The Effects of Maternal Iron Deficiency and Iron Deficiency Anemia on the Developing Fetal and Neonatal Brain

Iron is an essential micronutrient for fetal and postnatal neurodevelopment because of its role in critical neurologic processes, including myelination, monoamine neurotransmitter metabolism, neuronal adenosine triphosphate generation and structural development, and epigenetic modification of synaptic plasticity genes and networks. All these processes begin in the fetal stage and are at risk when the fetus is iron-deficient. Pregnancy places a tremendous negative strain on maternal iron status because of the expansion of her blood volume, coupled with placental and fetal iron demand. Fetal iron deficiency occurs as a function of multiple common gestational conditions, including maternal iron deficiency, intrauterine growth restriction, premature delivery, and maternal glucose intolerance. Maternal iron deficiency in the first 2 trimesters increases the risk of low birthweight, which, irrespective of fetal iron status, is a risk to neurodevelopment. It also increases the risk of autism and schizophrenia, whereas third trimester iron deficiency is associated with long-term neurocognitive deficits. Fetal iron underloading also increases the risk of postnatal iron deficiency and its attendant short and long-term neurodevelopmental consequences. Current studies are attempting to establish maternal iron status action thresholds early in pregnancy to trigger iron interventions that would better ensure adequate fetal iron status and protect the developing fetal brain. One study demonstrates that a maternal serum ferritin >60 mcg/L is necessary at 15 weeks gestation to ensure adequate fetal loading throughout pregnancy and protect neurodevelopment. In low- and middle-income countries, where moderate to severe iron deficiency is common, early pregnancy iron interventions generally improve maternal status, but it is unclear whether the improvement is sufficient to protect the fetal brain and the child's neurodevelopment.