BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective 
effect in preclinical models of neonatal brain injury, and phase 2 trials have 
suggested possible efficacy; however, the benefits and safety of this therapy in 
extremely preterm infants have not been established.
METHODS: In this multicenter, randomized, double-blind trial of high-dose 
erythropoietin, we 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.
RESULTS: 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; 95% confidence 
interval, 0.81 to 1.32; P = 0.80). 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.
CONCLUSIONS: 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. (Funded by the National Institute of Neurological Disorders 
and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).