title: Lipid-based nutrient supplements do not affect the risk of malaria or respiratory morbidity in 6- to 18-month-old Malawian children in a randomized controlled trial.
abstract: BACKGROUND
  There is evidence to support the use of lipid-based nutrient supplements (LNSs) to promote child growth and development in low-income countries, but there is also a concern regarding the safety of using iron-fortified products in malaria-endemic areas.
  
  
  OBJECTIVE
  The objective of this study was to test the hypothesis that 6- to 18-mo-old rural Malawian children receiving iron-containing (6 mg/d) LNSs would not have excess morbidity compared with infants receiving no supplementation.
  
  
  METHODS
  A randomized controlled trial allocated 840 children to receive daily supplementation with 54 g/d LNS with milk protein base (milk-LNS), 54 g/d LNS with soy protein base (soy-LNS), 71 g/d corn-soy blend (CSB), or no supplementation from 6 to 18 mo of age. Morbidity was compared using a non-inferiority margin set at 20% excess morbidity in supplemented groups compared with the nonsupplemented group.
  
  
  RESULTS
  Baseline characteristics were similar across groups. The proportion of days with febrile illness between 6 and 18 mo was 4.9%, and there were no differences between the groups: 4.9% (95% CI: 4.3, 5.5%), 4.5% (95% CI: 3.9, 5.1%), 4.7% (95% CI: 4.1, 5.3%), and 5.5% (95% CI: 4.7-6.3%) in the milk-LNS, soy-LNS, CSB, and control groups, respectively. The proportion of days with respiratory problems and diarrhea between 6 and 18 mo also did not differ between groups. Compared with controls, the incident rate ratio (95% CI) for clinical malaria was 0.80 (0.59, 1.09), 0.77 (0.56, 1.06), and 0.79 (0.58, 1.08) in milk-LNS, soy-LNS, and CSB, respectively, with 95% CIs confirming non-inferiority. The incidence of febrile episodes, diarrhea, respiratory problems or admission to hospital, prevalence of malaria parasitemia throughout the follow-up, and mean change in hemoglobin concentration from baseline were also similar between the groups.
  
  
  CONCLUSIONS
  Daily supplementation with 54 g of milk-based or soy protein-based LNS or 71 g of CSB did not result in increases in malaria or respiratory morbidity in children in a malaria-endemic setting. However, we could not conclude whether LNSs did or did not increase diarrheal morbidity. This trial was registered at clinicaltrials.gov as NCT00524446.
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi; University of Tampere School of Medicine, Tampere, Finland; cmangani@medcol.mw.
authors.forename: Charles
authors.initials: C
authors.lastname: Mangani
authors.affiliation: University of Tampere School of Medicine, Tampere, Finland; Department of Paediatrics, Tampere University Hospital, Finland, Tampere, Finland;
authors.forename: Per
authors.initials: P
authors.lastname: Ashorn
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi;
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maleta
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi;
authors.forename: John
authors.initials: J
authors.lastname: Phuka
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi; University of Tampere School of Medicine, Tampere, Finland;
authors.forename: Chrissie
authors.initials: C
authors.lastname: Thakwalakwa
authors.affiliation: University of California, Davis, Davis, CA;
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dewey
authors.affiliation: Washington University School of Medicine, St. Louis, MO;
authors.forename: Mark
authors.initials: M
authors.lastname: Manary
authors.affiliation: Ministry for Social Affairs and Health, Helsinki, Finland; and.
authors.forename: Taneli
authors.initials: T
authors.lastname: Puumalainen
authors.affiliation: Duke-National University of Singapore Graduate Medical School, National University of Singapore, Singapore, Singapore.
authors.forename: Yin Bun
authors.initials: YB
authors.lastname: Cheung
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D019587:Dietary Supplements; D006801:Humans; D007223:Infant; D007225:Infant Food / Q000032:analysis; D007227:Infant Nutritional Physiological Phenomena; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology*; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control*; D008295:Malawi / Q000453:epidemiology; D044342:Malnutrition / Q000178:diet therapy / Q000517:prevention & control; D008892:Milk / Q000737:chemistry; D012140:Respiratory Tract Diseases; D012424:Rural Population; D013025:Glycine max / Q000737:chemistry
chemical_list: D004041:Dietary Fats; D008055:Lipids