The role of vitamin D deficiency in placental dysfunction: A systematic review

Introduction: Vitamin D plays a critical role in pregnancy, supporting placental function via angiogenesis, immune regulation, and nutrient transport. Deficiency in vitamin D during gestation is associated with complications such as preeclampsia, intrauterine growth restriction (IUGR), and preterm birth. However, the mechanisms linking vitamin D deficiency to placental dysfunction remain inadequately understood, highlighting the need for systematic evaluation. Methods: A systematic review was conducted in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with searches in PubMed, Scopus, and Web of Science for studies published within the last 20 years. Inclusion criteria targeted human studies examining the association between vitamin D and placental function, including randomized controlled trials, cohort studies, and case-control studies. A total of 10 studies were included following rigorous screening and quality assessment. Results: Findings from human studies indicate that maternal vitamin D deficiency significantly impairs placental function by reducing vascular integrity, downregulating nutrient transporters, and promoting inflammation. Mechanistic evidence highlights decreased expression of vascular endothelial growth factor (VEGF) and increased inflammatory cytokines in vitamin D-deficient pregnancies. Supplementation with active vitamin D [1α,25(OH)2D3] mitigated these adverse effects, restoring placental growth, improving nutrient transport, and reducing inflammation. Notably, population-specific differences and sex-specific responses to vitamin D sufficiency were observed. Conclusions: Vitamin D is essential for optimal placental function and pregnancy outcomes. This review underscores the need for standardized supplementation protocols and further research into long-term and population-specific effects of vitamin D. Addressing these gaps can inform targeted interventions to reduce pregnancy complications and improve maternal-fetal health.