title: A double blind randomised controlled trial comparing standard dose of iron supplementation for pregnant women with two screen-and-treat approaches using hepcidin as a biomarker for ready and safe to receive iron.
abstract: Until recently, WHO recommended daily iron supplementation for all pregnant women (60 mg/d iron combined with 400ug/d folic acid) where anaemia rates exceeded 40 %. Recent studies indicate that this may pose a risk to pregnant women. Therefore, there is a need to explore screen-and-treat options to minimise iron exposure during pregnancy using an overall lower dosage of iron that would achieve equivalent results as being currently recommended by the WHO. However, there is a lack of agreement on how to best assess iron deficiency when infections are prevalent. Here, we test the use of hepcidin a peptide hormone and key regulator of iron metabolism, as a potential index for 'safe and ready to receive' iron.
  
  
  
  This is a 3-arm randomised-controlled proof-of-concept trial. We will test the hypothesis that a screen-and-treat approach to iron supplementation using a pre-determined hepcidin cut-off value of <2.5 ng/ml will achieve similar efficacy in preventing iron deficiency and anaemia at a lower iron dose and hence will improve safety. A sample of 462 pregnant women in rural Gambia will be randomly assigned to receive: a) UNU/UNICEF/WHO international multiple micronutrient preparation (UNIMMAP) containing 60 mg/d iron (reference arm); b) UNIMMAP containing 60 mg/d iron but based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not; c) or UNIMMAP containing 30 mg/d iron as in (b) for 12 weeks in rural Gambia. The study will test if the screen-and-treat approach is non-inferior to the reference arm using the primary endpoint of haemoglobin levels at a non-inferiority margin of 0.5 g/dl. Secondary outcomes of adverse effects, compliance and the impact of iron supplementation on susceptibility to infections will also be assessed.
  
  
  
  This trial is expected to contribute towards minimising the exposure of pregnant women to iron that may not be needed and therefore potentially harmful. If the evidence in this study shows that the overall lower dosage of iron is non-inferior to 60 mg/day iron, this may help decrease side-effects, improve compliance and increase safety. The potential for the use of hepcidin for a simple point-of-care (PoC) diagnostic for when it is most safe and effective to give iron may improve maternal health outcomes.
  
  
  
  ISRCTN21955180.
authors.affiliation: MRC Unit The Gambia & MRC International Nutrition Group, PO Box 273, Banjul, The Gambia. Amat.Bah@lshtm.ac.uk.
authors.forename: Amat
authors.initials: A
authors.lastname: Bah
authors.affiliation: MRC Unit The Gambia & MRC International Nutrition Group, PO Box 273, Banjul, The Gambia.
authors.forename: Rita
authors.initials: R
authors.lastname: Wegmuller
authors.affiliation: MRC Unit The Gambia & MRC International Nutrition Group, PO Box 273, Banjul, The Gambia.
authors.forename: Carla
authors.initials: C
authors.lastname: Cerami
authors.affiliation: MRC Unit The Gambia, PO Box 273, Banjul, The Gambia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kendall
authors.affiliation: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
authors.forename: Sant-Rayn
authors.initials: SR
authors.lastname: Pasricha
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge, CB1 9NL, UK.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.affiliation: MRC Unit The Gambia & MRC International Nutrition Group, PO Box 273, Banjul, The Gambia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005714:Gambia; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000008:administration & dosage*; D062145:Maternal Serum Screening Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D014131:Trace Elements / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D064451:Hepcidins; D014131:Trace Elements; D007501:Iron
keywords: Anaemia; Hepcidin; Iron deficiency; Lower dose iron; Pregnancy; UNIMMAP