Zinc Supplementation Accelerates Bilirubin Reduction in Neonates with Hyperbilirubinemia: A Double-Blind Randomized Clinical Trial

Background Neonatal hyperbilirubinemia affects up to 80% of infants, and despite phototherapy as standard care, zinc inhibits heme oxygenase, lowers bilirubin and CO, and offers antioxidant benefits. This study evaluated the effect of zinc supplementation on the incidence and severity of neonatal hyperbilirubinemia. Methods A double-blind, block-randomized trial was conducted from December 2024 to February 2025 at Prof. Dr. R. D. Kandou Hospital NICU. Neonates with serum bilirubin >5 mg/dL were randomized to receive zinc 5 mg, zinc 10 mg, or placebo, all with phototherapy. Bilirubin levels were measured at baseline, 72 hours, and 120 hours, and outcomes were analyzed using bivariate and multivariate methods. Results Ninety neonates, median age 3.0 days; 67% male; 62% birth weight ≥2.5 kg, were evenly distributed among groups with no significant differences at baseline. By day 3, the 10 mg zinc group showed significantly lower median bilirubin levels (5.3 mg/dL) compared to other groups (p=0.027). By day 5, bilirubin levels further declined across all groups: 3.5 mg/dL (placebo), 2.5 mg/dL (5 mg), and 2.4 mg/dL (10 mg) (p=0.025). Hyperbilirubinemia resolution by day 5 was achieved in 67% (placebo), 90% (zinc 5 mg), and 87% (zinc 10 mg) (p=0.044). Multivariate analysis revealed that 5 mg zinc significantly increased the odds of bilirubin resolution (OR 8.0; 95% CI 1.48-44.22; p=0.016), whereas 10 mg did not. Vomiting occurred in 13.3% of neonates receiving 10 mg zinc. Conclusions Zinc 5 mg supplementation significantly accelerates bilirubin reduction compared to 10 mg zinc or placebo in neonates with hyperbilirubinemia.