Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants
Armitage, AE; Agbla, SC; Betts, M; Sise, EA; Jallow, MW; Sambou, E; Darboe, B; Worwui, A; Weinstock, GM; Antonio, M; Pasricha, SR; Prentice, AM; Drakesmith, H; Darboe, MK; Kwambana-Adams, BA
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, season and growth influenced plasma hepcidin and ferritin concentrations during infancy using longitudinal data from two birth-cohorts of rural Gambian infants (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 sTfR 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 additionally observed significant negative associations between hepcidin and antecedent weight gain. Correspondingly, longitudinal fixed effects modelling 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 most responsive to oral iron interventions.