High-Dose Erythropoietin in Extremely Low Gestational Age Neonates Does Not Alter Risk of Retinopathy of Prematurity

Abstract

Introduction: The Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial sought to determine the safety and efficacy of early high-dose Epo as a potential neuroprotective treatment. We hypothesized that Epo would not increase the incidence or severity of retinopathy of prematurity (ROP).

Methods: A total of 941 infants born between 24-0/7 and 27-6/7 weeks' gestation were randomized to 1,000 U/kg Epo or placebo intravenously for 6 doses, followed by subcutaneous or sham injections of 400 U/kg Epo 3 times a week through 32 weeks post-menstrual age. In this secondary analysis of PENUT trial data, survivors were evaluated for ROP. A modified intention-to-treat approach was used to compare treatment groups. In addition, risk factors for ROP were evaluated using regression methods that account for multiples and allow for adjustment for treatment and gestational age at birth.

Results: Of 845 subjects who underwent ROP examination, 503 were diagnosed with ROP with similar incidence and severity between treatment groups. Gestational age at birth, birth weight, prenatal magnesium sulfate, maternal antibiotic exposure, and presence of heart murmur at 2 weeks predicted the development of any ROP, while being on high-frequency oscillator or high-frequency jet ventilation (HFOV/HFJV) at 2 weeks predicted severe ROP.

Conclusion: Early high-dose Epo followed by maintenance dosing through 32 weeks does not increase the risk of any or severe ROP in extremely low gestational age neonates. Gestational age, birth weight, maternal treatment with magnesium sulfate, antibiotic use during pregnancy, and presence of a heart murmur at 2 weeks were associated with increased risk of any ROP. Treatment with HFOV/HFJV was associated with an increased risk of severe ROP.

Trial registration: ClinicalTrials.gov NCT01378273.

Keywords: Erythropoietin; Extreme prematurity; Retinopathy of prematurity.

Conflict of interest statement

Conflict of Interest Statement: The authors have no conflicts of interest relevant to this article to disclose. The authors have no financial relationships relevant to this article to disclose. NINDS funded this project, but had no role in data collection, analysis, data interpretation, writing of the manuscript, or submission for publication.

© 2020 S. Karger AG, Basel.

Figures

Figure 1.

ROP Status by Treatment Group. In the Placebo group, 61.3% were diagnosed with ROP and 57.5% were diagnosed with ROP in the Epo group. No significant differences were noted between the study groups.

Figure 2.

Forest Plot of Predictors of Any ROP Disease. Significant differences were noted for decreasing gestational age birth, increasing birth weight, prenatal magnesium sulfate treatment, heart murmur at 2 weeks of age, and antibiotics during pregnancy.