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The Effects of Vitamin D Supplementation During Pregnancy on Maternal, Neonatal, and Infant Health: A Systematic Review and Meta-analysis.

  • 2024-07-01
  • Nutrition reviews 83(3)
    • Wen-Chien Yang
    • Ramaa Chitale
    • Karen M O'Callaghan
    • Christopher R Sudfeld
    • Emily R Smith

Study Design

Type
Meta-Analysis
Sample size
n = 9,954
Population
pregnant women
Methods
systematic review and meta-analysis of randomized controlled trials; MEDLINE, PubMed, Europe PMC, Scopus, Cochrane Database of Systematic Reviews, Web of Science, and CINAHL databases searched; risk ratios and mean differences pooled for 38 maternal, birth, and infant outcomes using random effects models

Context

Previous research linked vitamin D deficiency in pregnancy to adverse pregnancy outcomes.

Objective

Update a 2017 systematic review and meta-analysis of randomized controlled trials (RCTs) on the effect of vitamin D supplementation during pregnancy, identify sources of heterogeneity between trials, and describe evidence gaps precluding a clinical recommendation.

Data sources

The MEDLINE, PubMed, Europe PMC, Scopus, Cochrane Database of Systematic Reviews, Web of Science, and CINAHL databases were searched. Articles were included that reported on RCTs that included pregnant women given vitamin D supplements as compared with placebo, no intervention, or active control (≤600 IU d-1). Risk ratios (RRs) and mean differences were pooled for 38 maternal, birth, and infant outcomes, using random effects models. Subgroup analyses examined effect heterogeneity. The Cochrane risk of bias tool was used.

Data extraction

Included articles reported on a total of 66 trials (n = 17 276 participants).

Data analysis

The median vitamin D supplementation dose was 2000 IU d-1 (range: 400-60 000); 37 trials used placebo. Antenatal vitamin D supplementation had no effect on the risk of preeclampsia (RR, 0.81 [95% CI, 0.43-1.53]; n = 6 trials and 1483 participants), potentially protected against gestational diabetes mellitus (RR, 0.65 [95% CI, 0.49-0.86; n = 12 trials and 1992 participants), and increased infant birth weight by 53 g (95% CI, 16-90; n = 40 trials and 9954 participants). No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found. A total of 25 trials had at least 1 domain at high risk of bias.

Conclusion

Additional studies among the general pregnant population are not needed, given the many existing trials. Instead, high-quality RCTs among populations with low vitamin D status or at greater risk of key outcomes are needed. Benefits of supplementation in pregnancy remain uncertain because current evidence has high heterogeneity, including variation in study context, baseline and achieved end-line 25-hydroxyvitamin D level, and studies with high risk of bias.

Systematic review registration

PROSPERO registration no. CRD42022350057.

Research Insights

  • Vitamin D→Increased Birth Weight

    increased infant birth weight by 53 g (95% CI, 16-90; n = 40 trials and 9954 participants)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    median 2000 IU/day (range 400-60,000)
  • Vitamin D→Reduced Low Birth Weight Risk

    No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found.

    Effect
    Neutral
    Effect size
    Small
    Dose
    median 2000 IU/day (range 400-60,000)
  • Vitamin D→Reduced Preterm Births

    No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found.

    Effect
    Neutral
    Effect size
    Small
    Dose
    median 2000 IU/day (range 400-60,000)
  • Vitamin D→Reduced Prevalence of Gestational Diabetes Mellitus

    potentially protected against gestational diabetes mellitus (RR, 0.65 [95% CI, 0.49-0.86]; n = 12 trials and 1992 participants)

    Effect
    Beneficial
    Effect size
    Large
    Dose
    median 2000 IU/day (range 400-60,000)
  • Vitamin D→Reduced Risk of Preeclampsia

    Antenatal vitamin D supplementation had no effect on the risk of preeclampsia (RR, 0.81 [95% CI, 0.43-1.53]; n = 6 trials and 1483 participants)

    Effect
    Neutral
    Effect size
    Small
    Dose
    median 2000 IU/day (range 400-60,000)
  • Vitamin D→Reduced Risk of Small-for-Gestational Age

    No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found.

    Effect
    Neutral
    Effect size
    Small
    Dose
    median 2000 IU/day (range 400-60,000)
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