Effect of Phototherapy on Calcium, Magnesium, and Vitamin D Levels in Neonates with Hyperbilirubinemia: A Systematic Review and Meta-Analysis

Introduction: This study aimed to evaluate the impact of phototherapy on serum calcium, magnesium, and vitamin D levels in term neonates. Methods: This study was conducted in accordance with the PRISMA statement. A comprehensive search of PubMed, Scopus, Web of Science, the Cochrane Library, and the Scientific Information Database (SID) was performed up to August 20, 2025. Pooled effect sizes were calculated as Hedges' g and mean differences (MD) with 95% Confidence Intervals (CIs) using random-effects models. Heterogeneity was assessed using the I2 statistic. Study quality was appraised using the Newcastle- Ottawa Scale, ROBINS-I, and RoB 2 tools, and the certainty of evidence was evaluated per GRADE methodology. Results: Twenty-seven studies were included. Phototherapy was associated with a significant decrease in serum calcium (Hedges' g = -0.67; 95% CI: -0.89 to -0.45; MD: -0.57 mg/dL; 95% CI: - 0.75 to -0.40; 22 studies; 2,406 participants) and magnesium levels (Hedges' g = -1.09; 95% CI: - 1.54 to -0.63; MD: -0.21 mg/dL; 95% CI: -0.33 to -0.10; 10 studies; 863 participants), with considerable heterogeneity observed for both outcomes. Vitamin D levels showed a non-significant overall increase (Hedges' g = 0.40; 95% CI: -0.06 to 0.87; MD: 5.86 nmol/L; 95% CI: -2.06 to 13.77; 7 studies; 517 participants; p = 0.091). The pooled prevalence of hypocalcemia and hypomagnesemia following phototherapy was 26.1% (95% CI: 20.8% to 32.3%) and 23.8% (95% CI: 18.6% to 30.0%), respectively. The certainty of evidence was rated as low for calcium and magnesium, and very low for vitamin D. Discussion: This meta-analysis indicates that phototherapy in term neonates is associated with significant decreases in serum calcium and magnesium, while its effect on vitamin D remains inconclusive. These findings highlight the need for monitoring electrolyte balance in at-risk neonates, although routine supplementation is not currently supported by the evidence. Conclusion: Phototherapy is associated with a significant decrease in calcium and magnesium levels in term neonates. Given the low certainty of evidence, high-quality randomized controlled trials with standardized protocols are warranted to guide clinical practice. PROSPERO registration number: CRD42025638904.