Albertine Donker

Chapter 7 250 a significant increase. 21 Altogether, our data suggest that the set point of serum hepcidin relative to indicators of stored and circulating iron changes during human growth and development. Until now, lack of harmonization and standardization of hepcidin measurements 51 has hampered comparison with other hepcidin reference studies in children. 24,26,27 To some extent, comparison is possible with the data obtained by Uijterschout et a l 25 from children aged 0.5-3 years (n=400). They used the same assay as we did, before standardization. However, standardization only slightly altered its values, i.e. standardized results were found to be a factor 1.054351 higher compared to historic results obtained without standardization. In their study median hepcidin was slightly higher (3.6 nmol/L; p2.5-p97.5 0.6-13.9 nmol/L) than in our age group of 0-<2 years (n=17) (1.8 nmol/L; p2.5-p75 0.2-6.3 nmol/L), with overlapping ranges. The finding of ferritin as the most important indicator of serum hepcidin concentration after adjustment for sampling time, and age was consistent between the study of Uijterschout et al and our study. The strength of our study is the unique and well-defined population (e.g. no underlying disease, CRP< 5 mg/L), covering the range from infancy to adolescence. We established hepcidin values relative to indicators of iron status, described in ratios, enabling diagnosis of iron loading and iron deficiency disorders. Moreover, we used an assay that was standardized using a recently validated and value assigned 2 nd RM. 22 Therefore, the here-defined values can be used by all other analytically validated hepcidin assays that are standardized using the same RM. Our study has several limitations. First, young children, children of non-Western European descent and children with under- and overweight were underrepresented. Second, we used age > 12 years as a proxy for the discrimination between prepuberal and postpuberal stage which might not be accurate in all children. Furthermore, our study population might contain children with undiagnosed iron related disorders like IRIDA, or hereditary hemochromatosis, since we performed no genotyping of TMPRSS6 and HFE in the subjects. However, given the low prevalence of these disorders, 52,53 we expect only a few of these cases, if any, among our participants.