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Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial

Department of Neonatology, University Children's Hospital Regensburg, Hospital St Hedwig of the Order of St John, University of Regensburg, Regensburg, Germany. Division of Neonatology, University Children's Hospital Basel, University of Basel, Basel, Switzerland. Department of Neonatology and Pediatric Intensive Care, University Children's Hospital Zurich, Zurich, Switzerland. Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. Department of Biostatistics, Institute of Epidemiology, Biostatistics and Prevention, University of Zurich, Zurich, Switzerland. Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria. Clinic of Neonatology, Department of Women Mother Child, University Center Hospital and University of Lausanne, Vaud, Switzerland. Newborn Research, Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

JAMA network open. 2022;5(12):e2244744
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PICO Summary

Population

Preterm infants with intraventricular haemorrhage enrolled in the EpoRepair trial, in 8 Swiss and Austrian tertiary neonatal units (n= 121).

Intervention

Intravenous high-dose erythropoietin (n= 60).

Comparison

Placebo (n= 61).

Outcome

The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. Both groups had similar baseline characteristics and morbidities. Up to term-equivalent age (TEA), 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 (95% CI 0.74 to 7.66)). Infants receiving erythropoietin had higher mean haematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.
Abstract
IMPORTANCE Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date. OBJECTIVE To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH. DESIGN, SETTING, AND PARTICIPANTS Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022. INTERVENTIONS Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life. MAIN OUTCOMES AND MEASURES Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023). RESULTS Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores. CONCLUSIONS AND RELEVANCE This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02076373.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine