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Objective: To compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same weekly dose, 500 U/kg, in very low birth weight (VLBW) infants., Study Design: Eighty VLBW infants were stratified into two gestational age groups and randomized to receive 500 U/kg of r-EPO either two or five times a week; 72 infants completed at least 4 weeks of study. The primary outcome variable was absolute reticulocyte counts at 4 weeks. Secondary outcome variables were hematocrits, transfusions, iatrogenic blood losses, infections, and serum ferritins. Multiple regression analysis was used to evaluate the secondary outcome variables., Results: By 4 weeks, absolute reticulocyte counts were higher in the infants given r-EPO five times a week [mean (SEM)]: 173 000/mm(3) (15 000) vs 220 000/mm(3) (18 000), two versus five doses per week, respectively. Hematocrits, 34.9% (0.9) vs 34.1% (0.8), and transfusions per infant, 2.06 (0.4) vs 2.11 (0.4), were not different between the groups. Additionally, 79% of the variance in the amount of blood transfused was accounted for by iatrogenic blood loss, the latter primarily associated with number of days ventilated. Episodes of sepsis and necrotizing enterocolitis were significantly associated with decreased absolute reticulocyte counts and increased transfusions., Conclusions: More frequent dosing of the same weekly amount of r-EPO produced a significant and sustained increase in stimulated erythropoiesis in VLBW infants. The importance of this finding on reducing transfusions was not able to be demonstrated because this study was not intended to differentiate transfusions. In this population of infants and at the dose level of r-EPO, iatrogenic blood loss contributed more to transfusions than a lower level of erythropoiesis, the former primarily associated with mechanical ventilation. Based on this and other studies, when VLBW infants are at risk for greater phlebotomy losses, it may be justifiable to use more vigorous r-EPO treatment, and when at lower risk to use less frequent dosing to enhance cost-effectiveness.

Design and Methods: We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines., Results: Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups., Conclusion: We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.