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

Systematic review and meta-analysis of randomized clinical trials in pregnant women not previously treated with vitamin D before gestation. Across 59 active intervention arms, 4,777 participants were included overall, with trials conducted in multiple countries and enrolling women at varying gestational ages and preeclampsia risk levels.

Vitamin D supplementation during pregnancy was evaluated in multiple randomized trials using a wide range of regimens, including vitamin D3 and vitamin D2, given orally as daily doses, weekly doses, every-2-week dosing, or single/loading doses for durations ranging from a few weeks to the remainder of pregnancy. Several regimens also included calcium co-supplementation, but the review concluded that calcium did not add benefit beyond vitamin D.

Vitamin D supplementation was associated with a lower risk of incident preeclampsia. The pooled effect was OR 0.37, 95% CI 0.26 to 0.52, with no between-study heterogeneity reported for this estimate (I2 = 0%). Benefit was stronger when supplementation started up to 20 weeks of gestation, with OR 0.35, 95% CI 0.24 to 0.50. Higher vitamin D doses were linked to greater risk reduction, while co-administration with calcium did not provide additional benefit.

Interpretation is limited by substantial variation across trials in vitamin D form, dose, timing, and use of calcium co-supplementation. Many studies were small, and the supplied extract does not provide arm-specific baseline data, adverse-event detail, or individual trial outcome estimates. Generalizability is also limited by mixed populations, gestational ages, and risk profiles across countries and decades of study conduct.