Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage
Authors: Wellmann Sven , Hagmann Cornelia F. , von Felten Stefanie , Held Leonard , Klebermass-Schrehof Katrin , Truttmann Anita C. , Knöpfli Claudia , Fauchère Jean-Claude , Bührer Christoph , Bucher Hans Ulrich , Rüegger Christoph M. ,   Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair) Investigators, Meyer Philipp , Konetzny Gabriel , Däster Corinne , Schulzke Sven M , Kasser Severin , Gerull Roland , Nelle Mathias , Bubl Benedikt , Bär Walter , Scharrer Brigitte , Riedel Thomas , Tolsa Jean-François , Rogdo Bjarte , Hoigne Irene , Birkenmaier André , Natalucci Giancarlo , Berger Angelika , Thajer Alexandra 
Published: December 2022

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 &amp;lt;32 weeks or birth weight &amp;lt;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