Background: Neonatal hyperbilirubinemia is a common neonatal condition that may lead to serious neurological complications if inadequately treated. Phototherapy is the standard treatment, but prolonged exposure is associated with several limitations. Vitamin D has been proposed as an adjunct therapy due to its antioxidant and hepatic regulatory effects. Objective: This study aimed to evaluate the effect of vitamin D supplementation combined with phototherapy on bilirubin reduction in neonates with hyperbilirubinemia, and to explore potential sources of heterogeneity related to vitamin D dosage and route of administration. Methods: Electronic databases (PubMed, Embase, Cochrane Library, Google Scholar, and ResearchGate) and gray literature were systematically searched. Eligible studies were evaluated. Outcomes assessed included changes in total serum bilirubin at multiple time points. Risk of bias was evaluated using standardized assessment criteria. Results: Four studies published between 2019 and 2025 from India, Egypt, and Pakistan were included. Baseline bilirubin levels were comparable between intervention and control groups. No significant bilirubin reduction was observed during the early treatment period (up to 96 hours). However, a statistically significant reduction favoring vitamin D supplementation emerged at 120 hours. All studies used oral vitamin D, while dosages ranged from 400 IU to 1000 IU. Trials using higher doses demonstrated more consistent bilirubin reduction and shorter phototherapy duration. Overall risk of bias was low, indicating adequate methodological quality for quantitative synthesis. Conclusion: Vitamin D supplementation appears to be a beneficial adjunct to phototherapy in neonatal hyperbilirubinemia, particularly with sustained treatment and higher dosages. Further large-scale, standardized trials are needed to establish optimal dosing and treatment duration.

Anthea Sarah Caguitla is a pediatrician who earned her Doctor of Medicine from Far Eastern University–Nicanor Reyes Medical Foundation and completed residency training at Quirino Memorial Medical Center. She has been involved in clinical research and academic activities, with a strong interest in advancing child health and evidence-based pediatric care.