Early Erythropoietin Administration does not Increase the Risk of Retinopathy in Preterm Infants

Abstract

Background: Erythropoietin (EPO) administration prevents anemia of prematurity and may be associated with a significant increase in the risk of retinopathy of prematurity (ROP) in preterm infants. Nonetheless, early EPO treatment may prevent damage following retinal neovascularization. The aim of this meta-analysis was to elucidate whether EPO administration increases the risk of ROP.

Methods: We searched MEDLINE, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Central Register of Controlled Trials with no language restrictions. Randomized controlled trials that reported the association between EPO treatment in preterm infants and ROP were eligible. All of the included studies were stratified into two groups according to the age of initiation of EPO treatment: before 8 days of age (early EPO), and 8-28 days of age (late EPO).

Results: Thirteen studies were identified that included a total of 1999 preterm infants. EPO administration did not increase the risk of ROP of any stage or Stage ≥3 (any relative risk: 0.99, 95% confidence interval: 0.84-1.16, p = 0.89; Stage ≥3 relative risk: 1.34, 95% confidence interval: 0.90-1.99, p = 0.15). This trend remained unchanged in both the early and late EPO groups. There did not seem to be any evidence of publication bias for outcomes as the funnel plots were symmetrical.

Conclusion: EPO administration did not significantly increase the risk of ROP of any stage reported or Stage ≥3. Further clinical trials investigating the impact of EPO on ROP in premature infants should include all confounding factors to clarify this important issue.

Keywords: erythropoietin; meta-analysis; retinopathy of prematurity.