Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

Objective Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of under- or over-grown fetuses. We sought to develop contemporary fetal growth standards for four self-identified U.S. racial/ethnic groups. Study Design We recruited for prospective follow-up 2,334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers between July 2009 and January 2013. The cohort comprised: 614 (26%) non-Hispanic Whites, 611 (26%) non-Hispanic Blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18–40 years; body mass index 19.0–29.9 kg/m2; healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among four ultrasonology schedules for longitudinal fetal measurement using the Voluson E8 GE Healthcare. In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1,737 (74%) women continued to be low-risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and socio-demographic factors. Results Estimated fetal weight differed significantly by race/ethnicity after 20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 grams for White, 2633, 3336, and 4226 grams for Hispanic, 2621, 3270, and 4078 grams for Asian, and 2622, 3260, and 4053 grams for Black women (adjusted global p<0.001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the White group erroneously classifies as much as 15% of non-White fetuses as growth-restricted (estimated fetal weight < 5th percentile). Conclusions Significant differences in fetal growth were found among the four groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Objective The objective of this prospective cohort study was to determine if sleep disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus. Methods Nulliparous women underwent in-home sleep disordered breathing assessments in early (6–15 weeks) and mid-pregnancy (22–31 weeks). Participants and providers were blinded to the sleep test results. An apnea-hypopnea index (AHI) of ≥5 was used to define sleep disordered breathing. Exposure-response relationships were examined grouping participants into four AHI groups: AHI=0, 0

Objective To assess cerclage to prevent recurrent preterm birth in women with short cervix. Study Design Women with prior spontaneous preterm birth <34 weeks were screened for short cervix, and randomly assigned to cerclage if cervical length was <25 mm. Results Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered <35 weeks (p=0.09). In planned analyses, birth <24 weeks (p=0.03) and perinatal mortality (p=0.046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth <35 weeks (p = 0.006) was reduced in the <15 mm stratum with a null effect in the 15–24 mm stratum. Conclusion In women with a prior spontaneous preterm birth <34 weeks and cervical length <25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth <35 weeks, unless cervical length was <15 mm.

Among a large and geographically diverse cohort of nulliparous women with singleton gestations, non-Hispanic black women are most likely to experience preterm birth, hypertensive disease of pregnancy, and SGA birth. These disparities were not materially altered for preterm birth or SGA birth by adjustment for demographic differences and did not appear to be explained by differences in self-reported psychosocial factors.

Objective The primary aim of The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) is to determine maternal characteristics, including genetic, physiological response to pregnancy, and environmental factors that predict adverse pregnancy outcomes (APOs). Methods Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at three study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine and cervico-vaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending prior to 37+0 weeks gestation. Key study hypotheses involve APOs of spontaneous preterm birth, preeclampsia, and fetal growth restriction. Results 10,037 women were recruited to the study. Basic characteristics of the cohort at screening are reported in this Methods paper. Conclusion The nuMoM2b cohort study methods and procedures presented can help investigators when planning future projects.

I.

Background Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. The present study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids. Methods Brain development and affective problems were evaluated in fifty-four children (56% female), ages 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging (MRI) scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist. Results Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). Over 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Further, children with more affective problems had a thinner left rACC. Conclusions Fetal exposure to synthetic glucocorticoids has neurological consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raises the possibility that glucocorticoid associated neurological changes increase vulnerability to mental health problems.