Association between higher cumulative doses of recombinant erythropoietin and risk for retinopathy of prematurity

Background: Retinopathy of prematurity is a complication of premature birth that varies in its severity. The incidence and severity of retinopathy of prematurity at our perinatal center in a regional referral hospital changed substantially during 1995 to 1998 and presented us with an opportunity to examine whether there was a protective effect on risk of retinopathy associated with exposure to recombinant erythropoietin. Methods: We undertook a retrospective cohort study. From January 1995 through December 1998, charts of infants weighing < 1500 g, who were 30 weeks' gestation or less, and who were admitted and survived to the first eye examination at 6 weeks were reviewed. Primary and secondary risk factors were recorded from the first 6 weeks of life. Of the eligible infants, 327 of 390 (84%) had complete records and retinal examinations. The probability for progression of retinopathy was estimated by logistic regression multivariate analysis using the continuation-ratio model. Results: The overall incidence of retinopathy of prematurity was 36%. Recombinant erythropoietin exposure, as total 6-week dose, was independently associated with an increased risk for progression of retinopathy, OR = 1.27 per 500 units/kg (95%Cl = 1.04, 1.55, P = 0.02). Postnatal day of recombinant erythropoietin initiation also was associated with retinopathy risk but did not reach conventional statistical significance, OR = 1.07 (Cl = 1.00, 1.14, P = 0.07). Conclusions: These findings identify an association between cumulative recombinant erythropoietin exposure, used to reduce blood transfusions in premature infants, and an increased risk for retinopathy of prematurity. The nonhematopoietic properties of erythropoietin may account for the above findings, however further evaluation with confirmation is required.