Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction.
Bibliographical noteFunding Information:
Presented at the workshop “Iron Screening and Supplementation in Iron-Replete Pregnant Women and Young Children” held by the NIH Office of Dietary Supplements, Bethesda, MD, 28–29 September 2016. Supported by the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R-01HD-29421). Address correspondence to MKG (e-mail: firstname.lastname@example.org). Abbreviations used: ID, iron deficiency; IDA, iron deficiency anemia; RBC, red blood cell; SF, serum ferritin. First published online October 25, 2017; doi: https://doi.org/10.3945/ajcn. 117.155846.
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- Iron status
- brain dysfunction