Albertine Donker

Iron Function and Iron Handling from Fetus to Adult 67 2 DEVELOPMENTAL ASPECTS OF IRON ANDIRONHANDLINGFROMFETUSTOADULT Maturation of iron handling during growth and development As reviewed in the second section, hepcidin plays a crucial role in systemic iron homeostasis. Noteworthy, serum hepcidin levels reflect the integration of various (opposing) signals important for systemic iron homeostasis, and the relative contribution of these stimuli, such as the above-mentioned hormones, might differ from those in adults, requiring further elucidation of iron handling in childhood. In order to assess iron handling in childhood, we recently performed a study on serum hepcidin values in childhood, relative to ferritin and transferrin saturation, in Dutch children aged 0.3-17 years. We found that hepcidin values, hepcidin/ferritin and TSAT/ hepcidin ratios in children between the age of 0.3-17 years were age dependent, suggesting a changing set point of serum hepcidin relative to stored and circulating iron. (www.hepcidinanalysis.com 4 2 ). 43 Furthermore, while in adults the majority of iron is dedicated to hemoglobin synthesis, 11 distribution of iron between the different iron-demanding might differ and mature between during childhood. One clinical study indicated that iron distribution between the erythropoietic system and storage compartment changes during childhood, since dietary iron intake was positively associated with hemoglobin levels in infants aged 9-12 months, while it was positively associated with serum ferritin levels in toddlers aged 12-17 months. 9 This suggests a maturation process regarding the channeling of iron inside the human body to either the bone marrow or the liver and spleen. 9 Moreover, in vitro studies suggest the existence of protection mechanisims during periods of low iron supply; in case of ID erythropoiesis was suppressed with return of iron from the bone marrow into the circulation, probably in order to protect other vital iron-dependent organ systems from an iron deficit. 89,98-100 Whether such survival strategies also occur during human early life is unclear. However, several animal and human studies suggest that during the fetal and infant period, iron is prioritized to the erythroblasts over all other organ systems, including the central nervous system, irrespective of a negative iron balance. 77