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

Fertil Steril. 2015 May;103(5):1278-88.e4. doi: 10.1016/j.fertnstert.2015.02.019. Epub 2015 Mar 23.


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.

Keywords: Vitamin D; maternal outcomes; meta-analysis; neonatal outcomes; pregnancy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Birth Weight
  • Chi-Square Distribution
  • Dietary Supplements*
  • Female
  • Humans
  • Infant, Newborn
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / prevention & control*
  • Prenatal Care / methods*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Treatment Outcome
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / diagnosis
  • Vitamin D Deficiency / prevention & control*


  • Biomarkers
  • Vitamin D
  • 25-hydroxyvitamin D