It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants’ length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, −0.93±1.05; prenatal 4200, −1.11±1.12; prenatal 16,800, −0.97±0.97; prenatal 28,000, −1.06±1.07; and prenatal and postpartum 28,000, −0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013.)

Background: Plasma volume expansion is an important physiologic change across gestation. High or low expansion has been related to adverse pregnancy outcomes, yet there is a limited understanding of normal/healthy plasma volume expansion. We aimed to evaluate the pattern of plasma volume expansion across healthy pregnancies from longitudinal studies.Methods: We conducted a systematic review and meta-analysis to identify original studies that measured plasma volume in singleton pregnancies of healthy women. Specifically, we included studies that measured plasma volume at least two times across gestation and one time before or after pregnancy in the same women. PubMed, Web of Science, Cochrane, CINAHL, andclinicaltrials.govdatabases were searched from the beginning of each database to February 2019. We combined data across studies using a random effects model.Results: Ten observational studies with a total of 347 pregnancies were eligible. Plasma volume increased by 6% (95% CI 3–9) in the first trimester compared to the nonpregnant state. In the second trimester, plasma volume was increased by 18% (95% CI 12–24) in gestational weeks 14–20 and 29% (95% CI 21–36) in weeks 21–27 above the nonpregnant state. In the third trimester, plasma volume was increased by 42% (95% CI 38–46) in weeks 28–34 and 48% (95% CI 44–51) in weeks 35–38. The highest rate of increase occurred in the first half of the second trimester. Included studies were rated from moderate to high quality; 7 out of 10 studies were conducted over 30 years ago.Conclusions: In healthy pregnancies, plasma volume begins to expand in the first trimester, has the steepest rate of increase in the second trimester, and peaks late in the third trimester. The patterns observed from these studies may not reflect the current population, partly due to the changes in BMI over the last several decades. Additional longitudinal studies are needed to better characterize the range of normal plasma volume expansion across maternal characteristics.

OBJECTIVE: To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis. DATA SOURCES: PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020. METHODS OF STUDY SELECTION: We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis. TABULATION, INTEGRATION, AND RESULTS: One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68–7.29] and 5.88 [95% CI 3.68–9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93–9.45] and 3.90 [95% CI 2.74–5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive. CONCLUSION: Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156812.

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.