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Despite being the most abundant metal on earth, iron is the most prevalent single nutrient deficiency worldwide. The term newborn possesses about 75 mg of elemental iron/kg (0.25–0.5 g of total body iron) and must absorb about 4.5 g of iron during childhood, or about 1 mg/d, to achieve the nearly 5.0 g of body iron in the average adult. An additional 0.2 to 0.5 mg/day of absorbed iron is required to balance physiologic losses (eg, desquamation of epithelial cells in the gastrointestinal tract). During periods of maximal growth—infancy and adolescence—the iron requirements for expanding blood volume and muscle mass may exceed the rate of dietary iron accrual.

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Epidemiology

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Iron deficiency is the most common global nutritional deficiency with an estimated 2 billion affected persons.1 Iron deficiency affects all age groups, but is particularly common in infants, young children, and women of childbearing age. Iron-deficiency anemia is the most common hematologic disease of infancy and childhood.2

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In industrialized nations, the most common etiology of iron deficiency is insufficient dietary iron. The availability of iron-fortified formula, in conjunction with initiatives such as the US federal Special Supplemental Nutrition Program for Women, Infants and Children (WIC) and the American Academy of Pediatrics’ promotion of formula in place of cow’s milk, have greatly reduced the prevalence of iron deficiency in developed countries. According to the Fourth National Health and Nutrition Examination Survey (NHANES-IV), iron deficiency without anemia exists in 7% of toddlers ages 1 to 2 years, 9% of adolescent girls, and 16% of women of childbearing age.3 Low income, minority ethnicity, and poor maternal iron status are recognized socioeconomic risk factors for iron-deficiency anemia.4-7 In developing countries, the higher prevalence of iron-deficiency anemia related to nutritional deficiency is compounded by the contribution of chronic blood loss related to parasitic infections.

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Pathophysiology and Genetics

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The majority of body iron is incorporated into the hemoglobin of circulating erythrocytes and their marrow precursors. Only a small fraction of the average daily requirement to support erythropoiesis is absorbed from the diet. The majority of the daily erythroid iron requirement is supplied by recovery of heme iron through the phagocytosis of senescent erythrocytes by reticuloendothelial macrophages and degradation of hemoglobin. This recycled iron is then made available to the developing erythroid precursors in the bone marrow.

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Because only about 10% of dietary iron is absorbed, the child’s diet must contain 10 to 15 mg of iron to maintain a positive iron balance. During infancy, when only small amounts of iron-rich foods may be consumed, this level of iron intake is difficult to attain unless iron-fortified foods are provided. Infants and children from low-income families continue to have iron deficiency, despite a decline in the incidence of the condition over the past 30 years.

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Iron Absorption

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Nonheme dietary iron, primarily in the ferric (Fe...

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