Albertine Donker

Chapter 2 68 In this fourth section we review the various challenges regarding iron and the known insights regarding iron handling for the fetus, infant (0 – 2-3 years), child (2-3 – 11-12 years) and adolescent (11-12 years – 17 years). Iron and the fetal period Iron requirements in utero The greatest increase in body weight, length and brain mass occurs during fetal life; the velocity of in utero linear growth is maximal at about 18 weeks of gestational age in the human. At this time, the fetus grows four times more rapidly than at any time postnatal. Increases in body weight follow a similar temporal pattern. The maternal-placental environment in which the fetus develops is a critical factor in this process. A sufficient supply of micronutrients, including iron, from the mother to the fetus is a prerequisite to obtain this phenomenal growth. 5,6,123,124 A term fetus requires approximately 270 mg 125,126 of iron and the placenta 90 mg 127 (reviewed in 128 ). Approximately 80% of fetal iron accrues in the last trimester of pregnancy by active placental transport from the mother to the fetus, rendering premature infants susceptible to ID and IDA at birth. 129 ( Figure 1 ) Maternal and fetal hepcidin are involved in iron sensing and iron transport in utero Under most circumstances, maternal iron status modulates the expression of placental iron transport in favor of the fetal demands. In healthy pregnancy, hepcidin increases in the first 130 trimester but then decreases till nearly undetectable levels during the second 130 and third trimester 131,132 in order to enhance iron availability. However, evidence exists that the regulatory system can no longer sustain sufficient transfer of iron from the mother to the fetus in case of severely exhausted maternal iron status, resulting in fetal ID that is associated with preterm labor, low birth weight or even fetal death. 133-136 This is a major problem in low- and middle income countries, 60 but might also occur in high income countries due to vegetarian and vegan diet habits during pregnancy. 137 Besides maternal also placental and fetal signals play a role in iron sensing and transport from the mother to the fetus. 128 Fetal hepcidin could influence placental iron transfer, 126,128 but how the systemic and local mechanisms regulate this is largely unknown, 126,128,129,131,135,138 as well as the molecular pathways of iron trafficking in the placenta on the cellular level. 126,128,138