Journal 2026 Vol.27 No.1
Zinc Supplementation for Reducing Mortality in Patients with Neonatal Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Aaron G. Tulay, M.D., Elizabeth E. Gallardo, M.D., Clinton B. Balud, M.D.

Abstract
Background: Neonatal sepsis remains a leading cause of neonatal mortality worldwide, disproportionately affecting low- and middle-income countries. Zinc, a micronutrient involved in immune regulation and host defense, has been proposed as an adjunct to antimicrobial therapy; however, evidence regarding its efficacy in reducing mortality and improving clinical outcomes in neonatal sepsis remains inconclusive.
Objective: This study performed a systematic review and meta-analysis to evaluate existing evidence from randomized controlled trials (RCTs) on the effect of zinc supplementation on mortality, length of hospital stay (LOS), and levels of CRP and procalcitonin in neonatal sepsis.
Methods: CENTRAL, MEDLINE, and EMBASE were comprehensively searched. Eligible studies included RCTs of neonates with sepsis receiving adjunctive zinc supplementation. Risk of bias was assessed using the Cochrane RoB 2 tool. Fixed-effect metaanalysis was performed with sensitivity analyses to explore heterogeneity.
Results: Four RCTs (n=1,082) were included for analysis. The pooled estimate showed no significant reduction in mortality with zinc supplementation (OR 0.81; 95% CI [0.54,1.24]; I²=49%). Sensitivity analysis excluding one lower-dose, shorter-duration study demonstrated a significant mortality reduction (OR 0.44; 95% CI [0.22,0.86]; I²=0%), suggesting a possible dose–response relationship. Zinc upplementation was associated with a greater decline in CRP and procalcitonin in two trials but did not significantly reduce LOS. Most included studies were judged to have a high risk of bias, limiting certainty of evidence.
Conclusion: Adjunctive zinc at doses ≥1.4 mg/kg/day for at least 10 days may reduce mortality rate and accelerate resolution of inflammatory markers in neonatal sepsis. Definitive, adequately powered multicenter trials are needed before routine implementation can be recommended.

KEYWORDS: Neonatal Sepsis, Zinc, Neonatal Mortality
https://doi.org/10.56964/pidspj20262701003
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