title: Iron-containing micronutrient powder provided to children with moderate-to-severe malnutrition increases hemoglobin concentrations but not the risk of infectious morbidity: a randomized, double-blind, placebo-controlled, noninferiority safety trial.
abstract: BACKGROUND
  A link between the provision of iron and infectious morbidity has been suggested, particularly in children with malnutrition. Two meta-analyses concluded that iron is not harmful, but malnourished children were underrepresented in most available studies.
  
  
  OBJECTIVE
  This study evaluated the effect of iron-containing micronutrient powder (iron MNP) on infectious morbidities when provided to children with moderate-to-severe malnutrition and anemia.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, noninferiority safety trial using a 2-mo course of daily iron MNP or placebo powder (PP) was conducted in 268 Bangladeshi children aged 12-24 mo with moderate-to-severe malnutrition (weight-for-age z score ≤ -2) and a hemoglobin concentration between 70 and 110 g/L. The primary endpoint was a composite of diarrhea, dysentery, and lower respiratory tract infection episodes (DDL) recorded through home visits every 2 d during the intervention and then weekly for 4 mo. The noninferiority margin was 1.2. Secondary endpoints included hemoglobin and anthropometric changes at 2 and 6 mo. All deaths and hospitalizations were documented. To capture seasonal variation, the study was repeated in the winter and summer with 2 distinct groups. An intention-to-treat analysis of recurrent events was performed by using the univariate Anderson-Gill model.
  
  
  RESULTS
  The baseline characteristics of the subjects were similar. Analysis of phase-aggregated DDL data showed that iron MNP was not inferior to PP (relative risk: 0.81; 95% CI: 0.62, 1.04) and improved hemoglobin concentrations (P < 0.0001). We recorded no deaths, and hospitalizations were rare.
  
  
  CONCLUSIONS
  Iron MNP is safe and efficacious when provided to children aged 12-24 mo with moderate-to-severe malnutrition and anemia. This trial is registered at clinicaltrials.gov as NCT00530374.
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemaire
authors.forename: Qazi Shafayetul
authors.initials: QS
authors.lastname: Islam
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.forename: Marufa Aziz
authors.initials: MA
authors.lastname: Khan
authors.forename: Monira
authors.initials: M
authors.lastname: Parveen
authors.forename: Fahmida
authors.initials: F
authors.lastname: Abedin
authors.forename: Farhana
authors.initials: F
authors.lastname: Haseen
authors.forename: Ziauddin
authors.initials: Z
authors.lastname: Hyder
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Zlotkin
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000188:drug therapy; D004311:Double-Blind Method; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007223:Infant; D017053:Infection Control; D007239:Infections / Q000209:etiology*; D007501:Iron / Q000008:administration & dosage*; D044342:Malnutrition / Q000097:blood / Q000188:drug therapy*; D018977:Micronutrients / Q000008:administration & dosage* / Q000627:therapeutic use; D009017:Morbidity; D011208:Powders; D011446:Prospective Studies; D012306:Risk
chemical_list: D006454:Hemoglobins; D018977:Micronutrients; D011208:Powders; D007501:Iron