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 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-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 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development 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 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. 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 (fifth, 50th, 95th percentiles) were derived from 15 to 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 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second 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. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-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 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

Spontaneous skull base cerebrospinal fluid leak during pregnancy: a case report and review of the literature.

BACKGROUND: Idiopathic intracranial hypertension can lead to dural defects and spontaneous leakage of cerebrospinal fluid (CSF) from the skull base. Skull base CSF leaks are rarely reported in pregnancy but pose unique challenges for obstetricians and anesthesiologists. CASE PRESENTATION: A 31-year-old G4P1021 at 14 weeks developed debilitating headaches and CSF rhinorrhea. Brain imaging revealed a bony defect of the sphenoid sinus with a meningoencephalocele and a partially empty sella, consistent with CSF leakage from a skull base defect. The patient was neurologically stable without signs of meningitis; thus, management was focused on symptomatic alleviation. A planned cesarean section was performed at 38 weeks under spinal anesthesia. The patient had spontaneous marked improvement of her symptoms postpartum. CONCLUSION: Pregnancy may exacerbate skull base CSF leaks, requiring careful management with a multidisciplinary team. Neuraxial anesthesia can safely be performed in pregnant individuals with spontaneous skull base CSF leakage, but further studies are needed to determine the safest mode of delivery in these patients.

Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes: a double-blind randomized trial.

BACKGROUND: Preterm prelabor rupture of membranes is a leading cause of preterm birth and is responsible for 18% to 20% of perinatal deaths in the United States. An initial course of antenatal corticosteroids has been shown to reduce morbidity and mortality in patients with preterm prelabor rupture of membranes. For patients who remain undelivered for 7 days or more after the initial course of antenatal corticosteroids, it is uncertain whether a booster course of antenatal corticosteroids reduces neonatal morbidity or increases the infection risk. The American College of Obstetricians and Gynecologists has concluded that the current evidence is insufficient to make a recommendation. OBJECTIVE: This study aimed to evaluate if a single booster course of antenatal corticosteroids improves neonatal outcomes after preterm prelabor rupture of membranes. STUDY DESIGN: We conducted a multicenter, placebo-controlled randomized clinical trial. The inclusion criteria were preterm prelabor rupture of membranes, gestational age of 24.0 to 32.9 weeks, singleton, initial antenatal corticosteroid course administered at least 7 days before randomization, and planned expectant management. Consenting patients were randomized in gestational age blocks to either receive booster antenatal corticosteroids (12 mg betamethasone every 24 hours for 2 days) or a saline placebo. The primary outcome was composite neonatal morbidity or death. A sample size of 194 patients was calculated to yield 80% power at P<.05 to detect a reduction in primary outcome from 60% in placebo group to 40% in antenatal corticosteroids group. RESULTS: From April 2016 through August 2022, 194 patients consented and were randomized (47% of 411 eligible patients). Intent-to-treat analysis was performed on 192 patients (2 placebo patients left hospital, outcomes unknown). The groups had similar baseline characteristics. The primary outcome occurred in 64% of patients who received booster antenatal corticosteroids vs in 66% of patients who received the placebo (odds ratio, 0.82; 95% confidence interval, 0.43-1.57; gestational age-stratified Cochran-Mantel-Haenszel test). Individual components of the primary outcome and secondary neonatal and maternal outcomes were not significantly different between the antenatal corticosteroids and placebo groups. Specifically, chorioamnionitis (22% vs 20%), postpartum endometritis (1% vs 2%), wound infections (2% vs 0%), and proven neonatal sepsis (5% vs 3%) were not different between the groups. CONCLUSION: A booster course of antenatal corticosteroids at least 7 days after the first antenatal corticosteroids course in patients with preterm prelabor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately-powered, double-blind randomized clinical trial. Booster antenatal corticosteroids did not increase maternal or neonatal infection.

Association of Maternal Caffeine Consumption During Pregnancy With Child Growth.

Importance: Greater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear. Objective: To 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 Participants: The 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. Exposures: Concentrations 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 Measures: Child 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. Results: In ECHO-FGS (median caffeine intake <50 mg/d), 788 children (mean [SD] age, 6.8 [1.0] years; 411 boys [52.2%]) of women in the fourth vs first quartile of plasma caffeine concentrations had lower height z scores (ß = -0.21; 95% CI, -0.41 to -0.02), but differences in weight z scores were only observed in the third quartile (ß = -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 (ß = -0.16 [95% CI, -0.31 to -0.01] at 4 years; ß = -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 (ß = -0.16 to -0.22). Results were consistent for paraxanthine concentrations in both cohorts. Conclusions and Relevance: Intrauterine 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.

Associations of Maternal Prenatal Stress and Depressive Symptoms With Childhood Neurobehavioral Outcomes in the ECHO Cohort of the NICHD Fetal Growth Studies: Fetal Growth Velocity as a Potential Mediator.

OBJECTIVE: 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. METHOD: 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 25th, 50th, and 75th percentiles; and moderation by biological sex and by race and ethnicity. RESULTS: Prenatal 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. CONCLUSION: 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.

The association between maternal pre-pregnancy BMI, gestational weight gain and child adiposity: A racial-ethnically diverse cohort of children.

BACKGROUND: The prevalence of obesity in US children has more than tripled in the past 40 years; hence, it is critical to identify potentially modifiable factors that may mitigate the risk. OBJECTIVES: To examine the association between maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and child adiposity as measured by BMI, waist circumference and percent body fat in a racial-ethnically diverse cohort. METHODS: In a prospective cohort study of healthy women without chronic disease, we examined the association between pre-pregnancy BMI, GWG and child adiposity. Children ages 4-8 years (n = 816) in the Environmental Influences on Child Health Outcomes-NICHD Fetal Growth Studies were assessed. Trained study staff ascertained maternal pre-pregnancy BMI, GWG and child adiposity. RESULTS: The odds of child obesity (≥95th BMI percentile) increased independently for each unit increase in maternal pre-pregnancy BMI [OR = 1.12 (95% CI: 1.08, 1.17)] and for each 5-kg increase in GWG [OR = 1.25 (95% CI: 1.07, 1.47)]. The odds of child waist circumference (≥85th percentile) also increased independently for pre-pregnancy BMI [OR = 1.09 (95% CI: 1.05, 1.12)] and GWG [OR = 1.18 (95% CI: 1.04, 1.34)]. CONCLUSIONS: Maternal pre-pregnancy BMI and GWG were each independently and positively associated with child obesity and high child waist circumference.

Early Exposure to Animals and Childhood Body Mass Index Percentile and Percentage Fat Mass.

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 (<85th percentile), overweight (85th to <95th), and obese (≥95th), and percent fat mass (continuous). Associations were analyzed using multinomial logistic regression and multivariable linear regression, respectively, with and without multiple imputation. RESULTS: First year animal exposure occurred in 245 of 770 (31.8%) children. Children with early animal exposure had 0.53 (95% CI: 0.28, 0.997) times the odds of being in the obese BMI category compared to those exposed to animals after controlling for covariates: maternal pre-pregnancy BMI, race/ethnicity, reported child activity level, receiving food assistance, age child began daycare (<1 year vs 1+), exclusively breastfed x6 months, and NICU admission (n=721). Children with early animal exposure had, on average, 1.5% (95% CI: -3.0, -0.1) less fat mass than exposed children after adjustment for maternal BMI, race/ethnicity, activity, food assistance, breastfeeding, and maternal education (n=548). Multiple imputation did not alter either result. CONCLUSION: These results provide evidence that exposure to dogs or farm animals in the first year of life is associated with lower odds of obesity and lower percent fat mass in childhood.

Association between gestational PFAS exposure and Children's adiposity in a diverse population.

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 (ß = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (ß = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (ß = 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.

Breastfeeding Associations with Childhood Obesity and Body Composition: Findings from a Racially Diverse Maternal-Child Cohort.

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 <95th percentile] and obesity (BMI ≥95th percentile) in relation to breastfeeding including duration of exclusive and total breastfeeding. Linear regression was used to evaluate association between breastfeeding and percentage body fat measured by bioelectrical impedance analysis. Results: Fifty-two percent of children were male, 32% non-Hispanic Black, 29% Hispanic, 27% non-Hispanic White, and 13% Asian; 16% were overweight and 13% obese. Six months of exclusive breastfeeding, compared with no breastfeeding, was associated with 60% lower odds of obesity (95% CI 0.18-0.91) adjusting for age, gender, race, socioeconomic status, maternal BMI, and child's activity. Percentage body fat was inversely associated with breastfeeding duration. For none, <6, and ≥6 months of exclusive breastfeeding, adjusted mean percentage body fat was 16.8, 14.5, and 13.4, respectively. Results did not differ by gender, race/ethnicity, or maternal BMI status. Conclusions: Exclusive breastfeeding for the first 6 months of life is inversely and significantly associated with obesity and percentage body fat at ages 4-8 years. These findings support current breastfeeding guidelines.

Complicated placenta accreta spectrum: identifying a high-risk cohort.

OBJECTIVE: To assess differences in the perioperative complication rate between patients with placenta accreta spectrum (PAS) with and without complicating factors. METHODS: This retrospective cohort study included subjects who underwent cesarean hysterectomy with histology-proven PAS between 23 0/7 and 42 0/7 weeks gestational age (GA) from 1 July 2008 to 11 April 2017. Perioperative outcomes were compared between those with uncomplicated PAS and "complicated PAS," defined as PAS subjects who experienced ≥2 bleeding episodes, preterm premature rupture of membranes (PPROM), or premature contractions requiring tocolysis. RESULTS: Overall, 26 complicated PAS and 27 uncomplicated PAS cases were compared; no difference in the rate of perioperative complications was identified. An increased proportion of complicated PAS cases required blood product transfusion before delivery: 2 (40%), 3 (27.3%), and 2 patients (20%) for those with PPROM, preterm contractions, and ≥2 bleeding episodes respectively, compared to patients with uncomplicated PAS, having no transfusions (p = .001). Time of delivery was earlier for patients with complicated compared to uncomplicated PAS (median GA 30.9 [Q1 = 27.9; Q3 = 31.9] and 34.9 [Q1 = 32.1; Q3 = 35.7], p < .001). Median birthweights were lower (p < .0144) and maternal length of stay longer (p < .0012) for complicated PAS. CONCLUSION: Patients with complicated PAS were not at higher risk for perioperative complications but were associated with earlier delivery, required more antenatal blood transfusions, and had a longer LOS.

Massive unilateral fetal axillary lymphangioma: A case report.

We report a substantial axillary lymphangioma in a fetus delivered at 38 weeks of gestation. Detailed fetal survey at 20 weeks revealed a 5.45 × 3.72 cm nonvascular cystic axillary structure without other malformations; amniocentesis was negative. Serial surveillance was performed throughout the pregnancy. A male infant weighing 3000 g with a 16 × 12 × 9 cm septated cystic mass arising from the left axilla was delivered via cesarean section. The newborn period was complicated by cellulitis overlying the mass and interval cystic hemorrhage requiring sclerotherapy and subsequent excision. Nonnuchal lymphangiomas may be etiologically distinct entities. The prognostic factors include anatomic location, presence of septa, and association with other congenital abnormalities. A thorough evaluation, multidisciplinary approach, and close surveillance should be undertaken to optimize neonatal outcomes.

Nutrition during Pregnancy: Findings from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort.

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.

Glycaemic status during pregnancy and longitudinal measures of fetal growth in a multi-racial US population: a prospective cohort study.

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.

Electronic Fetal Monitoring Credentialing Examination: The First 4000.

Objective Recognized variability in fetal heart rate interpretation led the Perinatal Quality Foundation (PQF) to develop a credentialing exam. We report an evaluation of the 1st 4000 plus PQF Fetal Monitoring Credentialing (FMC) exams. Study Design The PQF FMC exam is an online assessment for obstetric providers and nurses. The exam contains two question types: traditional multiple-choice evaluating knowledge and Script Concordance Theory (SCT) evaluating judgment. Reliability was measured through McDonald's Total Omega and Cronbach's Alpha. Pearson's correlations between knowledge and judgment were measured. Results From February 2014 through September 2018, 4,330 different individuals took the exam. A total of 4,057 records were suitable for reliability analysis: 2,105 (52%) physicians, 1,756 (43%) nurses, and 196 (5%) certified nurse midwives (CNMs). As a measure of test reliability, total Omega was 0.80 for obstetric providers and 0.77 for nurses. There was only moderate correlation between the knowledge scores and judgment scores for obstetric providers (0.38) and for nurses (0.43). Conclusion The PQF FMC exam is a reliable, valid assessment of both Electronic Fetal Monitoring (EFM) knowledge and judgment. It evaluates essential EFM skills for the establishment of practical credentialing. It also reports modest correlation between knowledge and judgment scores, suggesting that knowledge alone does not assure clinical competency.

Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma.

Objective: To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy. Methods: Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged. Results: Using the new sequencing technology, 1414 samples were analyzed. The findings showed sensitivities and specificities for the common trisomies and the sex chromosome aneuploidies at >99% (Trisomy 21 sensitivity 99.2 CI 95.6­99.2; specificity 99.9 CI 99.6­99.9). Positive predictive values among the trisomies varied from 85.2% (Trisomy 18) to 99.0% (Trisomy 21), reflecting their prevalence rates in the study. Comparisons with a meta-analysis of recent cell-free DNA screening publications demonstrated equivalent test performance. Conclusion: This new technology demonstrates equivalent test performance compared with alternative sequencing approaches, and demonstrates that each chromosome can be successfully interrogated using a single probe.

Ibuprofen and Postpartum Blood Pressure in Women With Hypertensive Disorders of Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of ibuprofen on blood pressure in women with a diagnosis of hypertensive disorders of pregnancy and mild hypertension during the immediate postpartum period. METHODS: In this double-blind controlled trial, we randomly assigned women with a diagnosis of hypertensive disorders of pregnancy and mild hypertension to receive a postpartum analgesic regimen with either ibuprofen or acetaminophen. The primary outcome was average mean arterial pressure during the postpartum hospital stay. Prespecified secondary outcomes included use of breakthrough opioid pain medications, length of hospital stay, and postpartum diuresis, defined as urine output of at least 200 mL/hour for 4 hours. A sample size of 56 participants was needed to detect a difference of 6 mm Hg in average mean arterial pressure between the study groups. RESULTS: From January 17, 2017, to February 24, 2018, 61 participants were randomized and completed the trial, 31 participants in the ibuprofen group and 30 in the control group. Baseline characteristics were similar between groups. Postpartum average arterial pressure did not differ between study groups (93±8 mm Hg for those in the ibuprofen group vs 93±7 mm Hg in the control group, P=.93). Breakthrough opioid medications were requested by 24% of the participants in the ibuprofen group compared with 30% in the control group (P=.62). The ibuprofen group did not have a longer length of stay (48 hours vs 43 hours in the control group) or decreased rate of postpartum diuresis (61% in ibuprofen group vs 77% in the control group, P=.2). CONCLUSION: In women with hypertensive disorders of pregnancy and mild hypertension, ibuprofen did not increase postpartum blood pressure compared with women not receiving nonsteroidal antiinflammatory drugs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03011567.

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.