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BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m(2)) and pattern of medication use during pregnancy in the United States is not well-studied. Higher prepregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m(2)), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

The placenta is a temporary endocrine organ that facilitates gas, nutrient, and waste exchange between maternal and fetal compartments, partially shielding the fetus from potentially hazardous environmental toxicants. However, rather than being "opaque", the placenta is translucent or even transparent to some potential fetal developmental hazards, including toxic trace elements (TEs), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and environmental phenols (EPs) to which women with pregnancy are frequently exposed. These agents are both passively and actively transferred to the fetal compartment, where endocrine disruption, oxidative stress, and epigenetic changes may occur. These pathologies may directly impact the fetus or deposit and accumulate in the placenta to indirectly impact fetal development. Thus, it is critical for clinicians to understand the potential placental toxicity and transfer of widely distributed environmental agents ubiquitous during pregnancy. With such knowledge, targeted interventions and clinical recommendations can be developed to limit those risks.

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

Background Systems of care that improve mental health and substance use disorder Screening, Brief Intervention and Referral to Treatment (SBIRT) for pregnant and postpartum women are needed. Aims The aim of this study is to determine if women receiving prenatal care from January 2020 to April 2021 are more likely to be screened, screen positive, be referred for treatment and attend treatment with technology facilitated SBIRT, compared to women receiving prenatal care and in‐person SBIRT January 2017 to December 2019. Materials & Methods Technology facilitated SBIRT, designated Listening to Women (LTW), includes text message‐based screening, phone‐based brief intervention, and referral to treatment by a remote care coordinator. A total of 3535 pregnant and postpartum women were included in the quasi‐experimental study and data were collected via text message and Electronic Health Record. Results In‐person SBIRT was completed by 65.2% (1947/2988) of women while 98.9% (547/553) of women approached agreed to take part in LTW and 71.9% (393/547) completed SBIRT via LTW. After controlling for potentially confounding variables, women enrolled in LTW were significantly more likely to be screened (relative risk [RR]: 1.10, 95% CI 1.03–1.16), screen positive (RR 1.91, 95% CI 1.72–2.10), referred to treatment (RR 1.55, 95% CI 1.43–1.69) and receive treatment (RR 4.95, 95% CI 3.93–6.23), compared to women receiving in‐person SBIRT. Black women enrolled in LTW were significantly more likely to screen positive (RR 1.65, 95% CI 1.35–2.01), be referred to treatment (RR 1.54, 95% CI 1.35–1.76) and attend treatment (RR 5.49, 95% CI 3.69–8.17), compared to Black women receiving in‐person SBIRT. Discussion LTW appears to increase the proportion of pregnant and postpartum women receiving key elements of SBIRT.

ImportanceGreater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear.ObjectiveTo evaluate the associations of pregnancy caffeine and paraxanthine measures with child growth in a contemporary cohort with low caffeine consumption and a historical cohort with high caffeine consumption.Design, Setting, and ParticipantsThe Environmental Influences on Child Health Outcomes cohort of the National Institute of Child Health and Human Development Fetal Growth Studies (ECHO-FGS; 10 sites, 2009-2013) was a pregnancy cohort with 1 child measurement between ages 4 and 8 years (follow-up in 2017-2019). The Collaborative Perinatal Project (CPP) was a pregnancy cohort (12 sites, 1959-1965) with child follow-up through 8 years (1960-1974). The current secondary analysis was conducted in 2021 and 2022.ExposuresConcentrations of caffeine and its primary metabolite, paraxanthine, were quantified from plasma (ECHO-FGS) and serum (CPP) collected in the first trimester. Cut points for analyses were defined by quartiles in ECHO-FGS and quintiles in CPP.Main Outcomes and MeasuresChild z scores for body mass index, weight, and height were evaluated, as well as fat mass index and percentage and obesity risk measured at 1 time between age 4 and 8 years in ECHO-FGS. In a secondary analysis of the CPP cohort, child z scores and obesity risk longitudinally through age 8 years were evaluated.ResultsIn ECHO-FGS (median caffeine intake z scores (β = −0.21; 95% CI, −0.41 to −0.02), but differences in weight z scores were only observed in the third quartile (β = −0.27; 95% CI, −0.47 to −0.07). In CPP, beginning at age 4 years, 1622 children (805 boys [49.7%]) of women in the highest caffeine quintile group had lower height z scores than their peers from the lowest group, with the gap widening with each successive year of age (β = −0.16 [95% CI, −0.31 to −0.01] at 4 years; β = −0.37 [95% CI, −0.57 to −0.16] at 8 years). There were slight reductions in weight at ages 5 to 8 years for children in the third vs first caffeine quintile (β = −0.16 to −0.22). Results were consistent for paraxanthine concentrations in both cohorts.Conclusions and RelevanceIntrauterine exposure to increasing levels of caffeine and paraxanthine, even in low amounts, was associated with shorter stature in early childhood. The clinical implication of reductions in height and weight is unclear; however, the reductions were apparent even with levels of caffeine consumption below clinically recommended guidelines of less than 200 mg per day.

The objective of the study was to determine whether adding longitudinal measures of fundal height (FH) to the standard cross-sectional FH to trigger third trimester ultrasound estimated fetal weight (EFW) would improve small for gestational age (SGA) prediction. We developed a longitudinal FH calculator in a secondary analysis of a prospective cohort study of 1,939 nonobese pregnant women who underwent serial FH evaluations at 12 U.S. clinical sites. We evaluated cross-sectional FH measurement ≤ -3 cm at visit 3 (mean: 32.0 ± 1.6 weeks) versus the addition of longitudinal FH up to and including visit 3 to trigger an ultrasound to diagnose SGA defined as birth weight10th percentile. If the FH cut points were not met, the SGA screen was classified as negative. If FH cut points were met and EFW was10th percentile, the SGA screen was considered positive. If EFW was ≥10th percentile, the SGA screen was also considered negative. Sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were computed. In a comparison of methods, 5.8% of women were classified as at risk of SGA by both cross-sectional and longitudinal classification methods; cross-sectional FH identified an additional 4.0%, and longitudinal fundal height identified a separate, additional 4.5%.Using cross-sectional FH as an ultrasound trigger, EFW had a PPV and NPV for SGA of 69 and 92%, respectively. After adding longitudinal FH, PPV increased to 74%, whereas NPV of 92% remained unchanged; however, the number of women who underwent triggered EFW decreased from 9.7 to 5.7%. An innovative approach for calculating longitudinal FH to the standard cross-sectional FH improved identification of SGA birth weight, while simultaneously reducing the number of triggered ultrasounds. As an essentially free-of-charge screening test, our novel method has potential to decrease costs as well as perinatal morbidity and mortality (through better prediction of SGA).· We have developed an innovative calculator for fundal height trajectory.. · Longitudinal fundal height improves detection of SGA.. · As a low cost screening test, the fundal height calculator may decrease costs and morbidity through better prediction of SGA..

Background: Studies suggest breastfeeding lowers obesity risk in childhood, but generalizability of existing evidence is limited. We examined associations of breastfeeding with childhood overweight, obesity, and percentage body fat, in a racially diverse maternal-child cohort. Methods: This cross-sectional study included 823 children, ages 4-8 years, enrolled in the Environmental Exposures and Child Health Outcomes (ECHO) cohort, a subset of the National Institute of Child Health and Human Development Fetal Growth Studies cohort. Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for overweight [BMI (kg/m2) 85th to

INTRODUCTION: A few studies have identified childhood animal exposure as associated with adiposity, but results are inconsistent and differ in timing. METHODS: We conducted an observational cohort study of children ages 4–8 in the Environmental Influences on Child Health Outcomes [ECHO] study. The main exposure was having a dog in the home and/or regular contact with farm animals during the first year of life. Outcomes of interest were child BMI percentile (adjusted for gender and age) categorized as normal/underweight (

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4&ndash, 8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child&rsquo, s race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.

Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian,1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

Maternal prenatal stress and mood symptoms are associated with risk for child psychopathology. Within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies (ECHO-FGS), a racially and ethnically diverse cohort, we studied associations between prenatal stress and depressive symptoms with child neurobehavior, and potential mediation by fetal growth velocity (FGV) in low-risk pregnancies.For 730 mother-child pairs, we had serial ultrasound measurements, self-reports of prenatal stress and depression, observations of child executive functions and motor skills from 4 to 8 years, and maternal reports of child psychiatric problems. We tested associations between prenatal stress and depressive symptoms with child neurobehavior in regression analyses, and associations with FGV in mixed effect models. Post hoc we tested severity of prenatal symptoms; FGV at 25Prenatal stress and depressive symptoms were associated with child psychiatric problems, and prenatal depressive symptoms with decrements in executive functions and motor skills, especially in biological male children. Neither prenatal stress nor depressive symptoms were associated with FGV.In one of the largest cohorts with observed child outcomes, and the first with broad representation of race and ethnicity in the United States, we found that prenatal stress and depressive symptoms were associated with greater reports of child psychiatric symptoms. Only prenatal depressive symptoms were associated with observed decrements in cognitive abilities, most significantly in biological male children. Stress during low-risk pregnancies may be less detrimental than theorized. There was no mediation by FGV. These findings support the need to attend to even small changes in prenatal distress, as these may have long-lasting implications.

BACKGROUND Birthweight discordance is well studied, with less known about longitudinal inter-twin differences in foetal growth. OBJECTIVE To examine inter-twin per cent differences in EFW (EFW% ), head (HC% ) and abdominal circumference (AC% ), and femur length (FL% ) across gestation in dichorionic twin gestations and explore associated characteristics. METHODS Foetal biometrics were assessed by ultrasound and EFW calculated at ≤6 study visits among women with dichorionic twin pregnancies enrolled in the NICHD Fetal Growth Studies cohort (US, 2012-2013). Inter-twin per cent difference was defined: ([Sizelarger twin - Sizesmaller twin ]/Sizelarger twin × 100). Linear mixed models evaluated per cent differences in foetal biometrics at 15 weeks and their change per week overall and by maternal/neonatal characteristics in unadjusted and adjusted models. RESULTS In 140 pregnancies, inter-twin per cent differences increased across gestation for EFW (0.18%/week, 95% confidence interval [CI] 0.10, 0.27), HC (0.03%/week, 95% CI 0.00, 0.06), and AC (0.03%/week, 95%CI -0.01, 0.08) but decreased for FL (-0.03%/week, 95% CI -0.09, 0.02). After adjustment, change in EFW% difference across gestation differed by pre-pregnancy body mass index (BMI [kg/m2 ]; underweight [

Experimental and observational data implicate phthalates as developmental toxicants. However, few data are available to assess the maternal risks of gestational exposure by race and infant sex. To begin to address this data gap, we characterized associations between maternal urinary phthalate metabolites and birth outcomes among African American and white mothers from a southeastern U.S. population. We enrolled pregnant African American (n = 152) and white (n = 158) women with singleton live births between 18 and 22 weeks gestation. We measured phthalate metabolites (mono-n-butyl phthalate (MBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), and the sums of DEHP (ΣDEHP) and DBP (ΣDBP) metabolites) in up to two gestational urine specimens from mothers, and evaluated confounder-adjusted associations per natural log unit greater concentration with birth weight for gestational age z-score, small for gestational age (SGA

Background Epidural analgesia is associated with a fourfold increased rate of intrapartum fever. The likely pathophysiology is a noninfectious maternal inflammatory activation. Safe interventions to reduce maternal and neonatal exposures to intrapartum fever and inflammation are needed. Objective The purpose of this study was to determine if prophylactic epidural steroids decrease fetal exposure to hyperthermia and inflammatory cytokines following epidural analgesia. Study Design This is a randomized, double-blinded, placebo controlled trial. Term nulliparous women requesting epidural analgesia received 80 mg methylprednisolone or preservative-free normal saline via the epidural catheter at placement. The primary outcome was maternal temperature >100.4°F. Secondary outcomes included fetal exposure to inflammation as assessed by cord blood interleukin-6 (IL-6) levels and rates of funisitis. Power analysis estimated a sample size requirement of 276, but new Food and Drug Administration (FDA) recommendations advising a black box warning on epidural steroids resulted in early study termination. Results A total of 116 subjects were enrolled: 58 treatments and 58 placebos. There was no difference in the rate of maternal intrapartum fever or cord blood IL-6 levels between treatment arms. No complications listed in the FDA warning occurred. Conclusion Prophylactic epidural methylprednisolone was not effective in reducing intrapartum fever or neonatal inflammation following epidural analgesia. Alternate mechanisms and preventative strategies should be considered.

Background: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women’s reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. Methods: We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. Results: Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%, p &lt, 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%, 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%, 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%, 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. Conclusions: Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.

Background Accumulating evidence indicates that maternal diets are important for optimizing maternal and offspring health. Existing research lacks comprehensive profiles of maternal diets throughout pregnancy, especially in a racially/ethnically diverse obstetrical population. Objective The aim was to characterize diets in a longitudinal US pregnancy cohort by trimester, race/ethnicity, and prepregnancy BMI. Methods Data were obtained from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton cohort (2009-2013). A food-frequency questionnaire (FFQ) at 8-13 wk of gestation assessed periconception and first-trimester diet (n = 1615). Automated, self-administered, 24-h dietary recalls targeted at 16-22, 24-29, 30-33, and 34-37 wk of gestation assessed second- and third-trimester diets (n = 1817 women/6791 recalls). The Healthy Eating Index-2010 (HEI-2010) assessed diet quality (i.e., adherence to US Dietary Guidelines). Variations in weighted energy-adjusted means for foods and nutrients were examined by trimester, self-identified race/ethnicity, and self-reported prepregnancy BMI. Results Mean (95% CI) HEI-2010 was 65.9 (64.9, 67.0) during periconception to the first trimester assessed with an FFQ and 51.6 (50.8, 52.4) and 51.5 (50.7, 52.3) during the second trimester and third trimester, respectively, assessed using 24-h recalls. No significant differences were observed between the second and third trimester in macronutrients, micronutrients, foods, or HEI-2010 components (P ≥ 0.05). Periconception to first-trimester HEI-2010 was highest among Asian/Pacific Islander [67.2 (65.9, 68.6)] and lowest among non-Hispanic Black [58.7 (57.5, 60.0)] women and highest among women with normal weight [67.2 (66.1, 68.4)] and lowest among women with obesity [63.5 (62.1, 64.9)]. Similar rankings were observed in the second/third trimesters. Conclusions Most pregnant women in this cohort reported dietary intakes that, on average, did not meet US Dietary Guidelines for nonpregnant individuals. Also, diet differed across race/ethnic groups and by prepregnancy BMI, with the lowest overall dietary quality in all trimesters among non-Hispanic Black women and women with obesity. No meaningful changes in dietary intake were observed between the second and third trimesters.

Background Adherence to alternate Healthy Eating Index (AHEI), alternate Mediterranean diet (AMED), and Dietary Approaches to Stop Hypertension (DASH) has been linked to lower risks of chronic diseases. However, their associations with common pregnancy complications are unclear. Objectives This study investigates the associations of AHEI, AMED, and DASH during periconception and pregnancy with common pregnancy complication risks. Methods The study included 1887 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons. Women responded to an FFQ at 8-13 gestational weeks, and they performed a 24-h dietary recall at 16-22 and 24-29 wk. Gestational diabetes (GDM), gestational hypertension, preeclampsia, and preterm delivery were ascertained using medical records. Results Healthier diet indicated by higher AHEI, AMED, and DASH scores was generally related to lower risks of pregnancy complications. Significant inverse associations were observed between AHEI score reported at 16-22 wk and GDM risk [adjusted RR (95% CI), highest (Q4) vs. lowest quartile (Q1): 0.32 (0.16, 0.66), P-trend = 0.002]; DASH score reported at both 8-13 [adjusted RR (95% CI), Q4 vs. Q1: 0.45 (0.17, 1.17), P-trend = 0.04] and 16-22 wk [adjusted RR (95% CI), Q4 vs. Q1: 0.19 (0.05, 0.65), P-trend = 0.01] and gestational hypertension risk; AHEI score reported at 24-29 wk and preeclampsia risk [adjusted RR (95% CI), Q4 vs. Q1: 0.31 (0.11, 0.87), P-trend = 0.03]; AMED score reported at 8-13 wk [adjusted RR (95% CI), Q4 vs. Q1: 0.50 (0.25, 1.01), P-trend = 0.03] and DASH score reported at 24-29 wk [adjusted RR (95% CI), Q4 vs. Q1: 0.50, (0.26, 0.96), P-trend = 0.03] and preterm delivery risk. Conclusions Adherence to AHEI, AMED, or DASH during periconception and pregnancy was related to lower risks of GDM, gestational hypertension, preeclampsia, and preterm delivery.This study was registered at ClinicalTrials.gov as NCT00912132.

Due to the mounting evidence that phthalates, specifically di-2-ethylhexyl phthalate and dibutyl phthalate, produce adverse endocrine effects in humans and wildlife, the use of other chemicals as replacements has increased. One of the most commonly encountered phthalate replacements is di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH). Currently, little is known about the prevalence of human exposure, bioactivity, and endocrine disrupting potential of DINCH. We sampled urine from 100 pregnant women during the second trimester of pregnancy living in Charleston, SC between 2011 and 2014 and measured the following DINCH metabolites by LC-MS/MS: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH), cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (oxo-MINCH), and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (cx-MINCH). These metabolites were also tested on human estrogen receptor alpha and progesterone receptor beta transactivation assays in vitro. OH-MINCH was detected in 98% of urine samples. The specific gravity-adjusted median (interquartile range) OH-MINCH concentration was 0.20 (0.25) ng/mL, and concentrations were significantly higher in African American women compared to Caucasian women (p = 0.01). DINCH metabolite concentrations were consistent between years, and they did not exhibit estrogenic or progestogenic activity in vitro. Human exposure to these emerging compounds should continue to be monitored, especially in vulnerable populations, to ensure the replacement of phthalates by DINCH is not a case of regrettable substitution.

Summary Background The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. Methods This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18–40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8–13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10–14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov , NCT00912132 . Findings Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28–40 (at week 37: 3061 g [95% CI 2967–3164] for women with gestational diabetes vs 2943 g [2924–2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10–14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983–3167] in the highest tertile vs 2853 g [2755–2955] in the lowest tertile, adjusted p=0·0009. Interpretation Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24–28 gestational weeks, when gestational diabetes is typically screened for in the USA. Funding National Institutes of Health.

The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4-8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (β = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (β = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (β = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.

Introduction: The health benefits of breastfeeding for both the mother and her offspring are well established, and breastfeeding may be especially important for mitigating negative health effects of pregnancy complicated by diabetes. Objective: This study sought to examine the association between race/ethnicity, maternal diabetes, and breastfeeding initiation in South Carolina (SC). Materials and Methods: Our study population is comprised of all live, singleton, full-term births in SC delivered January 2004 to December 2016 (292,468 non-Hispanic Whites, 173,158 non-Hispanic Blacks, and 52,174 Hispanics). Generalized estimating equations and an interaction term between race/ethnicity and maternal diabetes status were used to estimate the race/ethnic-specific odds ratio (OR) and 95% confidence intervals (CIs) that a mother with diabetes versus without diabetes initiated breastfeeding. Models were adjusted for maternal and infant sociodemographics (Model 1), additionally for clinical variables and birth outcomes (Model 2), and also for maternal prepregnancy body mass index (BMI) (Model 3). Results: We found statistically significant differences in breastfeeding initiation by race/ethnicity and diabetes status in Model 1. These associations were attenuated and lost significance upon additional adjustment. Non-Hispanic Black mothers with gestational diabetes were significantly more likely to initiate breastfeeding than nondiabetic non-Hispanic Black mothers, even after adjustment for prepregnancy BMI (OR: 1.07 [95% CI 1.02-1.12]). Conclusion: This large, population-based study of all live, singleton, full-term births in SC improves our understanding of how race/ethnicity and maternal metabolic disorders impact breastfeeding initiation, and may inform future hospital-based breastfeeding interventions in populations with the most need.

Background: Select phthalates have antiandrogenic activity, which raises concern for adverse developmental outcomes given widespread exposure of pregnant women. Investigators have reported associations between maternal urinary phthalates and altered anogenital distance (AGD), a marker of in utero androgen activity, among offspring. However, data assessing the impact of race on these associations is sparse. Objectives: To evaluate associations between prenatal phthalate exposure and AGD in a racially diverse newborn population. Methods: We prospectively collected second trimester urine from 187 African American and 193 white mothers, and used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure eight phthalate metabolites and calculate molar sums. We measured anopenile (APD) and anoscrotal (ASD) distances of 171 boys and anoclitoral (ACD) and anofourchette (AFD) distances of 128 girls at delivery. We collected sociodemographic and clinical data from questionnaires and delivery records. Results: We identified a statistically significant inverse association for mono-2-ethylhexyl phthalate (MEHP) and APD in boys (B=−1.57mm, p=0.02), which was stronger for African Americans (B=−2.07mm, p=0.04) than for whites (B=−1.23mm, p=0.22), although the racial interaction was not statistically significant (p=0.56). We found a longer ASD for higher molar sums of dibutyl phthalate (∑DBP; B=0.99mm, p=0.04), with stronger associations for whites (B=1.30mm, p=0.04) than for African Americans (B=0.39mm, p=0.59), again without a statistically significant racial interaction (p=0.34). Among girls, we found inverse associations for tertiles of MEHP with AFD and ACD, and statistically significant race-based interactions, in which ACD was longer for whites and shorter for African Americans, following exposure to monoethyl phthalate (MEP; p=0.01) and ∑DBP (p=0.08). Conclusions: Our findings suggest race and sex play important roles in phthalate-associated reproductive developmental toxicity, with important implications for designing future investigations and health interventions. Keywords: Phthalate, Anogenital distance, Prenatal exposure, Environmental chemicals, Prenatal development, Birth outcomes

Background Lifestyle changes are recommended for women diagnosed with gestational diabetes mellitus (GDM), yet there are few data available documenting whether women change their diet and exercise after GDM diagnosis. Objective The aim of this study was to assess whether, and to what extent, pregnant women receiving usual prenatal care change their diet and exercise after a GDM diagnosis. Design This study was a post-hoc secondary analysis using data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons (2009-2013), a prospective pregnancy cohort study. Participants/setting Pregnant US women without major chronic medical conditions were enrolled from 12 participating hospital centers at 8 to 13 weeks’ gestation. Diet analyses were based on 5,194 dietary recalls from 1,371 women. Exercise analyses were based on 6,440 physical activity assessments from 1,875 women. GDM was ascertained from medical records according to Carpenter and Coustan criteria. Women completed 24-hour dietary recalls and exercise assessments at weeks 16 to 22, 24 to 29, 30 to 33, 34 to 37, and 38 to 41 (exercise only). Main outcome measures The main outcome was the diet and exercise change from before to after GDM diagnosis or screening. Statistical analyses Diet and exercise changes with 95% CIs from before to after GDM diagnosis or screening for women with and without GDM were estimated using weighted multivariable linear mixed models. Results Women with GDM (n = 72) significantly reduced their total energy intake (–184 kcal/d; 95% CI –358 to –10 kcal/d) and carbohydrate intake (–47.6 g/d; 95% CI –71.4 to –23.7 g/d) from before to after GDM diagnosis; these changes were unique to women with GDM and not observed among women without GDM (n = 1,299). Women with GDM decreased intakes of juice (–0.4 cups/d; 95% CI –0.7 to –0.2 cups/d) and added sugar (–3.2 teaspoons/d; 95% CI –5.5 to –0.5 teaspoons/d) and increased cheese (0.3 cups/d; 95% CI 0.1 to 0.6 cups/d) and artificially sweetened beverages (0.2 cups/d; 95% CI 0.0 to 0.3 cups/d). Women with GDM (n = 84) did not change their exercise duration after diagnosis; women without GDM (n = 1,791) significantly decreased moderate (–19.5 min/wk; 95% CI –24.7 to –14.3 min/wk) and vigorous exercise (–8.8 min/wk; 05% CI –10.6 to –6.9 min/wk) after GDM screening. Conclusions Women with GDM made modest dietary improvements and maintained their prediagnosis exercise routine, yet opportunities remain to further improve dietary intake and exercise after a diagnosis of GDM.

Fetal growth restriction is associated with an increased risk for adverse neonatal outcomes. The Hadlock singleton growth reference is widely used to determine the estimated fetal weight percentile for both twin and singleton gestations. The Eunice Kennedy Shriver National Institute of Child Health and Human Development's twin-specific growth reference accounts for the different growth trajectory that twins follow during gestation. There is a lack of research comparing these different growth references in their ability to identify fetal growth restriction that is associated with adverse neonatal outcomes in dichorionic twin gestations.This study aimed to compare a twin-specific growth reference (the Eunice Kennedy Shriver National Institute of Child Health and Human Development's twin-specific growth reference) and a singleton growth reference (Hadlock) in their ability to identify fetal growth restriction associated with adverse neonatal outcomes in dichorionic twin gestations.This was a retrospective cohort study of dichorionic twin gestations at ≥32 weeks' gestation delivered at a single institution between 2004 and 2019 with the serial growth ultrasounds and neonatal outcomes data available for analysis. Using their last growth ultrasound before delivery, twins were classified into the following 3 categories: fetal growth restriction according to both the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development references, fetal growth restriction according to the Hadlock reference only, and no fetal growth restriction according to either reference, with fetal growth restriction defined as an estimated fetal weight of10th percentile for gestational age. Multivariable generalized linear mixed models were used to assess the adverse neonatal outcomes via pair-wise comparisons between the groups, with a random-effects component to account for twin-pair correlations.A total of 1460 dichorionic twin infants were included with 8.1% (n=118) of cases classified as fetal growth restricted by both the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Hadlock references, 8.8% (n=129) of cases classified as fetal growth restricted by the Hadlock reference only, and 83.1% (n=1213) of cases classified as no fetal growth restriction by either reference. Compared with twins with no fetal growth restriction by either reference, twins with fetal growth restriction by both references were more likely to experience mild (adjusted odds ratio, 2.38; confidence interval, 1.38-4.13) or severe (adjusted odds ratio, 2.82; confidence interval, 1.16-6.88) composite neonatal morbidity. Compared with twins with fetal growth restriction according to the Hadlock reference only, twins with fetal growth restriction according to both references were more likely to experience mild (adjusted odds ratio, 2.03; confidence interval, 1.00-4.14) but not severe (adjusted odds ratio, 3.70; confidence interval, 0.72-18.90) composite neonatal morbidity. Composite neonatal morbidity was not different between twins with fetal growth restriction according to the Hadlock reference only and those with no fetal growth restriction by either growth reference.The Eunice Kennedy Shriver National Institute of Child Health and Human Development's twin-specific growth reference better identifies the risk for adverse neonatal outcomes in dichorionic twin gestations diagnosed with fetal growth restriction. The use of the Hadlock singleton growth reference more than doubles the number of dichorionic twins identified with fetal growth restriction who seem to be at a low-risk for neonatal morbidity, leading to unnecessary maternal anxiety, increased antenatal testing, and possibly iatrogenic preterm delivery.

OBJECTIVES: Maternal weight and anthropometric trajectories may affect both fetal programming and maternal pregnancy health outcomes. We developed a statistical model that categorized concomitant changes in weight and body composition across gestation. METHODS: We conducted a secondary analysis of a prospective cohort of singletons (n = 2,353) enrolled from 11 US perinatal centers, 2009–2013. Weight, mid-upper arm circumference (MUAC), plus triceps and subscapular skinfold thickness (TSF, SSF) were measured up to 5 times across gestation. Prenatal weights were also abstracted from medical records. Gestational weight change (GWG) trajectories and time-varying, region-specific body composition (MUAC, TSF, SSF) were modeled jointly with a flexible latent class trajectory model, adjusting for prepregnancy BMI. RESULTS: Most women had prepregnancy normal weight (56.4%), while fewer were classified as overweight (27.2%) or obese (16.4%). Five trajectory patterns for weight and body composition were identified. (1) InitalHighSteadyGain (12.5%) had the highest 1(st) trimester weight gain and steady gain thereafter, with high model estimated total GWG (36.1 lbs). (2) InitialModerateSlowGain (19.8%) had moderate 1(st) trimester gain, then slow steady gain with the lowest total GWG (28.7 lbs). InitalHighSteadyGain and InitialModerateSlowGain showed relatively stable MUAC, while SSF and TSF increased in 1(st) and 2(nd) trimesters and decreased in 3(rd) trimester. Other GWG trajectory groups showed (3) 1(st) trimester weight loss (LossSteadyGain, 8.2%), (4) stability (StableSteadyGain, 21.5%), or (5) low gain (LowSteadyGain, 38.2%), then steady GWG in the 2(nd) and 3(rd) trimesters with estimated total GWG of 35.7, 36.8 and 32.8 lb, respectively. Small increases in MUAC and SSF were observed in LowSteadyGain across pregnancy, while TSF increased up to 30 wk and then decreased. LossSteadyGain and StableSteadyGain groups showed similarities in initial MUAC, TSF and SSF measurements with small increases in MUAC and TSF, and moderate increases in SSF over time. CONCLUSIONS: Joint modeling of prenatal weight and regional body composition changes identified five trajectory patterns, which offers a more advanced understanding of how these trajectories concomitantly change during pregnancy. FUNDING SOURCES: NICHD; HHS.

Objectives To evaluate the frequency with which gestational weight gain and estimated fetal weight do not track across gestation and to assess the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth weight as a function of tracking. Methods This study included a pregnancy cohort (2009–2013) of 2438 women from 4 racial/ethnic groups in the United States. We calculated race- and trimester-specific gestational weight gain and estimated fetal weight z scores. The prevalence of how often gestational weight gain and estimated fetal weight did not or did directly track was examined by grouping z scores into measure-specific categories ( 1 SD) and then examining 2-measure combinations. Trimester-specific relative risks for SGA and LGA births were estimated with a gestational weight gain and estimated fetal weight z score interaction. We estimated coefficients for selected gestational weight gain and estimated fetal weight values (–1 SD, 0 SD, and +1 SD) compared with the referent of 0 SD for both measures. Small and large for gestational age were calculated as birth weight below the 10th and at or above the 90th percentiles, respectively. Results Gestational weight gain and estimated fetal weight were within 1 SD 55.5%, 51.5%, and 48.2% of the time in the first, second, and third trimesters, respectively. There was no significant interaction between gestational weight gain and estimated fetal weight on the risk of SGA in the first and second trimesters (interaction term P = .48; P = .79). In the third trimester, there was a significant interaction (P = .002), resulting in a 71% (95% confidence interval, 1.45–2.02) increased risk of SGA when estimated fetal weight was low and gestational weight gain was high. These relationships were similar for the risk of LGA. Conclusions Deviations in either measure, even in the presence of average gestational weight gain or estimated fetal weight, still suggest an increased risk of SGA and LGA.

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.

Objective The objective of this study was to compare clinical outcomes of preeclamptic pregnancies according to the proteinuria level. Study Design Secondary analysis of a multicenter prospective cohort study of women with preeclampsia (PE) symptomatology. Nonproteinuria, mild-proteinuria, and massive-proteinuria PEs were defined as: Results Of the 406 analyzed pregnancies, 36 (8.8%) had massive-proteinuria PE, 268 (66.0%) mild-proteinuria PE, and 102 (25.1%) nonproteinuria PE. Compared with the other groups, massive-proteinuria PE women had significantly higher blood pressures (p Conclusion While potentially not important diagnostically, massive proteinuria is associated with more severe clinical manifestations of PE prompting earlier delivery.

OBJECTIVES: Gestational diabetes (GDM) is associated with increased risk for large-for-gestational-age birth. Yet, longitudinal fetal growth trajectories in women with GDM and the timing of alterations related to GDM is not well understood, particularly in early pregnancy. This study aims to investigate these critical data gaps. METHODS: The NICHD Fetal Growth Studies–Singleton Cohort enrolled women at 8w0d to 13w6d gestation from 12 U.S. clinical centers and randomized them among four ultrasonology schedules for longitudinal fetal measurement. Fetal biparietal diameter, head circumference (HC), abdominal circumference (AC), femurs length and humerus length were measured. Estimated fetal weight (EFW) was calculated using the Hadlock formula. GDM was defined using the Carpenter-Coustan Criteria, impaired glucose tolerance (IGT) was defined as 2-hour plasma glucose in the 75 g or 100 g oral glucose tolerance test (OGTT) 140–199 mg/dL, and normal glucose tolerance (NGT) was defined by no elevated values on either the OGTT or 50 g glucose challenge test. The fetal growth trajectories were modeled using linear mixed models with cubic spline adjusting for race, age, parity, pre-pregnancy BMI and infant sex. RESULTS: One hundred and seven women developed GDM, 118 developed IGT, and 2,020 had NGT. Most fetal growth measures were larger at 10–12 weeks and became smaller at 14–16 weeks in GDM than NGT group. At 28 weeks, AC and EFW became larger in GDM group, and the differences persisted through 40 weeks (at 40 weeks: AC: 368 vs. 355 mm, P = 0.03; EFW: 3866 vs. 3558 g, P = 0.003). The HC to AC ratio was smaller in GDM group 19–36 weeks. The associations were modified by the family history of diabetes (p-interaction

We sought to review the state of the science for research on multiple gestations. A literature search was performed with the use of PubMed for studies to quantify the representation of multiple gestations for a sample period (2012–2016) that were limited to phase III and IV randomized controlled trials, that were written in English, and that addressed at least 1 of 4 major pregnancy complications: fetal growth restriction or small-for-gestational-age fetus, gestational diabetes mellitus, preeclampsia, and preterm delivery. Of the 226 studies that are included in the analysis, multiple pregnancies were most represented in studies of preterm delivery: 17% of trials recruited both singleton and multiple pregnancies; another 18% of trials recruited only multiple pregnancies. For trials that studied preeclampsia, fetal growth restriction, and gestational diabetes mellitus, 17%, 8%, and 2%, respectively, recruited both singleton and multiple gestations. None of the trials on these 3 topics were limited to women with a multiple pregnancy. Women with a multiple pregnancy are at risk for complications similar to those of women with singleton pregnancies, but their risk is usually higher. Also, the pathophysiologic condition for some complications differs in multiple gestations from those that occur in singleton gestations. Conditions that are unique to multiple pregnancies include excess placenta, placental crowding or inability of the uteroplacental unit to support the normal growth of multiple fetuses, or suboptimal placental implantation sites with an increased risk of abnormal placental location. Other adverse outcomes in multiple gestations are also influenced by twin-specific risk factors, most notably chorionicity. Although twins have been well represented in many studies of preterm birth, these studies have failed to identify adequate predictive tests (short cervical length established over 2 decades ago remains the single best predictor), to establish effective interventions, and to differentiate the underlying pathophysiologic condition of twin preterm birth. Questions about fetal growth also remain. Twin growth deviates from that of singleton gestations starting at approximately 32 weeks of gestation; however, research with long-term follow-up is needed to better distinguish pathologic and physiologic growth deviations, which include growth discordance among pairs (or more). There are virtually no clinical trials that are specific to twins for gestational diabetes mellitus or preeclampsia, and subgroups for multiple pregnancies in existing trials are not large enough to allow definite conclusions. Another important area is the determination of appropriate maternal nutrition or micronutrient supplementation to optimize pregnancy and child health. There are also unique aspects to consider for research design in multiple gestations, such as designation and tracking of the correct fetus prenatally and through delivery. The correct statistical methods must be used to account for correlated data because multiple fetuses share the same mother and intrauterine environment. In summary, multiple gestations often are excluded from research studies, despite a disproportionate contribution to national rates of perinatal morbidity, mortality, and health-care costs. It is important to consider the enrollment of multifetal pregnancies in studies that target mainly women with singleton gestations, even when sample size is inadequate, so that insights that are specific to multiple gestations can be obtained when results of smaller studies are pooled together. The care of pregnant women with multiple gestations presents unique challenges; unfortunately, evidence-based clinical management that includes the diagnosis and treatment of common obstetrics problems are not well-defined for this population.

ObjectiveTo 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.DesignIn 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.SettingWomen were recruited from twelve US sites (2009–2013).ParticipantsNon-obese women with singleton pregnancies (n 2334).ResultsA 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).ConclusionsThe 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.

There is a robust association between altered angiogenic factor concentrations, which includes placental growth factor and clinically recognized preeclampsia. Alterations in concentrations of angiogenic factors precede the clinical onset of preeclampsia by several weeks. The temporal relationship between the measured angiogenic factors and the time to delivery in women with suspected preeclampsia at35 weeks gestation, however, remains to be clarified.The purposes of this study were to examine the relationship between placental growth factor and time to delivery in women at35 weeks gestation with signs or symptoms of preeclampsia and to compare the performance of placental growth factor to other clinical markers for prediction of time to delivery in preeclampsia.Women with signs or symptoms of preeclampsia between 20.0 and 35.0 weeks gestation were enrolled in a prospective, observational study at 24 centers. Blood was collected at presentation for placental growth factor, and subjects were evaluated and treated according to local protocols. Clinical outcomes were obtained, and all final diagnoses were adjudicated by an independent expert panel according to 2013 American College of Obstetricians and Gynecologists' Hypertension in Pregnancy criteria. Placental growth factor was measured retrospectively on the Alere, Inc, triage platform. A normal placental growth factor was defined as100 pg/mL; the assay's limit of detection is 12 pg/mL. Two-by-2 tables were constructed for comparison of test outcomes that included negative predictive value; time-to-delivery was analyzed by survival curves and Cox regression.Seven hundred fifty-three subjects were enrolled; 538 (71%) had a final diagnosis of preeclampsia; 542 (72%) delivered at37 weeks gestation, and 358 (47%) delivered at34 weeks gestation. Among the 279 women (37%) with a normal placental growth factor at presentation, the negative predictive value for preeclampsia delivered within 14 days or within 7 days was 90% and 93%, respectively. Compared with women with normal placental growth factor, women with placental growth factor ≤100 pg/mL have a hazard ratio of 7.17 (confidence interval, 5.08-10.13) in Cox regression for time to delivery after adjustment for both gestational age at enrollment and the final diagnosis of preeclampsia. The placental growth factor levels of normal (100 pg/mL), low (12-100 pg/mL), and very low (12 pg/mL) have well-separated distributions of time to delivery, with median values of 45, 10, and 2 days, respectively. Subjects with placental growth factor ≤100 pg/mL have a perinatal death rate of 5.7% and a small-for-gestational-age rate of 51.7%; subjects with placental growth factor100 pg/mL have a perinatal death rate of 0% (no observations in this cohort) and an a small-for-gestational-age rate of 16.8%.In women with suspected preeclampsia at35.0 weeks gestation, a low placental growth factor was correlated strongly with preterm delivery independent of a diagnosis of preeclampsia or gestational age at presentation, whereas a normal placental growth factor was associated with pregnancy prolongation, even in patients who ultimately had a final diagnosis of preeclampsia. This suggests that placental growth factor levels are superior to clinical markers in the prediction of adverse pregnancy in women with suspected preeclampsia.

While a mean age at menopause of 51 years has been reported in the United States (U.S.), some U.S. women experience menopause before age 45, possibly increasing risk of cardiovascular mortality; however, the role in all-cause and cerebrovascular-related mortality is unclear. The purpose of this study was to investigate the association between age at menopause and all-cause and cause-specific mortality by race, hormone replacement therapy (HRT) use, and smoking status. REasons for Geographic and Racial Differences in Stroke (REGARDS) is a population-based study of 30,239 participants aged ≥45 years enrolled between 2003 and 2007 of whom 14,361 were postmenopausal women. Age at menopause was defined as, Highlights • Increased all-cause mortality risk in ever-HRT users with menopause before age 45 • HRT use modified the association of menopause before age 45 and CHD mortality. • There were no differences in associations examined by race or smoking status.