Segmenting hypothalamic subunits in human newborn magnetic resonance imaging data.

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.

Prescription and Other Medication Use in Pregnancy.

OBJECTIVE: To characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy. METHODS: In a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined. RESULTS: Of the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication). CONCLUSION: In this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01322529.

Optimizing Subsequent Pregnancy Outcomes for Women with a Prior Preterm Birth.

Women with a prior preterm birth are at increased risk of recurrent preterm delivery in a subsequent pregnancy. Interventions during the preconception and prenatal periods can decrease this risk. Review of the circumstances of the prior delivery can elucidate whether delivery was spontaneous or indicated, anticipate recurrence risk, and guide management in a subsequent pregnancy. Preconception interventions for women with prior preterm birth should include cessation of tobacco and substance abuse, control of underlying maternal comorbidities, and encouraging a healthy body mass index. Effective contraception, including use of long-acting reversible methods, should be encouraged to facilitate planned pregnancies with optimal interpregnancy intervals. Interventions during prenatal care include screening and treatment of infections, nutritional supplementation, and enhanced prenatal care. Women with prior spontaneous preterm birth may benefit from progesterone supplementation and serial cervical length screening, while women with prior indicated preterm birth may benefit from daily aspirin.

Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes.

OBJECTIVE: To estimate the association between maternal 25-hydroxyvitamin D concentrations and risk of preterm birth subtypes. METHODS: We performed a case-cohort study using data and banked samples from patients at a teaching hospital in Pittsburgh, Pennsylvania. Eligible participants were women with a prenatal aneuploidy screening serum sample at or before 20 weeks of gestation who subsequently delivered a singleton, liveborn neonate. Of the 12,861 eligible women, we selected 2,327 at random as well as all remaining preterm birth cases for a total of 1,126 cases. Serum 25-hydroxyvitamin D was measured using liquid chromatography-tandem mass spectrometry. Multivariable log-binomial regression models were used to estimate associations between maternal vitamin D status and preterm birth at 37 weeks of gestation (separately by spontaneous or indicated) and preterm birth at less than 34 weeks of gestation. RESULTS: The incidence of preterm birth at less than 37 weeks of gestation was 8.6% overall and 11.3%, 8.6%, and 7.3% among mothers with serum 25-hydroxyvitamin D less than 50, 50-74.9, and 75 nmol/L or greater, respectively (P<.01). After adjustment for maternal race and ethnicity, prepregnancy body mass index, season, smoking, and other confounders, the risk of preterm birth at less than 37 weeks of gestation significantly decreased as 25-hydroxyvitamin D increased to approximately 90 nmol/L and then plateaued (test of nonlinearity P<.01). Results were similar when limiting to cases that were medically indicated or occurred spontaneously and cases occurring at less than 34 weeks of gestation. CONCLUSION: Our data support a protective association maternal vitamin D sufficiency and preterm birth that combined with extant epidemiologic data may provide justification for a randomized clinical trial of maternal vitamin D replacement or supplementation to prevent preterm birth.

Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort study.

CONTEXT: Inconsistent associations between maternal vitamin D status and fetal size have been published in small studies. OBJECTIVE: Our objective was to examine the association between maternal 25-hydroxyvitamin D [25(OH)D] levels and measures of newborn and placental weight. DESIGN AND SETTING: We measured maternal 25(OH)D in mothers from the Collaborative Perinatal Project, an observational cohort conducted in 12 U.S. medical centers from 1959 to 1965. PARTICIPANTS: Women delivering singleton, term, live births with 25(OH)D measured at a gestation of 26 wk or less (n = 2146). MAIN OUTCOME MEASURES: Birth weight, ponderal index, placental weight, the placental to fetal weight ratio, and small for gestational age were measured. Hypotheses were formulated after data collection. RESULTS: After confounder adjustment, mothers with 25(OH)D of 37.5 nmol/liter or greater gave birth to newborns with 46 g [95% confidence interval (CI), 9-82 g] higher birth weights and 0.13 cm (0.01-0.25 cm) larger head circumferences compared with mothers with less than 37.5 nmol/liter. Birth weight and head circumference rose with increasing 25(OH)D up to 37.5 nmol/liter and then leveled off (P < 0.05). No association was observed between 25(OH)D and ponderal index, placental weight, or the placental to fetal weight ratio. Maternal 25(OH)D of 37.5 nmol/liter or greater vs. less than 37.5 nmol/liter in the first trimester was associated with half the risk of small for gestational age (adjusted odds ratio 0.5; 95% CI 0.3-0.9), but no second-trimester association was observed. CONCLUSIONS: Maternal vitamin D status is independently associated with markers of physiological and pathological growth in term infants. Adequately powered randomized controlled trials are needed to test whether maternal vitamin D supplementation may improve fetal growth.

Vitamin D may be a link to black-white disparities in adverse birth outcomes.

UNLABELLED: In the United States, significant, intractable disparities exist in rates of major pregnancy outcomes between non-Hispanic black and non-Hispanic white women. A previously unexplored candidate influence on the black-white disparity in adverse birth outcomes is maternal vitamin D status. This review summarizes the evidence relating maternal vitamin D to preeclampsia, spontaneous preterm birth, gestational diabetes, and fetal growth restriction, and addresses gaps in our understanding of the contribution of vitamin D to the intractable black-white disparity in these conditions. The literature reviewed highlights strong biologic plausibility of role for vitamin D in the pathophysiology of these poor pregnancy outcomes. Data also suggest that maternal vitamin D deficiency may increase the risk of preeclampsia and fetal growth restriction. Less research has been done in support of relations with spontaneous preterm birth and gestational diabetes, and fetal and infant survival have rarely been studied. Few trials of vitamin D supplementation have been conducted in pregnant women with adequate power to test effects on birth outcomes. Importantly, black pregnant women have rarely been studied in vitamin D-birth outcomes research. Although vitamin D is a promising candidate influence on black-white disparities in preeclampsia, spontaneous preterm birth, fetal growth restriction, and gestational diabetes, these associations require further study in large samples of black US women. Because vitamin D deficiency is widespread and black-white disparities in pregnancy outcomes and infant survival have been resistant to previous interventions, research to test vitamin D as a causal factor is of major public health significance. TARGET AUDIENCE: Obstetricians & Gynecologist, Family Physicians. LEARNING OBJECTIVES: After completion of this educational activity, the reader will be able to appreciate risk factors for inadequate vitamin D status. Understand the basic aspects of vitamin D metabolism. Become aware of recent literature linking inadequate vitamin D status and adverse pregnancy outcomes such as preeclampsia and preterm birth.

Maternal cereal consumption and adequacy of micronutrient intake in the periconceptional period.

OBJECTIVE: To assess the adequacy of periconceptional intake of key micronutrients for perinatal health in relation to regular cereal consumption of pregnant women. DESIGN, SETTING AND SUBJECTS: Low-income pregnant women (n 596) in Pittsburgh, Pennsylvania, USA, who enrolled in a cohort study at <20 weeks' gestation. These women reported usual dietary intake in the three months around conception on an FFQ. Cereal consumers were women who reported consuming any dry cereal at least three times per week. High risk for nutrient inadequacy was defined as intake less than the Estimated Average Requirement. RESULTS: About 31 % of the women regularly consumed cereal. After adjusting for energy intake, race/ethnicity, marital status, breakfast consumption and supplement use, cereal eaters had significantly higher intakes of folate, Fe, Zn, Ca, fibre and vitamins A, C, D and E (all P < 0.01) and were approximately two to six times more likely to have intakes in the highest third of the distribution for folate, Fe, Zn, Ca, vitamins A and D, and fibre (all P < 0.01) than cereal non-eaters. Cereal consumption was also associated with reductions of 65-90 % in the risk of nutrient inadequacies compared with non-consumption (all P < 0.01). CONCLUSIONS: Encouraging cereal consumption may be a simple, safe and inexpensive nutrition intervention that could optimize periconceptional intake for successful placental and fetal development.

Maternal vitamin D deficiency increases the risk of preeclampsia.

CONTEXT: Vitamin D has direct influence on molecular pathways proposed to be important in the pathogenesis of preeclampsia, yet the vitamin D-preeclampsia relation has not been studied. OBJECTIVES: We aimed to assess the effect of maternal 25-hydroxyvitamin D [25(OH)D] concentration on the risk of preeclampsia and to assess the vitamin D status of newborns of preeclamptic mothers. DESIGN AND SETTING: We conducted a nested case-control study of pregnant women followed from less than 16 wk gestation to delivery (1997-2001) at prenatal clinics and private practices. PATIENTS: Patients included nulliparous pregnant women with singleton pregnancies who developed preeclampsia (n = 55) or did not develop preeclampsia (n = 219). Women's banked sera were newly measured for 25(OH)D. MAIN OUTCOME MEASURE: The main outcome measure was preeclampsia (new-onset gestational hypertension and proteinuria for the first time after 20 wk gestation). Our hypotheses were formulated before data collection. RESULTS: Adjusted serum 25(OH)D concentrations in early pregnancy were lower in women who subsequently developed preeclampsia compared with controls [geometric mean, 45.4 nmol/liter, and 95% confidence interval (CI), 38.6-53.4 nmol/liter, vs. 53.1 and 47.1-59.9 nmol/liter; P < 0.01]. There was a monotonic dose-response relation between serum 25(OH)D concentrations at less than 22 wk and risk of preeclampsia. After confounder adjustment, a 50-nmol/liter decline in 25(OH)D concentration doubled the risk of preeclampsia (adjusted odds ratio, 2.4; 95% CI, 1.1-5.4). Newborns of preeclamptic mothers were twice as likely as control newborns to have 25(OH)D less than 37.5 nmol/liter (adjusted odds ratio, 2.2; 95% CI, 1.2-4.1). CONCLUSIONS: Maternal vitamin D deficiency may be an independent risk factor for preeclampsia. Vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia and promoting neonatal well-being.

High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates.

In utero or early-life vitamin D deficiency is associated with skeletal problems, type 1 diabetes, and schizophrenia, but the prevalence of vitamin D deficiency in U.S. pregnant women is unexplored. We sought to assess vitamin D status of pregnant women and their neonates residing in Pittsburgh by race and season. Serum 25-hydroxyvitamin D (25(OH)D) was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in cord blood of their neonates. Over 90% of women used prenatal vitamins. Women and neonates were classified as vitamin D deficient [25(OH)D<37.5 nmol/L], insufficient [25(OH)D 37.5-80 nmol/L], or sufficient [25(OH)D>80 nmol/L]. At delivery, vitamin D deficiency and insufficiency occurred in 29.2% and 54.1% of black women and 45.6% and 46.8% black neonates, respectively. Five percent and 42.1% of white women and 9.7% and 56.4% of white neonates were vitamin D deficient and insufficient, respectively. Results were similar at <22 wk gestation. After adjustment for prepregnancy BMI and periconceptional multivitamin use, black women had a smaller mean increase in maternal 25(OH)D compared with white women from winter to summer (16.0+/-3.3 nmol/L vs. 23.2+/-3.7 nmol/L) and from spring to summer (13.2+/-3.0 nmol/L vs. 27.6+/-4.7 nmol/L) (P<0.01). These results suggest that black and white pregnant women and neonates residing in the northern US are at high risk of vitamin D insufficiency, even when mothers are compliant with prenatal vitamins. Higher-dose supplementation is needed to improve maternal and neonatal vitamin D nutriture.