05/12/2005
Recombinant EPO and iron supplementation in preterm infants

A clinical trial suggests that r-Hu EPO plus early iron supplementation could reduce transfusions needs in very low birthweight infants

Premature infants frequently develop anemia and need multiple transfusions, with an increased risk of disease transmission. At present, >90% of infants with birthweight < 1000 g and 40% of those weighing 1000 to 1500 g are given transfusions during the first 3 to 4 weeks of life. A low plasma erythropoietin (EPO) level is believed to be responsible for anemia in premature infants.

Recombinant human erythropoietin (r-Hu EPO) may be a treatment for anemia in premature infants, but its use is still controversial, although it has been shown that EPO could stimulate erythropoiesis and help the development of the gastrointestinal tract. In very low birthweight infants (VLBW), the incidence of necrotizing enterocolitis (NEC) is lower when r-Hu EPO is administered. Total volume of transfusions and iron loaded by transfusions are associated with increased risk of retinopathy in VLBW. In fact, iron induces release of oxygen radicals, involved in the pathogenesis of retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), broncopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH).
The aim of this nonblind, prospective, randomised observational study was to test the effect of r-Hu EPO plus enteral iron on the transfusion requirements and on the development of ROP, NEC, BPD, and IVH in VLBW infants < 1500 g. Patients were monitored for 12 weeks.
r-Hu EPO 750 U/kg per week was given subcutaneosly to the study group (n = 42) from day 5 to 40 and enteral iron supplementation of 2 to 6 mg/kg/day was administrated beginning on day 14, provided that patients were receiving at least 50% energy intake orally. In the control group, 51 infants received the same dose of enteral iron supplementation beginning at the end of the fourth week.
There was no significant difference in the median volume and the median number of transfusion between the study and the control groups. Only the number of transfusions per transfused infant was lower in the r-Hu EPO group. Transfusion needs were compared for infants ³ 1000 g (n = 63) and < 1000 g (n = 30). In the group of infants < 1000 g, the number of transfusions per infant, of patients transfused in the first two months and the packed red cells (PRC) volume transfused were significantly lower in the r-Hu EPO group.
However, the incidences of IVH, ROP, BPD and NEC were not significantly different in the r-Hu EPO and control groups with birthweight < 1000 g and ³ 1000 g.
The administration of r-Hu EPO plus enteral iron induced a significant reduction in transfusion requirements in the < 1000 g group. r-Hu EPO efficacy in the early weeks is reduced, due to the depressive effects of illness and of transfusions on erithropoiesis, but some studies noted a significant decrease in transfusions in the first two weeks. In the present study, reduced PRC transfusions in < 1000 g infants should be interpreted with caution because of the small study group. ROP, IVH, NEC and BPD risks were not increased by iron supplementation in the r-Hu EPO group.
In conclusion, this study showed that r-Hu EPO plus early iron supplementation do not increase the risk of ROP, BPD, NEC and IVH in infants with a birthweight < 1500 g and suggested that the same treatment is effective and safe in reducing transfusions needs of infants < 1000 g.

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