Erythropoietin and retinopathy of prematurity: a retrospective cohort study in Japan, 2008-2018

Background: Retinopathy of prematurity (ROP) is a developmental retinal vascular proliferative disease and a leading cause of blindness in children worldwide. Erythropoietin has an angiogenic effect on the retina and might increase the risk of ROP. However, the results of previous studies on the association between erythropoietin use and increased risk of ROP have been inconsistent and inconclusive. Methods: This retrospective cohort study included infants born at 22 0/7 to 27 6/7 weeks’ gestation between 2008 and 2018 who were admitted to neonatal intensive care units (NICUs) in the Neonatal Research Network of Japan. We compared mortality and morbidities during NICU stay between infants who received erythropoietin and those who did not. Results: Among 18 955 livebirth infants, this study included 16 031 infants, among which 14 373 infants (90%) received erythropoietin. The risk of ROP requiring treatment was significantly higher in the erythropoietin group than in the control group (33% vs. 26%; aOR 1.46 [95%CI 1.25-1.71]). The risk of chronic lung disease (CLD) was also significantly higher in the erythropoietin group (49% vs. 35%; aOR 1.60 [95%CI 1.38-1.86]). On the other hand, the erythropoietin group had significantly lower risks of death before discharge, and necrotizing enterocolitis. The composite outcomes of “death or ROP” and “death or CLD” were not significantly different between the two groups. Conclusions: This study with a large sample size found that erythropoietin use was associated with increased risk of ROP requiring treatment and CLD, while being associated with reductions in deaths and NEC.