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Ferrata Storti Foundation
Haematologica 2019 Volume 104(8):1542-1553
Iron metabolism & its Disorders
Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants
Andrew E. Armitage,1* Schadrac C. Agbla,2* Modupeh Betts,3 Ebrima A. Sise,3 Momodou W. Jallow,3 Ellen Sambou,4 Bakary Darboe,3 Archibald Worwui,3 George M. Weinstock,5 Martin Antonio,4 Sant-Rayn Pasricha,1,6,7
Andrew M. Prentice,3 Hal Drakesmith,1,8 Momodou K. Darboe3,**
and Brenda Anna Kwambana-Adams4,9,**
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; 2Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK; 3MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia, Africa; 4WHO Collaborating Center for New Vaccines Surveillance, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia, Africa; 5The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; 6Walter and Eliza Hall Institute for Medical Research, Melbourne, VIC, Australia; 7Department of Medical Biology, The University of Melbourne, VIC, Melbourne, Australia; 8Haematology Theme, Oxford Biomedical Research Centre, Oxford, UK and 9NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London, UK
*Contributed equally to this work. **Contributed equally as senior co-authors.
ABSTRACT
Iron deficiency and iron deficiency anemia are highly prevalent in low-income countries, especially among young children. Hepcidin is the major regulator of systemic iron homeostasis. It controls dietary iron absorption, dictates whether absorbed iron is made available in cir- culation for erythropoiesis and other iron-demanding processes, and pre- dicts response to oral iron supplementation. Understanding how hep- cidin is itself regulated is therefore important, especially in young chil- dren. We investigated how changes in iron-related parameters, inflam- mation and infection status, seasonality, and growth influenced plasma hepcidin and ferritin concentrations during infancy using longitudinal data from two birth cohorts of infants in rural Gambia (n=114 and n=193). This setting is characterized by extreme seasonality, prevalent childhood anemia, undernutrition, and frequent infection. Plasma was collected from infants at birth and at regular intervals, up to 12 months of age. Hepcidin, ferritin and plasma iron concentrations declined markedly during infancy, with reciprocal increases in soluble transferrin receptor and transferrin concentrations, indicating declining iron stores and increasing tissue iron demand. In cross-sectional analyses at 5 and 12 months of age, we identified expected relationships of hepcidin with iron and inflammatory markers, but also observed significant negative associations between hepcidin and antecedent weight gain. Correspondingly, longitudinal fixed effects modeling demonstrated weight gain to be the most notable dynamic predictor of decreasing hep- cidin and ferritin through infancy across both cohorts. Infants who grow rapidly in this setting are at particular risk of depletion of iron stores, but since hepcidin concentrations decrease with weight gain, they may also be the most responsive to oral iron interventions.
Correspondence:
ANDREW E. ARMITAGE/BRENDA ANNA KWAMBANA-ADAMS andrew.armitage@imm.ox.ac.uk/ rekgbak@ucl.ac.uk
Received: October 25, 2018. Accepted: January 31, 2019. Pre-published: February 7, 2019.
doi:10.3324/haematol.2018.210146
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/8/1542
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