title: The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.
abstract: BACKGROUND
  Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children.
  
  
  METHODS
  A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4).
  
  
  RESULTS
  After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 μg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001).
  
  
  CONCLUSIONS
  IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.
authors.affiliation: Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland. dominik.glinz@usb.ch.
authors.forename: Dominik
authors.initials: D
authors.lastname: Glinz
authors.affiliation: Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland. richard.hurrell@hest.ethz.ch.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hurrell
authors.affiliation: Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. mamadou_ouatt@yahoo.fr.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Ouattara
authors.affiliation: Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland. michael.zimmermann@hest.ethz.ch.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zimmermann
authors.affiliation: Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, USA. gmb31@cumc.columbia.edu.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Brittenham
authors.affiliation: Hôpital Général de Taabo, Taabo Cité, Côte d'Ivoire. adiossanlukas@yahoo.fr.
authors.forename: Lukas G
authors.initials: LG
authors.lastname: Adiossan
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. aurelierighetti@gmail.com.|University of Basel, Basel, Switzerland. aurelierighetti@gmail.com.
authors.forename: Aurélie A
authors.initials: AA
authors.lastname: Righetti
authors.affiliation: Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland. seifert@ifspm.uzh.ch.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.affiliation: Université Alassane Ouattara, Bouaké, Côte d'Ivoire. sebagnoh@gmail.com.
authors.forename: Victorine G
authors.initials: VG
authors.lastname: Diakité
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. juerg.utzinger@unibas.ch.|University of Basel, Basel, Switzerland. juerg.utzinger@unibas.ch.
authors.forename: Jürg
authors.initials: J
authors.lastname: Utzinger
authors.affiliation: Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. eliezerngoran@yahoo.fr.|Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire. eliezerngoran@yahoo.fr.
authors.forename: Eliézer K
authors.initials: EK
authors.lastname: N'Goran
authors.affiliation: Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland. rwegmuller@mrc.gm.
authors.forename: Rita
authors.initials: R
authors.lastname: Wegmüller
mesh_terms: D000655:Amodiaquine / Q000008:administration & dosage / Q000627:therapeutic use; D000740:Anemia / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D007560:Cote d'Ivoire / Q000453:epidemiology; D011756:Diphosphates / Q000008:administration & dosage / Q000627:therapeutic use; D004338:Drug Combinations; D004492:Edetic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D005290:Ferric Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D005527:Food, Fortified; D006454:Hemoglobins; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000453:epidemiology; D007501:Iron / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000090463:Iron Deficiencies; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D015995:Prevalence; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D011756:Diphosphates; D004338:Drug Combinations; D005290:Ferric Compounds; D006454:Hemoglobins; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D004492:Edetic Acid; D007501:Iron; C019179:Fe(III)-EDTA; C049051:ferric pyrophosphate; D011739:Pyrimethamine