Zinc or Multiple Micronutrient Supplementation to Reduce Diarrhea and Respiratory Disease in South African Children: A Randomized Controlled Trial

Kany-Kany Angelique Luabeya,Jan Van Den Broeck,Inga Elson,Meera Chhagan,Andrew Tomkins,Michael L Bennish,Malanie Mackay,Nontobeko Mpontshane,Honorine Ward,Jose M Belizan

doi:10.1371/journal.pone.0000541

Abstract

BackgroundProphylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain.ObjectiveTo determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence.DesignRandomized, double-blind, controlled trial.SettingRural community in South Africa.ParticipantsThree cohorts: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers.InterventionsChildren received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly.Outcome MeasuresPrimary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker.ResultsAmong HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts.ConclusionWhen compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.Trial RegistrationClinicalTrials.gov NCT00156832

Highlights

Micronutrient deficiencies are common in children in developing countries, including children in South Africa.[1,2,3] Zinc deficiency is especially thought to be associated with an increased susceptibility to infection, and a greater severity of disease when infection occurs.[4]
Uninfected children born to HIV-infected mothers, information was missing for 2 children in the vitamin A group and 2 children in the multiple micronutrient group
In the cohort of HIV-uninfected children born to HIV-infected mothers, hemoglobin determinations were not available for 26 children who received vitamin A, 28 children who received vitamin A+zinc, and 20 children who received multiple micronutrients

Summary

Introduction

Micronutrient deficiencies are common in children in developing countries, including children in South Africa.[1,2,3] Zinc deficiency is especially thought to be associated with an increased susceptibility to infection, and a greater severity of disease when infection occurs.[4]. Zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence. Among HIV-uninfected children born to HIVinfected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIVuninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in children in the vitamin A group; 1.8% in children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.

Objectives

Methods

Results

Conclusion