Albertine Donker

Standardized Pediatric Hepcidin Values 249 7 ability to shut down ferroportin and limit the export of iron from the intestines and the macrophages into the circulation, it has an important role in the innate immune system. 45 We hypothesize that the high hepcidin levels in young children, relative to adolescents might result in a survival advantage during a critical period of high vulnerability for serious infections. 44,45 We observed a positive correlation of CRP levels (between 0.1 and 5 mg/L) with serum hepcidin levels, suggesting that, as described earlier, 46 even minor infections and/or inflammation induce hepcidin production in children, consistent with the suggested protective antimicrobial activity of hepcidin. 2 Importantly, the relatively high hepcidin levels for ferritin in young children as compared to adolescents did not result in IDA in these subjects, despite the enormous growth during infancy that is accompanied by a considerable increase of circulating blood volume and other tissues requiring iron. Studies in suckling mice suggest that enterocyte ferroportin is hyporesponsive to hepcidin during infancy. 47 Alterations to ferroportin that prevent hepcidin binding during suckling may allow iron absorption to remain sufficient regardless of hepcidin expression levels, reducing the likelihood of iron deficiency during development. 47 Whether in young children ferroportin is still functional in the presence of increased hepcidin levels, as seen in infant mice, remains to be investigated. In both males and females hepcidin levels were considerably lower after the age of 12 years, dropping below normal adult levels 21 , suggesting a different regulation of hepcidin production during adolescence. We suggest that the decrease in hepcidin levels in older children can be attributed to the direct influence of the gonadal hormones testosterone, 48 estrogens, 49 and also to the indirect influence of these hormones since both testosterone and estrogen stimulate growth hormone/IGF-1 secretion, which in turn inhibits hepcidin production. 50 The relatively low hepcidin levels in relation to body iron status in post-pubertal compared to pre-pubertal children might reflect an adaptation in order to guarantee sufficient iron in this period of rapid development and maturation. Compared with adults, young children have relatively high and children > 12 years relatively low hepcidin/ferritin ratios. 21 TSAT/hepcidin ratios in our population are comparable to those in adults until the age of 12 years. Thereafter we observe