Calcium and vitamin D supplementation for prevention of preeclampsia: a systematic review and network meta-analysis

Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings.