Abstract
Abstract: :
Purpose: Recombinant human erythropoietin (rHuEPO) is broadly used clinically for the treatment of anemia of prematurity. Erythropoietin has been shown to have angiogenic potential and can stimulate neovascularization, implying a role for erythropoietin in vasoproliferative processes. The objective of this study was to evaluate the association between the development of retinopathy of prematurity (ROP) and the cumulative dose of rHuEPO received by premature neonates in a neonatal intensive care setting. Methods: The case records of 67 neonates evaluated for ROP while in the neonatal intensive care unit between the periods of July 2002 and September 2003 were subjected to a retrospective review. The maximum stage of ROP achieved, including treatment for threshold disease, and the cumulative dose of rHuEPO received from birth until the time of maximal stage was determined for each case. This data, along with confounding variables of birth weight, gestational age and use of supplemental oxygen was subjected to bivariable comparison using the Spearman correlation coefficient test and Mantel–Haenszel chi–square test, as well as multivariable analysis using a logistic regression model. Results: There was a statistically significant moderate positive correlation between the dosage of rHuEPO received and the maximum stage of ROP achieved (Spearman, r=0.48 p<0.0001). Patients treated with rHuEPO were more likely to develop higher stages of ROP than patients not treated with rHuEPO, with all the patients who received laser treatment (n=6) for threshold ROP belonging to the rHuEPO treated group (Mantel–Haenszel p=0.058). However, when controlling for the risk factors of gestational age, birth weight, and use of supplemental oxygen in the multi–variable analysis, there was no statistically significant increase in risk of developing ROP (p=0.23) or higher stages of ROP (p=0.27) with increasing dosage of rHuEPO. Conclusion: This retrospective cohort study showed an association between the development of ROP and the use of rHuEPO. This association may be due to the increased use of rHuEPO in neonates who at baseline are at more of a risk for the development of ROP. Given that the multi–factorial nature of ROP has not yet been fully elucidated, further evaluation of erythropoietins role in ROP with a randomized controlled clinical study may be warranted.
Keywords: retinopathy of prematurity • retinal neovascularization • clinical (human) or epidemiologic studies: risk factor assessment