Comparison Between Two and Five Doses a Week of Recombinant Human Erythropoietin for Anemia of Prematurity: A Randomized Trial

Abstract

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/mm3 (15 000) vs 220 000/mm3(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.