Don’t Give Up on Erythropoietin as a Neuroprotective Agent

Abstract

To the Editor .— Ohls et al1 recently reported in Pediatrics that recombinant erythropoietin (rEpo), given in a randomized, controlled clinical trial to reduce transfusions in extremely low birth weight (ELBW) infants, did not significantly influence the neurodevelopmental outcome at 18 to 22 months’ corrected age. The question of the neurodevelopmental outcome of rEpo-treated ELBW infants became of highest interest since animal studies using a variety of models for hypoxic-ischemic brain injury (see refs 2 and 3 for review) as well as the first clinical trial in humans with stroke provided substantial evidence for significant neuroprotective effects of rEpo.4 It is indeed neither unexpected nor disappointing that ELBW infants who received rEpo (400 U/kg body weight 3 times weekly, given intravenously[ iv] or subcutaneously [sc]) from 96 hours of age and until the 35th postmenstrual week did not show a benefit in the neurodevelopmental outcome. This needs additional explanation, because specific aspects of the biology of Epo and its receptor (Epo-R) in the central nervous system (CNS) need to be considered for future strategies in using rEpo as a neuroprotective agent in neonates. Such aspects concern (1) Epo-R expression, (2) endogenous Epo production, and (3) time and dosage of rEpo treatment, particularly regarding its transport across …