerations in children with low birth weight.

PubMed

O'Connell, Susan; O'Connell, Anne; O'Mullane, Elaine; Hoey, Hilary

2009-01-01

It is estimated that 8 to 26 percent of infants are born with low birth weight (LBW) worldwide. These children are at risk for medical problems in childhood and adulthood and often have poor oral health. The influence of fetal growth on birth weight and its relevance to childhood growth and future adult health is controversial. Evidence now indicates that the postnatal period is a critical time when nutrition may predispose the child to lifelong metabolic disturbance and obesity. Given the lack of consensus on optimum infant nutrition for LBW, premature, and small-for-gestational-age infants, many such infants may be suboptimally managed. This may result in rapid postnatal weight gain and ongoing health problems. The purpose of this review was to summarize medical terminology and issues related to fetal growth, morbidity associated with being born low birth weight, premature, or small for gestational age, and the importance of appropriate nutrition in such infants. Pediatric dentists can play an important role in supporting healthy feeding practices and improving long-term health in these children. Early integrated medical and dental care should be encouraged for all children with low birth weight.

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. Pregnancies with a birthweight <3 rd , compared to those ≥3 rd percentile, had higher deviations from normal in fetal biometry, maternal cardiac output, stroke volume, heart rate and peripheral vascular resistance and UT-PI. Multivariate logistic regression analysis demonstrated that in the prediction of birth weight ≤3 rd percentile, maternal hemodynamics provided significant improvement to the prediction provided by maternal demographics, fetal biometry and UT-PI, UA-PI and MCA-PI (difference between AUCs 0.18, 95% CI 0.06-0.29, p=0.002). In contrast, there was no significant independent contribution from maternal hemodynamics in the prediction of subsequent abnormal fetal Dopplers. In pregnancies with SGA fetuses there is decreased maternal cardiac output and stroke volume and increased peripheral vascular resistance and MAP and the deviations from normal are most marked in cases of redistribution in the fetal circulation and reduced amniotic fluid volume. This article is protected by copyright. All rights reserved.

Transabdominal recordings of fetal heart rate in extremely small fetuses.

PubMed

Odendaal, Hein; Groenewald, Coen; Hankins, Gary D V; du Plessis, Carlie; Myers, Michael M; Fifer, William P

2017-11-12

As part of the fetal assessment for the Safe Passage Study, we recorded raw data of the fetal ECG via five maternal abdominal wall electrodes from 20 weeks to 23 weeks 6 days' gestation. For this study were extracted and analyzed the FHR patterns from the stored raw data in 16 stillbirths where the fetus weighed less than 1000 g and where autopsy was performed. Birth weights ranged from 190 to 970 g. The proportion FHR signal loss ranged from 0.3% to 21.1%. In the smallest fetus the heart weighed 1.3 g, yet the FHR signal loss was only 0.9%.

Effects of hesperidin on formaldehyde-induced toxicity in pregnant rats

PubMed Central

Merzoug, Sameha; Toumi, Mohamed Lamine

2017-01-01

This experimental study aimed to investigate the protective effect of a bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological and behavioral outcomes in pregnant rats and developmental aspects in their offspring. Female Wistar rats were subjected to perigestational exposure to FA (2 mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os). Pregnant rats were weighed throughout gestation and tested in two behavioral paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and 19 to evaluate the anxiety-like behavior and locomotive alterations. Another subset of rats was decapitated at GD19 to determine the hematological profile along with cortisol, 17β-estradiol, and progesterone plasma levels. Reproductive and fetal measures and observations were also performed to check for developmental deformities. Significant body weight loss, hemato-immune decline, hormonal changes, anxiety and lethargy signs, locomotor disabilities, reproductive failure and fetal weight decrease were observed in FA-exposed rats. Treatment with HP alleviated the reproductive and fetal weight defects. Its behavioral benefits were only seen at GD1 and 10. This flavanone ameliorated some hematological parameters, decreased cortisol levels and increased 17β-estradiol rates. A potential preventive impact of HP was found against FA toxicity in pregnant rats. PMID:28507483

Toxic effects of sodium selenite on pregnant mice and modification of the effects by vitamin E or reduced glutathione.

PubMed

Yonemoto, J; Satoh, H; Himeno, S; Suzuki, T

1983-12-01

Toxic effects of sodium selenite (SS) on dams and/or conceptuses and modification of the effects by vitamin E (VE) or reduced glutathione (GSH) were investigated in pregnant mice during late gestation. Dose-dependent fetocidal effects and fetal growth retardation were observed in mothers injected SC with SS on day 12 but not on day 16 of gestation. On day 12, abortion occurred only at a dose level of 58.8 mumol/kg SS, whereas on day 16 it occurred at two dose levels: 27.2 and 40.0 mumol/kg SS. Pregnant mice were treated with or without VE (50 mg/kg, SC, daily from day 7 to day 11) and injected with a single dose of SS (46.2 mumol/kg, SC) on day 12. VE prevented abortion and maternal death, but none of the other effects such as fetal loss, fetal growth retardation, and decrease in body weight gain of the dams. Pretreatment with GSH (0, 2, or 5 mM/kg, SC) 20 min before SS injection on day 12 exacerbated maternal death, abortion, and decrease in body weight gain of the dams. No effect were observed in the number of live offspring, and in body weight of offspring.

Perceptions of low-income African-American mothers about excessive gestational weight gain.

PubMed

Herring, Sharon J; Henry, Tasmia Q; Klotz, Alicia A; Foster, Gary D; Whitaker, Robert C

2012-12-01

A rising number of low-income African-American mothers gain more weight in pregnancy than is recommended, placing them at risk for poor maternal and fetal health outcomes. Little is known about the perceptions of mothers in this population that may influence excessive gestational weight gain. In 2010-2011, we conducted 4 focus groups with 31 low-income, pregnant African-Americans in Philadelphia. Two readers independently coded the focus group transcripts to identify recurrent themes. We identified 9 themes around perceptions that encouraged or discouraged high gestational weight gain. Mothers attributed high weight gain to eating more in pregnancy, which was the result of being hungrier and the belief that consuming more calories while pregnant was essential for babies' health. Family members, especially participants own mothers, strongly reinforced the need to "eat for two" to make a healthy baby. Mothers and their families recognized the link between poor fetal outcomes and low weight gains but not higher gains, and thus, most had a greater pre-occupation with too little food intake and weight gain rather than too much. Having physical symptoms from overeating and weight retention after previous pregnancies were factors that discouraged higher gains. Overall, low-income African-American mothers had more perceptions encouraging high gestational weight gain than discouraging it. Interventions to prevent excessive weight gain need to be sensitive to these perceptions. Messages that link guideline recommended weight gain to optimal infant outcomes and mothers' physical symptoms may be most effective for weight control.

Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology.

PubMed

Kenna, Kelly; De Matteo, Robert; Hanita, Takushi; Rees, Sandra; Sozo, Foula; Stokes, Victoria; Walker, David; Bocking, Alan; Brien, James; Harding, Richard

2011-10-01

High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ∼145 DGA). Maternal and fetal arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (∼0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.

Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

PubMed

Turan, Sifa; Aberdeen, Graham W; Thompson, Loren P

2017-10-01

Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( n = 7) or hypoxia (10.5% O 2 , n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( n = 21) and hypoxic ( n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure. Copyright © 2017 the American Physiological Society.

Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition

PubMed Central

Merzouk, H; Bouchenak, M; Loukidi, B; Madani, S; Prost, J; Belleville, J

2000-01-01

Aims—To determine the effects of fetal macrosomia related to maternal type 1 diabetes on the lipid transport system. Methods—Serum lipoprotein concentrations and composition and lecithin:cholesterol acyltransferase (LCAT) activity were investigated in macrosomic newborns (mean birth weight, 4650 g; SEM, 90) and their mothers with poorly controlled type 1 diabetes, in appropriate for gestational age newborns (mean birth weight, 3616 g; SEM, 68) and their mothers with well controlled type 1 diabetes, and macrosomic (mean birth weight, 4555 g; SEM, 86) or appropriate for gestational age (mean birth weight, 3290 g; SEM, 45) newborns and their healthy mothers. Results—In mothers with well controlled type 1 diabetes, serum lipids, apolipoproteins, and lipoproteins were comparable with those of healthy mothers. Similarly, in their infants, these parameters did not differ from those of appropriate for gestational age newborns. Serum triglyceride, very low density lipoprotein (VLDL), apolipoprotein B100 (apo B100), and high density lipoprotein (HDL) triglyceride concentrations were higher, whereas serum apo A-I and HDL3 concentrations were lower in mothers with diabetes and poor glycaemic control than in healthy mothers. Their macrosomic newborns had higher concentrations in all serum lipids and lipoproteins, with high apo A-I and apo B100 values compared with appropriate for gestational age newborns. In macrosomic infants of healthy mothers, there were no significant differences in lipoprotein profiles compared with those of appropriate for gestational age infants. LCAT activity was similar in both groups of mothers and newborns. Conclusion—Poorly controlled maternal type 1 diabetes and fetal macrosomia were associated with lipoprotein abnormalities. Macrosomic lipoprotein profiles related to poor metabolic control of type 1 diabetes appear to have implications for later metabolic diseases. Key Words: apolipoproteins • lipids • lipoproteins • lecithin:cholesterol acyltransferase • fetal macrosomia • maternal type 1 diabetes PMID:11265176

Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS)-induced intrauterine growth restriction IUGR in mice.

PubMed

Lewis, Joshua B; Mejia, Camilo; Jordan, Clinton; Monson, Troy D; Bodine, Jared S; Dunaway, Todd M; Egbert, Kaleb M; Lewis, Adam L; Wright, Tanner J; Ogden, K Connor; Broberg, Dallin S; Hall, Parker D; Nelson, Shawn M; Hirschi, Kelsey M; Reynolds, Paul R; Arroyo, Juan A

2017-12-01

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS + semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P ≤ 0.0001) and placental weight (1.13-fold, P ≤ 0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P ≤ 0.05), JNK (2.4-fold, P ≤ 0.05) and p38 (2.1-fold, P ≤ 0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P ≤ 0.05) and IL-1β (1.03-fold, P ≤ 0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P < 0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.

Meat Science and Muscle Biology Symposium: developmental programming in cattle: consequences for growth, efficiency, carcass, muscle, and beef quality characteristics.

PubMed

Robinson, D L; Cafe, L M; Greenwood, P L

2013-03-01

This paper reviews results of studies on effects of fetal programming and maternal nutrition during pregnancy on growth, efficiency, carcass, muscle, and meat quality characteristics of cattle. It includes results from our Australian Beef Cooperative Research Centre studies on factors such as chronic severe nutritional restriction from approximately d 80 of pregnancy to parturition and/or throughout lactation used to create early-life growth differences in the offspring of cows within pasture-based systems and the effect of these treatments on production characteristics to 30 mo of age. Fetal programming and related maternal effects are most pronounced and explain substantial amounts of variation for growth-related production characteristics such as BW, feed intake, carcass weight, muscle weights, meat yield, and fat and bone weights at any given age but are less evident when assessed at the same BW and carcass weight. Some effects of maternal and early-life factors in our studies were evident for efficiency traits but fewer affected beef quality characteristics at 30 mo of age, explaining only small amounts of variation in these traits. It is difficult to uncouple maternal nutritional effects specific to prenatal life from those that carry over to the postnatal period until weaning, particularly the effects of maternal nutrition during pregnancy on subsequent lactational performance. Hence, experimental design considerations for studying fetal programming effects on offspring during later life are discussed in relation to minimizing or removing prenatal and postnatal confounding effects. The relative contribution of fetal programming to the profitability of beef production systems is also briefly discussed. In this regard, the importance of health and survival of cows and calves, the capacity of cows to rebreed in a timely manner, and the efficiency with which feed and other resources are used cannot be overemphasized in relation to economics, welfare, and the environment.

Prenatal centrifugation: A model for fetal programming of adult weight?

NASA Astrophysics Data System (ADS)

Baer, Lisa A.; Rushing, Linda; Wade, Charles E.; Ronca, April E.

2005-08-01

'Fetal programming' is a newly emerging field that is revealing astounding insights into the prenatal origins of adult disease, including metabolic, endocrine, and cardiovascular pathophysiology. In the present study, we tested the hypothesis that rat pups conceived, gestated and born at 2-g have significantly reduced birth weights and increased adult body weights as compared to 1-g controls. Offspring were produced by mating young adult male and female rats that were adapted to 2-g centrifugation. Female rats underwent conception, pregnancy and birth at 2-g. Newborn pups in the 2-g condition were removed from the centrifuge and fostered to non-manipulated, newly parturient dams maintained at 1-g. Comparisons were made with 1-g stationary controls, also cross- fostered at birth. As compared to 1-g controls, birth weights of pups gestated and born at 2-g were significantly reduced. Pup body weights were significantly reduced until Postnatal day (P)12. Beginning on P63, body weights of 2-g-gestated offspring exceeded those of 1-g controls by 7-10%. Thus, prenatal rearing at 2-g restricts neonatal growth and increases adult body weight. Collectively, these data support the hypothesis that 2-g centrifugation alters the intrauterine milieu, thereby inducing persistent changes in adult phenotype.

Prenatal Centrifugation: A Mode1 for Fetal Programming of Body Weight?

NASA Technical Reports Server (NTRS)

Baer, Lisa A.; Rushing, Linda; Wade, Charles E.; Ronca, April E.

2005-01-01

'Fetal programming' is a newly emerging field that is revealing astounding insights into the prenatal origins of adult disease, including metabolic, endocrine, and cardiovascular pathophysiology. In the present study, we tested the hypothesis that rat pups conceived, gestated and born at 2-g have significantly reduced birth weights and increased adult body weights as compared to 1-g controls. Offspring were produced by mating young adult male and female rats that were adapted to 2-g centrifugation. Female rats underwent conception, pregnancy and birth at 2-g. Newborn pups in the 2-g condition were removed from the centrifuge and fostered to non-manipulated, newly parturient dams maintained at 1 -g. Comparisons were made with 1-g stationary controls, also crossfostered at birth. As compared to 1-g controls, birth weights of pups gestated and born at 2-g were significantly reduced. Pup body weights were significantly reduced until Postnatal day (P) 12. Beginning on P63, body weights of 2-g-gestated offspring exceeded those of 1-g controls by 7-10%. Thus, prenatal rearing at 2-g restricts neonatal growth and increases adult body weight. Collectively, these data support the hypothesis that 2-g centrifugation alters the intrauterine milieu, thereby inducing persistent changes in adult phenotype.

Maternal nutrition, fetal weight, body composition and disease in later life.

PubMed

Zadik, Z

2003-09-01

Nutritional and hormonal milieu in utero affect fetal growth. Both parties involved have an independent chance, for the occurrence of a developmental error at any stage of their constant developing system. Studies suggest that pregnancy outcome is associated with fetal demand for nutrients and the materno-placental capacity to meet that demand. Failure of the materno-placental supply line to satisfy fetal nutrient requirements results in a range of fetal adaptations and developmental changes, and may lead to permanent alterations in the body's structure and metabolism, and thereby to cardiovascular and metabolic disease in adult life. Changes in the in-utero homeostasis may lead to programming of endocrine and metabolic systems so that feedback systems and reactions are permanently changed. At the present stage, short- and long-term hazards of intra-uterine growth retardation (IUGR) have been identified, but preventive strategies are still lacking. It is unlikely that a single factor will reduce a multi-causal outcome like IUGR. Appropriate population-specific interventions should be a priority.

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

Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM ...

EPA Pesticide Factsheets

this file contains the raw data on the effects of in utero administration of di-iso-butyl phthalate on maternal weight gain during dosing and the numbers of fetuses and fetal resorptions. The data have all been previously published, as described on the file metadata sheet. Raw data file from our published studies on DIBP specifically requested (6/14/2016) by NCEA scientists for analysis and inclusion in their assessment of this chemical.

Efficiency of energy recovery from municipal solid waste and the resultant effect on the greenhouse gas balance.

PubMed

Gohlke, Oliver

2009-11-01

Global warming is a focus of political interest and life-cycle assessment of waste management systems reveals that energy recovery from municipal solid waste is a key issue. This paper demonstrates how the greenhouse gas effects of waste treatment processes can be described in a simplified manner by considering energy efficiency indicators. For evaluation to be consistent, it is necessary to use reasonable system boundaries and to take the generation of electricity and the use of heat into account. The new European R1 efficiency criterion will lead to the development and implementation of optimized processes/systems with increased energy efficiency which, in turn, will exert an influence on the greenhouse gas effects of waste management in Europe. Promising technologies are: the increase of steam parameters, reduction of in-plant energy consumption, and the combined use of heat and power. Plants in Brescia and Amsterdam are current examples of good performance with highly efficient electricity generation. Other examples of particularly high heat recovery rates are the energy-from-waste (EfW) plants in Malmö and Gothenburg. To achieve the full potential of greenhouse gas reduction in waste management, it is necessary to avoid landfilling combustible wastes, for example, by means of landfill taxes and by putting incentives in place for increasing the efficiency of EfW systems.

Serum Zinc in Mothers and from Cord Blood of Appropriate Birth-Weight Full Term and Preterm Newborn Infants, and of Low-Birth-Weight Full Term Infants.

ERIC Educational Resources Information Center

Trindade, Cleide Enoir Petean; And Others

1984-01-01

Studied the maternal plasmatic zinc behavior at delivery time and the cord blood zinc concentration from appropriate and low-birth-weight full-term infants and appropriate preterm infants. Findings indicated that neither prematurity nor fetal growth delay interfere in maternal or newborn infants' zinc levels. (BJD)

DENGUE DURING PREGNANCY: ASSOCIATION WITH LOW BIRTH WEIGHT AND PREMATURITY

PubMed Central

RIBEIRO, Christiane Fernandes; LOPES, Vânia Glória Silami; Brasil, Patricia; da Silva, Licinio Esmeraldo; RIBEIRO, Pedro Henrique Fernandes Josephson; UGENTI, Luca Cipriani; NOGUEIRA, Rita Maria Ribeiro

2016-01-01

The aim of this study was to evaluate the effects of dengue virus infection during pregnancy and its correlation with low birth weight, prematurity, and asphyxia. A non-concurrent cohort study reveals the association of dengue during pregnancy with prematurity and low birth weight, when birth occurred during the maternal-fetal viremia period (p = 0.016 and p < 0.0001, respectively). PMID:26910454

Relationship Between Third-Trimester Sonographic Estimate of Fetal Weight and Mode of Delivery.

PubMed

Yee, Lynn M; Grobman, William A

2016-04-01

Some have suggested, based on limited data, that knowledge of an estimated fetal weight from a sonogram in a low-risk population, particularly in the setting of a larger fetus, is associated with increased risk of cesarean delivery. We aimed to investigate, among women delivering neonates weighing greater than 3500 g, whether having had a sonographically estimated fetal weight in temporal proximity to delivery was associated with the risk of cesarean delivery. We conducted a retrospective cohort study of term nulliparous women delivering live-born, cephalic, singleton, nonanomalous fetuses with birth weights of greater than 3500 g. The study was powered to detect a 30% change in cesarean delivery frequency with the presence of a sonographic examination after 36 weeks' gestation. Of the 2099 women meeting inclusion criteria, 419 (20%) had a sonographic examination after 36 weeks' gestation. Women were similar with respect to demographic and obstetric characteristics regardless of whether they underwent sonography. There were no differences in rates of cesarean delivery regardless of whether women had or did not undergo sonography after 36 weeks (33.2% versus 29.4%, respectively; P = .13). There also were no differences in rates of chorioamnionitis, postpartum hemorrhage, episiotomy, third- or fourth-degree perineal laceration, or neonatal adverse outcomes based on sonographic status. Findings were similar in a multivariable analysis, as well as when the study population was restricted to those with birth weights of greater than 4000 and 4500 g. In this population of neonates weighing greater than 3500 g, the presence of a sonographic examination was not associated with the frequency of cesarean delivery. © 2016 by the American Institute of Ultrasound in Medicine.

Congenital Heart Defects and Measures of Fetal Growth in Newborns with Down Syndrome or 22q11.2 Deletion Syndrome.

PubMed

Matthiesen, Niels B; Agergaard, Peter; Henriksen, Tine B; Bach, Cathrine C; Gaynor, J William; Hjortdal, Vibeke; Østergaard, John R

2016-08-01

To estimate the association between congenital heart defects (CHD) and indices of fetal growth in Down and 22q11.2 deletion syndromes. We established 2 Danish nationwide cohorts of newborn singletons with either Down syndrome (n = 670) or 22q11.2 deletion syndrome (n = 155), born 1997-2011. In both cohorts, we analyzed the association between CHD, CHD severity, and indices of fetal growth by multivariable linear regression adjusted for potential confounders. We report mean differences in gestational age specific z-scores compared with newborns without CHD. Down syndrome and 22q11.2 deletion syndrome were both associated with lower mean birth weight and head circumference z-scores. We found no association between CHD or CHD severity and indices of fetal growth. In Down syndrome, the association between any CHD and the mean difference in head circumference z-score was 0.03 (95% CI -0.12, 0.18), and the estimate regarding birth weight z-score was 0.09 (95% CI -0.08, 0.25). The corresponding estimates in 22q11.2 deletion syndrome were 0.00 (95% CI -0.33, 0.32) and -0.09 (95% CI -0.45, 0.26). We found no association between CHD and fetal growth measures in newborns with Down syndrome or 22q11.2 deletion syndrome. Thus, in certain subtypes of CHD, the contribution of genetic factors to prenatal growth impairment may be more important than circulatory disturbances. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Dynamic interaction between fetal adversity and a genetic score reflecting dopamine function on developmental outcomes at 36 months.

PubMed

Bischoff, Adrianne R; Pokhvisneva, Irina; Léger, Étienne; Gaudreau, Hélène; Steiner, Meir; Kennedy, James L; O'Donnell, Kieran J; Diorio, Josie; Meaney, Michael J; Silveira, Patrícia P

2017-01-01

Fetal adversity, evidenced by poor fetal growth for instance, is associated with increased risk for several diseases later in life. Classical cut-offs to characterize small (SGA) and large for gestational age (LGA) newborns are used to define long term vulnerability. We aimed at exploring the possible dynamism of different birth weight cut-offs in defining vulnerability in developmental outcomes (through the Bayley Scales of Infant and Toddler Development), using the example of a gene vs. fetal adversity interaction considering gene choices based on functional relevance to the studied outcome. 36-month-old children from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment) were classified according to birth weight ratio (BWR) (SGA ≤0.85, LGA >1.15, exploring a wide range of other cut-offs) and genotyped for polymorphisms associated with dopamine signaling (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10- repeat, Met/Met-COMT), composing a score based on the described function, in which hypofunctional variants received lower scores. There were 251 children (123 girls and 128 boys). Using the classic cut-offs (0.85 and 1.15), there were no statistically significant interactions between the neonatal groups and the dopamine genetic score. However, when changing the cut-offs, it is possible to see ranges of BWR that could be associated with vulnerability to poorer development according to the variation in the dopamine function. The classic birth weight cut-offs to define SGA and LGA newborns should be seen with caution, as depending on the outcome in question, the protocols for long-term follow up could be either too inclusive-therefore most costly, or unable to screen true vulnerabilities-and therefore ineffective to establish early interventions and primary prevention.

Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination.

PubMed

Faure, Alice; Panait, Nicoleta; Panuel, Michel; Alessandrini, Pierre; D'Ercole, Claude; Chaumoitre, Kathia; Merrot, Thierry

2017-07-01

The objective of this study was to evaluate the accuracy of fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination to predict postnatal renal function (nadir creatinine at 1 year and eGFR) of men with posterior urethral valves (PUV). Between 2003 and 2014, 11 MRI were performed on fetuses (between 28 and 32 weeks) in whom second trimester sonography suggested severe bilateral urinary tract anomalies, suspected of PUV. The ADC of the 11 fetuses ranged from 1.3 to 2.86 mm 2  s -1 (median = 1.79 mm 2  s -1 , normal range for fetal kidney: 1.1-1.8). Two pregnancies with ADC > 2.6 mm 2  s -1 were interrupted; the autopsy confirmed PUV and Potter syndrome. For the remaining nine babies, the follow-up was 5.4 years (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease. The remaining five cases with normal nadir creatinine and eGFR had normal ADC. One case with unilateral elevated ADC had a poor ipsilateral renal function on dimercaptosuccinic acid scan. Here, it seems that diffusion-weighted magnetic resonance imaging with ADC determination could be useful in accurately evaluating fetal kidneys in PUV and predicting renal function. It may be an additional, non-invasive method when biologic and sonographic findings are inconclusive, especially in the case of oligohydramnios. Further studies are needed to confirm our data. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Cellular and Hormonal Disruption of Fetal Testis Development in Sheep Reared on Pasture Treated with Sewage Sludge

PubMed Central

Paul, Catriona; Rhind, Stewart M.; Kyle, Carol E.; Scott, Hayley; McKinnell, Chris; Sharpe, Richard M.

2005-01-01

The purpose of this study was to evaluate whether experimental exposure of pregnant sheep to a mixture of environmental chemicals added to pasture as sewage sludge (n = 9 treated animals) exerted effects on fetal testis development or function; application of sewage sludge was undertaken so as to maximize exposure of the ewes to its contents. Control ewes (n = 9) were reared on pasture treated with an equivalent amount of inorganic nitrogenous fertilizer. Treatment had no effect on body weight of ewes, but it reduced body weight by 12–15% in male (n = 12) and female (n = 8) fetuses on gestation day 110. In treated male fetuses (n = 11), testis weight was significantly reduced (32%), as were the numbers of Sertoli cells (34% reduction), Leydig cells (37% reduction), and gonocytes (44% reduction), compared with control fetuses (n = 8). Fetal blood levels of testosterone and inhibin A were also reduced (36% and 38%, respectively) in treated compared with control fetuses, whereas blood levels of luteinizing hormone and follicle-stimulating hormone were unchanged. Based on immunoexpression of anti-Müllerian hormone, cytochrome P450 side chain cleavage enzyme, and Leydig cell cytoplasmic volume, we conclude that the hormone changes in treated male fetuses probably result from the reduction in somatic cell numbers. This reduction could result from fetal growth restriction in male fetuses and/or from the lowered testosterone action; reduced immunoexpression of α-smooth muscle actin in peritubular cells and of androgen receptor in testes of treated animals supports the latter possibility. These findings indicate that exposure of the developing male sheep fetus to real-world mixtures of environmental chemicals can result in major attenuation of testicular development and hormonal function, which may have consequences in adulthood. PMID:16263515

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.

A novel mode-of-action mediated by the fetal muscle nicotinic acetylcholine receptor resulting in developmental toxicity in rats.

PubMed

Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Terry, Claire; Millar, Neil S; Zablotny, Carol L; Gibb, Alasdair; Marshall, Valerie; Collins, Toby; Carney, Edward W; Billington, Richard

2012-06-01

Sulfoxaflor (X11422208), a novel agricultural molecule, induced fetal effects (forelimb flexure, hindlimb rotation, and bent clavicle) and neonatal death in rats at high doses (≥ 400 ppm in diet); however, no such effects occurred in rabbit dietary studies despite achieving similar maternal and fetal plasma exposure levels. Mode-of-action (MoA) studies were conducted to test the hypothesis that the effects in rats had a single MoA induced by sulfoxaflor agonism on the fetal rat muscle nicotinic acetylcholine receptor (nAChR). The studies included cross-fostering and critical windows of exposure studies in rats, fetal ((α1)(2)β1γδ) and adult ((α1)(2)β1δε) rat and human muscle nAChR in vitro agonism experiments, and neonatal rat phrenic nerve-hemidiaphragm contracture studies. The weight of evidence from these studies supported a novel MoA where sulfoxaflor is an agonist to the fetal, but not adult, rat muscle nAChR and that prolonged agonism on this receptor in fetal/neonatal rats causes sustained striated muscle contracture resulting in concomitant reduction in muscle responsiveness to physiological nerve stimulation. Fetal effects were inducible with as little as 1 day of exposure at the end of gestation, but were rapidly reversible after birth, consistent with a pharmacological MoA. With respect to human relevance, sulfoxaflor was shown to have no agonism on human fetal or adult muscle nAChRs. Taken together, the data support the hypothesis that the developmental effects of sulfoxaflor in rats are mediated via sustained agonism on the fetal muscle nAChR during late fetal development and are considered not relevant to humans.

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

PubMed Central

Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

2016-01-01

Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart rate has an important influence on the pharmacokinetics of propofol during pregnancy. Much lower propofol concentration in the fetus compared to maternal concentrations explain limited placental transfer in in-vivo paired model, and less direct fetal cardiac depression we observed earlier with propofol supplemented inhalational anesthesia compared to higher dose inhalational anesthesia in humans and sheep. PMID:26752560

Prenatal dysthymia versus major depression effects on the neonate.

PubMed

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

2008-04-01

Depressed pregnant women were classified as dysthymic or major depression disorder based on the Structured Clinical Interview for Depression and followed to the newborn period. The newborns of dysthymic versus major depression disorder mothers had a significantly shorter gestational age, a lower birthweight, shorter birth length and less optimal obstetric complications scores. The neonates of dysthymic mothers also had lower orientation and motor scores and more depressive symptoms on the Brazelton Neonatal Behavioral Assessment Scale. These findings were not surprising given the elevated cortisol levels and the inferior fetal measures including lower fetal weight, fetal length, femur length and abdominal circumference noted in our earlier study on fetuses of dysthymic pregnant women.

Prenatal Dysthymia versus Major Depression Effects on the Neonate

PubMed Central

Field, Tiffany; Diego, Miguel

2008-01-01

Depressed pregnant women were classified as dysthymic or major depression disorder based on the Structured Clinical Inventory for Depression and followed to the newborn period. The newborns of dysthymic versus major depression disorder mothers had a significantly shorter gestational age, a lower birthweight, shorter birth length and less optimal obstetric complications scores. The neonates of dysthymic mothers also had lower orientation and motor scores and more depressive symptoms on the Brazelton Neonatal Behavioral Assessment Scale. These findings were not surprising given the elevated cortisol levels and the inferior fetal measures including lower fetal weight, fetal length, femur length and abdominal circumference noted in our earlier study on fetuses of dysthymic pregnant women PMID:18037494

Does gender of the fetus have any relation with fetal heart monitoring during the first and second stage of labor?

PubMed

Yohai, David; Baumfeld, Yael; Zilberstein, Tali; Yaniv Salem, Shimrit; Elharar, Debbie; Idan, Inbal; Mastrolia, Salvatore Andrea; Sheiner, Eyal

2017-01-01

To investigate fetal gender and its influences on neonatal outcomes, taking into consideration the available tools for the assessment of fetal well-being. We conducted a retrospective study comparing maternal, fetal and neonatal outcomes according to fetal gender, in women carrying a singleton gestation. A multivariate analysis was performed for the prediction of adverse neonatal outcomes according to fetal gender, after adjustment for gestational age, maternal age and fetal weight. A total of 682 pregnancies were included in the study, of them 56% (n = 383) were carrying a male fetus and 44% (n = 299) a females fetus. Male gender was associated with a significant higher rate of abnormal fetal heart tracing patterns during the first (67.7% versus 55.1, p = 0.001) and the second stage (77.6 versus 67.7, p = 0.01) of labor. Male gender was also significantly associated with lower Apgar scores at 1' (19.1% versus 10.7%, p < 0.01), as well as lower pH values (7.18 ± 0.15 versus 7.23 ± 0.18, p < 0.001), and significant differences in cord blood components (PCO 2 , PO 2 ) compared with female fetuses. In the multivariate analysis, male gender was found to be significantly associated with first (OR 1.76, 95% CI 1.28-2.43, p = 0.001) and second stage (OR 1.73, 95% CI 1.20-2.50, p < 0.01) pathological fetal heart tracing patterns, pH < 7.1, and for Apgar scores at 1'< 7. The present study confirms the general trend of a lower clinical performance of male neonates compared with females. In addition, the relation between fetal heart rate patterns during all stages of labor and fetal gender showed an independent association between male fetal gender and abnormal fetal heart monitoring during labor.

Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123

PubMed Central

Huebner, Shane M; Blohowiak, Sharon E; Kling, Pamela J; Smith, Susan M

2016-01-01

Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disabilities, and gestational iron deficiency (ID) selectively worsens learning and neuroanatomical and growth impairments in PAE. It is unknown why ID worsens outcomes in alcohol-exposed offspring. Objective: We hypothesized that PAE alters maternal-fetal iron distribution or its regulation. Methods: Nulliparous, 10-wk-old, Long-Evans rats were mated and then fed iron-sufficient (100 mg Fe/kg) or iron-deficient (≤4 mg Fe/kg) diets. On gestational days 13.5–19.5, dams received either 5.0 g ethanol/kg body weight (PAE) or isocaloric maltodextrin by oral gavage. On gestational day 20.5, maternal and fetal clinical blood counts, tissue mineral and iron transport protein concentrations, and hepatic hepcidin mRNA expression were determined. Results: In fetal brain and liver (P < 0.001) and in maternal liver (P < 0.005), ID decreased iron (total and nonheme) and ferritin content by nearly 200%. PAE reduced fetal bodyweight (P < 0.001) and interacted with ID (P < 0.001) to reduce it by an additional 20%. Independent of maternal iron status, PAE increased fetal liver iron (30–60%, P < 0.001) and decreased brain iron content (total and nonheme, 15–20%, P ≤ 0.050). ID-PAE brains had lower ferritin, transferrin, and transferrin receptor content (P ≤ 0.002) than ID-maltodextrin brains. PAE reduced fetal hematocrit, hemoglobin, and red blood cell numbers (P < 0.003) independently of iron status. Unexpectedly, and also independent of iron status, PAE increased maternal and fetal hepatic hepcidin mRNA expression >300% (P < 0.001). Conclusions: PAE altered fetal iron distribution independent of maternal iron status in rats. The elevated iron content of fetal liver suggests that PAE may have limited iron availability for fetal erythropoiesis and brain development. Altered fetal iron distribution may partly explain why maternal ID substantially worsens growth and behavioral outcomes in PAE. PMID:27146918

Perceptions of low-income African-American mothers about excessive gestational weight gain

PubMed Central

Herring, Sharon J.; Henry, Tasmia Q.; Klotz, Alicia; Foster, Gary D.; Whitaker, Robert C.

2013-01-01

Objective A rising number of low-income African-American mothers gain more weight in pregnancy than is recommended, placing them at risk for poor maternal and fetal health outcomes. Little is known about the perceptions of mothers in this population that may influence excessive gestational weight gain. Methods In 2010–2011, we conducted 4 focus groups with 31 low-income, pregnant African-Americans in Philadelphia. Two readers independently coded the focus group transcripts to identify recurrent themes. Results We identified 9 themes around perceptions that encouraged or discouraged high gestational weight gain. Mothers attributed high weight gain to eating more in pregnancy, which was the result of being hungrier and the belief that consuming more calories while pregnant was essential for babies’ health. Family members, especially participants own mothers, strongly reinforced the need to “eat for two” to make a healthy baby. Mothers and their families recognized the link between poor fetal outcomes and low weight gains but not higher gains, and thus, most had a greater pre-occupation with too little food intake and weight gain rather than too much. Having physical symptoms from overeating and weight retention after previous pregnancies were factors that discouraged higher gains. Conclusions Low-income African American mothers had more perceptions encouraging high gestational weight gain than discouraging it. Interventions to prevent excessive weight gain need to be sensitive to these perceptions. Messages that link guideline recommended weight gain to optimal infant outcomes and mothers’ physical symptoms may be most effective for weight control. PMID:22160656

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.

Fingolimod against endotoxin-induced fetal brain injury in a rat model.

PubMed

Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

2017-11-01

Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

Risk Factors for Dystocia in Pigtailed Macaques (Macaca nemestrina)

PubMed Central

Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

2011-01-01

Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources. PMID:21535929

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

Fetal gender effects on induction of labor in postdate pregnancies.

PubMed

Torricelli, Michela; Voltolini, Chiara; Vellucci, Francesca L; Conti, Nathalie; Bocchi, Caterina; Severi, Filiberto M; Challis, John R; Smith, Roger; Petraglia, Felice

2013-06-01

To determine delivery outcome in women undergoing induction of labor for postdate pregnancy in relation to fetal gender. A total of 365 nulliparous and 127 multiparous women carrying singleton postdate pregnancies with unfavorable cervix were enrolled. Clinical characteristics and delivery outcome were analyzed in relation to fetal gender. Women carrying male fetuses showed higher rate of caesarean section than those carrying females, in both nulliparous and multiparous women. Moreover, women carrying male fetuses presented more frequently with (i) interval between induction of labor and delivery >24 hours (P < .0002); (ii) augmentation of labor after cervical ripening (P < .0391); (iii) meconium-stained liquor (P< .0126); and (iv) higher neonatal weight (P < .0011) than those carrying females. Male fetuses are more likely to be associated with higher rates of cesarean section. In maternal fetal medicine, gender differences may add prognostic information on the delivery outcome in women induced for postdate pregnancy.

Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study.

PubMed

Peng, Mei; Gao, Keming; Ding, Yiling; Ou, Jianjun; Calabrese, Joseph R; Wu, Renrong; Zhao, Jingping

2013-08-01

This study aims to investigate the developmental effects of atypical antipsychotics on infants who were born to mothers taking an atypical antipsychotic throughout pregnancy. The developmental progress of 76 infants who experienced fetal exposure to atypical antipsychotics was compared to that of 76 matched control infants who had no fetal exposure to any antipsychotics. Planned assessment included Apgar score, body weight, height, and the cognitive, language, motor, social-emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Student's t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance. At 2 months of age, the mean composite scores of cognitive, motor, social-emotional, and adaptive behavior of BSID-III were significantly lower in atypical antipsychotic-exposed infants than the controls. More atypical antipsychotic-exposed infants had delayed development in cognitive, motor, social-emotional, and adaptive behavior domains as defined by the composite score of <85 in these subscales of BSID-III. At 12 months of age, there were no significant differences between the two groups in all mean composite scores of BSID-III. More atypical antipsychotic-exposed infants had low birth weight than the controls (13.2 vs. 2.6 %, P = 0.031), although there were no significant difference in mean birth weight and height between the two groups. Fetal exposure to atypical antipsychotics may cause short-term delayed development in cognitive, motor, social-emotional, and adaptive behavior, but not in language, body weight, or height.

Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

PubMed

Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

2003-01-01

This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

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.

Exposure to electromagnetic fields during pregnancy with emphasis on electrically heated beds: association with birthweight and intrauterine growth retardation.

PubMed

Bracken, M B; Belanger, K; Hellenbrand, K; Dlugosz, L; Holford, T R; McSharry, J E; Addesso, K; Leaderer, B

1995-05-01

Several animal and human studies indicate that fetal growth may be retarded following exposure to electromagnetic fields (EMF). We conducted a prospective study (N = 2,967) to evaluate the relation of birthweight and fetal growth retardation with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. A "nested" study design allowed monitoring of exposure at different stages of pregnancy using both direct and indirect methods. We assessed EMF exposure using personal monitors, home measurement, video display terminal use, and wire code. Exposure to EMF during pregnancy, either at conception, at < or = 16 weeks, or in the third trimester, showed no important relation to risk of low birth-weight or fetal growth retardation. This result was the same whether we used subjective measures of exposure or direct measurement. Use of video display terminals at home or work, exposure to > or = 2.0-milligauss fields as measured by home or personal monitors, and home wire code were unrelated to the reproductive outcomes studied. A time-weighted analysis of electric bed use, which accounted for strength of EMF exposure and hours of use, also showed evidence of no meaningful increase in risk. None of the exposure measures showed a dose response relation to risk. We conclude that risk of low birth-weight and intrauterine growth retardation is not increased after electrically heated bed use during pregnancy.

Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls.

PubMed

Tian, Fu-Ying; Wang, Xi-Meng; Xie, Chuanbo; Zhao, Bo; Niu, Zhongzheng; Fan, Lijun; Hivert, Marie-France; Chen, Wei-Qing

2018-01-01

Fibroblast growth factor receptor 2 ( FGFR2 ) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association. We conducted analyses for each of the five valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and found that per one standard deviation increase in the DNA methylation of CpG 11 at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in placental surface area ( β  = - 0.18; standard error = 0.08, p  = 0.02). The mediation effect of placental surface area on the association between DNA methylation and full-term low birth weight was significant in girls (OR = 1.38, 95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was 48.38%. Our findings suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner. Our study supported the importance of placental epigenetic changes in placental development and fetal growth.

Fetal Alcohol Spectrum Disorders

MedlinePlus

... between the nose and upper lip Small head size Shorter-than-average height Low body weight Poor coordination Hyperactive behavior Difficulty with attention and memory Learning disabilities and difficulty in school ...

The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth

PubMed Central

Lam, Juleen; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

2014-01-01

Background: In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action. Objectives: We applied the Navigation Guide systematic review method to answer the question “Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?” and to rate the strength of the experimental animal evidence. Methods: We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence. Results: Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of –0.023 g (95% CI: –0.029, –0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as “moderate” and “low” quality, respectively. Conclusion: Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals. Citation: Koustas E, Lam J, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1015–1027; http://dx.doi.org/10.1289/ehp.1307177 PMID:24968374

Animal models for clinical and gestational diabetes: maternal and fetal outcomes.

PubMed

Kiss, Ana Ci; Lima, Paula Ho; Sinzato, Yuri K; Takaku, Mariana; Takeno, Marisa A; Rudge, Marilza Vc; Damasceno, Débora C

2009-10-19

Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Experimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women presenting uncontrolled clinical diabetes. On the other hand, the mild diabetes model caused mild hyperglycemia during pregnancy, although it was not enough to reproduce the increased rate of macrosomic fetuses seen in women with gestational diabetes.

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.

Maternal physical activity mode and fetal heart outcome.

PubMed

May, Linda E; Suminski, Richard R; Berry, Andrew; Langaker, Michelle D; Gustafson, Kathleen M

2014-07-01

Maternal leisure-time physical activity (LTPA) improves cardiac autonomic function in the fetus. The specific physical activity attributes (e.g., mode) that produce this benefit are not well understood. To determine if more time spent performing non-continuous LTPA during pregnancy is significantly associated with lower fetal heart rate (HR) and increased heart rate variability (HRV). This paper presents a retrospective analysis of previously reported data. Fetal magnetocardiograms (MCG) were recorded from 40 pregnant women at 36-wk gestational age. Metrics of fetal HR and HRV, self-reported min of continuous and non-continuous LTPA performed during the 3-months preceding the 36-wk assessment point and covariates (maternal weight change pre to 36-wk, age, and resting HR and fetal activity state during MCG recordings. Positive correlations were significant (p<0.05) between min of continuous LTPA, the time domain metrics that describe fetal overall HRV, short-term HRV and a frequency domain metric that reflects vagal activity. Time spent in non-continuous LTPA was positively correlated (p<0.05) with two HRV metrics that reflect fetal overall HRV. In the multiple regression analyses, minutes of non-continuous LTPA remained associated with fetal vagal activity (p<0.05) and the relationships between minutes of non-continuous LTPA and fetal overall HRV (p<0.005) persisted. These data suggest non-continuous physical activity provides unique benefits to the fetal autonomic nervous system that may give the fetus an adaptive advantage. Further studies are needed to understand the physiological mechanisms and long-term health effects of physical activity (both non-continuous and continuous) performed during pregnancy to both women and their offspring. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maternal Engineered Nanomaterial Exposure and Fetal Microvascular Function: Does the Barker Hypothesis Apply?

PubMed Central

STAPLETON, Phoebe A.; MINARCHICK, Ms. Valerie C.; YI, Jinghai; ENGELS, Mr. Kevin; McBRIDE, Mr. Carroll R.; NURKIEWICZ, Timothy R.

2013-01-01

Objective The continued development and use of engineered nanomaterials (ENM) has given rise to concerns over the potential for human health effects. While the understanding of cardiovascular ENM toxicity is improving, one of the most complex and acutely demanding “special” circulations is the enhanced maternal system to support fetal development. The “Barker Hypothesis” proposes that fetal development within a hostile gestational environment may predispose/program future sensitivity. Therefore, the objective of this study was two-fold: 1) to determine if maternal ENM exposure alters uterine and/or fetal microvascular function and 2) test the Barker Hypothesis at the microvascular level. Study Design Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide aerosols (11.3±0.039 (mg/m3)*hour, 5 hours/day, 8.2±0.85 days) to evaluate the maternal and fetal microvascular consequences of maternal exposure. Microvascular tissue isolation (gestation day 20) and arteriolar reactivity studies (<150μm passive diameter) of the uterine premyometrial and fetal tail arteries were conducted. Results ENM exposures led to significant maternal and fetal microvascular dysfunction which presented as robustly compromised endothelium-dependent and -independent reactivity to pharmacologic and mechanical stimuli. Isolated maternal uterine arteriolar reactivity was consistent with a metabolically impaired profile and hostile gestational environment, impacting fetal weight. The fetal microvessels isolated from exposed dams demonstrate significant impairments to signals of vasodilation specific to mechanistic signaling and shear stress. Conclusion To our knowledge, this is the first report providing evidence that maternal ENM inhalation is capable of influencing fetal health, thereby supporting that the Barker Hypothesis is applicable at the microvascular level. PMID:23643573

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.

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 development. Copyright © 2016 Elsevier Inc. All rights reserved.

Cooking fuel choices and garbage burning practices as determinants of birth weight: a cross-sectional study in Accra, Ghana

PubMed Central

2012-01-01

Background Effect of indoor air pollution (IAP) on birth weight remains largely unexplored but yet purported as the most important environmental exposure for pregnant women in developing countries due to the effects of second-hand smoke. We investigated the associations between the determinants of indoor air quality in households and birth weight. Methods A cross-sectional study of 592 mothers and their newborns using postnatal services at the Korle Bu Teaching Hospital located in Accra, Ghana was conducted in 2010 to collect information on characteristics of indoor environment and other potential determinants of fetal growth. Birth weight was recorded from hospital records. Results Household cooking fuel choices and garbage burning practices were determinants of birth weight. Multivariate linear regression analysis adjusting for age, social class, marital status and gravidity of mothers, and sex of neonate resulted in a 243g (95% CI: 496, 11) and 178g (95% CI: 421, 65) reduction in birth weight for use of charcoal, and garbage burning respectively compared with use of LPG only. The estimated reductions in birth weight was not statistically significant. Applying the ordinal scale exposure parameter nonetheless revealed a significant exposure-response relationship between maternal exposures from charcoal use and garbage burning, and birth weight. Generalized linear models adjusting for confounders resulted in a 41% (risk ratio [RR] = 1.41; 95% CI: 0.62, 3.23) and 195% (RR=2.95; 95% CI: 1.10, 7.92) increase in the risk of low birth weight (LBW) for use of charcoal, and garbage burning respectively compared with use of LPG only. A combination of charcoal use and household garbage burning during pregnancy on fetal growth resulted in a 429g (95% CI: 259, 599) reduction in birth weight and 316% (RR=4.16; 95% CI: 2.02, 8.59) excess risk of LBW. Sensitivity analysis performed by restricting the analysis to term births produced similar results. Conclusions Maternal use of charcoal as a cooking fuel during pregnancy and burning of garbage at home are strong determinants of average fetal growth and risk of LBW. Efforts to reduce maternal exposures to IAP are thus important to improve birth outcomes. PMID:23075225

Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project.

PubMed

Cheikh Ismail, L; Knight, H E; Bhutta, Z; Chumlea, W C

2013-09-01

The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards. © 2013 Royal College of Obstetricians and Gynaecologists.

Fetal bladder catheterization in severe obstructive uropathy before the 24th week of pregnancy.

PubMed

Szaflik, K; Kozarzewski, M; Adamczewski, D

1998-01-01

Fetal obstructive uropathy is simple to diagnose before the 24th week of life. Drainage of the pathologically enlarged fetal bladder avoids development of hydronephrosis and destruction of kidneys and, obviously, prevents development of secondary oligohydramnios and pulmonary hypoplasia. The aim of our study was to evaluate the usefulness of a fetal bladder shunt in cases of obstructive uropathy before the 24th week of gestation. From January 1997 we diagnosed 6 cases of fetal obstructive uropathy before the 24th week of gestation. In all cases oligohydramnios or ahydramnios was also observed. After evaluation of the renal function on the basis of fetal urine samples, we shunted 5 fetuses. After routine preparation of the operative field, a special puncture needle was inserted through the abdominal wall of mother and fetus into the fetal bladder. Through the needle a fetal bladder catheter was inserted between the fetal bladder and the amniotic sac. After shunt placement, fetal urine fills the amniotic sac and the fetal bladder is decompressed. After the procedure, the patients were hospitalized and serial sonographic examinations were performed to evaluate shunt function. Bladder size, presence and size of hydronephrosis, and volume of amniotic fluid were evaluated. The Rocket Medical catheters have an excellent 'shape memory'. All but 1 newborns had a good perinatal outcome. Mean Apgar score was 8 at 1 min, weight at delivery was between 1,700 and 3,100 g. No pulmonary hypoplasia was observed. All deliveries were after the 33rd week of gestation (range 33-38 weeks). The minimum drainage time was 11 weeks, maximum 18 weeks. In 2 cases premature delivery occurred because of premature rupture of the membranes. One newborn died of respiratory distress syndrome. Early bladder drainage (before the 24th week of gestation) enables delivery of newborns with a good perinatal outcome, without pulmonary hypoplasia. This method of therapy limits renal damage and allows time for normal development of the fetal lungs.

Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig.

PubMed

Harnett, Erica L; Dickinson, Michelle A; Smith, Graeme N

2007-08-01

This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury. Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 microg LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 using enzyme-linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain. Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mug/kg LPS (P < .05). The dose effect was brain region-dependent (P < .05). A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.

Assessment of fetal well-being in cattle by ultrasonography in normal, high-risk, and cloned pregnancies

PubMed Central

Buczinski, Sébastien; Fecteau, Gilles; Lefebvre, Réjean C.; Smith, Lawrence C.

2011-01-01

This study determined ultrasonographic parameters of fetuses and uterine adnexa in late pregnancy in normal, cloned, and high-risk pregnancies in relation to perinatal and neonatal outcome. Ten cows with normal pregnancies (CONTROL, mean pregnancy length 273 d), 10 sick cows with potentially compromised pregnancies (HIGH-RISK, mean pregnancy length 267 d), and 10 heifers with cloned pregnancies (CLONED, mean pregnancy length 274 d) were examined at more than 260 d of gestation. There was no difference in mean fetal heart rates among the groups. The cloned calves were heavier (57 ± 8 kg) than calves from CONTROL group (36 ± 7 kg), and calves from HIGH-RISK group (37 ± 13 kg) (P = 0.003). The diameter of the thoracic aorta was positively correlated (R = 0.62) with fetal birth weight in the CONTROL group (P = 0.01). Fetal activity was not associated with survival. The results suggest that transabdominal ultrasonographic assessment of the fetal well-being may serve as a potential tool for evaluation of the fetoplacental unit. PMID:21532817

Semi-automatic segmentation of the placenta into fetal and maternal compartments using intravoxel incoherent motion MRI

NASA Astrophysics Data System (ADS)

You, Wonsang; Andescavage, Nickie; Zun, Zungho; Limperopoulos, Catherine

2017-03-01

Intravoxel incoherent motion (IVIM) magnetic resonance imaging is an emerging non-invasive technique that has been recently applied to quantify in vivo global placental perfusion. We propose a robust semi-automated method for segmenting the placenta into fetal and maternal compartments from IVIM data, using a multi-label image segmentation algorithm called `GrowCut'. Placental IVIM data were acquired on a 1.5T scanner from 16 healthy pregnant women between 21-37 gestational weeks. The voxel-wise perfusion fraction was then estimated after non-rigid image registration. The seed regions of the fetal and maternal compartments were determined using structural T2-weighted reference images, and improved progressively through an iterative process of the GrowCut algorithm to accurately encompass fetal and maternal compartments. We demonstrated that the placental perfusion fraction decreased in both fetal (-0.010/week) and maternal compartments (-0.013/week) while their relative difference (ffetal-fmaternal) gradually increased with advancing gestational age (+0.003/week, p=0.065). Our preliminary results show that the proposed method was effective in distinguishing placental compartments using IVIM.

Fetal programming of appetite and obesity.

PubMed

Breier, B H; Vickers, M H; Ikenasio, B A; Chan, K Y; Wong, W P

2001-12-20

Obesity and related metabolic disorders are prevalent health issues in modern society and are commonly attributed to lifestyle and dietary factors. However, the mechanisms by which environmental factors modulate the physiological systems that control weight regulation and the aetiology of metabolic disorders, which manifest in adult life, may have their roots before birth. The 'fetal origins' or 'fetal programming' paradigm is based on the observation that environmental changes can reset the developmental path during intrauterine development leading to obesity and cardiovascular and metabolic disorders later in life. The pathogenesis is not based on genetic defects but on altered genetic expression as a consequence of an adaptation to environmental changes during fetal development. While many endocrine systems can be affected by fetal programming recent experimental studies suggest that leptin and insulin resistance are critical endocrine defects in the pathogenesis of programming-induced obesity and metabolic disorders. However, it remains to be determined whether postnatal obesity is a consequence of programming of appetite regulation and whether hyperphagia is the main underlying cause of the increased adiposity and the development of metabolic disorders.

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

PubMed

Krishna, Gokul; Muralidhara

2018-05-25

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Embryo-fetal development studies with the dietary supplement vinpocetine in the rat and rabbit.

PubMed

Catlin, Natasha; Waidyanatha, Suramya; Mylchreest, Eve; Miller-Pinsler, Lutfiya; Cunny, Helen; Foster, Paul; Sutherland, Vicki; McIntyre, Barry

2018-06-01

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child-bearing potential. Vinpocetine is a semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6-20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose-dependent increases in postimplantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose-dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in postimplantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine. © 2018 Wiley Periodicals, Inc.

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.

Maternal diabetes alters the development of ductus venosus shunting in the fetus.

PubMed

Lund, Agnethe; Ebbing, Cathrine; Rasmussen, Svein; Kiserud, Torvid W; Kessler, Jörg

2018-05-11

Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous (UV) distribution, including increased ductus venosus (DV) shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on UV and DV flow is not known. In this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36. The blood velocity and the mean diameters of the UV and DV were used for calculating blood flow volumes. The development of the UV flow, DV flow and DV shunt fraction (% of UV blood shunted through the DV) was compared with a reference population, and the effect of HbA 1c on the DV flow was assessed. The UV flow was larger in pregnancies with pregestational diabetes mellitus than in low-risk pregnancies (p<0.001), but smaller when normalized for fetal weight (p=0.036). The distributional pattern of the DV flow developed differently in diabetic pregnancies, particularly during the third trimester, being smaller (p=0.007), also when normalized for fetal weight (p<0.001). Correspondingly the DV shunt fraction was reduced (p<0.0001), most prominently at 36 weeks. There were negative relations between the maternal HbA 1c and the DV flow velocity, flow volume and shunt fraction. In pregnancies with pregestational diabetes mellitus, prioritized UV distribution to the fetal liver, and lower DV shunt capacity, both reduce the compensatory capability of the fetus and may represent an augmented risk during hypoxic challenges during late pregnancy and birth. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

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.

Effect of number of pig embryos in the uterus on their survival and development and on maternal metabolism.

PubMed

Père, M C; Dourmad, J Y; Etienne, M

1997-05-01

The effects of pig embryo number on fetal survival and growth and maternal metabolism were evaluated with 114 Large White gilts. Gilts were assigned at 38 kg to three treatments: control (CTR), ligature of the left oviduct (LIG), or right hemi-hysteroovariectomy (HHO). Insemination occurred at 311 +/- 18 d of age. A laparotomy was performed at d 35 of gestation, and gilts were slaughtered at d 112. Ovulation rate per uterine horn was 4.30, 8.70, and 17.12 in the LIG, CTR, and HHO groups, respectively. The hierarchy was the same for litter size at d 35 of gestation, but the relative differences were reduced (3.24, 5.98, and 8.40 fetuses/uterine horn, respectively). Litter size per uterine horn was similar in the CTR and HHO groups at d 112 of pregnancy (2.93, 4.69, and 4.76 fetuses in the LIG, CTR, and HHO groups, respectively). Early (before d 35 of gestation), late, and total fetal mortality increased with embryo potential per uterine horn. There was a compensation between early and late fetal mortality in the CTR and HHO groups. Fetal weight at d 112 was related to litter size in early pregnancy (1.50, 1.38, and 1.27 kg in the LIG, CTR, and HHO groups, respectively). Uterine capacity limits litter size and fetal development, even in sows with a conventional potential of embryos. Availability of energetic and gluconeogenic substrates was higher at 110 than at 60 d of gestation in the three groups. Blood substrate levels suggested that lipid mobilization and glucose uptake were higher in the gilts with a larger litter weight.

Maternal exposure to diluted diesel engine exhaust alters placental function and induces intergenerational effects in rabbits.

PubMed

Valentino, Sarah A; Tarrade, Anne; Aioun, Josiane; Mourier, Eve; Richard, Christophe; Dahirel, Michèle; Rousseau-Ralliard, Delphine; Fournier, Natalie; Aubrière, Marie-Christine; Lallemand, Marie-Sylvie; Camous, Sylvaine; Guinot, Marine; Charlier, Madia; Aujean, Etienne; Al Adhami, Hala; Fokkens, Paul H; Agier, Lydiane; Boere, John A; Cassee, Flemming R; Slama, Rémy; Chavatte-Palmer, Pascale

2016-07-26

Airborne pollution is a rising concern in urban areas. Epidemiological studies in humans and animal experiments using rodent models indicate that gestational exposure to airborne pollution, in particular diesel engine exhaust (DE), reduces birth weight, but effects depend on exposure duration, gestational window and nanoparticle (NP) concentration. Our aim was to evaluate the effects of gestational exposure to diluted DE on feto-placental development in a rabbit model. Pregnant females were exposed to diluted (1 mg/m(3)), filtered DE (NP diameter ≈ 69 nm) or clean air (controls) for 2 h/day, 5 days/week by nose-only exposure (total exposure: 20 days in a 31-day gestation). DE exposure induced early signs of growth retardation at mid gestation with decreased head length (p = 0.04) and umbilical pulse (p = 0.018). Near term, fetal head length (p = 0.029) and plasma insulin and IGF1 concentrations (p = 0.05 and p = 0.019) were reduced. Placental function was also affected, with reduced placental efficiency (fetal/placental weight) (p = 0.049), decreased placental blood flow (p = 0.009) and fetal vessel volume (p = 0.002). Non-aggregated and "fingerprint" NP were observed at various locations, in maternal blood space, in trophoblastic cells and in the fetal blood, demonstrating transplacental transfer. Adult female offspring were bred with control males. Although fetoplacental biometry was not affected near term, second generation fetal metabolism was modified by grand-dam exposure with decreased plasma cholesterol (p = 0.008) and increased triglyceride concentrations (p = 0.015). Repeated daily gestational exposure to DE at levels close to urban pollution can affect feto-placental development in the first and second generation.

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.

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.

Effects of maternal blood loss on embryonic and placental development in the rat.

PubMed

Bruce, N W; Cabral, D A

1975-11-01

The effects of acute loss of maternal blood on embryonic and placental development was examined in 50 rats on Days 8 or 9 of gestation. Blood was withdrawn from conscious, cannulated rats over a 1-min period at 1-0 or 2-0 ml/100 g body weight. These degrees of blood loss were expected to produce a mild (about 50%) and severe (about 80%) reduction in uterine blood flow, respectively, for at least 15 min. There was no evidence that loss of blood affected either fetal survival and malformation rates or fetal weights and sex ratios. The anaemia resulting from haemorrhage lasted no longer than 6 days. Placental weights were 11% higher in rats losing 2-0 ml blood/100 g than in controls (P less than 0-05). It appears that the 8- or 9- day rat embryo is highly resistant to the partial reduction in uterine blood flow, maternal anaemia and other possible challenges induced by maternal loss of blood at levels sufficient to affect the mothers.

How maternal malnutrition affects linear growth and development in the offspring.

PubMed

Papathakis, Peggy C; Singh, Lauren N; Manary, Mark J

2016-11-05

Maternal malnutrition is common in the developing world and has detrimental effects on both the mother and infant. Pre-pregnancy nutritional status and weight gain during pregnancy are positively related to fetal growth and development. Internationally, there is no agreement on the method of diagnosis or treatment of moderate or severe malnutrition during pregnancy. Establishing clear guidelines for diagnosis and treatment will be essential in elevating the problem. Possible anthropometric measurements used to detect and monitor maternal malnutrition include pre-pregnancy BMI, weight gain, and mid upper arm circumference. Food supplements have the potential to increase gestational weight gain and energy intake which are positively associated with fetal growth and development. Overall more studies are needed to conclude the impact of food/nutrient supplements on infant growth in undernourished pregnant women in developing countries. Currently, a study underway may provide much needed documentation of the benefits of treating malnutrition in pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dietary Iron Fortification Normalizes Fetal Hematology, Hepcidin, and Iron Distribution in a Rat Model of Prenatal Alcohol Exposure.

PubMed

Huebner, Shane M; Helfrich, Kaylee K; Saini, Nipun; Blohowiak, Sharon E; Cheng, Adrienne A; Kling, Pamela J; Smith, Susan M

2018-06-01

Prenatal alcohol exposure (PAE) causes neurodevelopmental disability. Clinical and animal studies show gestational iron deficiency (ID) exacerbates PAE's behavioral and growth deficits. In rat, PAE manifests an inability to establish iron homeostasis, increasing hepcidin (maternal and fetal), and fetal liver iron while decreasing brain iron and promoting anemia. Here, we hypothesize dietary iron fortification during pregnancy may mitigate alcohol's disruption of fetal iron homeostasis. Pregnant Long-Evans rats, fed iron-sufficient (100 ppm iron) or iron-fortified (IF; 500 ppm iron) diets, received either 5 g/kg alcohol (PAE) or isocaloric maltodextrin daily on gestational days (GD) 13.5 through 19.5. Maternal and fetal outcomes were evaluated on GD20.5. PAE reduced mean fetal weight (p < 0.001) regardless of maternal iron status, suggesting iron fortification did not improve fetal growth. Both PAE (p < 0.01) and IF (p = 0.035) increased fetal liver iron. In fetal brain, PAE (p = 0.015) affected total (p < 0.001) and nonheme iron (p < 0.001) such that iron fortification normalized (p = 0.99) the alcohol-mediated reductions in brain iron and nonheme iron. Iron fortification also improved fetal hematologic indices in PAE including hemoglobin, hematocrit, and mean cell volume (ps<0.001). Iron fortification also normalized hepcidin expression in alcohol-exposed maternal and fetal liver. Neither diet nor PAE affected transferrin (Tf) and ferritin (FTN) content in fetal liver, nor Tf or transferrin receptor in fetal brain. However, IF-PAE fetal brains trended to less FTN content (p = 0.074), suggesting greater availability of nonstorage iron. In PAE, hepcidin levels were linearly related to increased liver iron stores and decreased red blood cell count and brain iron. Maternal oral iron fortification mitigated PAE's disruption of fetal iron homeostasis and improved brain iron content, hematologic indices, and hepcidin production in this rat PAE model. Clinical studies show maternal ID substantially enhances fetal vulnerability to PAE, and our work supports increased maternal dietary iron intake may improve fetal iron status in alcohol-exposed pregnancies. Copyright © 2018 by the Research Society on Alcoholism.

In utero exposure to chloroquine alters sexual development in the male fetal rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clewell, Rebecca A.; Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709; Pluta, Linda

Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenancemore » doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.« less

Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

PubMed Central

Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

2016-01-01

Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

Cell-based and biomaterial approaches to connective tissue repair

NASA Astrophysics Data System (ADS)

Stalling, Simone Suzette

Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in vitro as well as in a subcutaneous mouse model. Stable MA-MC hydrogels, of varying weight percentages, demonstrated tunable swelling and mechanical properties in the absence of cytotoxic degradation products. In vivo, 6wt% MA-MC hydrogels maintained their shape and mechanical integrity while eliciting a minimal inflammatory response; highly desirable properties for soft tissue reconstruction. These cellulose-based photopolymerizable hydrogels can be further optimized for drug delivery and tissue engineering applications to enhance wound repair.

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

Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2012-06-01

The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2 ± 4.3 ng/ml in the IUGR group, 14.1 ± 3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1 ± 3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6 ± 3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and blood pressure and inverse correlation between endoglin and infant birth weight and additionally higher levels of ENG in patients with pregnancy complicated by HELLP syndrome (hemolysis, increased liver enzymes, low platelet count) or eclampsia suggest that endoglin may be a marker of severity of these pregnancy disorders.

Reported Estimates of Adverse Pregnancy Outcomes among Women with and without Syphilis: A Systematic Review and Meta-Analysis

PubMed Central

Qin, Jiabi; Yang, Tubao; Xiao, Shuiyuan; Tan, Hongzhuan; Feng, Tiejian; Fu, Hanlin

2014-01-01

Background To estimate probability of adverse pregnancy outcomes (APOs) among women with and without syphilis through a systematic review of published literatures. Methodology/Principal Findings Chinese and English literatures were searched for studies assessing pregnancy outcomes in the presence of maternal syphilis through August 2013. The prevalence estimates were summarized and analyzed by meta-analysis. Fifty-four literatures involving 11398 syphilitic women and 43342 non-syphilitic women were included from 4187 records initially found. Among untreated mothers with syphilis, pooled estimates were 76.8% for all APOs, 36.0% for congenital syphilis, 23.2% for preterm, 23.4% for low birth weight, 26.4% for stillbirth or fetal loss, 14.9% for miscarriage and 16.2% for neonatal deaths. Among syphilitic mother receiving treatment only in the late trimester (>28 weeks), pooled estimates were 64.4% for APOs, 40.6% for congenital syphilis, 17.6% for preterm, 12.4% for low birth weight, and 21.3% for stillbirth or fetal loss. Among syphilitic mothers with high titers (≥1∶8), pooled estimates were 42.8% for all APOs, 25.8% for congenital syphilis, 15.1% for preterm, 9.4% for low birth weight, 14.6% for stillbirth or fetal loss and 16.0% for neonatal deaths. Among non-syphilitic mothers, the pooled estimates were 13.7% for all APOs, 7.2% for preterm birth, 4.5% for low birth weight, 3.7% for stillbirth or fetal loss, 2.3% for miscarriage and 2.0% for neonatal death. Begg's rank correlation test indicated little evidence of publication bias (P>0.10). Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (I 2 = 93.9%; P<0.0001) and women without syphilis (I 2 = 94.8%; P<0.0001). Conclusions/Significance Syphilis continues to be an important cause of substantial perinatal morbidity and mortality, which reminds that policy-makers charged with resource allocation that the elimination of mother-to-child transmission of syphilis is a public health priority. PMID:25025232

The Bidirectional Transfer and Fetal Vascular Pressure Changes Due to the Presence of 125 I-Labeled Inhibin A in the ex-vivo Human Placental Model

PubMed Central

Ghetie, Victor

2003-01-01

Objective: The purpose of this study was to investigate the transport of inhibin A and to determine its effects on fetal vascular pressure at elevated levels in the human placenta using 125I -labeled synthetic glycoprotein. Methods: Synthetic inhibinAwas prepared and was shown to be consistent with the natural form by high-pressure liquid chromatography (HPLC) and molecular weight determination by gas-chromatography mass spectrometry. The standardized Na125I process yielded 125I -labeled inhibin A with a radioactivity of 106 cpm/μg. This compound was placed in the human placenta in maternal–fetal and fetal–maternal studies using antipyrine and 14C -labeled inulin as controls to determine the bidirectional transfer of the compound. Results: Maternal–fetal and fetal–maternal clearance indices were 0.045± 0.003 and 0, respectively. In eight placentas there was no evidence of vascular pressure changes due to the presence of up to 5000 pg of inhibin A. Conclusions: There is minimal maternal–fetal transfer and no detectable fetal–maternal transfer in normotensive and pregnancy-induced hypertensive placentas. In addition, there are no pressure changes in the fetal vascular system due to the clinically significant levels of inhibin A. PMID:14627215

Matching of maternal and fetal flow ratios in the sheep placenta.

PubMed

Stock, M K; Reid, D L; Phernetton, T M; Rankin, J H

1989-01-01

Local interaction of maternal and fetal placental blood flows was studied in two groups of unanaesthetized near-term sheep. Five sheep were exposed to a simulated dive to 100 feet of seawater (4.03 atmospheres) for 25 min. Six fetuses received an infusion of noradrenaline (6.8 micrograms/[kg x min]). Radioactive microspheres were administered simultaneously to mother and fetus before (control) and after (test) the experimental manipulation. Maternal and fetal relative activities, defined as % of total placental radioactivity divided by % of total placental weight, were calculated for 1-g pieces of cotyledonary tissue under control and test conditions. Pieces of cotyledons were defined as matched if the direction of change in relative activity from control to test was the same for mother and fetus. In the absence of an interaction between the maternal and fetal placental circulations, the probability of a piece of cotyledon being matched is 0.5. In each series of experiments the proportion of all cotyledon pieces having maternal and fetal relative activities that changed in the same direction was significantly greater than 0.5. Thus, the majority of the placental mass responds to a physical or chemical perturbation of the fetus in such a way that changes in relative perfusion are qualitatively matched in the adjacent maternal and fetal placental circulations.

Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy.

PubMed

Suzumori, Nobuhiro; Sekizawa, Akihiko; Ebara, Takeshi; Samura, Osamu; Sasaki, Aiko; Akaishi, Rina; Wada, Seiji; Hamanoue, Haruka; Hirahara, Fumiki; Izumi, Haruna; Sawai, Hideaki; Nakamura, Hiroaki; Yamada, Takahiro; Miura, Kiyonori; Masuzaki, Hideaki; Yamashita, Takahiro; Okai, Takashi; Kamei, Yoshimasa; Namba, Akira; Murotsuki, Jun; Tanemoto, Tomohiro; Fukushima, Akimune; Haino, Kazufumi; Tairaku, Shinya; Matsubara, Keiichi; Maeda, Kazutoshi; Kaji, Takashi; Ogawa, Masanobu; Osada, Hisao; Nishizawa, Haruki; Okamoto, Yoko; Kanagawa, Takeshi; Kakigano, Aiko; Kitagawa, Michihiro; Ogawa, Masaki; Izumi, Shunichiro; Katagiri, Yukiko; Takeshita, Naoki; Kasai, Yasuyo; Naruse, Katsuhiko; Neki, Reiko; Masuyama, Hisashi; Hyodo, Maki; Kawano, Yukie; Ohba, Takashi; Ichizuka, Kiyotake; Nagamatsu, Takeshi; Watanabe, Atsushi; Shirato, Nahoko; Yotsumoto, Junko; Nishiyama, Miyuki; Hirose, Tatsuko; Sago, Haruhiko

2018-05-01

The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlation between fetal mild ventriculomegaly and biometric parameters.

PubMed

Fishel-Bartal, Michal; Shai, Daniel; Shina, Avi; Achiron, Reuven; Katorza, Eldad

2017-09-19

The aim of this study was to assess the correlation between fetal lateral ventricle width and biometric measurements. A prospective study on 335 fetuses, 101 fetuses with isolated mild ventriculomegaly and a control group of 234 fetuses with a normal US examination. All fetuses underwent a detailed brain ultrasound scan and a full biometric evaluation. To further compare biometric parameters, we matched, according to gestational week and gender, 91 fetuses from the study group to 91 fetuses from the control group. The mean gestational week during the exam was significantly different between the groups (29.6 weeks in the study group versus 28.3 in the control group, p = .001). The mean maternal age, obstetrical history, mode of conception, or fetal gender did not differ between the groups. After matching according to gestational age and fetal gender, the mean gestational week between the matched groups did not differ and was 29 + 5 weeks in both groups. The study group had significantly larger head circumference (p = .009), biparietal diameter (p < .001), femur length (p = .023), and estimated fetal weight (p = .024) compared with the control group. Isolated mild ventriculomegaly could be related to other larger fetal biometric measurements and does not necessarily mean a pathological condition.

Adverse factors increase preeclampsia-like changes in pregnant mice with abnormal lipid metabolism.

PubMed

Ding, Xiaoyan; Yang, Zi; Han, Yiwei; Yu, Huan

2014-01-01

Preeclampsia (PE) is a multifactorial pregnancy complication. Maternal underlying condition and adverse factors both influence the pathogenesis of PE. Abnormal lipid metabolism as a maternal underlying disease may participate in the occurrence and development of PE. This study aimed to observe the effects of adverse factors on PE-like symptoms of pregnant mice with genetic abnormal lipid metabolism. Apolipoprotein C-III (ApoC3) transgenic mice with abnormal lipid metabolism were subcutaneously injected with L-arginine methyl ester (L-NAME) or normal saline (NS) daily starting at Day 7 or 16 of pregnancy (ApoC3+L-NA and ApoC3+NS groups), and wild-type (WT) mice served as a control (WT+L-NA and WT+NS groups). All mice were subdivided into early and late subgroups by injection time. The mean arterial pressure (MAP) and urinary protein were measured. Pregnancy outcomes, including fetal weight, placental weight, live birth rate, and fetal absorption rate, were analyzed. Pathologic changes in the placenta were observed by hematoxylin-eosin staining. One-way analysis of variance, t-test, and χ(2) test were used for statistical analysis. MAP significantly increased for ApoC3+NS groups compared with WT+NS groups (P < 0.05), without significant difference in urine protein. Following L-NAME injection, MAP and urinary protein significantly increased for ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), and the increase for ApoC3+L-NA was more obvious. Urinary protein levels in early ApoC3+L-NA and WT+L-NA significantly increased compared with the corresponding late groups (P < 0.05). Fetal absorption rate significantly increased and fetal and placental weights significantly decreased in early ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), without significant difference in late ApoC3+L-NA and WT+L-NA groups. Fetal weight in early ApoC3+L-NA was significantly lower than in early WT+L-NA group (P < 0.05). Morphologic examination of placentas from early ApoC3+L-NA and WT+L-NA groups showed varying degrees of fibrinoid necrosis. ApoC3 transgenic mice with abnormal lipid metabolism showed gestational hypertension. Adverse factors and early effect time could aggravate the PE-like symptoms for ApoC3 transgenic mice.

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 gestation constructed in this study may provide a useful tool for a more accurate assessment of fetal growth in twin pregnancies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight.

PubMed

Green, Benjamin B; Armstrong, David A; Lesseur, Corina; Paquette, Alison G; Guerin, Dylan J; Kwan, Lauren E; Marsit, Carmen J

2015-06-01

Maternal stress has been linked to infant birth weight outcomes, which itself may be associated with health later in life. The placenta acts as a master regulator for the fetal environment, mediating intrauterine exposures to stress through the activity of genes regulating glucocorticoids, including the 11beta-hydroxysteroid dehydrogenase (HSD11B) type 1 and 2 genes, and so we hypothesized that variation in these genes will be associated with infant birth weight. We investigated DNA methylation levels at six sites across the two genes, as well as mRNA expression for each, and the relationship to infant birth weight. Logistic regressions correcting for potential confounding factors revealed a significant association between methylation at a single CpG site within HSD11B1 and being born large for gestational age. In addition, our analysis identified correlations between methylation and gene expression, including sex-specific transcriptional regulation of HSD11B2. Our work is one of the first comprehensive views of DNA methylation and expression in the placenta for both HSD11B types 1 and 2, linking epigenetic alterations with the regulation of fetal stress and birth weight outcomes. © 2015 by the Society for the Study of Reproduction, Inc.

Serum Levels of Fetal Antigen 1 in Extreme Nutritional States

PubMed Central

Andries, Alin; Niemeier, Andreas; Støving, Rene K.; Abdallah, Basem M.; Wolf, Anna-Maria; Hørder, Kirsten; Kassem, Moustapha

2012-01-01

Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum concentrations were assessed in a cross-sectional study design at defined time points after gastric restrictive surgery for 25 MO patients and 15 women with AN. Results. Absolute FA1 serum levels were within the assay normal range and were not different between the groups at baseline. However, the ratio of FA1/BMI was significantly higher in AN. FA1 was inversely correlated with BMI before and after weight change in AN, but not in MO patients. In addition, MO patients displayed a significant concomitant decrease of FA1 and insulin with the first 25% of EWL, while in AN patients a significant increase of FA1 was observed in association with weight gain. Conclusion. FA1 is a sensitive indicator of metabolic adaptation during weight change. While FA1 serum levels in humans generally do not correlate with BMI, our results suggest that changes in FA1 serum levels reflect changes in adipose tissue turnover. PMID:22844611

Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus

PubMed Central

Wang, Kimberley C W; Brooks, Doug A; Thornburg, Kent L; Morrison, Janna L

2012-01-01

In vitro studies using rat and fetal sheep cardiomyocytes indicate that, in addition to its role as a clearance receptor, the insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy. In the present study, we have determined the effect of specific activation of the IGF-2R in the heart of the late gestation fetus on cardiomyocyte development. Leu27IGF-2, an IGF-2R agonist, was infused into the fetal left circumflex coronary artery for 4 days beginning at 128.1 ± 0.4 days gestation. Ewes were humanely killed at 132.2 ± 1.2 days gestation (term, 150 days). Fetuses were delivered and hearts dissected to isolate the cardiomyocytes and to collect and snap-freeze tissue. Leu27IGF-2 infusion into the left circumflex coronary artery of fetal sheep increased the area of binucleated cardiomyocytes in the left, but not the right, ventricle. However, this infusion of Leu27IGF-2 did not change fetal weight, heart weight, blood pressure, blood gases or cardiomyocyte proliferation/binucleation. The increase in cardiomyocyte size in the Leu27IGF-2-infused group was associated with increased expression of proteins in the Gαs, but not the Gαq, signalling pathway. We concluded that infusion of Leu27IGF-2 into the left circumflex coronary artery causes cardiac IGF-2R activation in the left ventricle of the heart, and this stimulates cardiomyocyte hypertrophy in a Gαs-dependent manner. PMID:22930271

The Association Between Maternal Subclinical Hypothyroidism and Growth, Development, and Childhood Intelligence: A Meta-analysis

PubMed

Liu, Yahong; Chen, Hui; Jing, Chen; Li, FuPin

2018-06-01

To explore the association between maternal subclinical hypothyroidism (SCH) in pregnancy and the somatic and intellectual development of their offspring. Using RevMan 5.3 software, a meta-analysis of cohort studies published from inception to May 2017, focusing on the association between maternal SCH in pregnancy and childhood growth, development and intelligence, was performed. Sources included the Cochrane Library, Pub-Med, Web of Science, China National Knowledge Infrastructure and Wan Fang Data. Analysis of a total of 15 cohort studies involving 1.896 pregnant women with SCH revealed that SCH in pregnancy was significantly associated with the intelligence (p=0.0007) and motor development (p<0.00001) of the offspring. SCH was also significantly associated with the child’s weight in four studies involving 222 women (p=0.02). Maternal SCH in pregnancy was identified as a risk factor for fetal growth restriction with a combined relative risk (RR) value of 2.4 [95% confidence interval (CI): 1.56, 3.7]. Meta-analysis of 10 studies that provided numbers of preterm infants revealed a significant association between maternal SCH in pregnancy and premature delivery, with a combined RR of 1.96 (95% CI: 1.34, 2.88). There was a significant effect of maternal SCH in pregnancy on fetal distress in utero (p=0.003). Maternal SCH in pregnancy is associated with increased risk of adverse neonatal outcomes, including delayed intellectual and motor development, low birth weight, premature delivery, fetal distress and fetal growth restriction.

Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus.

PubMed

Mahmoudian, Alireza; Rajaei, Ziba; Haghir, Hossein; Banihashemian, Shahaboldin; Hami, Javad

2012-04-01

The aim of the present study was to determine the effects of valerian (Valeriana officinalis) consumption in pregnancy on cortical volume and the levels of zinc and copper, two essential elements that affect brain development and function, in the brain tissues of mouse fetuses. Pregnant female mice were treated with either saline or 1.2 g/kg body weight valerian extract intraperitoneally daily on gestation days (GD) 7 to 17. On GD 20, mice were sacrificed and their fetuses were collected. Fetal brains were dissected, weighed and processed for histological analysis. The volume of cerebral cortex was estimated by the Cavalieri principle. The levels of zinc and copper in the brain tissues were measured by atomic absorption spectroscopy. The results indicated that valerian consumption in pregnancy had no significant effect on brain weight, cerebral cortex volume and copper level in fetal brain. However,it significantly decreased the level of zinc in the brain (P<0.05). Using valerian during midgestation do not have an adverse effect on cerebral cortex; however,it caused a significant decrease in zinc level in the fetal brain. This suggests that valerian use should be limited during pregnancy.

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.

[Severe neonatal hyperthyroidism which reveals a maternal Graves' disease].

PubMed

Guérin, B; Vautier, V; Boin-Gay, V; Estrade, G; Choulot, J-J; Doireau, V

2004-04-01

Two of every thousand pregnancies are complicated by Graves' disease. Diagnosis is suggested by maternal disorders (tachycardia, exophthalmia, weight loss.) or fetal disorders (tachycardia, intra-uterine growth retardation, preterm birth.). Due to transfer into the fetal compartment of maternal antibodies which stimulate the fetal thyroid by binding to the thyroid thyrotropin (TSH) receptor, only 1% of children born to these mothers are described as having hyperthyroidism. Neonatal thyrotoxicosis disappears with clearance of the maternal antibodies; clinical signs usually disappear during the first four Months of life. The most frequent neonatal clinical signs of thyrotoxicosis are tachycardia, goiter, hyperexcitability, poor weight gain, hepatosplenomegaly, stare and eyelid retraction. Diagnosis is based on determination of the blood level of triiodothyronine (T3), thyroxine (T4) and TSH. To confirm the nature of hyperthyroidism, thyroid-stimulating immunoglobulins (TSI) should be assayed. The kinetics of TSI provides a guide for therapeutic adaptation and disappearance of TSI is a sign of recovery. Rare cases of familial non-autoimmune hyperthyroidism have been shown to be caused by germline mutation of the thyrotropin receptor. We report a case of severe neonatal hyperthyroidism which led to the diagnosis of maternal Graves' disease.

Severe perineal lacerations in nulliparous women and episiotomy type.

PubMed

Aytan, Hakan; Tapisiz, Omer L; Tuncay, Gorkem; Avsar, Filiz A

2005-07-01

To determine the patient-related factors associated with severe perineal lacerations in nulliparous women and to evaluate the effect of episiotomy type on the risk of severe perineal tears. In all, 400 nulliparous women admitted in labor between June and December 2001 were prospectively enrolled. Maternal height, perineal length, fetal birth weight, fetal head circumference, and severe perineal lacerations (third and fourth degrees) were recorded. The rate of severe perineal lacerations was 2% (8/400); 3% with midline, 1% with mediolateral groups. In patients with severe lacerations, perineal length was significantly (p < 0.001) shorter and the head circumference of their babies in the midline significantly (p < 0.05) greater than normal, and birth weights were also significantly (p < 0.05) greater in the mediolateral group. A cut-off value for perineal length of 3.05 cm was found for severe lacerations in the midline group. If episiotomy is to be performed, it must be borne in mind that patients with a perineal length of < or = 3 cm have an elevated risk of severe perineal lacerations, and if clinical or ultrasound examination suggests that the fetal head is large, mediolateral episiotomy may be preferred. Otherwise, midline episiotomy must be considered.

Fetal exposure to environmental neurotoxins in Taiwan.

PubMed

Jiang, Chuen-Bin; Hsi, Hsing-Cheng; Fan, Chun-Hua; Chien, Ling-Chu

2014-01-01

Mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) are recognized neurotoxins in children that particularly affect neurodevelopment and intellectual performance. Based on the hypothesis that the fetal basis of adult disease is fetal toxic exposure that results in adverse outcomes in adulthood, we explored the concentrations of key neurotoxins (i.e., Hg, Pb, Cd, and As) in meconium to identify the risk factors associated with these concentrations. From January 2007 to December 2009, 545 mother-infant pairs were recruited. The geometric mean concentrations of Pb and As in the meconium of babies of foreign-born mothers (22.9 and 38.1 µg/kg dry weight, respectively) were significantly greater than those of babies of Taiwan-born mothers (17.5 and 33.0 µg/kg dry weight, respectively). Maternal age (≥30 y), maternal education, use of traditional Chinese herbs during pregnancy, and fish cutlet consumption (≥3 meals/wk) were risk factors associated with concentrations of key prenatal neurotoxins. The Taiwan government should focus more attention on providing intervention programs for immigrant mothers to help protect the health of unborn babies. Further investigation on how multiple neurotoxins influence prenatal neurodevelopment is warranted.

Fetal Exposure to Environmental Neurotoxins in Taiwan

PubMed Central

Jiang, Chuen-Bin; Hsi, Hsing-Cheng; Fan, Chun-Hua; Chien, Ling-Chu

2014-01-01

Mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) are recognized neurotoxins in children that particularly affect neurodevelopment and intellectual performance. Based on the hypothesis that the fetal basis of adult disease is fetal toxic exposure that results in adverse outcomes in adulthood, we explored the concentrations of key neurotoxins (i.e., Hg, Pb, Cd, and As) in meconium to identify the risk factors associated with these concentrations. From January 2007 to December 2009, 545 mother-infant pairs were recruited. The geometric mean concentrations of Pb and As in the meconium of babies of foreign-born mothers (22.9 and 38.1 µg/kg dry weight, respectively) were significantly greater than those of babies of Taiwan-born mothers (17.5 and 33.0 µg/kg dry weight, respectively). Maternal age (≥30 y), maternal education, use of traditional Chinese herbs during pregnancy, and fish cutlet consumption (≥3 meals/wk) were risk factors associated with concentrations of key prenatal neurotoxins. The Taiwan government should focus more attention on providing intervention programs for immigrant mothers to help protect the health of unborn babies. Further investigation on how multiple neurotoxins influence prenatal neurodevelopment is warranted. PMID:25299345

Ocular growth in the fetus. 1. Comparative study of axial length and biometric parameters in the fetus.

PubMed

Denis, D; Righini, M; Scheiner, C; Volot, F; Boubli, L; Dezard, X; Vola, J; Saracco, J B

1993-01-01

The knowledge of ocular growth during fetal life, when compared with other fetal biometric parameters, could not only provide a better definition of malformation syndromes but could also give a better understanding of certain pathological processes in premature babies and in newborns. As the literature concerning prenatal ocular dimensions contains few data, the aim of this study was to measure the axial length of the globe (AL) in fetuses and compare this measurement with their gestational age, weight, height, head circumference (HC) and thoracic circumference (TC) in order to compile a reference table. In the present study, 76 globes from 38 fetuses (18-41 weeks gestational age) from the Department of Pathology (Timone University Hospital, Marseille) were examined. Ultrasonography A and B were used to measure the AL, and a pathological examination determined fetal weight, HC, TC and height. We were interested to find out which of the parameters studied would give the best correlation with ocular growth. Statistical analysis showed that HC remained the most discriminant factor and correlated best with ocular growth. We thus obtained an equation for ocular size according to HC that could serve as a basis for detecting pre- or postnatal ocular defects.

Maternal Nutritional Status Predicts Adverse Birth Outcomes among HIV-Infected Rural Ugandan Women Receiving Combination Antiretroviral Therapy

PubMed Central

Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

2012-01-01

Objective Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Design Prospective cohort. Methods HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Results Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. Conclusions In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Trial Registration Clinicaltrials.gov NCT00993031 PMID:22879899

Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

PubMed

Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

2012-01-01

Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Prospective cohort. HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Clinicaltrials.gov NCT00993031.

Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: An experimental study in mice.

PubMed

Benevenuto, Sarah G; Domenico, Marlise D; Martins, Marco Antônio G; Costa, Natália S; de Souza, Ana Rosa L; Costa, Jose L; Tavares, Marina F M; Dolhnikoff, Marisa; Veras, Mariana Matera

2017-02-01

The prevalence of marijuana use among pregnant women is high. However, the effects on gestation and fetal development are not well known. Epidemiological and experimental studies present conflicting results because of the route of administration, dose, time of exposure, species used, and how Cannabis toxicity is tested (prepared extracts, specific components, or by pyrolysis). In this study, we experimentally investigated the effects of maternal inhalation of Cannabis sativa smoke representing as nearly as possible real world conditions of human marijuana use. Pregnant mice (n=20) were exposed (nose-only) daily for 5min to marijuana smoke (0.2g of Cannabis) from gestational day (GD) 5.5 to GD17.5 or filtered air. Food intake and maternal weight gain were recorded. Ultrasound biomicroscopy was performed on 10.5 and 16.5dpc.On GD18.5, half of the dams were euthanized for the evaluation of term fetus, placenta, and resorptions. Gestation length, parturition, and neonatal outcomes were evaluated in the other half. Five minutes of daily (low dose) exposure during pregnancy resulted in reduced birthweight, and litter size was not altered; however, the number of male pups per litter was higher. Besides, placental wet weight was increased and fetal to placental weight ratio was decreased in male fetuses, showing a sex-specific effect. At the end of gestation, females from the Cannabis group presented reduced maternal net body weight gain, despite a slight increase in their daily food intake compared to the control group. In conclusion, our results indicate that smoking marijuana during pregnancy even at low doses can be embryotoxic and fetotoxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

The Electric Field and Waves Instruments on the Radiation Belt Storm Probes Mission

NASA Astrophysics Data System (ADS)

Wygant, J. R.; Bonnell, J. W.; Goetz, K.; Ergun, R. E.; Mozer, F. S.; Bale, S. D.; Ludlam, M.; Turin, P.; Harvey, P. R.; Hochmann, R.; Harps, K.; Dalton, G.; McCauley, J.; Rachelson, W.; Gordon, D.; Donakowski, B.; Shultz, C.; Smith, C.; Diaz-Aguado, M.; Fischer, J.; Heavner, S.; Berg, P.; Malsapina, D. M.; Bolton, M. K.; Hudson, M.; Strangeway, R. J.; Baker, D. N.; Li, X.; Albert, J.; Foster, J. C.; Chaston, C. C.; Mann, I.; Donovan, E.; Cully, C. M.; Cattell, C. A.; Krasnoselskikh, V.; Kersten, K.; Brenneman, A.; Tao, J. B.

2013-11-01

The Electric Fields and Waves (EFW) Instruments on the two Radiation Belt Storm Probe (RBSP) spacecraft (recently renamed the Van Allen Probes) are designed to measure three dimensional quasi-static and low frequency electric fields and waves associated with the major mechanisms responsible for the acceleration of energetic charged particles in the inner magnetosphere of the Earth. For this measurement, the instrument uses two pairs of spherical double probe sensors at the ends of orthogonal centripetally deployed booms in the spin plane with tip-to-tip separations of 100 meters. The third component of the electric field is measured by two spherical sensors separated by ˜15 m, deployed at the ends of two stacer booms oppositely directed along the spin axis of the spacecraft. The instrument provides a continuous stream of measurements over the entire orbit of the low frequency electric field vector at 32 samples/s in a survey mode. This survey mode also includes measurements of spacecraft potential to provide information on thermal electron plasma variations and structure. Survey mode spectral information allows the continuous evaluation of the peak value and spectral power in electric, magnetic and density fluctuations from several Hz to 6.5 kHz. On-board cross-spectral data allows the calculation of field-aligned wave Poynting flux along the magnetic field. For higher frequency waveform information, two different programmable burst memories are used with nominal sampling rates of 512 samples/s and 16 k samples/s. The EFW burst modes provide targeted measurements over brief time intervals of 3-d electric fields, 3-d wave magnetic fields (from the EMFISIS magnetic search coil sensors), and spacecraft potential. In the burst modes all six sensor-spacecraft potential measurements are telemetered enabling interferometric timing of small-scale plasma structures. In the first burst mode, the instrument stores all or a substantial fraction of the high frequency measurements in a 32 gigabyte burst memory. The sub-intervals to be downloaded are uplinked by ground command after inspection of instrument survey data and other information available on the ground. The second burst mode involves autonomous storing and playback of data controlled by flight software algorithms, which assess the "highest quality" events on the basis of instrument measurements and information from other instruments available on orbit. The EFW instrument provides 3-d wave electric field signals with a frequency response up to 400 kHz to the EMFISIS instrument for analysis and telemetry (Kletzing et al. Space Sci. Rev. 2013).

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.

Effects of estrogen coadministration on epoxiconazole toxicity in rats.

PubMed

Stinchcombe, Stefan; Schneider, Steffen; Fegert, Ivana; Rey Moreno, Maria Cecilia; Strauss, Volker; Gröters, Sibylle; Fabian, Eric; Fussell, Karma C; Pigott, Geoffrey H; van Ravenzwaay, Bennard

2013-06-01

Epoxiconazole (EPX; CAS-No. 133855-98-8) is a triazole class-active substance of plant protection products. At a dose level of 50 mg/kg bw/day, it causes a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (gestation day [GD] 7-18 or 21), as reported previously (Taxvig et al., 2007, 2008) and confirmed in these studies. Late fetal resorptions occurred in the presence of significant maternal toxicity such as clear reduction of corrected body weight gain, signs of anemia, and, critically, a marked reduction of maternal estradiol plasma levels. Furthermore, estradiol supplementation at dose levels of 0.5 or 1.0 μg/animal/day of estradiol cyclopentylpropionate abolished the EPX-mediated late fetal resorptions. No increased incidences of external malformations were found in rats cotreated with 50 mg/kg bw/day EPX and estradiol cyclopentylpropionate, indicating that the occurrence of malformations was not masked by fetal mortality under the study conditions. Overall, the study data indicate that fetal mortality observed in rat studies with EPX is not the result of direct fetal toxicity but occurs indirectly via depletion of maternal estradiol levels. The clarification of the human relevance of the estrogen-related mechanism behind EPX-mediated late fetal resorptions in rats warrants further studies. In particular, this should involve investigation of the placenta (Rey Moreno et al., 2013), since it is the materno-fetal interface and crucial for fetal maintenance. The human relevance is best addressed in a species which is closer to humans with reference to placentation and hormonal regulation of pregnancy, such as the guinea pig (Schneider et al., 2013). © 2013 Wiley Periodicals, Inc.

Effect of a micronutrient‐rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP)

PubMed Central

Lawande, Ashwin; Di Gravio, Chiara; Potdar, Ramesh D.; Sahariah, Sirazul A.; Gandhi, Meera; Chopra, Harsha; Sane, Harshad; Kehoe, Sarah H.; Marley‐Zagar, Ella; Margetts, Barrie M.; Jackson, Alan A.

2017-01-01

Abstract Improving micronutrient intakes of under‐nourished mothers in low‐ and middle‐income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food‐based supplement affected fetal growth. Non‐pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient‐rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower‐micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First‐trimester (median: 10 weeks, interquartile range: 9–12 weeks) fetal crown‐rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19–20 weeks) and third trimesters (29, 28–30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient‐rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative. PMID:28251804

Effect of a micronutrient-rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP).

PubMed

Lawande, Ashwin; Di Gravio, Chiara; Potdar, Ramesh D; Sahariah, Sirazul A; Gandhi, Meera; Chopra, Harsha; Sane, Harshad; Kehoe, Sarah H; Marley-Zagar, Ella; Margetts, Barrie M; Jackson, Alan A; Fall, Caroline H D

2018-01-01

Improving micronutrient intakes of under-nourished mothers in low- and middle-income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food-based supplement affected fetal growth. Non-pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient-rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower-micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First-trimester (median: 10 weeks, interquartile range: 9-12 weeks) fetal crown-rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19-20 weeks) and third trimesters (29, 28-30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient-rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative. © 2017 The Authors. Maternal & Child Nutrition Published by John Wiley & Sons Ltd.

Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

Evaluation of maternal and perinatal outcomes among overweight women who experienced stillbirth.

PubMed

Çınar, Mehmet; Timur, Hakan; Aksoy, Rıfat Taner; Güzel, Ali İrfan; Tokmak, Aytekin; Bedir Fındık, Rahime; Uygur, Dilek

2017-01-01

To investigate associations between overweight and adverse clinical outcomes among women who experienced stillbirth. 234 pregnant women (stillbirth group, n = 115; live birth group, n = 119) were included in this retrospective case-control study. Recorded risk factors were age, gravidity, parity, gestational weeks, fetal birth weight, gestational diabetes mellitus (GDM), preeclampsia (PE), intrauterine growth restriction (IUGR), levels of prenatal test markers (alpha-fetoprotein (AFP), pregnancy-associated plasma protein, human chorionic gonadotropin (β-hCG) and E3) and body mass index (BMI). Statistically significant differences were observed between the groups in terms of birth weight, IUGR, GDM, PE, AFP level, β-hCG level, maternal E3 level and BMI (p < 0.05). Subgroup analyses revealed that 34 and 81 patients in the stillbirth group were of normal weight and overweight, respectively, fetal birth weight, IUGR, GDM, PE, AFP level, β-hCG level and E3 level differed significantly between these subgroups and the live birth group (p < 0.05). Women who experience stillbirth tend to be more overweight than those who experience live birth. Additionally, IUGR, GDM and PE are more common among overweight women. Therefore, overweight women should be encouraged to lose weight before pregnancy. If they become pregnant without losing weight, they should be followed up closely to avoid adverse perinatal outcomes.

Position of the Academy of Nutrition and Dietetics: Obesity, Reproduction, and Pregnancy Outcomes.

PubMed

Stang, Jamie; Huffman, Laurel G

2016-04-01

It is the position of the Academy of Nutrition and Dietetics that all women of reproductive age receive education about maternal and fetal risks associated with prepregnancy obesity, excessive gestational weight gain, and significant postpartum weight retention, including potential benefits of lifestyle changes. Behavioral counseling to improve dietary intake and physical activity should be provided to overweight and obese women, beginning in the preconception period and continuing throughout pregnancy, for at least 12 to 18 months postpartum. Weight loss before pregnancy may improve fertility and reduce the risk of poor maternal-fetal outcomes, such as preterm birth, gestational diabetes, gestational hypertension, pre-eclampsia, assisted delivery, and select congenital anomalies. Lifestyle interventions that moderate gestational weight gain may reduce the risk of poor pregnancy outcomes, such as gestational diabetes, gestational hypertension, large for gestational age, and macrosomia, as well as lower the risk for significant postpartum retention. Postpartum interventions that promote healthy diet and physical activity behaviors may reduce postpartum weight retention and decrease obesity-related risks in subsequent pregnancies. Analysis of the evidence suggests that there is good evidence to support the role of diet, physical activity, and behavior changes in promoting optimal weight gain during pregnancy; however, there is currently a relative lack of evidence in other areas related to reproductive outcomes. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Evidence for sex differences in fetal programming of physiological stress reactivity in infancy.

PubMed

Tibu, Florin; Hill, Jonathan; Sharp, Helen; Marshall, Kate; Glover, Vivette; Pickles, Andrew

2014-11-01

Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

HIV Protease Inhibitor Use During Pregnancy Is Associated With Decreased Progesterone Levels, Suggesting a Potential Mechanism Contributing to Fetal Growth Restriction

PubMed Central

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R.; Yudin, Mark H.; Murphy, Kellie E.; Walmsley, Sharon L.; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. PMID:25030058

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

PubMed

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R; Yudin, Mark H; Murphy, Kellie E; Walmsley, Sharon L; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Clinical outcomes and predictors of fetal and maternal consequences of pregnancy in lupus nephritis patients.

PubMed

Lv, Jiaxuan; Wang, Wei; Li, Yuehong

2015-08-01

To define the outcomes and risk predictors of fetal and maternal consequences of pregnancy in lupus nephritis (LN) patients. Maternal and fetal outcomes of pregnancy in 52 systemic lupus erythematosus (SLE) patients were observed. Patients were allocated into two groups according to the presence or absence of LN. LN patients were subject to a higher risk of fetal complications, including fetal loss (7/24, 29.2 %, P = 0.001), lower birth weight (2548.2 ± 540.8 vs. 2949.1 ± 592.6 g, P = 0.028) and a higher frequency of small for gestational age births (33.3 vs. 10.7 %, P = 0.002). Higher rates of lupus flares (83.3 vs. 21.4 %, P = 0.001) and increased LAI-P scores (0.65 ± 0.36 vs. 0.21 ± 0.27, P = 0.001) during pregnancy were observed in LN patients. Multivariate analysis showed that increased SLE activity (P = 0.02, OR 4.2, 95 % CI 1.2-14.5), renal damage (P = 0.001, OR 8.4, 95 % CI 2.2-31.8), hypocomplementemia (P = 0.05, OR 3.23, 95 % CI 1.0-10.7), hypoalbuminemia (P = 0.011, OR 5.62, 95 % CI 1.4-23.0) and hypertension (P = 0.021, OR 6.0, 95 % CI 1.5-24.2) during pregnancy were predictors of adverse fetal outcomes. Pregnancy in LN patients should be monitored before and during pregnancy because of poor fetal and maternal outcomes. Increased LAI-P scores, renal damage, hypocomplementemia, hypoalbuminemia and hypertension are predictors of adverse fetal outcomes for SLE patients.

Fetal growth in relation to gestational weight gain in women with type 2 diabetes: an observational study.

PubMed

Parellada, C B; Asbjörnsdóttir, B; Ringholm, L; Damm, P; Mathiesen, E R

2014-12-01

To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI < 25, 25-29.9, ≥ 30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations). Excessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9-32) vs. 7.0 (-5-16) kg (P < 0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs. 3258 g; P = 0.001), birth weight z-score (1.14 vs. -0.01, P = 0.001) and prevalence of large-for-gestational-age infants (48 vs. 20%; P < 0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [β=0.1 (95% CI 0.06-0.14), P < 0.001]. Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain. © 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Fetal growth in relation to gestational weight gain in women with Type 2 diabetes: an observational study

PubMed Central

Parellada, C B; Ásbjörnsdóttir, B; Ringholm, L; Damm, P; Mathiesen, E R

2014-01-01

Aims To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. Methods A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI  < 25, 25–29.9,  ≥ 30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations). Results Excessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9–32) vs 7.0 (−5–16) kg (P < 0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs 3258 g; P = 0.001), birth weight z-score (1.14 vs -0.01, P = 0.001) and prevalence of large-for-gestational-age infants (48 vs 20%; P < 0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [β=0.1 (95% CI 0.06–0.14), P < 0.001]. Conclusions Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain. PMID:25081349

THE ESTROGENIC ENDOCRINE DISRUPTING CHEMICAL BISPHENOL A (BPA) AND OBESITY

PubMed Central

vom Saal, Frederick S.; Nagel, Susan C.; Coe, Benjamin L.; Angle, Brittany M.; Taylor, Julia A.

2012-01-01

There is increasing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent increase in adult obesity and other components of metabolic syndrome. In particular, there is evidence that epigenetic changes associated with the use of manmade chemicals may interact with other factors that influence fetal and postnatal growth in contributing to the current obesity epidemic. The focus of this review is on the developmental effects of estrogenic endocrine disrupting chemicals (EDCs), and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA), on adipocytes and their function, and the ultimate impact on adult obesity; BPA exposure also results in impaired reproductive capacity. We discuss the interaction of EDCs with other factors that impact growth during fetal and neonatal life, such as placental blood flow and nutrient transport to fetuses, and how these influence fetal growth and abnormalities in homeostatic control systems required to maintain normal body weight throughout life. PMID:22249005

The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity.

PubMed

Vom Saal, Frederick S; Nagel, Susan C; Coe, Benjamin L; Angle, Brittany M; Taylor, Julia A

2012-05-06

There is increasing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent increase in adult obesity and other components of metabolic syndrome. In particular, there is evidence that epigenetic changes associated with the use of manmade chemicals may interact with other factors that influence fetal and postnatal growth in contributing to the current obesity epidemic. The focus of this review is on the developmental effects of estrogenic endocrine disrupting chemicals (EDCs), and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA), on adipocytes and their function, and the ultimate impact on adult obesity; BPA exposure also results in impaired reproductive capacity. We discuss the interaction of EDCs with other factors that impact growth during fetal and neonatal life, such as placental blood flow and nutrient transport to fetuses, and how these influence fetal growth and abnormalities in homeostatic control systems required to maintain normal body weight throughout life. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

Co-variables in first trimester maternal serum screening.

PubMed

de Graaf, I M; Cuckle, H S; Pajkrt, E; Leschot, N J; Bleker, O P; van Lith, J M

2000-03-01

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres were studied. Maternal serum free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) concentrations had been measured in all pregnancies, and pregnancy associated plasma protein (PAPP)-A levels had been measured in 924. All results were expressed as multiples of the gestation specific median (MoM) values after regression, using each centre's own medians. Information on maternal weight was available in 2259 pregnancies, on self-reported current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), on gravidity in 1371, parity in 1303 and fetal gender in 253. All three markers showed a statistically significant negative association with maternal weight (p<0.0005) and in the subsequent analyses MoM values were weight adjusted using standard methods. The median PAPP-A level in smokers was 0.81 MoM, a significant reduction (p<0.005); free beta-hCG was also reduced (median 0.89 MoM) but not significantly (p=0.17), and AFP was unaltered. The median AFP level in primagravidas was highly significantly greater than that in gravid women (p<0.0005). In PAPP-A the reverse effect was seen but it did not reach statistical significance (p=0.15) and there was no effect for free beta-hCG. Results of a similar magnitude and direction were found for parity. The median level of free beta-hCG was higher (p=0.0005), and the median AFP lower in female pregnancies. Maternal weight and, for PAPP-A, maternal smoking are important first trimester screening co-variables. Gravidity, parity and fetal gender also seem to influence one or more first trimester markers. Copyright 2000 John Wiley & Sons, Ltd.

Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data

PubMed Central

Olesen, Charlotte; de Vries, Corinne S; Thrane, Nana; MacDonald, Tom M; Larsen, Helle; Sørensen, Henrik Toft

2001-01-01

Aims The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. Methods During 1991–98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. Results Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. Conclusions Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings. PMID:11259987

Dynamic interaction between fetal adversity and a genetic score reflecting dopamine function on developmental outcomes at 36 months

PubMed Central

Pokhvisneva, Irina; Léger, Étienne; Gaudreau, Hélène; Steiner, Meir; Kennedy, James L.; O’Donnell, Kieran J.; Diorio, Josie; Meaney, Michael J.; Silveira, Patrícia P.

2017-01-01

Background Fetal adversity, evidenced by poor fetal growth for instance, is associated with increased risk for several diseases later in life. Classical cut-offs to characterize small (SGA) and large for gestational age (LGA) newborns are used to define long term vulnerability. We aimed at exploring the possible dynamism of different birth weight cut-offs in defining vulnerability in developmental outcomes (through the Bayley Scales of Infant and Toddler Development), using the example of a gene vs. fetal adversity interaction considering gene choices based on functional relevance to the studied outcome. Methods 36-month-old children from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment) were classified according to birth weight ratio (BWR) (SGA ≤0.85, LGA >1.15, exploring a wide range of other cut-offs) and genotyped for polymorphisms associated with dopamine signaling (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10- repeat, Met/Met-COMT), composing a score based on the described function, in which hypofunctional variants received lower scores. Results There were 251 children (123 girls and 128 boys). Using the classic cut-offs (0.85 and 1.15), there were no statistically significant interactions between the neonatal groups and the dopamine genetic score. However, when changing the cut-offs, it is possible to see ranges of BWR that could be associated with vulnerability to poorer development according to the variation in the dopamine function. Conclusion The classic birth weight cut-offs to define SGA and LGA newborns should be seen with caution, as depending on the outcome in question, the protocols for long-term follow up could be either too inclusive—therefore most costly, or unable to screen true vulnerabilities—and therefore ineffective to establish early interventions and primary prevention. PMID:28505190

Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla

PubMed Central

Liu, Feng; Garland, Marianne; Duan, Yunsuo; Stark, Raymond I.; Xu, Dongrong; Dong, Zhengchao; Bansal, Ravi; Peterson, Bradley S.; Kangarlu, Alayar

2008-01-01

Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1–6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term ~185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T1 and T2) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally. PMID:18155925

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.

Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

PubMed

Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

2015-01-01

To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome.

PubMed

Recabarren, Monica; Carrasco, Albert; Sandoval, Daniel; Diaz, Felipe; Sir-Petermann, Teresa; Recabarren, Sergio E

2017-09-07

The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

Extreme Temperatures May Increase Risk for Low Birth Weight at Term

MedlinePlus

... research in the United States and throughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit ...

Salt sensitivity of children with low birth weight.

PubMed

Simonetti, Giacomo D; Raio, Luigi; Surbek, Daniel; Nelle, Mathias; Frey, Felix J; Mohaupt, Markus G

2008-10-01

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.

[Prevention of shoulder dystocia risk factors before delivery].

PubMed

Fuchs, F

2015-12-01

To determine whether it is possible to prevent the occurrence of risk factors for shoulder dystocia before or during pregnancy. The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. Studied measures were exercise before or during pregnancy, dietary management, and gestational diabetes management in obese and non-obese patients. No study has proven that the correction of these risk factors (except gestational diabetes) would reduce the risk of shoulder dystocia. In the general population, physical exercise is recommended either before or during pregnancy to reduce the risk of gestational diabetes (physical activity before pregnancy) (grade B), fetal macrosomia (grade C) or maternal weight gain during pregnancy (grade C). No dietary regimen is recommended to reduce these issues (grade B). In overweight or obese (body mass index [BMI]>25), physical activity coupled with dietary management is recommended (grade A) because it reduces fetal macrosomia (EL1). In addition, it allows a modest reduction in maternal weight gain during pregnancy (EL2), but did have an effect on the occurrence of gestational diabetes (EL1). In case of gestational diabetes, diabetes care is recommended (diabetic diet, glucose monitoring, insulin if needed) (grade A) as it reduces the risk of macrosomia and shoulder dystocia (EL1). The recommended weight gain during pregnancy is 11.5 kg to 16 kg for normal BMI patients (grade B). Obese patients should be aware of the importance of controlling their weight gain during pregnancy (professional consensus). It is recommended that patients regain their pre-conception weight, and ideally a BMI between 18 and 25 kg/m(2), 6 months postpartum (grade B) to reduce the risk of gestational diabetes and macrosomia in a subsequent pregnancy (EL2). Physical activity is recommended before and during pregnancy to reduce the occurrence of risk factors for shoulder dystocia. In obese patients, physical activity should be coupled with dietary measures to reduce fetal macrosomia and weight gain during pregnancy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Body size at birth and blood pressure among children in developing countries.

PubMed

Law, C M; Egger, P; Dada, O; Delgado, H; Kylberg, E; Lavin, P; Tang, G H; von Hertzen, H; Shiell, A W; Barker, D J

2001-02-01

Studies in developed countries have shown that reduced fetal growth is related to raised blood pressure in childhood and adult life. Little is known about this association in developing countries, where fetal growth retardation is common. In 1994-1995, we measured blood pressure in 1570 3-6-year-old children living in China, Guatemala, Chile, Nigeria and Sweden. We related their blood pressure to patterns of fetal growth, as measured by body proportions at birth. The children were all born after 37 weeks gestation and weighed more than 2.5 kg at birth. In each country, blood pressure was positively related to the child's current weight. After adjusting for this and gender, systolic pressure was inversely related to size at birth in all countries except Nigeria. In Chile, China and Guatemala, children who were proportionately small at birth had raised systolic pressure. For example, in Chile, systolic pressure adjusted for current weight increased by 4.9 mmHg (95% CI : 2.1, 7.7) for every kilogram decrease in birthweight, by 1 mmHg (95% CI : 0.4, 1.6) for every centimetre decrease in birth length, and by 1.3 mmHg (95% CI : 0.4, 2.2) for every centimetre decrease in head circumference at birth. In Sweden, systolic pressure was higher in children who were disproportionately small, that is thin, at birth. Systolic pressure increased by 0.3 mmHg (95% CI : 0.0, 0.6) for every unit (kg/m3) decrease in ponderal index at birth. These associations were independent of the duration of gestation. Raised blood pressure among children in three samples from China, Central and South America is related to proportionate reduction in body size at birth, which results from reduced growth throughout gestation. The relation between fetal growth and blood pressure may be different in African populations. Proportionately reduced fetal growth is the prevalent pattern of fetal growth retardation in developing countries, and is associated with chronic undernutrition among women. Improvement in the nutrition and health of girls and young women may be important in preventing cardiovascular disease in developing countries.

Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

PubMed

Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

2018-04-01

Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

Perinatal Outcomes Associated With Isolated Velamentous Cord Insertion in Singleton and Twin Pregnancies.

PubMed

Sinkin, Joshua A; Craig, Wendy Y; Jones, Michael; Pinette, Michael G; Wax, Joseph R

2018-02-01

To evaluate perinatal outcomes in singleton and twin pregnancies with pathologically confirmed velamentous cord insertion without vasa previa. This retrospective case-control study included all nonanomalous singleton and twin pregnancies with pathologically confirmed velamentous cord insertion delivered in a single institution between January 1, 2005, and July 1, 2015, and having an ultrasound examination by maternal-fetal medicine. For each case, the next 2 consecutive deliveries matched for gestational age at delivery ± 1 week and, in twins, amnionicity and chorionicity served as controls. Primary outcomes included surgical delivery for a nonreassuring intrapartum fetal heart rate tracing, umbilical arterial cord pH of less than 7.2, 5-minute Apgar score of less than 7, birth weight below the 10th percentile, neonatal intensive care unit admission, fetal or neonatal death, and cord avulsion necessitating manual placental extraction. Outcomes were available for 53 singletons with 103 matched controls and 33 twin pregnancies with 65 matched controls. In singletons, velamentous cord insertion was associated with cord pH of less than 7.2 (odds ratio [OR] 3.5; 95% confidence interval [CI], 1.1-11.2; P = .039), 5-minute Apgar score of less than 7 (OR, 5.3; 95% CI, 0.99-28.1; P = .045), and cord avulsion requiring manual placental extraction (7.5% versus 0%; P = .012). Associations were suggested with increased surgical delivery for a nonreassuring intrapartum fetal heart rate tracing (OR, 2.4; 95% CI, 0.9-6.9; P = .14), birth weight below the 10th percentile (OR, 2.1; 95% CI, 0.8-5.9; P = .21), and fetal or neonatal death (3.8% versus 0%; P = .11). Velamentous cord insertions were also associated with placental abruption in singletons (7.5% versus 0%; P = .013). Among twins, velamentous cord insertion was associated with fetal or neonatal death (9.1% versus 0%; P = .036). Isolated confirmed velamentous cord insertion is associated with adverse perinatal outcomes in singleton and twin gestations. © 2017 by the American Institute of Ultrasound in Medicine.

Animal models for clinical and gestational diabetes: maternal and fetal outcomes

PubMed Central

Kiss, Ana CI; Lima, Paula HO; Sinzato, Yuri K; Takaku, Mariana; Takeno, Marisa A; Rudge, Marilza VC; Damasceno, Débora C

2009-01-01

Background Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. Methods On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Results Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Conclusion Experimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women presenting uncontrolled clinical diabetes. On the other hand, the mild diabetes model caused mild hyperglycemia during pregnancy, although it was not enough to reproduce the increased rate of macrosomic fetuses seen in women with gestational diabetes. PMID:19840387

Effect of QSOX1 on cattle carcass traits as well as apoptosis and triglyceride production in bovine fetal fibroblasts and mammary epithelial cells.

PubMed

Liu, Xiaochuan; Yang, Yuwei; Jiang, Ping; Li, Xiaohui; Ge, Yanliang; Cao, Yang; Zhao, Zhihui; Fang, Xibi; Yu, Xianzhong

2018-05-30

QSOX1 (quiescin-sulfhydryl oxidase 1) is involved in various processes, including apoptosis and the development of breast diseases. Here, we investigated the effect of QSOX1 on the meat quality of Simmental cattle by analyzing the correlation between QSOX1 single nucleotide polymorphisms (SNPs), I2 204 C>T and I2 378 C>T, and certain meat quality traits. The effects of QSOX1 on triglyceride synthesis and cell apoptosis were further validated by gene silencing or overexpression in bovine fetal fibroblasts and mammary epithelial cells. The results showed that I2 204 C>T and I2 378 C>T had significant correlations with loin thickness, hind hoof weight, fat coverage, liver weight, heart weight, marbling and back fat thickness (P<0.05). QSOX1 overexpression also increased triglyceride production and suppressed apoptosis. In summary, QSOX1 is an important factor for meat quality, lipid metabolism, and cell apoptosis, indicating that QSOX1 could be used as a biomarker to assist in breeding cattle with superior meat.

[General characteristics of an experiment to study the ontogeny of rats on board the Kosmos-1514 biosatellite].

PubMed

Serova, L V; Denisova, L A; Apanasenko, Z I; Briantseva, L A; Chel'naia, N A

1985-01-01

Ten female Wistar rats were exposed to zero-g during 5 days, i. e., from gestation day 13 to day 18. After recovery the flight animals showed a significant delay in weight gain, thymus involution, decreased liver weight, hemoglobin concentration. Nevertheless, their reproductive function did not differ from that of the controls: the rate of preimplantation and total fetal mortality as well as the number of live fetuses were very similar in the experimental and control animals. The flight group showed a slight decline of fetal weight and water content. The size of the litters produced by the flight and control rats was identical but the mortality rate of those former during the first 7 days after birth was significantly higher. This experiment has demonstrated that the mammalian fetus exposed to zero-g during the last term of pregnancy, i. e., at the stage of active organogenesis, can grow and develop in the normal way. A large body of biological material has been obtained for biochemical and histological examinations that will help evaluate the condition of dams, fetuses, and newborns.

In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

PubMed Central

Fowler, Paul A.; Dorà, Natalie J.; McFerran, Helen; Amezaga, Maria R.; Miller, David W.; Lea, Richard G.; Cash, Phillip; McNeilly, Alan S.; Evans, Neil P.; Cotinot, Corinne; Sharpe, Richard M.; Rhind, Stewart M.

2008-01-01

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome. PMID:18436539

Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions.

PubMed

Vonnahme, K A; Hess, B W; Nijland, M J; Nathanielsz, P W; Ford, S P

2006-12-01

Maternal nutrient restriction from early to midgestation can lead to fetal growth retardation, with long-term impacts on offspring growth, physiology, and metabolism. We hypothesized that ewes from flocks managed under markedly different environmental conditions and levels of nutrition might differ in their ability to protect their own fetus from a bout of maternal nutrient restriction. We utilized multiparous ewes of similar breeding, age, and parity from 2 flocks managed as 1) ewes adapted to a nomadic existence and year-long, limited nutrition near Baggs, WY (Baggs ewes), and 2) University of Wyoming ewes with a sedentary lifestyle and continuous provision of more than adequate nutrition (UW ewes). Groups of Baggs ewes and UW ewes were fed 50 (nutrient restricted) or 100% (control fed) of National Research Council recommendations from d 28 to 78 of gestation, then necropsied, and fetal and placental data were obtained. Although there was a marked decrease (P < 0.05) in fetal weight and blood glucose concentrations in nutrient-restricted vs. control fed UW ewes, there was no difference in these fetal measurements between nutrient-restricted and control-fed Baggs ewes. Nutrient-restricted and control-fed UW ewes exhibited predominantly type A placentomes on d 78, but there were fewer (P c0.05) type A and greater (P < 0.05) numbers of type B, C, and D placentomes in nutrient-restricted than control-fed Baggs ewes. Placental efficiency (fetal weight/placentomal weight) was reduced (P = 0.04) in d 78 nutrient-restricted UW ewes when compared with control-fed UW ewes. In contrast, nutrient-restricted and control-fed Baggs ewes exhibited similar placental efficiencies on d 78. This is the first report of different placental responses to a nutritional challenge during pregnancy when ewes were selected under different management systems. These data are consistent with the concept that Baggs ewes or their conceptuses, which were adapted to both harsh environments and limited nutrition, initiated conversion of type A placentomes to other placentomal types when subjected to an early to mid-gestational nutrient restriction, whereas this conversion failed to occur in UW ewes. This early placentomal conversion in the Baggs ewes may function to maintain normal nutrient delivery to their developing fetuses during maternal nutrient restriction.

Measurement and evaluation of fetal fat layer in the prediction of fetal macrosomia in pregnancies complicated by gestational diabetes.

PubMed

Elessawy, Mohamed; Harders, Christina; Kleinwechter, Helmut; Demandt, Norbert; Sheasha, Ghada Abu; Maass, Nicolai; Pecks, Ulrich; Eckmann-Scholz, Christel

2017-09-01

To explore the predictive power of measuring the abdominal fetal fat layer (FFL) as a soft tissue marker at 31, 34, and 37 weeks' gestation to improve the detection of fetal macrosomia in pregnant women with GDM, in addition to the biometric values with close monitoring of maternal blood sugar level and BMI changes. We conducted a prospective observational study at the Department of Obstetrics, University Hospitals, Campus Kiel, Germany, in collaboration with diabetic clinic staff. Participants underwent a third-trimester scan and extra FFL measurements were performed at 31, 34, and 37 weeks of gestation. The clinical outcomes of pregnancy and birth weight were collected from the obstetric record. All of the enrolled women had an early pregnancy ultrasound scan to confirm gestational age. The FFL at 34 and 37 weeks, with respective cutoff values of >0.48 cm and >0.59 cm, showed a very good sensitivity of 60% for both gestational points, and specificity of 89.3 and 90.6%, respectively. The probability of fetal macrosomia could be more than doubled if the FFL at 34 weeks was more than 0.48 cm. However, the probability of macrosomia dropped to 16% if the FFL was ≤0.48 cm. The median FFLs of macrosomic fetuses at 34 and 37 weeks were 0.50 (IQR 0.10) and 0.60 (IQR 0.25) cm, respectively. The mean age of the study population (n = 80) was 32.26 (SD = 5.06) years. In our study population, ten newborns were born with birth weight >4000 g. The body mass index (BMI) for the mothers of later-onset macrosomic newborns showed higher median values of 30 (IQR 8), 32 (IQR 5), and 33 (IQR 9) at 31, 34, and 37 weeks, respectively, in comparison to mothers of non-macrosomic newborn. However, the BMI did not show any statistically significant difference from those with normal-weight newborn and did not show any specific sensitivity for predicting macrosomia. Measuring the FFL at 34 and 37 weeks of gestation, in addition to the standard measurement, might be useful for predicting macrosomia and is worth further evaluation.

Pacemaker therapy in low-birth-weight infants.

PubMed

Fuchigami, Tai; Nishioka, Masahiko; Akashige, Toru; Shimabukuro, Atsuya; Nagata, Nobuhiro

2018-02-01

Infants born with complete atrioventricular block (CAVB) and fetal bradycardia are frequently born with low birth weight. Three low-birth-weight CAVB infants underwent temporary pacemaker implantation, followed by permanent single-chamber pacemaker implantation at median body weights of 1.7 and 3.2 kg, respectively. All infants caught up with their growth curves and had >3 years of estimated residual battery life. This two-stage strategy was successful in facilitating permanent pacemaker implantation in low-birth-weight babies. Placement of single-chamber pacemaker on the apex of the left ventricle appears to be associated with longer battery lifespan. © 2018 Wiley Periodicals, Inc.

Noninvasive fetal RhCE genotyping from maternal blood.

PubMed

Geifman-Holtzman, O; Grotegut, C A; Gaughan, J P; Holtzman, E J; Floro, C; Hernandez, E

2009-01-01

The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA. To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used. English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966-2007), Ovid (1966-2007), CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation. A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded. From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy. We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was consistently the best source of fetal RhCE genotyping in 147/147 (100%) for RhC/c and 168/168 (100%) for RhE/e. The combined accuracy of noninvasive fetal RhC/c or RhE/e determination using maternal peripheral blood is 96.3% and 98.2%, respectively. FfDNA in maternal plasma is a better source for genotyping reported to be 100% correct for both RHCE genotypes. Further studies and reports of accuracy from laboratories performing the tests are required before prenatal determination of fetal RhC/c or RhE/e genotypes from maternal blood can safely replace the current methods used in the management of the RhC/c or RhE alloimmunised pregnancies.

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 birth certificates from 2006 to 2012 to examine GWG trend by prepregnancy body mass index, to calculate the risk of small- and large-for-gestational age (SGA and LGA), and macrosomia (birthweight >4000 g or >4500 g) infants, and to estimate the PARs of GWG below or above the guidelines. Of 869,531 women who delivered singleton live births at 22-44 weeks of gestation, 4.5% were underweight, 48.9% were normal weight, 23.9% were overweight, and 22.7% were obese before pregnancy. About 36.5% of underweight, 52.6% of normal weight, 72.5% of overweight, and 62.4% of obese women gained weight above the guidelines, with only slight changes from 2006 to 2012. Also, 34.9% of underweight, 20.1% of normal weight, 16.3% of overweight, and 27.0% of obese women gained weight below the guidelines. The PAR of GWG below or above the guidelines was -13% for SGA, 32.6% for LGA, 28.1% for macrosomia >4000 g, and 48.3% for macrosomia >4500 g, mostly driven by currently GWG above the guidelines in normal weight, overweight, and obese women. A high percentage of pregnant women gained weight outside of the current IOM GWG guidelines; however, changes from 2006 to 2012 were small. GWG above the IOM guidelines significantly contributed to a large proportion of LGA and macrosomic infants in the general population. © 2015 John Wiley & Sons Ltd.

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.