Abstract
BackgroundHepcidin, a key regulator of iron homeostasis, is increased in response to inflammation and some infections, but the in vivo role of hepcidin, particularly in children with iron deficiency anemia (IDA) is unclear. We investigated the relationships between hepcidin, cytokines and iron status in a pediatric population with a high prevalence of both anemia and co-morbid infections.Methodology/Principal FindingsAfrican refugee children <16 years were consecutively recruited at the initial post-resettlement health check with 181 children meeting inclusion criteria. Data on hematological parameters, cytokine levels and co-morbid infections (Helicobacter pylori, helminth and malaria) were obtained and urinary hepcidin assays performed. The primary outcome measure was urinary hepcidin levels in children with and without iron deficiency (ID) and/or ID anaemia (IDA). The secondary outcome measures included were the relationship between co-morbid infections and (i) ID and IDA, (ii) urinary hepcidin levels and (iii) cytokine levels. IDA was present in 25/181 (13.8%). Children with IDA had significantly lower hepcidin levels (IDA median hepcidin 0.14 nmol/mmol Cr (interquartile range 0.05–0.061) versus non-IDA 2.96 nmol/mmol Cr, (IQR 0.95–6.72), p<0.001). Hemoglobin, log-ferritin, iron, mean cell volume (MCV) and transferrin saturation were positively associated with log-hepcidin levels (log-ferritin beta coefficient (β): 1.30, 95% CI 1.02 to 1.57) and transferrin was inversely associated (β: −0.12, 95% CI −0.15 to −0.08). Cytokine levels (including IL-6) and co-morbid infections were not associated with IDA or hepcidin levels.Conclusions/SignificanceThis is the largest pediatric study of the in vivo associations between hepcidin, iron status and cytokines. Gastro-intestinal infections (H. pylori and helminths) did not elevate urinary hepcidin or IL-6 levels in refugee children, nor were they associated with IDA. Longitudinal and mechanistic studies of IDA will further elucidate the role of hepcidin in paediatric iron regulation.
Highlights
Iron deficiency anemia (IDA) is one of the commonest nutritional deficiencies globally, with young children, women of childbearing age and pregnant women at highest risk [1]
Our findings suggest that such a phenomenon is uncommon in African children who have a high prevalence of both iron deficiency anemia (IDA) and H. pylori infection, but show no relationship between the two diagnoses
We found that anemia was not increased in those with H. pylori infection, which showed no relationship with hepcidin, and our data do not support the proposal that hepcidin is the primary mechanism of H. pylori-induced anemia [8]
Summary
Iron deficiency anemia (IDA) is one of the commonest nutritional deficiencies globally, with young children, women of childbearing age and pregnant women at highest risk [1]. Nutritional deficiencies are prevalent in resettled pediatric refugees, who often have significant co-morbidities (including acute chronic infection and/or hemoglobinopathies) which may exacerbate IDA [4]. It has been proposed that the refractory IDA associated with Helicobacter pylori infection may be mediated by inflammation-driven hepcidin production [8]. There are few in vivo human data, in children, to substantiate these putative roles of hepcidin in either IDA or in infections. A key regulator of iron homeostasis, is increased in response to inflammation and some infections, but the in vivo role of hepcidin, in children with iron deficiency anemia (IDA) is unclear. We investigated the relationships between hepcidin, cytokines and iron status in a pediatric population with a high prevalence of both anemia and co-morbid infections
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