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

27 randomized controlled trials in pregnant women (ages 15–45; commonly 18–40) at varying risk for preeclampsia; total 4,777 participants (2,487 in vitamin D groups vs 2,290 controls) across multiple countries. Study designs included multicenter or single-center randomized, double-blind or placebo-controlled, parallel-group trials; many participants had not been treated with vitamin D before gestation.

Vitamin D supplementation during pregnancy with regimens varying across trials: bolus doses (e.g., 350,000–360,000 IU given once) and daily doses (approximately 1,000–3,600 IU/day, e.g., 1,000; 3,200; 3,600 IU/day), sometimes co-supplemented with calcium (commonly 500–1,000 mg/day) or probiotics (in one trial). Start typically in mid-pregnancy (around 14–28 weeks) and continue through pregnancy (delivery in some trials, or to a specified duration).

Vitamin D supplementation during pregnancy reduced preeclampsia risk (odds ratio 0.37; 95% CI 0.26–0.52; I2=0%). When supplementation began by 20 weeks’ gestation, risk reduction was slightly larger (OR 0.35; 95% CI 0.24–0.50; p<0.001). Benefits were largely independent of calcium co-supplementation, the specific vitamin D regimen, or study design. Higher vitamin D doses were associated with greater risk reduction (slope of log odds ratio ≈ −1.1; p<0.001). Authors conclude vitamin D supplementation may be useful for preventing preeclampsia and call for definitive trials to establish optimal dosing and timing.

Regimen heterogeneity (varying doses and timing) and co-supplementation across trials; risk-of-bias in some trials; potential publication bias; limited data on achieved serum 25(OH)D and baseline vitamin D status; findings may not generalize to all populations; need for large, well-designed trials to define optimal dosing and safety.