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


Silvia Fogacci | Federica Fogacci | Maciej Banach | Erin D. Michos | Adrian V.  Hernandez | Gregory Y.H. Lip | Michael J. Blaha | Peter P. Toth | Claudio Borghi | Arrigo F.G. Cicero | on behalf ofthe Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group

First published: September 04, 2019 |



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).


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).


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).


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.

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Authors' contribution

Silvia Fogacci and Federica Fogacci conceived, designed and performed the analysis; Maciej Banach and Arrigo F.G. Cicero verified the analytical methods; Silvia FogacciFederica FogacciMaciej Banach and Arrigo F.G. Cicero wrote the paper; Michael J. BlahaSilvia FogacciAdrian V. HernandezGregory Y.H. Lip, Erin D. Michos and Peter P. Toth provided critical revision of the manuscript; all Authors discussed the results and contributed to the final manuscript.


The present paper was written independently; no company or institution supported it financially. No professional writer was involved in the preparation of this meta-analysis.

Conflict of interest

Maciej Banach has served on the speakers bureau of Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Sanofi-Aventis, Servier and Valeant, has served as a consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Lilly, MSD, Resverlogix, Sanofi-Aventis, and has received grants from Sanofi and Valeant; Claudio Borghi has served as a consultant to Menarini and Servier; Arrigo F.G. Cicero has given talks, furnished scientific consultancies and/or participated in trials sponsored by Amgen, Angelini, Menarini and Mylan; Federica Fogacci has served as a consultant to Mylan; Peter P. Toth is a speaker and/or consultant for Amarin, Amgen, AstraZeneca, Kowa, Novo-Nordisk, Regeneron, Resverlogix, and Sanofi; Michael J. BlahaSilvia FogacciAdrian V. HernandezGregory Y.H. Lip and Erin D. Michos have no conflict of interest.

Appendix A. Supplementary data

Supplementary data to this article can be found online at

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