Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa

BACKGROUND: The efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of HIV-exposed children. Potential modifying factors such as stunting need addressing. OBJECTIVE: To determine whether adding zinc, or zinc plus multiple micronutrients, to vitamin A reduces diarrhoea incidence, and whether this differs between strata of stunted or HIV-infected children. METHODS: We analyzed data from a randomized, controlled double-blinded trial (ClinicalTrials.gov NCT00156832) of prophylactic micronutrient supplementation to children aged 6–24 months. Three cohorts of children: 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers, received vitamin A, vitamin A plus zinc, or multiple micronutrients that included vitamin A and zinc. The main outcome was incidence of diarrhoea. Poisson regression was used in intent-to-treat analyses. Stratified analyses followed testing for statistical interaction between intervention and stunting. RESULTS: We observed no significant differences in overall diarrhoea incidence among treatment arms. Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence if supplemented with zinc or multiple micronutrients compared to vitamin A alone (2.04 and 2.23 vs 3.92 episodes/year respectively, P=0.024). No meaningful sub-group analyses could be done in the cohort of HIV-infected children. CONCLUSION: Compared with vitamin A alone, supplementation with zinc, and with zinc and multiple micronutrients, reduced diarrhoea morbidity in stunted rural South African children. Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups.