Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy

• Published in: Pediatric neurology 2014-11, Vol.51 (5), p.657-662
• Main Authors: Rogers, Elizabeth E., MD, Bonifacio, Sonia L., MD, Glass, Hannah C., MDCM, Juul, Sandra E., MD, Chang, Taeun, MD, Mayock, Dennis E., MD, Durand, David J., MD, Song, Dongli, MD, Barkovich, Anthony J., MD, Ballard, Roberta A., MD, Wu, Yvonne W., MD, MPH
• Format: Article
• Language: English
• Subjects: Brain - drug effects; Child, Preschool; Cognition Disorders - etiology; Dose-Response Relationship, Drug; erythropoietin; Erythropoietin - therapeutic use; Female; Follow-Up Studies; Humans; Hypothermia, Induced - methods; Hypoxia-Ischemia, Brain - complications; Hypoxia-Ischemia, Brain - pathology; Hypoxia-Ischemia, Brain - therapy; hypoxic-ischemic encephalopathy; Infant; Magnetic Resonance Imaging; Male; neonatal encephalopathy; neurodevelopmental outcomes; Neurology; neuroprotection; Neuropsychological Tests; Pediatrics; Treatment Outcome
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2014.08.010

Abstract Background Erythropoietin is neuroprotective in animal models of neonatal hypoxic-ischemic encephalopathy. We previously reported a phase I safety and pharmacokinetic study of erythropoietin in neonates. This article presents the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial. Methods We enrolled 24 newborns with hypoxic-ischemic encephalopathy in a dose-escalation study. Patients received up to six doses of erythropoietin in addition to hypothermia. All infants underwent neonatal brain magnetic resonance imaging (MRI) reviewed by a single neuroradiologist. Moderate-to-severe neurodevelopmental disability was defined as cerebral palsy with Gross Motor Function Classification System levels III-V or cognitive impairment based on Bayley Scales of Infant Development II mental developmental index or Bayley III cognitive composite score. Results Outcomes were available for 22 of 24 infants, at mean age 22 months (range, 8-34 months). There were no deaths. Eight (36%) had moderate-to-severe brain injury on neonatal MRI. Moderate-to-severe disability occurred in one child (4.5%), in the setting of moderate-to-severe basal ganglia and/or thalamic injury. Seven infants with moderate-to-severe watershed injury exhibited the following outcomes: normal (three), mild language delay (two), mild hemiplegic cerebral palsy (one), and epilepsy (one). All 11 patients with a normal brain MRI had a normal outcome. Conclusions This study is the first to describe neurodevelopmental outcomes in infants who received high doses of erythropoietin and hypothermia during the neonatal period. The findings suggest that future studies are warranted to assess the efficacy of this new potential neuroprotective therapy.