Albertine Donker

Chapter 2 64 Animal studies indicate that both ID and iron excess early in life negatively influence the growth and maturation of the brain, whereby the severity of the neurodevelopmental deficit depends on timing, severity and duration of aberrant iron levels. 79,80 There are also growing concerns about the effects of excessive iron exposure early in life on brain ageing and the development of neurodegenerative disease. 81-83 Based on these animal studies, ID with and without IDA but also iron excess that occurs during the brain growth spurt in early life is thought to have negative and longlasting effects on the mental and psychomotor development of the child. 84-91 Placebo-controlled randomized clinical studies on the effect of iron supplementationin infants and toddlers with IDA show no convincing evidence for a positive effect on psychomotor or coginitive skills within 1-4 months. 92,93 This might indicate that data from rodent studies regarding the negatieve effects of ID on the central nervous system cannot be extrapolated to human infants directly, or that critical iron-dependent windows of brain development have already passed at this age, making it inpossible to correct the ID-related neurodevelopmental deficits, consistent with the above- mentioned theory. Of note, exposure to iron-fortified formula at infant age might even result 94 in poorer cognitive outcomes than exposure to low-iron formula feeding. 95,96 Theses data underscore the importance of accurate iron supplementation in infancy. However, the optimal level of iron suppletion is unclear for this age. Another important question is if and how the human body prioritizes the available iron between bone marrow, brain and other iron-dependent tissues during critical periods of growth and development and during periods of scarcity of micronutrients including iron. Isotope studies show that in adults approximately 80% of the absorbed iron is incorporated into the red blood cells, while this percentage is much lower (~50%) in infants, suggesting that the distribution of iron between the different iron- demanding organ systems is age dependent. 97 Furthermore, in vitro studies suggest partly suppression of erythropoiesis and return of iron from the bone marrow to the circulation during periods of limited iron supply in order te protect the brain and other vital iron-dependent organs with iron. 89,98-100 However, several animal and human studies suggest that in case of a negative iron balance during the fetal and infant period, iron is still prioritized to the erythroblasts over all other organ systems, including the central nervous system. 77 Importantly, accesible biomarkers in serum, saliva, urine of CSF that