Background: Several clinical trials evaluated the effect of zinc supplementation on mortality in children, but the results were inconsistent. We aimed to conduct a systematic review and meta-analysis on the impact of zinc supplementation on mortality in under ۵-year children.Methods: A comprehensive search was conducted by using the electronic (PubMed, Scopus, Web of Science) databases, and Google Scholar, up to June ۲۰۲۰.
Randomized clinical trials (RCTs) that reported the effect of zinc supplementation on death incidence in under ۵-year children were included in the analysis. Screening was performed based on title/abstract and full-text. A random effects model was applied to calculate the summary relative risk (SRR). Risk of Bias ۲.۰ tool was used to rate the quality of trials. The body of evidence was assessed by the GRADE approach.Results: Combining ۳۰ RRs from ۲۸ RCTs including ۲۳۷,۰۶۸ participants revealed that zinc supplementation has significantly reduced the risk of all-causes mortality by ۱۶% in children (SRR: ۰.۸۴, ۹۵%CI: ۰.۷۴, ۰.۹۶). A follow up duration of less than ۱ year after supplementation resulted in ۵۴% reduced risk of mortality (۰.۴۶; ۰.۳۳, ۰.۶۳) with no heterogeneity between investigations. Subgroup analysis by zinc dosage showed that assigning ≥۱۰ mg/d zinc to under five children and duration of less than ۱۱ months of intervention decreased the risk of all-cause mortality by ۴۴% (۰.۵۶; ۰.۴۲, ۰.۷۵) and ۴۸% (۰.۵۲; ۰.۳۸, ۰.۷۲), respectively. In low-birthweight (LBW) infants, zinc supplementation was reduced all-cause mortality by ۵۲% (۰.۴۸;۰.۲۳, ۱.۰۰).
Zinc supplementation significantly reduced the risk of death from pneumonia (۰.۷۰: ۰.۶۴, ۰.۹۸) and infection (۰.۵۴; ۰.۳۹, ۰.۷۶), also changed the risk of mortality from diarrhea by ۱۵% (۰.۸۵; ۰.۷۰, ۱.۰۳) and sepsis by ۵۷% (۰.۴۳; ۰.۱۸, ۱.۰۲).Conclusion: This meta-analysis on RCTs revealed that zinc supplementation in under-fiveyear children has significantly reduced the risk of all-cause mortality. Notable decreases were found in trials with a dose of ۱۰mg/d or more zinc supplementation, a maximum of ۱۱ months of supplementation, a follow up less than one year and especially in LBW infants.