Vitamin D supplementation and incident preeclampsia: A systematic review and meta-analysis of randomized clinical trials

the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group, Adrian Vladimir Hernández Diaz, Silvia Fogacci, Federica Fogacci, Maciej Banach, Erin D. Michos, Gregory Y.H. Lip, Michael J. Blaha, Peter P. Toth, Claudio Borghi, Arrigo F.G. Cicero

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


BACKGROUND: Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D supplementation in preventing preeclampsia is controversial. To assess the impact of vitamin D supplementation on the risk of preeclampsia, we performed a systematic review of the literature and a meta-analysis of the available randomized clinical trials (RCTs).

METHODS: The primary outcome was preeclampsia. Subgroup analyses were carried out considering the timing of the supplementation, type of intervention and the study design. Meta-regression analysis, including the amount of vitamin D and maternal age, were planned to explore heterogeneity (PROSPERO database registration number: CRD42019119207).

RESULTS: Data were pooled from 27 RCTs comprising 59 arms, which included overall 4777 participants, of whom 2487 were in the vitamin D-treated arm and 2290 in the control arm. Vitamin D administration in pregnancy was associated with a reduced risk of preeclampsia (odd ratio [OR] 0.37, 95% confidence interval [CI]: 0.26, 0.52; I2 = 0%). If the vitamin D supplementation was started up to 20 weeks' gestation, the odds was a little lower (OR 0.35, 95% CI: 0.24, 0.50, p < 0.001). The effect was largely independent of the supplementation cessation (until delivery or not), type of intervention (vitamin D alone or in association with calcium), and study design. Increasing dose of vitamin D was associated with reduced incidence of preeclampsia (slope of log OR: -1.1, 95% CI: -1.73, -0.46; p < 0.001).

CONCLUSIONS: Results suggest that vitamin D supplementation may be useful in preventing preeclampsia. These data are especially useful for health-care providers who engage in the management of pregnant women at risk for preeclampsia. Our findings are a call for action to definitively address vitamin D supplementation as a possible intervention strategy in preventing preeclampsia in pregnancy.

Original languageAmerican English
Pages (from-to)1742-1752
Number of pages11
JournalClinical Nutrition
Issue number6
StatePublished - 1 Jan 2019


  • Adolescent
  • Adult
  • Avitaminosis/blood
  • Dietary Supplements/adverse effects
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Pre-Eclampsia/diagnosis
  • Pregnancy
  • Protective Factors
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • Vitamin D/adverse effects
  • Young Adult


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