Albertine Donker

Chapter 2 74 a mean chronologic age of 11.5 years. Boys grow a mean of 28 cm, and girls grow 25 cm between takeoff and cessation of growth, according to a study performed in the United Kingdom. 6 The pubertal growth spurt is accompanied by a large increase of circulating blood volume, from on average 2800 mL in an 11-years male to 4500 mL in a 17-years male, requiring an increase of approximately 1000 mg iron dedicated to erythopoiesis alone (see also Figure 1, Table 2 ). Iron stores relatively decrease during adolescence related to the progression of genital stages, as concluded from a decrease in serum ferritin levels and an increase in the ratio soluble transferrin receptor/ferritin. 197,198 Growth during the pubertal phase largely depends on the direct and indirect effects of the gonadal steroids estrogen and testosterone. Direct effect of the gonadal steroids involve the stimulation of the production of IGF1 and other growth factors locally in the bone. Indirect effects involve the induction of GH secretion by sex steroids. Both mechanisms result in a considerable increase in length during puberty. 6,57 During adolescence hepcidin levels decrease in response to stimulation of endogenous production of both estrogens and testosterone. 7 This suggests a regulatory mechanism in order to adapt to increased iron demands due to rapid growth and development during puberty in both boys and girls and due to menstrual blood loss in girls. 196,199 This corroborates our results of a study on serum hepcidin values recently performed in Dutch children, showing a significant decrease of serum hepcidin relative to indicators of stored and circulating iron after the age of 12 years (www.hepcidinanalysis.com 42 ). 43 Overall aspects of developmental aspects of iron metabolism from fetus to adult Iron is crucial during the journey from fetus to adult. The growing child is dependent on iron for the huge expansion of the blood volume during childhood and for the maturation of many organs and physiological systems including the skeleton, the brain, the immune system and the gut microbiota. According to results of MRI imaging, especially the iron content of the brain is thought to considerably increase during childhood and adolescence. 78 Morover, hormonal systems that highly influence growth during childhood, as the thyroid and GH system, are associated with iron status. Therefore, in children iron demands are relatively high, compared to adults ( Figure 1, Table 2 ). Unbalanced iron status during critical iron-dependent windows