Albertine Donker

Iron Function and Iron Handling from Fetus to Adult 69 2 Iron and fetal epigenetic programming Importantly, environmental factors (maternal health, placental function, stress, life style, nutrients and also paternal diet 139 ) that affect growth and development in early life can profoundly influence human biology and long-term health by epigenetic mechanisms of gene regulation that may be inheritable and passed on to the next generation. 124 Undernutrition in utero and stress are well-documented examples of conditions that increase the risk of metabolic disease as type II diabetes and cardiovascular disease, known as the Barker-hypothesis or Barker mismatch paradigm. 140,141 The fetus or young infants adequately adapts to maternally transmitted environmental challenges as undernutrition or stress by changing metabolic set points via epigenetic programming of the expression of relevant genes, which persist into adulthood (i.e. metabolic memory). If these adaptations are functional in the mature environment of the older child and adult, the risk of metabolic disease is low. However, if these adaptations are not functional, e.g. the mature environment does not match the prenatal and early life environment, the risk of metabolic disease increases. 124,140 Since both maternal anemia and ID negatively influence fetal growth, these conditions are suggested to increase the risk of adult hypertension of the offspring. 123,142,143 Furthermore, in rodents, several genes involved in hippocampal plasticity, change their expression profiles in response to early ID. 79,144,145 Whether exposure to inadequately low or high iron status in early life affects the expression of systemic iron regulation genes is unclear. Iron and infancy Iron status during the neonatal period At birth, maternal iron status accounts for 6% of the variants in infant stores and birth, and the remaining causes in the highly variable size of birth iron endowment are unknown, but likely include gestational age, intrauterine growth restriction, time of cord clamping, maternal smoking habits and diabetes. 125,146,147 After the fetal period, characterized by large iron requirements, iron demands remain high to meet the quantities needed for the rapid growth of the newborn and the concomitant increase of circulating blood volume. Weight and height increase approximately 15-20 mg/kg/day during the first months and approximately 25 cm in the first year and 12.5 cm in the second year of life, respectively, with height velocity