Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials123

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ABSTRACT

Background:

Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea.

Objective:

We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea.

Design:

We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models.

Results:

Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations.

Conclusion:

Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

KEY WORDS

Diarrhea
diarrheal disease
malnutrition
meta-analysis
randomized controlled trial
zinc
children
infants
developing countries
zinc supplementation
nutrition
zinc deficiency

Cited by (0)

1

From the Aga Khan University Medical Centre, Karachi, Pakistan; the Medical Research Council Biostatistics Unit, Cambridge, United Kingdom; the Johns Hopkins School of Public Health, Baltimore; the University of California, Davis; the University of the West Indies, Mona, Jamaica; Trisakti University, Jakarta, Indonesia; Dhaka Medical College, Dhaka, Bangladesh; Emory University, Atlanta; the National Institute of Nutrition, Hanoi, Vietnam; the Nutrition Research Institute, Lima, Peru; the National Institute of Nutrition, Mexico City; the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh; the Institute of Nutrition of Central America and Panama, Guatemala City; and the All India Institute of Medical Sciences, New Delhi.

2

Supported by the Johns Hopkins Family Health and Child Survival Cooperative Agreement with the US Agency for International Development and the World Health Organization, Division of Child Health and Development, which provided support for the pooled analysis. REB drafted the manuscript while in residence at the Rockefeller Foundation Bellagio Study and Conference Center.

3

Address reprint requests to RE Black, Department of International Health, The Johns Hopkins School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205. E-mail: [email protected].