Efficacy of zinc sulfate supplementation in managing neonatal hyperbilirubinemia: a meta-analysis

Ghadirzadeh et al., 2025 | J Matern Fetal Neonatal Med | Meta Analysis

Citation

Ghadirzadeh Babak, Afshar Maziar, ... Moradi Yousef. Efficacy of zinc sulfate supplementation in managing neonatal hyperbilirubinemia: a meta-analysis. J Matern Fetal Neonatal Med. 2025-Dec;38(1):2528696. doi:10.1080/14767058.2025.2528696

Abstract

OBJECTIVE: To consolidate clinical study data regarding zinc supplementation for neonatal jaundice. The primary objectives were to evaluate the impact of zinc sulfate supplementation on serum bilirubin levels and the duration of phototherapy while secondary objectives evaluated safety and included complications. STUDY DESIGN: Randomized controlled trials (RCTs) within which zinc supplementation and routine phototherapy were compared to placebo/standard care in newborns. RESULTS: Of 1596 studies, 20 RCTs, including 2127 neonates, met inclusion criteria; from which zinc sulfate accompanying phototherapy was given to 1124. Zinc supplementation reduced bilirubin in meta-analysis, although severe heterogeneity showed variability. Subgroup studies showed better efficacy in term neonates and normal-birth-weight newborns, but only at 12 h post-supplementation. Phototherapy duration caused fluctuations, including a paradoxical bilirubin increase at 24-48 h. Zinc supplementation did not cause diarrhea, rash, or vomiting, but publication bias was found. GRADE assessments graded bilirubin decrease evidence as low certainty due to heterogeneity and moderate certainty for adverse effects. CONCLUSIONS: Zinc sulfate may alleviate neonatal hyperbilirubinemia in particular circumstances, but its use requires thorough evaluation of individual patient factors. The variability in results underscores the necessity for personalized treatment in neonatal care and the requirement for more research on zinc supplements.

Key Findings

Of 1596 studies, 20 RCTs, including 2127 neonates, met inclusion criteria; from which zinc sulfate accompanying phototherapy was given to 1124. Zinc supplementation reduced bilirubin in meta-analysis, although severe heterogeneity showed variability. Subgroup studies showed better efficacy in term neonates and normal-birth-weight newborns, but only at 12 h post-supplementation. Phototherapy duration caused fluctuations, including a paradoxical bilirubin increase at 24-48 h. Zinc supplementation

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 1596
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Zinc Sulfate
  • Infant, Newborn
  • Hyperbilirubinemia, Neonatal
  • Dietary Supplements
  • Phototherapy
  • Randomized Controlled Trials as Topic
  • Bilirubin

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Review
  • Vertical: zinc

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09