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      Iron Supplementation during Pregnancy and Infancy: Uncertainties and Implications for Research and Policy

      review-article
      1 , 2 , * , 2
      Nutrients
      MDPI
      iron supplementation, iron-replete, pregnancy, infancy

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          Abstract

          Iron is particularly important in pregnancy and infancy to meet the high demands for hematopoiesis, growth and development. Much attention has been given to conditions of iron deficiency (ID) and iron deficient anemia (IDA) because of the high global prevalence estimated in these vulnerable life stages. Emerging and preliminary evidence demonstrates, however, a U-shaped risk at both low and high iron status for birth and infant adverse health outcomes including growth, preterm birth, gestational diabetes, gastrointestinal health, and neurodegenerative diseases during aging. Such evidence raises questions about the effects of high iron intakes through supplementation or food fortification during pregnancy and infancy in iron-replete individuals. This review examines the emerging as well as the current understanding of iron needs and homeostasis during pregnancy and infancy, uncertainties in ascertaining iron status in these populations, and issues surrounding U-shaped risk curves in iron-replete pregnant women and infants. Implications for research and policy are discussed relative to screening and supplementation in these vulnerable populations, especially in developed countries in which the majority of these populations are likely iron-replete.

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          Iron deficiency and brain development.

          Iron deficiency (ID) is common in pregnant women and infants worldwide. Rodent models show that ID during gestation/lactation alters neurometabolism, neurotransmitters, myelination, and gene/protein profiles before and after iron repletion at weaning. Human infants with iron deficiency anemia test lower in cognitive, motor, social-emotional, and neurophysiologic development than comparison group infants. Iron therapy does not consistently improve developmental outcome, with long-term differences observed. Poorer outcome has also been shown in human and monkey infants with fetal/neonatal ID. Recent randomized trials of infant iron supplementation show benefits, indicating that adverse effects can be prevented and/or reversed with iron earlier in development or before ID becomes severe or chronic. This body of research emphasizes the importance of protecting the developing brain from ID.
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            Current understanding of iron homeostasis.

            Iron is an essential trace element, but it is also toxic in excess, and thus mammals have developed elegant mechanisms for keeping both cellular and whole-body iron concentrations within the optimal physiologic range. In the diet, iron is either sequestered within heme or in various nonheme forms. Although the absorption of heme iron is poorly understood, nonheme iron is transported across the apical membrane of the intestinal enterocyte by divalent metal-ion transporter 1 (DMT1) and is exported into the circulation via ferroportin 1 (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around the body to sites of utilization with the erythroid marrow having particularly high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1 on the surface of most body cells, and after endocytosis of the complex, iron enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used for metabolic functions, stored within cytosolic ferritin, or exported from the cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption and iron export from the tissues into the plasma are regulated by the liver-derived peptide hepcidin. When tissue iron demands are high, hepcidin concentrations are low and vice versa. Too little or too much iron can have important clinical consequences. Most iron deficiency reflects an inadequate supply of iron in the diet, whereas iron excess is usually associated with hereditary disorders. These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload. Despite major recent advances, much remains to be learned about iron physiology and pathophysiology.
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              Long-Lasting Neural and Behavioral Effects of Iron Deficiency in Infancy

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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                06 December 2017
                December 2017
                : 9
                : 12
                : 1327
                Affiliations
                [1 ]Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
                [2 ]Office of Dietary Supplements, National Institutes of Health, 6100 Executive Blvd, 3B01, Bethesda, MD 20892, USA; TaylorCL3@ 123456od.nih.gov
                Author notes
                [* ]Correspondence: pmb22@ 123456cornell.edu ; Tel.: +1-607-255-3770; Fax: +1-607-255-1033
                Author information
                https://orcid.org/0000-0002-3952-2266
                Article
                nutrients-09-01327
                10.3390/nu9121327
                5748777
                29210994
                5f85bb9e-a87f-485d-a735-a2279a3d6775
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 October 2017
                : 28 November 2017
                Categories
                Review

                Nutrition & Dietetics
                iron supplementation,iron-replete,pregnancy,infancy
                Nutrition & Dietetics
                iron supplementation, iron-replete, pregnancy, infancy

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