Shedding light on gestational loss: The role of Vitamin D 25(OH)D deficiency in miscarriage – A systematic review and meta-analysis

A BSTRACT Objectives: Miscarriage is a common pregnancy complication with various contributing factors. Recent studies suggest that maternal Vitamin D deficiency may increase the risk of early pregnancy loss. Vitamin D is essential for immune regulation, placental development, and fetal growth. This meta-analysis aimed to evaluate the association between maternal Vitamin D status and miscarriage. Materials and Methods: This meta-analysis followed PRISMA 2020 guidelines, including observational studies from PubMed, EMBASE, Scopus, Web of Science, and Cochrane (2018–2025). Eligible studies reported serum 25(OH)D levels and miscarriage outcomes. Data on serum Vitamin D, miscarriage incidence, and odds ratios (ORs) were extracted. Study quality was assessed using the Newcastle–Ottawa Scale. Statistical analyses were performed using Review Manager 5.4 and R, with evaluation of heterogeneity and publication bias. Results: Women who experienced miscarriage had significantly lower Vitamin D levels than those with ongoing pregnancies (mean difference: −5.48 ng/mL; 95% confidence interval [CI]: −9.77 to −1.19; P = 0.02). The miscarriage rate was higher among Vitamin D-deficient women (34%; 95% CI: 0.21–0.47) than in those with sufficient levels (16%; 95% CI: 0.08–0.24). Deficiency was significantly associated with miscarriage risk (OR: 2.02; 95% CI: 1.37–2.98; P = 0.0004). No significant publication bias was observed. Conclusion: Maternal Vitamin D deficiency is significantly associated with an increased risk of miscarriage. These findings support the potential benefit of assessing and optimizing Vitamin D status in preconception and antenatal care to improve the pregnancy outcomes.