Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis

Systematic review and network meta-analysis of randomized controlled trials in pregnant women, including both low-risk and high-risk pregnancies from multiple countries. The active intervention arms included calcium (n=13,060), vitamin D (n=154), and calcium plus vitamin D (n=585), each compared with matched placebo/control groups in the included trials.

This systematic review evaluated calcium supplementation, vitamin D supplementation, and calcium plus vitamin D during pregnancy, each compared with placebo or control. Across the active intervention arms, calcium was studied in 16 RCTs, vitamin D in 3 RCTs, and calcium plus vitamin D in 4 RCTs; supplementation often started before 20 weeks' gestation in several trials.

Overall, calcium supplementation reduced preeclampsia risk and vitamin D also showed a possible benefit, although the vitamin D evidence was less certain. In direct meta-analysis, preeclampsia risk was lower with calcium versus placebo (RR 0.54, 95% CI 0.41 to 0.70), vitamin D versus placebo (RR 0.47, 95% CI 0.24 to 0.89), and calcium plus vitamin D versus placebo (RR 0.50, 95% CI 0.32 to 0.78). Network meta-analysis showed a similar pattern for calcium (RR 0.49, 95% CI 0.35 to 0.69), while vitamin D (RR 0.43, 95% CI 0.17 to 1.11) and calcium plus vitamin D (RR 0.57, 95% CI 0.30 to 1.10) were imprecise. Calcium had an estimated NNT of 19 (95% CI 15 to 32) for preventing preeclampsia.

The vitamin D and calcium plus vitamin D estimates were based on few trials and were less precise than calcium alone. Trials varied in pregnancy risk status, gestational age at enrollment, and geographic setting, and follow-up was short-term; adverse events were not reported in the provided text. The review also noted that larger, well-designed randomized trials are still needed, especially for vitamin D alone or in combination with calcium.