Albertine Donker

Chapter 2 50 ABSTRACT Iron is indispensable for human life. However, iron is also a potential toxicant to cells since unbound iron can catalyze the formation of harmful oxidative radicals. Moreover, iron makes the human body an attractive host for iron-dependent pathogens. Therefore, iron homeostasis is tightly regulated both on the systemic and cellular level in order to prevent both iron deficiency and overload. The opposing forces regarding iron metabolism are even more critical for children than for adults. Rapid growth and development during childhood requires large amounts of iron, while (especially young) children are vulnerable to infections with iron-dependent pathogens because of a still immature immune system. Moreover, both iron deficiency and iron excess early in life may have longlasting effects on the central nervous system, the immune system and the gut microbiota that persist into adulthood. In this narrative review we assess the critical roles of iron for growth and development and how the human body adapts to the physiological high iron demands during the journey from fetus to adult, with a focus on the systemic level. We finally summarize unmet needs and research ideas exploring the developmental aspects of iron homeostasis, as a first step on the road to the development of clinical guidelines on a balanced iron supply and on the accurate diagnosis and treatment of iron disorders of the growing and developing child. Key words iron metabolism, fetus, neonate, adolescent, developmental, hepcidin