Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity

To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988±227 gm; gestational age 27.6±1.2 weeks; age 41±15 days; all values mean ±SD) to receive either transfusion or subcutaneously administered erythropoletin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2%±1% to 7%±2% (p<0.001) and hematocrits increased from 27%±2% to 30%±4% (p<0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28%±4% to 41%±2% after initial transfusion (p<0.001) and had decreased to 34%±5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that intants receiving erythropoietin had greater percentages of erythropoietic precursors (p<0.001), greater concentrations of mature erythroid progenitors (p<0.001), and higher cycling rates of erythroid progenitors (p<0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p<0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8±0.9×10³ cells/μl) than in the infants who underwant transfusion (3.9±1.9×10³ cells/μl; p<0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity.