Erythropoietin treatment does not provide neuroprotection to preterm infants: NEJM
USA: The administration of high-dose erythropoietin treatment to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not lower the risk of severe neurodevelopmental impairment or death at 2 years of age, according to a recent study published in the New England Journal of Medicine.
In preclinical models of neonatal brain injury, high-dose erythropoietin has been shown to have a neuroprotective effect. Phase 2 trials have suggested possible efficacy. However, the safety and benefits of this therapy has not been established in extremely preterm infants.
Sandra E. Juul, Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, WA, and colleagues determined the safety and benefits of high-dose erythropoietin in extremely preterm infants in this multicenter, randomized, double-blind trial of high-dose erythropoietin.
For the purpose, the researchers assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections.
The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.
Key findings of the study include:
- A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo.
- There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03).
- There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.
"High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age," concluded the authors.
The study, "A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants," is published in the New England Journal of Medicine.