Phototherapy for Neonatal Hyperbilirubinemia: Vitamin D, Calcium, and Magnesium: A Systematic Review and Meta-analysis.

Abstract

Objective: Phototherapy (PT) is the first-line treatment for neonatal hyperbilirubinemia, yet concerns persist regarding its effects on mineral and vitamin homeostasis. The aim of this study was to evaluate the effects of PT on serum levels of vitamin D, Ca, and Mg in newborns with hyperbilirubinemia.

Study design: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we conducted a systematic review and meta-analysis of studies from PubMed, Scopus, Web of Science, CINAHL, Cochrane Library, and Medline (through June 2025). The quantitative studies that investigated relation to PT with vitamin D, Ca, ionized calcium (iCa), and Mg levels by random-effects models pooled mean differences (MDs) with 95% confidence intervals (CIs). Risk of bias was assessed using ROBINS-E (Risk Of Bias In Non-randomized Studies of Exposures) and RoB 2 (Risk of Bias Assessment Tool-2) tools; evidence certainty was rated using the Grading of Recommendations Assessment Development and Evaluation.

Results: Fifty-three studies involving 5,413 newborns were included. PT was associated with significant reductions in serum Ca (MD: -0.66 mg/dL, 95% CI: -0.82 to -0.51; I ² = 95.56%), iCa (MD: -0.11 mmol/L, 95% CI: -0.15 to -0.06; I ² = 95.63%), and Mg (MD: -0.70 mg/dL, 95% CI: -1.14 to -0.27; I ² = 96.06%), with moderate-certainty evidence. The effect on vitamin D levels remained inconclusive due to very low-certainty evidence (⊕◯◯◯; MD: 2.34 ng/mL, 95% CI: -2.22 to 6.89; I ² = 97.39%). Subgroup analysis revealed that head covering significantly attenuated Ca decline (MD: +0.82 mg/dL, 95% CI: 0.23-1.41). Meta-regression identified younger age and longer PT duration as significant predictors of electrolyte reductions.

Conclusion: PT induces predominantly asymptomatic reductions in serum Ca, iCa, and Mg levels in newborns with hyperbilirubinemia. Head covering is a promising, low-cost preventive strategy to mitigate Ca decline. Selective electrolyte monitoring in newborns with hyperbilirubinemia, especially in high-risk newborns represents prudent practice.

Key points: · This systematic review demonstrates phototherapy induces statistically significant but predominantly asymptomatic reductions in serum Ca, iCa, and Mg levels in neonates with hyperbilirubinemia.. · Head covering emerges as a promising simple, low-cost preventive strategy to mitigate Ca decline.. · The effect of phototherapy on vitamin D levels remains inconclusive due to substantial heterogeneity and conflicting results across studies.. · Selective electrolyte monitoring in high-risk neonates represents prudent practice..