Iron Therapy for Preterm Infants

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Preterm infants are at risk for both iron deficiency and iron overload. The role of iron in multiple organ functions suggests that iron supplementation is essential for the preterm infant. Conversely, the potential for iron overload and the poorly developed antioxidant measures in the preterm infant argue against indiscriminate iron supplementation in this population. This article reviews the predisposing factors and consequences of iron deficiency and iron overload in the preterm infant, discusses the current recommendation for iron supplementation and its appropriateness, and describes potential management strategies that strike a balance between iron deficiency and iron toxicity.

Section snippets

Risk of iron deficiency in preterm infants

Between 25% and 85% of preterm infants develop evidence of iron deficiency during infancy.3, 4, 5, 6, 7, 8 Unlike full-term infants, in whom the condition typically occurs during the second half of infancy, preterm infants are at risk for developing iron deficiency during their first 6 postnatal months.5, 6, 7, 8, 9 Gestationally more premature and smaller preterm infants are at greater risk for developing iron deficiency at an earlier age.5, 9, 10 Iron deficiency is more common in preterm

Risk of iron overload in preterm infants

In the absence of genetic conditions, such as congenital hemochromatosis, iatrogenic factors are responsible for excessive iron accumulation in preterm infants. There are, however, no specific data on the incidence of iron overload caused by nutritional iron therapy in preterm infants.

Determining the Iron Requirements of Preterm Infants

The goal of nutrient delivery to preterm infants is to mimic the intrauterine accretion rate and to maintain normal serum levels.47 Using this analogy, a preterm infant would require a daily iron intake of 1.6 to 2.0 mg/kg intravenously48 or 5 to 6 mg/kg enterally, because enteral iron absorption is approximately 30%.49 Such supplementation is neither practical nor physiologic soon after birth, however. Enteral nutrition is not feasible soon after birth in most VLBW preterm infants. Unlike

Fortification of Human Milk

The iron content of human milk is approximately 0.5 mg/L.54 Although human milk meets the iron requirements of full-term infants during the first 4 to 6 months of life, additional iron is necessary to meet the needs of erythropoiesis and growth of preterm infants.16 The iron status of preterm infants receiving nonfortified breast milk starts to deteriorate within 1 to 4 months.7, 9, 10 Cow milk–based human milk fortifiers that are currently available in the United States contain 3.5 to 14.4

Enteral supplementation through medicinal iron

Enteral administration is used commonly for supplementing iron in preterm infants. There are wide variations in the dose, initiation, and duration of supplementation and in the iron compounds used for enteral supplementation.2 The recommendations of various pediatric societies47, 56, 57 are given in Table 1. Iron supplementation is not recommended nor is it necessary during the transition period soon after birth.56 An exogenous source of 2 to 4 mg/kg d−1 of iron is recommended during the period

Other preventive measures for iron deficiency

Delaying the clamping the umbilical cord for 30 to180 seconds after birth improves iron status.86 Data, however, are insufficient to recommend this practice as a general policy, given the potential impact of a large volume expansion on the fragile cerebral circulation of the preterm infant. Limiting phlebotomy losses, avoiding cow milk, and using iron pots for cooking4 are other preventive measures that may improve the iron status of preterm infants. Of note, it is not possible to enhance the

Timing and Frequency of Screening

Periodic assessment of hemoglobin or hematocrit is recommended for screening the iron nutritional status of full-term infants, with an initial screening between 9 and 12 months of age and a second screening 6 months later (ie, between 15 and 18 months).87 Although there are no specific recommendations for preterm infants, it is considered prudent to screen them at approximately 4 months.87 Because many preterm infants develop iron deficiency before that age,8, 15 screening at 2 months or at

Preventive and therapeutic measures for iron excess

Setting guidelines for erythrocyte transfusions based on specific hematologic parameters potentially would avoid iron excess. There are practical difficulties in adhering to the practice,40 however, because transfusions often are administered for nonhematologic reasons. Use of rHuEPO in lieu of transfusions may be another strategy. Nevertheless, most studies have demonstrated only a modest decrease in the frequency of erythrocyte transfusions with the use of rHuEPO.67 Furthermore, a

Summary and future directions

Iron deficiency and iron excess are significant nutritional problems in the preterm infant. The potential risk of neurodevelopmental impairments caused by iron deficiency warrants frequent screening and preventive measures via the fortification of breast milk or the use of iron-fortified formula. Iron supplementation also seems to be effective and safe. Nevertheless, there are unresolved issues concerning the practice. Iron overload remains a significant concern in multiply transfused sick

Acknowledgment

The authors thank Jennifer L.M. Super, RD, LD, for assistance with the iron content of formula and additives and Caitlyn Nystedt for assistance with manuscript preparation.

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    This work was supported by grant HD 29421-14 from the National Institutes of Health.

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