Vitamin D Supplementation during Pregnancy: An Evidence Analysis Center Systematic Review and Meta-Analysis

Given the high rates of vitamin D deficiency among pregnant women and possible effects on offspring health, a systematic review on this topic was conducted to help inform future practice guidelines.

To evaluate associations between maternal vitamin D supplementation, maternal 25-hydroxyvitamin D (25(OH)D) concentrations, and health outcomes.

A PubMed literature search was conducted to identify studies that examined the health effects of vitamin D supplementation during pregnancy on maternal and infant health outcomes published from 2000 to 2016. Among 976 identified publications, 20 randomized clinical trials met the inclusion criteria. The initial search was extended to include five studies published between July 2016 and September 2018.

Maternal and infant 25(OH)D concentrations, gestational diabetes, preeclampsia or gestational hypertension, cesarean section, maternal parathyroid hormone and calcium concentrations, and infant gestational age, birth weight, and birth length.

Mean differences, odds ratios, and 95% CIs were calculated, only for the initial search, using separate random-effects meta-analyses for each outcome.

Evidence was good or strong that maternal vitamin D supplementation significantly increased maternal (13 studies, n=18, mean difference, 14.1 ng/mL [35.2 nmol/L]; 95% CI=9.6-18.6 ng/mL [24.0-46.4 nmol/L]) and infant (nine studies, n=12; 9.7, 5.2, 14.2 ng/mL [24.2, 12.9, 35.5 nmol/L]) 25(OH)D concentrations, although heterogeneity was significant (I²=95.9% and I²=97.4, respectively, P<0.001). Evidence was fair that vitamin D supplementation significantly decreases maternal homeostatic model assessment-insulin resistance (five studies, n=7; -1.1, -1.5, -0.7) and increases infant birth weight (nine studies, n=11, 114.2, 63.4, 165.1 g), both had insignificant heterogeneity. A null effect of maternal supplementation on other maternal (preeclampsia, cesarean section) and infant (gestational age, birth length) outcomes was found.

Results show vitamin D supplementation during pregnancy improves maternal and infant 25(OH)D concentrations and may play a role in maternal insulin resistance and fetal growth. To further inform practice and policies on the amount of vitamin D, which supports a healthy pregnancy, high quality dose-response randomized clinical trials, which assess pregnancy-specific 25(OH)D thresholds, and appropriately powered clinical outcomes are needed.