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

Abstract

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.