title: Erythropoietin and hypothermia for hypoxic-ischemic encephalopathy.
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.
authors.affiliation: Department of Neonatology, UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Rogers
authors.affiliation: Department of Neonatology, UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Bonifacio
authors.affiliation: Department of Neonatology, UCSF Benioff Children's Hospital, San Francisco, California; Department of Neurology, UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Glass
authors.affiliation: Department of Neonatology, University of Washington, Seattle, Washington.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Juul
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington DC.
authors.forename: Taeun
authors.initials: T
authors.lastname: Chang
authors.affiliation: Department of Neonatology, University of Washington, Seattle, Washington.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Mayock
authors.affiliation: Department of Neonatology, Children's Hospital & Research Center Oakland, Oakland, California.
authors.forename: David J
authors.initials: DJ
authors.lastname: Durand
authors.affiliation: Department of Neonatology, Santa Clara Valley Medical Center, San Jose, California.
authors.forename: Dongli
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Neurology, UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Barkovich
authors.affiliation: Department of Neonatology, UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Ballard
authors.affiliation: Department of Neonatology, UCSF Benioff Children's Hospital, San Francisco, California; Department of Neurology, UCSF Benioff Children's Hospital, San Francisco, California. Electronic address: wuy@neuropeds.ucsf.edu.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Wu
mesh_terms: D001921:Brain / Q000187:drug effects; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology / Q000628:therapy*; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D016896:Treatment Outcome
chemical_list: D004921:Erythropoietin
keywords: erythropoietin; hypoxic-ischemic encephalopathy; neonatal encephalopathy; neurodevelopmental outcomes; neuroprotection