#VisualAbstract: A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants

1. In this randomized controlled trial involving extremely preterm infants, high dose erythropoietin did not reduce the risk of death or severe neurodevelopmental impairment at two years of age versus placebo.

2. This finding contradicts the results of previous studies involving different dosing regimens and more mature babies.

Evidence Rating Level: 1 (Excellent)

Study Rundown: While advances in care have dramatically improved survival, preterm infants remain at high risk of functional and cognitive impairment. Erythropoietin is an erythropoietic agent that has also been shown to have neuroprotective effects in preclinical models and a meta-analysis of four randomized controlled trials. This placebo-controlled, double-blind trial was conducted to evaluate whether these benefits extended to extremely preterm infants, finding that there was no difference between groups in the primary outcome of death or severe neurodevelopmental impairment. Serious adverse events and common complications of prematurity occurred at similar rates in both groups. These results indicate the possibility that erythropoiesis-stimulating agents do indeed inhibit neurologic dysfunction but with a magnitude of effect that is overshadowed by the numerous unresponsive pathways in the most premature infants. While this study had a larger sample size than previous studies, it was limited by its reliance on testing at 2 years, as assessments at older ages are much more accurate predictors of neurodevelopmental outcomes. Another limitation was that infants with poorer prognoses who may have benefited the most from treatment were excluded from participation.

Click here to read the study in NEJM