There has been increased interest in iron deficiency, with data suggesting that mental and developmental test scores are lower in infants with iron deficiency anemia and that iron therapy sufficient to correct the anemia is insufficient to reverse the behavioral and developmental disorders in many infants. This indicates that certain ill effects are persistent depending on the timing, severity, or degree of iron-deficiency anemia during infancy.

Iron stores in the preterm infant are lower than in the term baby because these stores are relatively proportional to body weight. Iron depletion occurs at the time the infant doubles her/his birth-weight and thus iron therapy should begin by two to four weeks of life in the preterm infant when enteral feedings are tolerated. VLBW infants may need as much as 4–6 mg/kg per day, with about 2 mg/kg per day provided by iron-fortified formula and the remainder as iron supplementation at 2–4 mg/kg per day. A higher dose is also necessary for infants being given erythropoietin. Although premature infant formulas, both with and without iron fortification, are manufactured with ample amounts of vitamin E and a polyunsaturated fatty acid-to-E ratio of 6.0 or greater, premature infants on human milk and receiving supplemental iron should also be supplemented with 4 to 5 mg (6 to 8 IU) of vitamin E per day. This can be readily accomplished by use of an oral multivitamin with iron.

To avoid the risk of iron toxicity related to immature antioxidant systems in VLBW infants, the AAP and other organizations do not recommend using iron prior to two weeks of age.