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Haematologica. 2019 Aug;104(8):1542-1553. doi: 10.3324/haematol.2018.210146. Epub 2019 Feb 7.

Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants.

Author information

1
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK andrew.armitage@imm.ox.ac.uk rekgbak@ucl.ac.uk.
2
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
3
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia, Africa.
4
WHO Collaborating Center for New Vaccines Surveillance, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia, Africa.
5
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
6
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
7
Walter and Eliza Hall Institute for Medical Research, Melbourne, VIC, Australia.
8
Department of Medical Biology, The University of Melbourne, VIC, Melbourne, Australia.
9
Haematology Theme, Oxford Biomedical Research Centre, Oxford, UK.
10
WHO Collaborating Center for New Vaccines Surveillance, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia, Africa andrew.armitage@imm.ox.ac.uk rekgbak@ucl.ac.uk.
11
NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London, UK.

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 circulation for erythropoiesis and other iron-demanding processes, and predicts response to oral iron supplementation. Understanding how hepcidin is itself regulated is therefore important, especially in young children. We investigated how changes in iron-related parameters, inflammation 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 hepcidin 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.

PMID:
30733275
DOI:
10.3324/haematol.2018.210146
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