title: Effect of iron fortification on malaria incidence in infants and young children in Ghana: a randomized trial.
abstract: OBJECTIVE
  In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and iron deficiency is among the most prevalent nutritional deficiencies. In 2006, the World Health Organization and the United Nations Children's Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas.
  
  
  OBJECTIVE
  To determine the effect of providing a micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area.
  
  
  METHODS
  Double-blind, cluster randomized trial of children aged 6 to 35 months (n = 1958 living in 1552 clusters) conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia (hemoglobin level <7 g/dL), or severe wasting (weight-for-length z score <-3).
  
  
  METHODS
  Children were randomized by cluster to receive a MNP with iron (iron group; 12.5 mg/d of iron) or without iron (no iron group). The MNP with and without iron were added to semiliquid home-prepared foods daily for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated.
  
  
  METHODS
  Malaria episodes in the iron group compared with the no iron group during the 5-month intervention period.
  
  
  RESULTS
  In intention-to-treat analyses, malaria incidence overall was significantly lower in the iron group compared with the no iron group (76.1 and 86.1 episodes/100 child-years, respectively; risk ratio (RR), 0.87 [95% CI, 0.79-0.97]), and during the intervention period (79.4 and 90.7 episodes/100 child-years, respectively; RR, 0.87 [95% CI, 0.78-0.96]). In secondary analyses, these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall (adjusted RR, 0.87; 95% CI, 0.75-1.01) and during the intervention period (adjusted RR, 0.86; 95% CI, 0.74-1.00).
  
  
  CONCLUSIONS
  In a malaria-endemic setting in which insecticide-treated bed nets were provided and appropriate malaria treatment was available, daily use of a MNP with iron did not result in an increased incidence of malaria among young children.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01001871.
authors.affiliation: Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada. stanley.zlotkin@sickkids.ca
authors.forename: Stanley
authors.initials: S
authors.lastname: Zlotkin
authors.forename: Samuel
authors.initials: S
authors.lastname: Newton
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Aimone
authors.forename: Irene
authors.initials: I
authors.lastname: Azindow
authors.forename: Seeba
authors.initials: S
authors.lastname: Amenga-Etego
authors.forename: Kofi
authors.initials: K
authors.lastname: Tchum
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mahama
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Thorpe
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000453:epidemiology / Q000517:prevention & control*; D002675:Child, Preschool; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D057148:Insecticide-Treated Bednets; D007501:Iron / Q000008:administration & dosage* / Q000009:adverse effects; D008288:Malaria / Q000453:epidemiology* / Q000517:prevention & control*; D008297:Male; D012306:Risk
chemical_list: D007501:Iron