title: Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa.
abstract: OBJECTIVE
  The efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of human immunodeficiency virus (HIV)-exposed children. Potential modifying factors, such as stunting, need to be addressed. The objective of this study was to determine whether adding zinc or zinc plus multiple micronutrients to vitamin A reduces diarrhoea incidence, and whether this differs between the 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, which 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 when supplemented with zinc or multiple micronutrients compared with vitamin A alone (2.04 and 2.23 vs 3.92 episodes/year, respectively, P=0.024). No meaningful subgroup analyses could be done in the cohort of HIV-infected children.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Private Bag 7, Congella, 4013, South Africa. chhagan@ukzn.ac.za
authors.forename: M K
authors.initials: MK
authors.lastname: Chhagan
authors.forename: J
authors.initials: J
authors.lastname: Van den Broeck
authors.forename: K-Ka
authors.initials: KK
authors.lastname: Luabeya
authors.forename: N
authors.initials: N
authors.lastname: Mpontshane
authors.forename: K L
authors.initials: KL
authors.lastname: Tucker
authors.forename: M L
authors.initials: ML
authors.lastname: Bennish
mesh_terms: D015331:Cohort Studies; D003968:Diarrhea, Infantile / Q000453:epidemiology* / Q000517:prevention & control; D019587:Dietary Supplements; D004311:Double-Blind Method; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D005942:Gluconates / Q000627:therapeutic use; D006130:Growth Disorders / Q000150:complications*; D015658:HIV Infections / Q000150:complications; D006801:Humans; D015994:Incidence; D007223:Infant; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018977:Micronutrients / Q000009:adverse effects / Q000627:therapeutic use*; D009748:Nutrition Disorders / Q000517:prevention & control; D012424:Rural Population; D013019:South Africa; D014801:Vitamin A / Q000008:administration & dosage / Q000627:therapeutic use*; D015032:Zinc / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005296:Ferrous Compounds; D005942:Gluconates; D018977:Micronutrients; D014801:Vitamin A; D007501:Iron; D015032:Zinc; C030691:gluconic acid; C031621:ferrous fumarate