Meta-analysis shows oral zinc sulfate significantly lowers bilirubin levels in infants with neonatal hyperbilirubinemia across multiple time points

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Frontiers in Medicine Published May 18, 2026 Medically reviewed May 18, 2026 DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Oral zinc sulfate significantly reduces serum bilirubin in infants with hyperbilirubinemia, though high heterogeneity limits certainty and safety data are lacking.

This meta-analysis evaluated the efficacy of oral zinc sulfate for treating neonatal hyperbilirubinemia. The study pooled data from multiple trials involving a total sample size of 1,405 infants. Researchers measured changes in total serum bilirubin levels at specific intervals following intervention.

results indicated a consistent reduction in bilirubin concentrations over time. At twenty-four hours, the mean difference was negative one point one two milligrams per deciliter. By four days, the reduction reached negative one point five seven milligrams per deciliter. All reductions were statistically significant with p-values less than zero point zero five.

Statistical heterogeneity was substantial across the outcomes, with I-squared values exceeding ninety percent. Despite this variability, the direction of effect remained uniform. Safety data were limited as adverse events were not reported in the source studies. Clinicians should interpret these findings with caution regarding generalizability and safety profiles.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundPrevious investigations into the impact of oral zinc sulfate on serum bilirubin levels of newborns have yielded conflicting results. This meta-analysis aimed to clarify the efficacy of zinc sulfate in infants with hyperbilirubinemia by combining the evidence from published randomized controlled trials (RCTs).MethodsIn this systematic review, PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science were searched in August 2024, with an update on 25 October 2025, for the RCTs investigating zinc sulfate in infants with hyperbilirubinemia. The primary outcome was the change in total serum bilirubin (mg/dL). Mean difference (MD) with 95% confidence interval [95% confidence interval (CI)] was used to estimate the overall effect of the outcomes. A random-effects model was used to pool the results.ResultsA total of 14 RCTs comprising 1,405 infants were analyzed. Zinc sulfate significantly reduced bilirubin levels at 24 h [MD: −1.12 mg/dL, 95% CI (−1.73; −0.52), p = 0.0003, I2 = 90.5%], at 48 h [MD: −1.23 mg/dL, 95% CI (−2.19; −0.28), p = 0.0116, I2 = 89.1%], at 72 h [MD: −1.35 mg/dL, 95% CI (−2.57; −0.14), p = 0.0294, I2 = 95.4%], and at 4 days [MD: −1.57 mg/dL, 95% CI (−2.33; −0.81), p