Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis

Vitamin D has well-defined classical functions related to calcium metabolism and bone health but also has non-classical effects that may influence other aspects of health. There has been considerable recent interest in the role of vitamin D on outcomes related to pregnancy and young child health but few efforts have been made to systematically consolidate this evidence to inform the research and policy agenda for low-income countries. A systematic review was undertaken to identify intervention and observational studies of vitamin D supplementation, intake or status (25-hydroxy-vitamin D) during pregnancy on perinatal and infant health outcomes. Data from trials and observational studies isolating the effect of vitamin D supplementation and intake were extracted and study quality was evaluated. Meta-analysis was used to pool effect estimates. We identified five randomised trials with outcomes of relevance to our review. All had small sample size and dosage amount, duration and frequency varied as did the ability to correct deficiency. Pooled analysis of trials using fixed-effects models suggested protective effects of supplementation on low birthweight (three trials, risk ratio (RR) = 0.40 [95% confidence interval (CI) 0.23, 0.71]) and non-significant but suggestive effects of daily supplementation on small-for-gestational age (two trials, RR = 0.67 [0.40, 1.11]). No effect on preterm delivery (<37 weeks) was evident (two trials, RR = 0.77 [0.35, 1.66]). Little evidence from trials exists to evaluate the effect of vitamin D supplementation during pregnancy on maternal, perinatal or infant health outcomes. Based on both trials and observational studies, we recommend that future research explore small-for-gestational age, preterm delivery, pre-eclampsia, and maternal and childhood infections, as outcomes of interest. Trials should focus on populations with a high prevalence of vitamin D deficiency, explore the relevance of timing of supplementation, and the dosage used in such trials should be sufficient to correct deficiency.