Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children

Abstract

Iron deficiency is the most common micronutrient deficiency in the world. Women of reproductive age and young children are particularly vulnerable. Iron deficiency in late prenatal and early postnatal periods can lead to long-term neurobehavioral deficits, despite iron treatment. This may occur because screening and treatment of iron deficiency in children is currently focused on detection of anemia and not neurodevelopment. Anemia is the end-stage state of iron deficiency. The brain becomes iron deficient before the onset of anemia due to prioritization of the available iron to the red blood cells (RBCs) over other organs. Brain iron deficiency, independent of anemia, is responsible for the adverse neurological effects. Early diagnosis and treatment of impending brain dysfunction in the pre-anemic stage is necessary to prevent neurological deficits. The currently available hematological indices are not sensitive biomarkers of brain iron deficiency and dysfunction. Studies in non-human primate models suggest that serum proteomic and metabolomic analyses may be superior for this purpose. Maternal iron supplementation, delayed clamping or milking of the umbilical cord, and early iron supplementation improve the iron status of at-risk infants. Whether these strategies prevent iron deficiency-induced brain dysfunction has yet to be determined. The potential for oxidant stress, altered gastrointestinal microbiome and other adverse effects associated with iron supplementation cautions against indiscriminate iron supplementation of children in malaria-endemic regions and iron-sufficient populations.

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

“…Overall, our findings are consistent with those of previous studies demonstrating the potential importance of maternal iron status in fetal programming and lifelong health [3][4][5][6]13,20,25,[55][56][57]. Although a previous review concluded that maternal nutritional status has no effect on offspring neurodevelopmental outcomes, [28] differences in iron status indicators, iron measurements during pregnancy, and the domains assessed [58] could explain some of these inconsistencies.…”

The Effects of Delayed Cord Clamping on 12-Month Brain Myelin Content and Neurodevelopment: A Randomized Controlled Trial

“…ID can result in epigenetic changes via both deoxyribonucleic acid methylation and histone modification pathways potentially leading to the negative long-term neurodevelopmental impact seen in children with ID in infancy. 16,33 Infants in this study who received DCC left less blood (34%) behind in the placenta compared to those who had ICC. This confirms a placental transfusion occurred with DCC.…”

Perinatal Iron Deficiency: Implications for Mothers and Infants

“…Permanent ID-related neurodevelopmental delays might occur well before anemia is present. Ferritin, zinc protoporphyrin to heme ratios, and reticulocyte hemoglobin content are more sensitive tests in the neonate [19-22]. …”