Differences In Fetal Growth Research Articles

FRI477 The Effect Of Gestational Selective Serotonin Reuptake Inhibitor (SSRI) Treatment On Newborn Thyroid Screen

Abstract Disclosure: A. Brener: None. O. Raviv: None. E. Cohen-Sela: None. M. Yackobovitch-Gavan: None. S. Almashanu: None. R. Marom: None. L. Hiersch: None. Y. Lebenthal: None. Background: Clinical depression treated by selective serotonin reuptake inhibitors (SSRIs) has become relatively common in women of childbearing age. The effect of gestational exposure to SSRIs on the newborn’s hypothalamic-pituitary-thyroid postnatal adaptation has not yet been determined. We aimed to investigate the characteristics of the mother–infant dyad of term infants of mothers treated with SSRIs for depression during pregnancy. Methods: This observational study included mother-infant dyads of infants delivered at term in a single tertiary medical center between 2011 and 2021. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital’s electronic database. The clinical data were linked with the newborn thyroid screening results of total thyroxin (TT4) obtained at 48-72 hours since delivery. Excluded from analysis were mothers with other chronic medical conditions and newborns with genetic syndromes. Primary outcome measures were newborn TT4 levels and fetal growth as expressed by neonatal birthweight z-scores (WHO charts). Results: SSRI anti-depression treatment during gestation was reported in 2577 (2.4%) out of 106,173 infant-mother dyads. Mothers treated with SSRIs were older (35.0±4.8 vs 32.6±4.8 years, p<0.001), had a higher pre-pregnancy body mass index (23.4±4.5 vs 22.7±4.1, p<0.001) and a similar mean weight gain of 13 kg during pregnancy. Elective and emergent cesarean deliveries were more common among SSRI-treated mothers (14.8% vs 11.1% and 16.5% vs 8.6%, respectively, p<0.001). Infants of those mothers were born earlier (gestational age [GA] 38.7±1.9 vs 39.5±11.5 weeks, p<0.001), had lower birthweight z-scores (-0.48±1.24 vs -0.04±0.92, p<0.001) and lower TT4 levels (14.7±3.9 vs 15.0±3.7, p=0.001). A multivariate linear regression model revealed that sex, GA and birthweight z-score were highly significant contributors to TT4 levels (p<0.001 for all), while SSRI treatment during pregnancy was not (p=0.497). Conclusions: Our findings suggest that anti-depressant use of SSRIs during pregnancy does not have a direct effect on the postnatal adaptation of the hypothalamic-pituitary-thyroidal axis. However, differences in fetal growth and in characteristics of delivery may determine newborn thyroid function. Presentation: Friday, June 16, 2023

Ancestry dependent balancing selection of placental dysferlin at high-altitude.

Introduction: The placenta mediates fetal growth by regulating gas and nutrient exchange between the mother and the fetus. The cell type in the placenta where this nutrient exchange occurs is called the syncytiotrophoblast, which is the barrier between the fetal and maternal blood. Residence at high-altitude is strongly associated with reduced 3rd trimester fetal growth and increased rates of complications such as preeclampsia. We asked whether altitude and/or ancestry-related placental gene expression contributes to differential fetal growth under high-altitude conditions, as native populations have greater fetal growth than migrants to high-altitude. Methods: We have previously shown that methylation differences largely accounted for altitude-associated differences in placental gene expression that favor improved fetal growth among high-altitude natives. We tested for differences in DNA methylation between Andean and European placental samples from Bolivia [La Paz (∼3,600m) and Santa Cruz, Bolivia (∼400m)]. One group of genes showing significant altitude-related differences are those involved in cell fusion and membrane repair in the syncytiotrophoblast. Dysferlin (DYSF) shows greater expression levels in high- vs. low-altitude placentas, regardless of ancestry. DYSF has a single nucleotide variant (rs10166384;G/A) located at a methylation site that can potentially stimulate or repress DYSF expression. Following up with individual DNA genotyping in an expanded sample size, we observed three classes of DNA methylation that corresponded to individual genotypes of rs10166384 (A/A < A/G < G/G). We tested whether these genotypes are under Darwinian selection pressure by sequencing a ∼2.5kb fragment including the DYSF variants from 96 Bolivian samples and compared them to data from the 1000 genomes project. Results: We found that balancing selection (Tajima's D = 2.37) was acting on this fragment among Andeans regardless of altitude, and in Europeans at high-altitude (Tajima's D = 1.85). Discussion: This supports that balancing selection acting on dysferlin is capable of altering DNA methylation patterns based on environmental exposure to high-altitude hypoxia. This finding is analogous to balancing selection seen frequency-dependent selection, implying both alleles are advantageous in different ways depending on environmental circumstances. Preservation of the adenine (A) and guanine (G) alleles may therefore aid both Andeans and Europeans in an altitude dependent fashion.

Standardized Complex Gut Microbiomes Influence Fetal Growth, Food Intake, and Adult Body Weight in Outbred Mice.

Obesity places a tremendous burden on individual health and the healthcare system. The gut microbiome (GM) influences host metabolism and behaviors affecting body weight (BW) such as feeding. The GM of mice varies between suppliers and significantly influences BW. We sought to determine whether GM-associated differences in BW are associated with differences in intake, fecal energy loss, or fetal growth. Pair-housed mice colonized with a low or high microbial richness GM were weighed, and the total and BW-adjusted intake were measured at weaning and adulthood. Pups were weighed at birth to determine the effects of the maternal microbiome on fetal growth. Fecal samples were collected to assess the fecal energy loss and to characterize differences in the microbiome. The results showed that supplier-origin microbiomes were associated with profound differences in fetal growth and excessive BW-adjusted differences in intake during adulthood, with no detected difference in fecal energy loss. Agreement between the features of the maternal microbiome associated with increased birth weight here and in recent human studies supports the value of this model to investigate the mechanisms by which the maternal microbiome regulates offspring growth and food intake.

Maternal serum cortisol levels during pregnancy differ by fetal sex

BackgroundMales and females have different patterns of fetal growth, resulting in different sizes at birth. Increased maternal cortisol levels in pregnancy negatively impact fetal growth. However, it is unknown whether sexual dimorphism displays differences in maternal cortisol levels already during early pregnancy and to what extent it explains sex differences in intra-uterine growth. The present cross-sectional study investigated whether fetal sex was associated with the level of maternal serum total cortisol in first half of pregnancy and its contribution to sex differences in fetal growth. MethodThe study population comprised 3049 pregnant women from the Amsterdam Born Children and their Development (ABCD)–cohort). Total serum cortisol levels were determined during pregnancy. Multivariable linear regression was used to determine fetal sex differences in maternal cortisol levels and its association with sex differences in fetal growth measured as birth weight standardized for gestational age, parity and sex. ResultsMaternal serum total cortisol increased during pregnancy from on average 390 ± 22 nmol/L (at 5th week) to 589 ± 15 nmol/L (at 20th week). Women carrying a female fetus had higher maternal total cortisol levels. This sex difference was not significant before the 11th week; at the 12th week the difference was 15 ± 7 nmol/L which increased to 45 ± 22 nmol/L at the 20th week (p-for-interaction=0.05). Maternal total cortisol levels were associated with birth weight (ß:−0.22;P < 0.001). However, sex differences in birth weight were not explained by related maternal total cortisol levels. ConclusionThe sexual dimorphic maternal serum total cortisol levels are apparent after the first trimester but do not explain the different patterns of fetal growth.

Assessment of fetal growth in twins: Which method to use?

Fetal growth restriction contributes to the excess perinatal mortality and morbidity associated with twin pregnancies. Regular ultrasound monitoring for fetal growth restriction is an essential component of antenatal care of twin gestations. It is accepted that twins have divergent growth trajectories around 28-30 weeks' gestation and are born smaller compared to singletons. Despite this well-established difference in fetal growth, twin pregnancies have been traditionally managed using growth standards developed for singleton pregnancies. Numerous recent studies have demonstrated a strong case supporting the use of twin-specific growth standards, but clinical implementation has been lacking. In this paper, we will review the evidence on factors affecting fetal growth, the rationale for twin-specific reference charts, clinical evidence for their use, and future direction of research. Applying singleton growth standards to twin pregnancies inflates the abnormal growth rate, and recent clinical evidence from several studies suggests that they are too stringent for classification of twins. The association of adverse perinatal and maternal outcomes such as perinatal death, preterm birth, neonatal care unit admission, hypertensive disorders of pregnancy, and composite neonatal morbidity is stronger when classification is made using twin-specific standards compared to singletons.

Umbilical venous diameter and flow in monochorionic diamniotic twin pregnancy: association with placental sharing and fetal demise.

To examine the association of umbilical venous diameter and flow in monochorionic diamniotic twin pregnancy with placental sharing and fetal demise. This was a prospective longitudinal cohort study of a consecutive series of monochorionic diamniotic twin pregnancies that underwent ultrasound assessments at 12, 16, 20 and 28 weeks' gestation. Fetal biometry (crown-rump length at 12 weeks or estimated fetal weight (EFW) thereafter) and cord insertion sites were recorded at each visit, as well as the diameter of the umbilical vein (UV) in both the intra-abdominal part and a free loop of the umbilical cord. Time-averaged maximum velocity in the intra-abdominal part of the UV was measured to calculate UV-flow. Univariate and multivariate linear regression analyses were performed to assess the relationship between intertwin ratios of these variables and placental sharing at 12, 16, 20 and 28 weeks' gestation. Placental sharing was calculated by dividing the larger by the smaller placental share, as measured on placental injection studies after birth. Additionally, the Mann-Whitney U-test and receiver-operating-characteristics-curve analysis were used to explore the relationship between the occurrence of fetal demise and intertwin differences in fetal biometry, cord insertion sites, UV diameters and flow at 12, 16, 20 and 28 weeks. Of 200 consecutive monochorionic twin pregnancies enrolled, injection studies were performed in 165 (82.5%) placentas. On univariate analysis, intertwin differences in fetal biometry, cord insertions and UV variables were associated significantly with placental sharing at 12, 16, 20 and 28 weeks' gestation. On multivariate analysis, intertwin differences in fetal biometry, cord insertions and all three UV variables remained associated significantly with placental sharing at 12 and 16 weeks. However, at 20 and 28 weeks, only the intertwin EFW ratio was associated consistently with placental sharing. Fetal demise of one or both twins complicated 26 (13.0%) pregnancies. Differences in EFW and cord insertion sites were not associated significantly with fetal demise, while at 16 weeks, differences in intra-abdominal UV diameter and flow were associated with an increased risk of subsequent fetal demise. At 12 and 16 weeks' gestation, intertwin differences in UV diameter and flow reflect placental sharing more accurately than do differences in fetal growth and cord insertion sites. At 16 weeks, discordance in intra-abdominal UV diameter and flow is also associated with an increased risk of fetal demise. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Differential fetal growth rates mediated by sociodemographic factors in Yucatan, Mexico: an epidemiological study

Background Fetal growth restriction (FGR) may be related to ethnicity. Additionally, ethnic groups experience adverse socioeconomic circumstances that increase FGR risk. However, the dearth of evidence of the interaction between socioeconomic factors and FGR highlights the need for additional research. Objective To analyze the association between socioeconomic factors and FGR in Maya and non-Maya populations in Yucatan, Mexico. Methods A total of 21,320 singleton births in 2017 in Yucatan were analyzed. The student’s t-test and the chi-square test were used to compare the means and proportions of maternal and perinatal variables between the FGR group and the birthweight appropriate for gestational age (AGA) group. Path analysis was performed to identify the direct and indirect effects of socioeconomic factors on FGR and mediators between predictors and FGR. Results The prevalence of FGR at birth was 9.06%; this rate was higher in the Maya population (12.4, 95% CI 11.3–13.5), without differences between socioeconomic levels. Path analysis revealed sociostructural variables (ethnicity and poverty) are reliable predictors of FGR at birth mediated by maternal education (β = −.152, p < .001) and teenage pregnancy (β = .065, p = .037). The proposal path model had a good fit index CFI = .968, TLI = .920, RMSEA = .046. Conclusion The prevalence of FGR was higher among Maya women than non-Maya women The socioeconomic conditions associated with FGR at birth were ethnicity, poverty, maternal education, and teenage pregnancy. Maternal education and teenage pregnancy act as mediators between sociostructural variables and FGR at birth.

The Effect of Maternal US Nativity on Racial/Ethnic Differences in Fetal Growth.

While racial/ethnic differences in fetal growth have been documented, few studies have examined whether they vary by exogenous factors, which could elucidate underlying causes. The purpose of this study was to characterize longitudinal fetal growth patterns by maternal sociodemographic, behavioral, and clinical factors and examine whether associations with maternal race/ethnicity varied by these other predictors. Between 2016 and 2019, pregnant women receiving prenatal care at NYU Langone Health (New York, New York) were invited to participate in a birth cohort study. Women completed questionnaires, and clinical data were abstracted from ultrasound examinations. Maternal characteristics were assessed in relation to fetal biometric measures throughout pregnancy using linear mixed models. Maternal race/ethnicity was consistently associated with fetal biometry: Black, Hispanic, and Asian women had fetuses with smaller head circumference, abdominal circumference, and biparietal diameter than White women. The associations between race/ethnicity and fetal growth varied by nativity for Asian women, such that the disparity between Asian and White women was much greater for US-born women than for foreign-born women. However, associations for Black and Hispanic women did not vary by nativity. While race/ethnicity-specific fetal growth standards have been proposed, additional work is needed to elucidate what could be driving these differences, including factors that occur in parallel and differentially affect fetal growth.

Novel insights from fetal and placental phenotyping in 3 mouse models of Down syndrome

In human fetuses with Down syndrome, placental pathology, structural anomalies and growth restriction are present. There is currently a significant lack of information regarding the early life span in mouse models of Down syndrome. The objective of this study was to examine embryonic day 18.5 and placental phenotype in the 3 most common mouse models of Down syndrome (Ts65Dn, Dp(16)1/Yey, Ts1Cje). Based on prenatal and placental phenotyping in 3 mouse models of Down syndrome, we hypothesized that one or more of them would have a similar phenotype to human fetuses with trisomy 21, which would make it the most suitable for in utero treatment studies. Here, C57BL6J/6 female mice were mated to Dp(16)1/Yey and Ts1Cje male mice and Ts65Dn female mice to C57BL/B6Eic3Sn.BLiAF1/J male mice. At embryonic day 18.5, dams were euthanized. Embryos and placentas were examined blindly for weight and size. Embryos were characterized as euploid or trisomic, male or female by polymerase chain reaction. A subset of embryos (34 euploid and 34 trisomic) were examined for malformations. The Ts65Dn mouse model showed the largest differences in fetal growth, brain development, and placental development when comparing euploid and trisomic embryos. For the Dp(16)1/Yey mouse model, genotype did not impact fetal growth, but there were differences in brain and placental development. For the Ts1Cje mouse model, no significant association was found between genotype and fetal growth, brain development, or placental development. Euploid mouse embryos had no congenital anomalies; however, 1 mouse embryo died. Hepatic necrosis was seen in 6 of 12 Dp(16)1/Yey (50%) and 1 of 12 Ts1Cje (8%) mouse embryos; hepatic congestion or inflammation was observed in 3 of 10 Ts65Dn mouse embryos (30%). Renal pelvis dilation was seen in 5 of 12 Dp(16)1/Yey (42%), 5 of 10 Ts65Dn (50%), and 3 of 12 Ts1Cje (25%) mouse embryos. In addition, 1 Ts65Dn mouse embryo and 1 Dp(16)1/Yey mouse embryo had an aortic outflow abnormality. Furthermore, 2 Ts1Cje mouse embryos had ventricular septal defects. Ts65Dn mouse placentas had increased spongiotrophoblast necrosis. Fetal and placental growth showed varying trends across strains. Congenital anomalies were primarily seen in trisomic embryos. The presence of liver abnormalities in all 3 mouse models of Down syndrome (10 of 34 cases) is a novel finding. Renal pelvis dilation was also common (13 of 34 cases). Future research will examine human autopsy material to determine if these findings are relevant to infants with Down syndrome. Differences in placental histology were also observed among strains.

726 Fetal growth by ultrasound prior to the diagnosis of gestational diabetes mellitus in nulliparous women

The timing of excess fetal growth in gestational diabetes mellitus (GDM) is uncertain. We therefore evaluated ultrasound patterns of fetal growth among women with and without GDM. Women in the NuMoM2b study who had their first GDM screening test after 24 weeks’ gestation and ultrasound biometry available from study visits 1 (between 16-22 weeks) and 2 (between 24-30 weeks) were included. Fetal growth parameters were compared between women with and without GDM. Reference values from the NICHD Fetal Growth Study was used to define estimated fetal weight and abdominal circumference 90th percentile. Multivariable logistic regression was used to assess the relationship between GDM and fetal growth. We also compared fetal growth parameters among women with normal GDM screening, mild glucose intolerance (defined as 1 abnormal OGTT value), and GDM. Of the 6,635 women included in this analysis, 265 (4.0%) had GDM. There were no differences in fetal growth at study visit 1 among women with and without GDM. By study visit 2, both estimated fetal weight and abdominal circumference >90th percentile were more common in women with GDM (Table 1). After adjusting for covariates, an abdominal circumference >90th percentile was more likely in women with GDM (Table 2). There were no differences in fetal abdominal circumference >90th percentile (aOR 1.0, 95% CI 0.6-1.5) or estimated fetal weight >90th percentile (aOR 1.1, 95% CI 0.8-1.5) between women without GDM and those with only one abnormal OGTT value. GDM was not associated with differences in ultrasound parameters of fetal growth in mid-pregnancy, but by 24-30 weeks’ a larger abdominal circumference was observed. Mild glucose intolerance did not impact fetal growth in either mid-pregnancy or at the start of the third trimester. Further studies are needed to assess the optimal timing of GDM screening and the level of maternal glycemia used for GDM diagnosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A Rabbit Model for Optimization of Amniotic Fluid Components in the EXTrauterine Environment for Newborn Development (EXTEND) System

In this model article, we present a protocol for continuous amniotic fluid exchange in rabbits using a novel system to test the effects of growth factor-deficient, artificial amniotic fluid on bowel development. Background: Ideally, the EXTrauterine Environment for Neonatal Development (EXTEND) will provide physiologic support to the extreme premature infant. An important component of that environment is the amniotic fluid. Thus, we developed an animal model to study the growth factors found within amniotic fluid and inform design of a synthetic fluid to optimize fetal development. Methods: We designed a model of amniotic fluid exchange within the pregnant rabbit, continuously removing the natural fluid from around 2 fetuses per doe and replacing it with a physiologic electrolyte solution during the final 100 h of gestation. Two fetuses from the contralateral uterine horn were used as sham-operated controls. Thirty-eight fetuses were analyzed, 19 in each group. We analyzed the fetal growth and bowel development. Results: Ultrasound after 100 h of exchange showed equivalent fluid volumes, p = 0.63. Cultures were negative for bacterial colonization. Final fluid protein concentrations were 11.6% that of control fluid (mean 1,451 ± 224.2 vs. 12,491 ± 849.2 μg/mL). There was no significant difference in fetal growth, with experimental weights 91.4% of control weights, p = 0.07. Fetal bowel weights (90.1%, p = 0.16) and lengths (94.2%, p = 0.49) were also not significantly less compared to controls. There was no significant difference in villous height or crypt depth measurements between the groups, and absorptive capacity of the bowel was not different between groups, p = 0.44. Conclusion: This animal model allows for manipulation of the components of amniotic fluid. Marked reduction of natural amniotic fluid proteins during gestation does not appear to significantly impair fetal growth or bowel development. Further work with this model will assess the importance of amniotic fluid components for normal development to inform design of a synthetic fluid for use during EXTEND.

Identification of Pathways Associated with Placental Adaptation to Maternal Nutrient Restriction in Sheep.

Maternal nutrient restriction impairs placental growth and development, but available evidence suggests that adaptive mechanisms exist, in a subset of nutrient restricted (NR) ewes, that support normal fetal growth and do not result in intrauterine growth restriction (IUGR). This study utilized Affymetrix GeneChip Bovine and Ovine Genome 1.0 ST Arrays to identify novel placental genes associated with differential fetal growth rates within NR ewes. Singleton pregnancies were generated by embryo transfer and, beginning on Day 35 of pregnancy, ewes received either a 100% National Research Council (NRC) (control-fed group; n = 7) or 50% NRC (NR group; n = 24) diet until necropsy on Day 125. Fetuses from NR ewes were separated into NR non-IUGR (n = 6) and NR IUGR (n = 6) groups based on Day 125 fetal weight for microarray analysis. Of the 103 differentially expressed genes identified, 15 were upregulated and 88 were downregulated in NR non-IUGR compared to IUGR placentomes. Bioinformatics analysis revealed that upregulated gene clusters in NR non-IUGR placentomes associated with cell membranes, receptors, and signaling. Downregulated gene clusters associated with immune response, nutrient transport, and metabolism. Results illustrate that placentomal gene expression in late gestation is indicative of an altered placental immune response, which is associated with enhanced fetal growth, in a subpopulation of NR ewes.

Examination of fetal growth trajectories following infertility treatment.

The objective of this retrospective cohort study was to compare fetal growth during the second and third trimesters for ovulation induction with intrauterine insemination (IUI), fresh embryo transfer (ET), frozen embryo transfer (FET), and spontaneous conception following infertility. Three hundred ninety-five women with viable pregnancies confirmed at a single academic fertility center participated. All women achieved pregnancy either by treatment or spontaneously after a diagnosis of infertility. Inclusion criteria included autologous singleton pregnancies. Exclusion criteria included pregnancies from donor oocytes, twins, unavailable ultrasound data, and treatment methods with small number of participants. Primary outcomes of interest were head circumference (HC), abdominal circumference (AC), HC/AC ratio, and estimated fetal weight (EFW). Conditional growth curve models were created, and growth curves were selected for each outcome of interest. For ovulation induction with IUI, fresh ET, FET, and spontaneous conception, the slope analysis of growth curves for per-week growth rate of HC, AC, HC/AC ratio, and EFW demonstrated no difference. A subgroup analysis of fresh ET and FET groups, for same outcomes, also showed no difference. These findings contribute to the very limited literature on fetal growth trajectories following infertility treatment and suggest no significant differences in fetal growth for ovulation induction with IUI, fresh ET, FET, and spontaneous conception following infertility. It is possible there were no differences in growth trajectories between these conception methods because the majority of children born following infertility are of normal birth weight. While results are reassuring, further research with larger populations is warranted.

Sex differences in fetal growth and immediate birth outcomes in a low-risk Caucasian population

BackgroundAccording to the WHO Multicentre Growth Reference Study Group recommendations, boys and girls have different growth trajectories after birth. Our aim was to develop gender-specific fetal growth curves in a low-risk population and to compare immediate birth outcomes.MethodsFirst, second, and third trimester fetal ultrasound examinations were conducted between 2002 and 2012. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancies, Caucasian ethnicity, and confirmation of gestational age by a crown-rump length (CRL) measurement in the first trimester. Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to align the time frames of the longitudinal fetal measurements, corresponding with the methods of the postnatal growth curves of the WHO MGRS Group.ResultsA total of 27,680 complete scans were selected from the astraia© ultrasound database representing 12,368 pregnancies. Gender-specific fetal growth curves for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were derived. The HC and BPD were significantly larger in boys compared to girls from 20 weeks of gestation onwards (p < 0.001) equating to a 3-day difference at 20–24 weeks. Boys were significantly heavier, longer, and had greater head circumference than girls (p < 0.001) at birth. The Apgar score at 1 min (p = 0.01) and arterial cord pH (p < 0.001) were lower in boys.ConclusionsThese longitudinal fetal growth curves for the first time allow integration with neonatal and pediatric WHO gender-specific growth curves. Boys exceed head growth halfway of the pregnancy, and immediate birth outcomes are worse in boys than girls. Gender difference in intrauterine growth is sufficiently distinct to have a clinically important effect on fetal weight estimation but also on the second trimester dating. Therefore, these differences might already play a role in early fetal or immediate neonatal management.

Fetal growth patterns in pregnancy-associated hypertensive disorders: NICHD Fetal Growth Studies

Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups. Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P < .008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P < .04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P < .0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P < .0001) than in the normotensive group. Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.

The effects of gestational diabetes mellitus on fetal growth and neonatal birth measures in an African cohort.

Fetal exposure to gestational diabetes mellitus (GDM) is said to alter fetal growth and increase the risk of macrosomia. However, little research on GDM exists in African populations. This study aimed to assess longitudinal fetal growth and neonatal birth measures among Black African babies exposed to GDM. Pregnant women (Soweto, South Africa) enrolled into a cohort study were followed up with repeated fetal ultrasounds. At 24-28 weeks' gestation a 2-h 75 g oral glucose tolerance test was performed and GDM was diagnosed using the World Health Organization's 2013 criteria. Neonatal birth measures were assessed. The study involved 741 women; 83 (11.2%) with GDM and 658 (88.8%) without. A total of 4040 fetal ultrasounds were performed. GDM exposure was associated with an increase in fetal growth measures, especially abdominal circumference, which was already seen at 16-18weeks' gestation. Male fetuses in particular, showed a significant association between GDM exposure and increased abdominal circumference (P=0.009). Most women with GDM (66.3%) received management; all received diet therapy and 32.7% were prescribed medication. There was no difference in birth measures between the GDM-exposed and unexposed neonates. Repeated ultrasound measures identified the effects of GDM as early as 16-18 weeks' gestation, well before a diagnosis of GDM would usually be made. Sex differences in fetal growth were observed, with GDM-exposed male fetuses being more affected with larger abdominal circumferences than females. A low rate of macrosomia was observed compared with historical GDM populations.

ELP‐VEGF Treatment Improves the Maternal Syndrome of Preeclampsia in the Dahl Salt Sensitive (S) Rat

Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus; however, there is currently no effective treatment for preeclampsia. The anti‐angiogenic protein sFlt‐1 has been implicated in the pathogenesis of preeclampsia through both clinical and experimental studies, leading us and others to propose that antagonism of sFlt‐1 via administration of vascular endothelial growth factor (VEGF) will reduce the maternal symptoms of hypertension and proteinuria in preeclamptic pregnancy. In this study, we tested the hypothesis that VEGF fused to the synthetic carrier elastin like polypeptide (ELP) will improve the maternal syndrome in the Dahl S rat model of superimposed preeclampsia. Female Dahl S rats (16–18 weeks of age) were placed in metabolic cages for 24‐hour urine collection, mated with Dahl S male rats, and randomly divided into control and ELP‐VEGF treated groups. ELP‐VEGF was administered via osmotic pump (5 mg/kg/day, Alzet 2ML1) beginning on day 10 of pregnancy, and pumps were replaced on day 17 of pregnancy. Urine was collected again on day 19, and blood and tissues were harvested on day 20. Urinary protein excretion (Bradford assay) did not differ between groups at baseline (87±11 vs 99±21 mg/d), but was significantly lower during late pregnancy in the ELP‐VEGF treated rats (* p=0.004, table). A subset of ELP‐VEGF‐treated rats (n=4) was implanted with telemetry transmitters (DSI) before mating. While previous studies have shown that blood pressure increases during pregnancy in the Dahl S rat, ELP‐VEGF treatment resulted in a fall in mean arterial pressure of 27±5 mmHg from day 9 to day 18 of pregnancy. No significant differences in fetal growth or litter size were observed following treatment. These data suggest that ELP‐VEGF treatment improves the maternal syndrome of preeclampsia without impairing fetal outcomes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study.

Three recently completed longitudinal cohort studies have developed intrauterine fetal growth charts, one in the United States and two international. This expert review compares and contrasts the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies, INTERGROWTH-21st and World Health Organization Multicentre Growth Reference Study conclusions in light of differences in aims, sampling frames, and analytical approaches. An area of controversy is whether a single growth reference is representative of growth, regardless of ethnic or country origin. The INTERGROWTH and World Health Organization Fetal studies used a similar approach as the World Health Organization Multicentre Growth Reference Study for infants and children, the aim of which was to create a single international reference for the best physiological growth for children aged 0-5 years. INTERGROWTH made the same assumption (ie, that there would be no differences internationally among countries or racial/ethnic groups in fetal growth when conditions were optimal). INTERGROWTH found differences in crown-rump length and head circumference among countries but interpreted the differences as not meaningful and presented a pooled standard. The World Health Organization Multicentre Growth Reference Study was designed to create a pooled reference, although they evaluated for and presented country differences, along with discussion of the implications. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Study was designed to assess whether racial/ethnic-specific fetal growth standards were needed, in recognition of the fact that fetal size is commonly estimated from dimensions (head circumference, abdominal circumference, and femur length) in which there are known differences in children and adults of differing racial/ethnic groups. A pooled standard would be derived if no racial/ethnic differences were found. Highly statistically significant racial/ethnic differences in fetal growth were found resulting in the publication of racial/ethnic-specific derived standards. Despite all 3 studies including low-risk status women, the percentiles for fetal dimensions and estimated fetal weight varied among the studies. Specifically, at 39 weeks, the 50th percentile for estimated fetal weight was 3502 g for whites, 3330 g for Hispanics, 3263 g for Asians, and 3256 for blacks in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study, compared with 3186 g for INTERGROWTH and 3403 g for World Health Organization Multicentre Growth Reference Study. When applying these standards to a clinical population, it is important to be aware that different percentages of small- and large-for-gestational-age fetuses will be identified. Also, it may be necessary to use more restrictive cut points, such as the 2.5th or 97.5th, for small-for-gestational-age or large-for-gestational-age fetuses, respectively. Ideally, a comparison of diagnostic accuracy, or misclassification rates, of small-for-gestational-age and large-for-gestational-age fetuses in relation to morbidity and mortality using different criteria is necessary to make recommendations and remains an important data gap. Identification of the appropriate percentile cutoffs in relation to neonatal morbidity and mortality is needed in local populations, depending on which fetal growth chart is used. On a final point, assessment of fetal growth with a one-time measurement remains standard clinical practice, despite recognition that a single measurement can indicate only size. Ultimately, it is knowledge about fetal growth in addition to other factors and clinical judgment that should trigger intervention.

Effects of applying universal fetal growth standards in a Scandinavian multi-ethnic population.

The question of whether universal growth charts can be used in multi-ethnic settings is of general interest. The Intergrowth-21st fetal growth and newborn size standards are suggested to represent optimal fetal growth regardless of country origin. Our aim was to examine whether women fulfilling the strict Intergrowth-21st inclusion criteria were healthier, showed less ethnic differences in fetal growth and newborn size, and less adverse perinatal outcomes. Data were drawn from a population-based multi-ethnic cohort of 823 presumably healthy pregnant women in Oslo, Norway. We assessed differences in fetal and neonatal gestational age specific z-scores and compared maternal health parameters, pregnancy and birth complications between pregnancies fulfilling and not fulfilling the Intergrowth-21st criteria. Only 21% of pregnancies enrolled in our cohort fulfilled the Intergrowth-21st criteria. Fetal growth deviated substantially from the new standards, in particular for ethnic Europeans. Ethnic differences persisted in pregnancies fulfilling the criteria. In South Asian fetuses, estimated fetal weight was -0.60 SD (95% confidence interval -1.00, -0.20) lower at 24 gestational weeks, and birthweight was -0.62 SD (-0.95, -0.29) lower, compared with ethnic Europeans. Corresponding numbers for Middle-East/North Africans were -0.13 (-0.62, 0.36) and -0.60 (-1.00, -0.20). Maternal health indicators and birth complications were similar in women fulfilling and not fulfilling the criteria, but the relation depended on ethnic origin. In an urban multi-ethnic Norwegian population, applying an extensive list of criteria to define "healthy" pregnancies excludes the majority of women but does not cancel ethnic differences in fetal growth.

OP23.08: Longitudinal growth evaluation in fetuses with neural tube defect with and without prenatal‐fetoscopic and open‐repair

Prenatal neural tube defect (NTD) repair exposes the fetus to anesthesia and in some cases to CO2 environment. Either of these could affect placental function. The aim of this study was to compare growth parameters in fetuses with NTD who had fetoscopic, open and postnatal repair. Biometrics were serially measured by ultrasound in a cohort of NTD fetuses, classified by type and timing of the repair: Group 1: Fetoscopic, Group 2: Open and Group 3: Postnatal. Estimated fetal weight percentiles (EFWp Hadlock standards), proportion of EFWp<10th(FGR), abdominal circumference (ACp) and head circumference percentiles (HCp) at diagnosis were compared in all groups and at 6 weeks (w) post-surgery in groups 1 and 2. Birth weight percentiles (BWp WHO standards), neonatal HCp and the proportion of BWp<10th were also compared. A linear mixed model analysed repeated measurements for each parameter to assess growth throughout gestation using random intercepts and slopes between 3 study groups. Correlations between duration of surgery and CO2 exposure (Group1) with biometrics were performed. Prior to surgery, Group 2 showed lower ACp than Group 3 (table 1). No biometric differences were detected at 6w post-surgery or at birth. Increase in HCp and EFWp over time was greater in Group 2 compared to Group 3(p=0.04 and 0.03). No differences in fetal growth were detected when comparing Group 1 to others. No significant correlations between surgical and fetal size parameters were detected. Fetoscopic and open NTD repairs are not associated with detrimental effects on fetal growth. EFWp at diagnosis [% FGR] EFWp 6w postop scan [%FGR] 16.5 (0.4-99.1) 24.5 (0.1-95) BWp [%BWp < 10th] 22.9 (0.1-99.9) 49.4 (0.1-99.9) 38.3 (0.1-99.9)