In addition to stimulating red blood cell production, erythropoietin is a trophic factor in fetal brain development. Meta-analysis of four randomized controlled trials has shown a neuroprotective effect of erythropoietin given to preterm infants born 27-30 weeks. The Preterm Erythropoietin Neuroprotection Trial (PENUT) was designed to investigate the neuroprotective benefits of early, high doses of erythropoietin given to preterm infants. The phase 3, randomized, placebo-controlled, multicenter PENUT trial enrolled 941 preterm infants who were born at 24 weeks to less than 28 weeks. There were 477 infants who received six doses of erythropoietin (100 U/kg) which were given every 48 hours starting within 24 hours of birth, followed by three weekly doses (400 U/kg) until 32 weeks of postmenstrual age; 464 infants in the placebo group received similar injections of saline. After two years, the incidence of death or severe neurodevelopmental impairment was 26% for both groups (relative risk, 1.03; 95% CI, 0.81-1.32; p=0.80). There were also no differences between arms in other secondary outcomes or adverse events. Infants in the erythropoietin group, however, received fewer transfusions and a lower cumulative volume of red blood cells. Although the dosing regimen of erythropoietin used in this trial did stimulate erythropoiesis, no neuroprotective effects were observed by 2 years of age.
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