Comparative effectiveness of statins, metformin, and vitamin D, for prevention of preeclampsia: a systematic review and network meta-analysis of randomized trials

Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality worldwide, yet effective pharmacological preventive strategies remain uncertain. Statins, metformin, and vitamin D, alone or combined with omega-3, have been investigated for potential protective effects, but comparative evidence is limited.

To compare the effectiveness of statins, metformin, and vitamin D in preventing preeclampsia and related adverse outcomes among high-risk pregnant women.

A systematic review and network meta-analysis of randomized controlled trials was conducted. PubMed, Scopus, Web of Science, Cochrane, and Epistemonikos were searched from September 11, 2020, to September 11, 2025. Eight trials involving 4,078 high-risk pregnant women were included. Participants were randomized to statins, metformin, or vitamin D at different doses versus placebo. The primary outcome was the incidence of preeclampsia. Secondary outcomes included gestational hypertension, preterm birth, low birth weight, neonatal intensive care unit admission, gestational diabetes, respiratory distress syndrome, and perinatal outcomes. Risk ratios with 95% confidence intervals were calculated, and interventions were ranked using the surface under the cumulative ranking probabilities.