Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials

Objective: To assess the effects of vitamin D supplementation during pregnancy on obstetric outcomes and birth variables. Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). Setting: Not applicable. Patient(s): Pregnant women and neonates. Intervention(s): PubMed and 5 other research databases were searched through March 2014 for RCTs evaluating vitamin D supplementation +/- calcium/vitamins/ferrous sulfate vs. a control (placebo or active) during pregnancy. Main Outcome Measure(s): Measures were: circulating 25-hydroxyvitamin D [25(OH)D] levels, preeclampsia, gestational diabetes mellitus (GDM), small for gestational age (SGA), low birth weight, preterm birth, birth weight, birth length, cesarean section. Mantel-Haenszel fixed-effects models were used, owing to expected scarcity of outcomes. Effects were reported as relative risks and their 95% confidence intervals (CIs). Result(s): Thirteen RCTs (n = 2,299) were selected. Circulating 25(OH) D levels were significantly higher at term, compared with the control group (mean difference: 66.5 nmol/L, 95% CI 66.2-66.7). Birth weight and birth length were significantly greater for neonates in the vitamin D group; mean difference: 107.6 g (95% CI 59.9-155.3 g) and 0.3 cm (95% CI 0.10-0.41 cm), respectively. Incidence of preeclampsia, GDM, SGA, low birth weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation. Across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous. Conclusion(s): Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH) D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes. Larger, better-designed RCTs evaluating clinically relevant outcomes are necessary to reach a definitive conclusion. (C) 2015 by American Society for Reproductive Medicine.