The NICHD Fetal 3D Study: A Pregnancy Cohort Study of Fetal Body Composition and Volumes.

There's a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.

Multiethnic Growth Standards for Fetal Body Composition and Organ Volumes Derived from 3D Ultrasonography.

BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of two-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established two-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by three-dimensional ultrasonography and compare growth trajectories with conventional two-dimensional measures where applicable. STUDY DESIGN: The NICHD Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to five scans per fetus (N=1,730 fetuses). Abdominal subcutaneous tissue thickness was measured from two-dimensional images and fetal limb soft tissue parameters extracted from three-dimensional multiplanar views. Cerebellar, lung, liver and kidney volumes were measured using virtual organ computer aided analysis (VOCAL). Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (5th, 50th, 95th percentiles) were derived from 15-41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27-29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29-30 weeks. In contrast, growth patterns for two-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the 2nd trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid arm and thigh circumferences were more linear with some decelerations. Cerebellar two-dimensional diameter increased linearly, whereas cerebellar three-dimensional volume growth gradually accelerated until 32 weeks and then decelerated. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26-27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for three-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional two-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic or environmental influences and pregnancy complications, in ways not identifiable using corresponding two-dimensional measures. Further investigation into the relationships of these three-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Nutritional Intake in Dichorionic Twin Pregnancies: A Descriptive Analysis of a Multisite United States Cohort.

INTRODUCTION: Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described. METHODS: In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012-2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency questionnaire during each trimester of pregnancy. We examined changes in means of total energy and energy-adjusted dietary components using linear mixed effects models. RESULTS: Mean energy intake (95% CI) across the three trimesters was 2010 kcal/day (1846, 2175), 2177 kcal/day (2005, 2349), 2253 kcal/day (2056, 2450), respectively (P = 0.01), whereas the Healthy Eating Index-2010 was 63.9 (62.1, 65.6), 64.5 (62.6, 66.3), 63.2 (61.1, 65.3), respectively (P = 0.53). DISCUSSION: Women with twin gestations moderately increased total energy as pregnancy progressed, though dietary composition and quality remained unchanged. These findings highlight aspects of nutritional intake that may need to be improved among women carrying twins.

Comparing Fetal Ultrasound Biometric Measurements to Neonatal Anthropometry at the Extremes of Birthweight.

OBJECTIVE: Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. STUDY DESIGN: We compared differences in head circumference (HC), abdominal circumference (AC), femur length, and EFW between ultrasound and corresponding birth measurements within 14 (n = 1,290) and 7 (n = 617) days of birth for small- (SGA, <10th percentile), appropriate- (AGA, 10th-90th), and large-for-gestational age (LGA, >90th) newborns. RESULTS: Average differences between EFW and birthweight for SGA neonates were: -40.2 g (confidence interval [CI]: -82.1, 1.6) at 14 days versus 13.6 g (CI: -52.4, 79.7) at 7 days; for AGA, -122.4 g (-139.6, -105.1) at 14 days versus -27.2 g (-50.4, -4.0) at 7 days; and for LGA, -242.8 g (-306.5, -179.1) at 14 days versus -72.1 g (-152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were the largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. CONCLUSION: Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared with AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3- to 4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research. KEY POINTS: · Ultrasound measurements may be inadequate to predict neonatal size at birth.. · Birthweight estimation error is higher for neonates >90th percentile.. · There is higher error in AC closer to birth..

Racial/Ethnic Differences in Prenatal Supplement and Medication Use in Low-Risk Pregnant Women.

OBJECTIVE: This study aimed to describe the overall quantity and type of supplements and medications used during pregnancy in a low-risk cohort and to examine any racial/ethnic differences in intake. STUDY DESIGN: We used data from 2,164 racially/ethnically diverse, nonobese, and low-risk pregnant women participating without pre-pregnancy chronic conditions in a prospective cohort study at 12 sites across the United States. Medication data were self-reported as free text in enrollment, follow-up visit questionnaires, and abstracted from medical records at delivery. Supplements and medications data were mapped to their active ingredients and categorized into corresponding classes using the Slone Drug Dictionary. The total number and classes of supplements and medications consumed during pregnancy were calculated. Modified Poisson regression models were used to estimate the racial/ethnic differences in supplements and medications intake. All models were adjusted for maternal sociodemographic factors and study site. RESULTS: 98% of women took at least one supplement during pregnancy, with prenatal vitamins/multivitamins being most common. While only 31% reported taking no medications during pregnancy, 23% took one, 18% took two, and 28% took three or more. The percentage of women taking at least one medication during pregnancy was highest among non-Hispanic white women and lowest among Asians (84 vs. 55%, p < 0.001). All racial/ethnic groups reported taking the same top four medication classes including central nervous system agents, gastrointestinal drugs, anti-infective agents, and antihistamines. Compared with non-Hispanic white women, Hispanic (adjusted relative risk [aRR]: 0.84, 95% confidence interval [CI]: 0.71-0.98), and Asian women (aRR: 0.83, 95% CI: 0.70-0.98) were less likely to take central nervous system agents, as well as gastrointestinal drugs (Hispanics aRR: 0.79, 95% CI: 0.66-0.94; Asians aRR = 0.75, 95% CI: 0.63-0.90), and antihistamines (Hispanics aRR: 0.65, 95% CI: 0.47-0.92). CONCLUSION: Supplement intake was nearly universal. Medication use was also common among this low-risk pregnancy cohort and differed by race/ethnicity. GOV IDENTIFIER: NCT00912132. KEY POINTS: · In women without chronic conditions, medication use is common.. · Racial/ethnic differences exist in prenatal medications use.. · Almost all women use supplements during pregnancy..

World Prematurity Day: it takes an NIH village to prevent preterm birth and improve treatments for preterm infants.

Prematurity remains a major cause of morbidity and mortality. Research to prevent preterm birth and improve treatments for preterm infants involves both intramural and extramural research, not just at the National Institute of Child Health and Human Development, but across many institutes and centers at the National Institutes of Health.

Advancing the Health of Populations Across the Life Course: 50 Years of Discoveries in the Division of Intramural Population Health Research.

In 2017, the Division of Intramural Population Health Research (DIPHR), within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), reached a significant milestone: 50 years in existence. DIPHR celebrated this anniversary with a scientific program that reviewed past accomplishments and reflected on future directions in support of promoting the health of populations across the life course. Extending from the scientific program, the impetus of this article is to contribute to archiving and consolidating the legacy of intramural population health research at NICHD over the past 50 years. We present a brief history of the origin and evolution of intramural population health research at NICHD. Next, we conduct an empirical assessment of the scientific impact and evolving scope of this research over the past five decades and present specific key discoveries emerging from topics spanning the life course: (1) reproductive health, (2) the health of pregnant women and fetuses, (3) the health of children, and (4) associated methodologies. We also explore the Division's service to the profession in the form of mentorship of the next generation of scientists in population health research. Finally, we conclude with thoughts about future directions of population health research and reaffirm the DIPHR's commitment to promoting the health and well-being of the many populations we serve, both locally and globally.

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

BACKGROUND: Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. OBJECTIVE: The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Longitudinal changes in maternal anthropometry in relation to neonatal anthropometry.

OBJECTIVE: To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition. DESIGN: In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15-28 weeks) and third trimester (28-39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes. SETTING: Women were recruited from twelve US sites (2009-2013).ParticipantsNon-obese women with singleton pregnancies (n 2334). RESULTS: A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (-0·57 to -0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (-0·05 to 0·06 mm per week). CONCLUSIONS: The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.

Fetal growth velocity: the NICHD fetal growth studies.

BACKGROUND: Accurately identifying pregnancies with accelerated or diminished fetal growth is challenging and generally based on cross-sectional percentile estimates of fetal weight. Longitudinal growth velocity might improve identification of abnormally grown fetuses. OBJECTIVE: We sought to complement fetal size standards with fetal growth velocity, develop a model to compute fetal growth velocity percentiles for any given set of gestational week intervals, and determine association between fetal growth velocity and birthweight. STUDY DESIGN: This was a prospective cohort study with data collected at 12 US sites (2009 through 2013) from 1733 nonobese, low-risk pregnancies included in the singleton standard. Following a standardized sonogram at 10w0d-13w6d, each woman was randomized to 1 of 4 follow-up visit schedules with 5 additional study sonograms (targeted ranges: 16-22, 24-29, 30-33, 34-37, and 38-41 weeks). Study visits could occur ± 1 week from the targeted GA. Ultrasound biometric measurements included biparietal diameter, head circumference, abdominal circumference, and femur length, and estimated fetal weight was calculated. We used linear mixed models with cubic splines for the fixed effects and random effects to flexibly model ultrasound trajectories. We computed velocity percentiles in 2 ways: (1) difference between 2 consecutive weekly measurements (ie, weekly velocity), and (2) difference between any 2 ultrasounds at a clinically reasonable difference between 2 gestational ages (ie, velocity calculator). We compared correlation between fetal growth velocity percentiles and estimated fetal weight percentiles at 4-week intervals, with 32 (±1) weeks' gestation for illustration. Growth velocity was computed as estimated fetal growth rate (g/wk) between ultrasound at that gestational age and from prior visit [ie, for 28-32 weeks' gestational age: velocity = (estimated fetal weight 32-28)/(gestational age 32-28)]. We examined differences in birthweight by whether or not estimated fetal weight and estimated fetal weight velocity were <5th or ≥5th percentiles using χ2. RESULTS: Fetal growth velocity was nonmonotonic, with acceleration early in pregnancy, peaking at 13, 14, 15, and 16 weeks for biparietal diameter, head circumference, femur length, and abdominal circumference, respectively. Biparietal diameter, head circumference, and abdominal circumference had a second acceleration at 19-22, 19-21, and 27-31 weeks, respectively. Estimated fetal weight velocity peaked around 35 weeks. Fetal growth velocity varied slightly by race/ethnicity although comparisons reflected differences for parameters at various gestational ages. Estimated fetal weight velocity percentiles were not highly correlated with fetal size percentiles (Pearson r = 0.40-0.41, P < .001), suggesting that these measurements reflect different aspects of fetal growth and velocity may add additional information to a single measure of estimated fetal weight. At 32 (SD ± 1) weeks, if both estimated fetal weight velocity and size were <5th percentile, mean birthweight was 2550 g; however, even when size remained <5th percentile but velocity was ≥5th percentile, birthweight increased to 2867 g, reflecting the important contribution of higher growth velocities. For estimated fetal weight ≥5th percentile, but growth velocity <5th, birthweight was smaller (3208 vs 3357 g, respectively, P < .001). CONCLUSION: We provide fetal growth velocity data to complement our previous work on fetal growth size standards, and have developed a calculator to compute fetal growth velocity. Preliminary findings suggest that growth velocity adds additional information over knowing fetal size alone.

Characterization of Thermal and Mechanical Indices from Serial Ultrasound Exams and Associations with Neonatal Anthropometry: The NICHD Fetal Growth Studies.

OBJECTIVE: This article aims to determine if the number of maternal ultrasound scans where the highest thermal (TI) or mechanical (MI) indices recorded during obstetrical ultrasound exceed 1.0 were associated with neonatal anthropometric measurements. STUDY DESIGN: A prospective cohort of 2,334 nonobese low-risk pregnant women from 12 U.S. clinical sites underwent a total of six ultrasound scans, for which the highest TI and MI values were recorded. Neonatal anthropometric measurements were obtained within 12 to 24 hours of delivery. Multiple linear regression models adjusted for maternal race/ethnicity, body mass index, weight gain, and gestational age were used to examine associations between the number of maternal ultrasounds during gestation with a TI or MI exceeding 1.0 and the mean change in neonatal anthropometry. RESULTS: Ultrasounds with TI or MI >1.0 were not associated with birth weight, neonatal length, nor head, chest, and abdominal circumferences. TI >1.0 was negatively associated with neonatal mid-upper arm and mid-upper thigh circumferences. MI >1.0 was negatively associated with neonatal skinfold measurements of the anterior thigh and triceps, and neonatal circumferences of the mid-upper thigh and umbilicus. CONCLUSION: Prenatal ultrasound examinations in which TI or MI intermittently exceeded 1.0 did not identify a pattern of alterations of birth size.

A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort.

AIMS/HYPOTHESIS: The aim of this study was to prospectively and longitudinally investigate maternal iron status during early to mid-pregnancy, and subsequent risk of gestational diabetes mellitus (GDM), using a comprehensive panel of conventional and novel iron biomarkers. METHODS: A case-control study of 107 women with GDM and 214 controls (matched on age, race/ethnicity and gestational week during blood collection) was conducted within the the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort (2009-2013), a prospective and multiracial pregnancy cohort. Plasma hepcidin, ferritin and soluble transferrin receptor (sTfR) were measured and sTfR:ferritin ratio was derived, twice before GDM diagnosis (gestational weeks 10-14 and 15-26) and at weeks 23-31 and 33-39. GDM diagnosis was ascertained from medical records. Adjusted ORs (aORs) for GDM were estimated using conditional logistic regression analysis, adjusting for demographics, prepregnancy BMI and other major risk factors. RESULTS: Hepcidin concentrations during weeks 15-26 were 16% higher among women with GDM vs controls (median 6.4 vs 5.5 ng/ml; p = 0.02 ), and were positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.61 (1.07, 6.36). Ferritin levels were also positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.43 (1.12, 5.28) at weeks 10-14 and 3.95 (1.38, 11.30) at weeks 15-26. The sTfR:ferritin ratio was inversely related to GDM risk; the aOR (95% CI) for highest vs lowest quartile was 0.33 (0.14, 0.80) at weeks 10-14 and 0.15 (0.05, 0.48) at weeks 15-26. CONCLUSIONS/INTERPRETATION: Our findings suggest that elevated iron stores may be involved in the development of GDM from as early as the first trimester. This raises potential concerns for the recommendation of routine iron supplementation among iron-replete pregnant women.

Validation of Self-reported Diagnosis of Gestational Diabetes at 6-weeks Postpartum.

BACKGROUND: Self-report is often used in identifying gestational diabetes events in epidemiologic studies; however, validity data are limited, with little to no data on self-reported severity or treatment. METHODS: We aimed to assess the validity of self-reported gestational diabetes diagnosis and evaluate the accuracy of glucose diagnosis results and gestational diabetes treatment self-reported at 6-week postpartum. Data were from 82 and 83 women with and without gestational diabetes, respectively, within the prospective National Institute Child Health and Human Development Fetal Growth Studies-Singletons (2009-2013). Medical record data were considered the gold standard. RESULTS: Sensitivity was 95% (95% confidence interval [CI] = 88, 98), and specificity was 100% (95% CI = 96, 100); four women with gestational diabetes incorrectly reported not having the disease, and none of the women without gestational diabetes reported having gestational diabetes. Sensitivity did not vary substantially across maternal characteristics including race/ethnicity. For women who attempted to recall their values (84/159 women), self-reported glucose challenge test results did not differ from the medical records (median difference: 0; interquartile range: 0-0 mg/dl). Medical records indicated that 42 (54%) of 78 women with confirmed gestational diabetes were treated by diet only and 33 (42%) were treated by medication. All 42 women with diet-treated gestational diabetes correctly reported having had diet and lifestyle modification, and 28 (85%) of 33 women with medication-treated gestational diabetes indicated postpartum that they had medication treatment. CONCLUSIONS: At 6-week postpartum, regardless of race/ethnicity or socioeconomic status, women accurately recalled whether they had gestational diabetes and, as applicable, their treatment method.

Maternal stress and neonatal anthropometry: the NICHD Fetal Growth Studies.

BACKGROUND: The effect of maternal mood disorders on neonatal measurements is not well-defined. The Fetal Growth Studies-Singletons provide a unique opportunity to evaluate the relationship between perceived maternal stress and neonatal growth measurements. OBJECTIVE: The purpose of this study was to determine whether perceived maternal stress during pregnancy is associated with anthropometric measurements in the neonate. STUDY DESIGN: This analysis was based on a prospective, multicenter longitudinal study of fetal growth. Women 18-40 years old with a body mass index of 19.0-29.9 kg/m2 were screened at 8+0 to 13+6 weeks gestation for low-risk status associated with optimal fetal growth (eg, healthy, nonsmoking) and underwent serial sonographic examination at 6 study visits throughout gestation. At each study visit, women completed the Cohen's Perceived Stress Survey, which could have a score that ranges from 0-40. We used a latent class trajectory model to identify distinct groupings (ie, classes) of the Perceived Stress Survey trajectories over pregnancy. Trend analysis was used to determine whether neonatal measurements including birthweight, length, head circumference, and abdominal circumference differed by Perceived Stress Survey class and whether this relationship was modified by maternal race/ethnicity, after adjustment for gestational age at delivery, maternal height, age, and parity. RESULTS: Of the 2334 women enrolled in the study, 1948 women had complete neonatal anthropometry and were included in the analysis. Latent class analysis identified 3 Perceived Stress Survey trajectory classes, with mean Perceived Stress Survey scores of 2.82 (low), 7.95 (medium), and 14.80 (high). Neonatal anthropometric measures of birthweight, length, head circumference and abdominal circumference were similar (P=.78, =.10, =.18, and =.40 respectively), regardless of the participants' Perceived Stress Survey class. There was no effect modification by maternal race/ethnicity. CONCLUSION: Neonatal measurements did not differ by levels of perceived stress among low-risk pregnant women.

Maternal Depressive Symptoms, Perceived Stress, and Fetal Growth.

OBJECTIVES: To determine whether longitudinal fetal growth is altered among pregnant women reporting greater perceived stress or more symptoms of depression. METHODS: This analysis was based on a multicenter longitudinal study of fetal growth. Women were screened at gestational ages of 8 weeks to 13 weeks 6 days for low-risk status and underwent serial sonographic examinations. At each study visit during pregnancy, women were asked to complete the Cohen Perceived Stress Scale (PSS) and Edinburgh Postpartum Depression Survey (EPDS). Growth curves for estimated fetal weight and individual biometric parameters were created by using linear mixed models with cubic splines and compared on the basis of whether women scored 15 or higher on the PSS or 10 or higher on the EPDS either at the start of or at any time during pregnancy. RESULTS: Of the 2334 women enrolled in the study, 2088 (89%) and 2108 (90%) completed the PSS and EPDS, respectively, at least once in all trimesters. The longitudinal growth curves of estimated fetal weight as well as all individual biometric parameters were similar (P > .05) regardless of whether the participants reported PSS of 15 or higher or EPDS of 10 or higher in the first trimester or whether these scores persisted throughout the pregnancy. Similarly, effect modification by race/ethnicity was not statistically significant for the biometric parameters under study (P > .05 for all race/ethnicity interactions). CONCLUSIONS: More depressive symptoms and greater perceived stress, as quantified by the EPDS and the PSS, respectively, are not associated with alterations in fetal growth throughout gestation.

Dichorionic twin trajectories: the NICHD Fetal Growth Studies.

BACKGROUND: Systematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation that are performed in controlled clinical settings. Currently, there are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated with the use of the same benchmarks as singleton growth. OBJECTIVES: Our objective was to define the trajectory of fetal growth in dichorionic twins empirically using longitudinal 2-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard that was developed by our group for singletons. STUDY DESIGN: A prospective cohort of 171 women with twin gestations was recruited from 8 US sites from 2012-2013. After an initial sonogram at 11 weeks 0 days-13 weeks 6 days of gestation during which dichorionicity was confirmed, women were assigned randomly to 1 of 2 serial ultrasonography schedules. Growth curves and percentiles were estimated with the use of linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education, and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories with the use of likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements in which there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests that were computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, which was defined as <10th percentile that would be introduced if fetal growth estimation for twins was based on an unweighted singleton standard. RESULTS: Women underwent a median of 5 ultrasound scans. The 50th percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks of gestation; biparietal diameter in twins was smaller from 34-36 weeks of gestation. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks of gestation, which indicated a comparatively asymmetric growth pattern. At 35 weeks of gestation, the average gestational age at delivery for twins, the estimated fetal weights for the 10th, 50th, and 90th percentiles were 1960, 2376, and 2879 g for dichorionic twins, respectively, and 2180, 2567, and 3022 g for the singletons, respectively. At 32 weeks of gestation, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age with the use of a singleton, non-Hispanic white standard. By 35 weeks of gestation, 38% of twins would be classified as small for gestational age. CONCLUSION: The comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks of gestation, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard.

Ultrasound Quality Assurance for Singletons in the National Institute of Child Health and Human Development Fetal Growth Studies.

OBJECTIVES: To report on the ultrasound quality assurance program for the National Institute of Child Health and Human Development Fetal Growth Studies and describe both its advantages and generalizability. METHODS: After training on an ultrasound system and software, research sonographers were expected to capture blank (unmeasured) images in triplicate for crown-rump length, biparietal diameter, head circumference, abdominal circumference, and femur length. A primary expert sonographer was designated and validated. A 5% sample (n = 740 of 14,785 scans) was randomly selected in 3 distinct rounds from within strata of maternal body mass index (round 1 only), gestational age, and research site. Unmeasured images were extracted from selected scans and measured with the ultrasound software by an expert sonographer. Correlations and coefficients of variation (CVs) were calculated, and the within-measurement standard deviation (ie, technical error of the measurement), was calculated. RESULTS: The reliability between the site sonographers and the expert was high, with correlations exceeding 0.99 for all dimensions in all rounds. The CV % values showed low variability, with the percentage differences being less than 2%, except for abdominal circumference in rounds 2 and 3, in which it averaged about 3%. Correlations remained high (>0.90) with increasing fetal size; there was a monotonic increase in technical errors of the measurement but without a corresponding increase in the CV %. CONCLUSIONS: Using rigorous procedures for training sonographers, coupled with quality assurance oversight, we determined that the measurements acquired longitudinally for singletons are both accurate and reliable for establishment of an ultrasound standard for fetal growth.

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

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.