Abstract
Background: Pre-eclampsia (PE) is a common and serious pregnancy complication, contributing significantly to maternal and neonatal morbidity and mortality. Emerging evidence suggests a potential link between vitamin D deficiency (VDD) and an increased risk of PE. However, the data remain inconclusive, and the precise role of vitamin D supplementation in preventing PE is still uncertain. This systematic review and meta-analysis aims to evaluate the association between maternal VDD and the risk of pre-eclampsia, specifically focusing on randomized controlled trials (RCTs) to assess the potential preventive effect of vitamin D supplementation during pregnancy. Methods: A systematic review and meta-analysis were conducted by reviewing RCTs that investigated the link between maternal VDD and the incidence of pre-eclampsia. The studies were sourced from major databases such as PubMed, Scopus, and Web of Science, with studies published from 2016 to 2025. A random-effects model was employed to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Results: A total of 2461 participants were included from the five RCTs. The meta-analysis revealed a significant reduction in the risk of pre-eclampsia among pregnant women receiving vitamin D supplementation (RR = 0.61, 95% CI: [0.50-0.75], p < 0.001), supporting its protective role. Subgroup analysis revealed that the association was particularly strong in women with serum vitamin D levels < 20 ng/mL. Additionally, supplementation with vitamin D showed a trend towards reducing the risk of pre-eclampsia, although the studies showed some heterogeneity regarding supplementation dosages and timing. Conclusions: This systematic review and meta-analysis provides robust evidence that maternal VDD is associated with an increased risk of pre-eclampsia. The findings suggest that correcting VDD through supplementation during pregnancy may be an effective preventive strategy to reduce the incidence of pre-eclampsia. However, further well-designed RCTs are required to determine the optimal timing, dosage, and long-term effects of vitamin D supplementation on maternal and neonatal health outcomes.