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Effect of zinc supplementation on mortality in under 5-year children: a systematic review and meta-analysis of randomized clinical trials

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Abstract

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 5-year children.

Methods

A comprehensive search was conducted using the electronic (PubMed, Scopus, Web of Science) databases, and Google Scholar, up to June 2020. Randomized clinical trials (RCTs) that reported the effect of zinc supplementation on death incidence in under 5-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 2.0 tool was used to rate the quality of trials. The body of evidence was assessed by the GRADE approach.

Results

Combining 30 RRs from 28 RCTs including 237,068 participants revealed that zinc supplementation has significantly reduced the risk of all-causes mortality by 16% in children (SRR: 0.84, 95% CI: 0.74, 0.96). A follow-up duration of less than 1 year after supplementation resulted in 54% reduced risk of mortality (0.46; 0.33, 0.63) with no heterogeneity between investigations. Subgroup analysis by zinc dosage showed that assigning ≥ 10 mg/d zinc to under five children and duration of less than 11 months of intervention decreased the risk of all-cause mortality by 44% (0.56; 0.42, 0.75) and 48% (0.52; 0.38, 0.72), respectively. In low birth weight (LBW) infants, zinc supplementation was reduced all-cause mortality by 52% (0.48; 0.23, 1.00). Zinc supplementation significantly reduced the risk of death from pneumonia (0.70: 0.64, 0.98) and infection (0.54; 0.39, 0.76), also changed the risk of mortality from diarrhea by 15% (0.85; 0.70, 1.03) and sepsis by 57% (0.43; 0.18, 1.02).

Conclusion

This meta-analysis on RCTs revealed that zinc supplementation in under 5-year children has significantly reduced the risk of all-cause mortality. Notable decreases were found in trials with a dose of 10 mg/d or more zinc supplementation, a maximum of 11 months of supplementation, a follow-up less than one year and especially in LBW infants.

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Abbreviations

BMI:

Body mass index

RR:

Relative risks

SRR:

Summary relative risks

95% CI:

95% Confidence intervals

HR:

Hazard ratio

OR:

Odds ratio

RCT:

Randomized clinical trial

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline

GRADE:

Grading of Recommendations, Assessment, Development and Evaluations

HIV:

Human immunodeficiency virus

VLBW:

Very low birth weight

LBW:

Low birth weight

MV:

Multi-vitamin

mg:

Milligram

kg:

Kilogram

mo:

Month

wk:

Week

NR:

Not reported

Y:

Year

RDA:

Recommended daily adequate

IU:

International unit

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Acknowledgements

We wish to thank Food Security Research Center of Isfahan University of Medical Sciences for financial support for the study.

Funding

The financial support for this study comes from Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Food Security Research Center had no role in the design/conduct of the study, collection/analysis/interpretation of the data, and preparation/review/approval of the manuscript.

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PR, MR and PS contributed in conception, design, statistical analyses, data interpretation and manuscript drafting. All authors approved the final manuscript for submission.

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Correspondence to Parvane Saneei.

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Authors declared no personal or financial conflicts of interest.

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394_2021_2604_MOESM1_ESM.pptx

Sensitivity analysis of the effect of zinc supplementation on all-causes mortality in under 5-year children (PPTX 200 kb)

394_2021_2604_MOESM2_ESM.pptx

Funnel plot of publication bias for the effect of zinc supplementation on all-causes mortality in under 5-year children (PPTX 36 kb)

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Rouhani, P., Rezaei Kelishadi, M. & Saneei, P. Effect of zinc supplementation on mortality in under 5-year children: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr 61, 37–54 (2022). https://doi.org/10.1007/s00394-021-02604-1

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