title: Efficacy and safety of hepcidin-based screen-and-treat approaches using two different doses versus a standard universal approach of iron supplementation in young children in rural Gambia: a double-blind randomised controlled trial.
abstract: Iron deficiency prevalence rates frequently exceed 50 % in young children in low-income countries. The World Health Organization (WHO) recommended universal supplementation of young children where anaemia rates are >40 %. However, large randomized trials have revealed that provision of iron to young children caused serious adverse effects because iron powerfully promotes microbial growth. Hepcidin - the master regulator of iron metabolism that integrates signals of infection and iron deficiency - offers the possibility of new solutions to diagnose and combat global iron deficiency. We aim to evaluate a hepcidin-screening-based iron supplementation intervention using hepcidin cut-offs designed to indicate that an individual requires iron, is safe to receive it and will absorb it.
  
  
  
  The study is a proof-of-concept, three-arm, double blind, randomised controlled, prospective, parallel-group non-inferiority trial. Children will be randomised to receive, for a duration of 12 weeks, one of three multiple micronutrient powders (MNP) containing: A) 12 mg iron daily; B) 12 mg or 0 mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not; C) 6 mg or 0 mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not. The inclusion criteria are age 6-23 months, haemoglobin (Hb) concentration between 7 and 11 g/dL, z-scores for Height-for-Age, Weight-for-Age and Weight-for-Height > -3 SD and free of malaria. Hb concentration at 12 weeks will be used to test whether the screen-and-treat approaches are non-inferior to universal supplementation. Safety will be assessed using caregiver reports of infections, in vitro bacterial and P. falciparum growth assays and by determining the changes in the gut microbiota during the study period.
  
  
  
  A screen-and-treat approach using hepcidin has the potential to make iron administration safer in areas with widespread infections. If this proof-of-concept study shows promising results the development of a point-of-care diagnostic test will be the next step.
  
  
  
  ISRCTN07210906 , 07/16/2014.
authors: MRC Unit The Gambia/MRC International Nutrition Group, Keneba, The Gambia. rwegmuller@mrc.gm.
authors: Rita
authors: 0000-0002-0269-1939
authors: R
authors: Wegmüller
authors: MRC Unit The Gambia/MRC International Nutrition Group, Keneba, The Gambia.
authors: Amat
authors: A
authors: Bah
authors: MRC Unit The Gambia, Fajara, The Gambia.
authors: Lindsay
authors: L
authors: Kendall
authors: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors: Morgan M
authors: MM
authors: Goheen
authors: MRC Unit The Gambia, Fajara, The Gambia.
authors: Sarah
authors: S
authors: Mulwa
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors: Carla
authors: C
authors: Cerami
authors: Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, 8092, Zurich, Switzerland.
authors: Diego
authors: D
authors: Moretti
authors: MRC Unit The Gambia/MRC International Nutrition Group, Keneba, The Gambia.
authors: Andrew M
authors: AM
authors: Prentice
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D003906:Developing Countries; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D005500:Follow-Up Studies; D005714:Gambia; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007223:Infant; D008297:Male; D008403:Mass Screening / Q000379:methods; D018977:Micronutrients / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D012423:Rural Health; D019035:Rural Health Services
chemical_list: D015415:Biomarkers; D005296:Ferrous Compounds; D006454:Hemoglobins; D064451:Hepcidins; D018977:Micronutrients; C031621:ferrous fumarate
keywords: Anaemia; Children; Gambia; Hepcidin; Iron deficiency; Iron deficiency anaemia; Iron supplementation; Safety; Sub-Saharan Africa