title: High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial.
abstract: To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy.
  
  
  
  In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar <5, pH <7.00 or base deficit ≥15, or resuscitation at 10 minutes); and received hypothermia. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale and Warner Initial Developmental Evaluation. Two independent observers rated MRI brain injury severity by using an established scoring system.
  
  
  
  The mean age at first study drug was 16.5 hours (SD, 5.9). Neonatal deaths did not significantly differ between Epo and placebo groups (8% vs 19%, P = .42). Brain MRI at mean 5.1 days (SD, 2.3) showed a lower global brain injury score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epo-treated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05).
  
  
  
  High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function.
authors.affiliation: Departments of Neurology, Pediatrics, and wuy@ucsf.edu.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Departments of Pediatrics and.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Mathur
authors.affiliation: Departments of Neurology and Neonatology, Children's National Health Systems, Washington, District of Columbia;
authors.forename: Taeun
authors.initials: T
authors.lastname: Chang
authors.affiliation: Radiology, Washington University School of Medicine, St Louis, Missouri;
authors.forename: Robert C
authors.initials: RC
authors.lastname: McKinstry
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Mulkey
authors.affiliation: Departments of Pediatrics and.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Mayock
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California;
authors.forename: Krisa P
authors.initials: KP
authors.lastname: Van Meurs
authors.affiliation: Pediatrics, and.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Rogers
authors.affiliation: Pediatrics, and.
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Gonzalez
authors.affiliation: Biostatistics, University of Washington, Seattle, Washington;
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Comstock
authors.affiliation: Departments of Pediatrics and.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Juul
authors.affiliation: Section of Developmental and Behavioral Pediatrics, Department of Pediatrics, University of Chicago Medicine, Comer Children's Hospital, Chicago, Illinois; and.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Msall
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California;
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Bonifacio
authors.affiliation: Departments of Neurology, Pediatrics, and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California;
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Glass
authors.affiliation: Neonatology, Children's National Health Systems, Washington, District of Columbia;
authors.forename: An N
authors.initials: AN
authors.lastname: Massaro
authors.affiliation: Department of Pediatrics, Kaiser Permanente Santa Clara, Santa Clara, California.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Dong
authors.affiliation: Biostatistics, University of Washington, Seattle, Washington;
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Tan
authors.affiliation: Biostatistics, University of Washington, Seattle, Washington;
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Heagerty
authors.affiliation: Pediatrics, and.
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Ballard
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007035:Hypothermia; D020925:Hypoxia-Ischemia, Brain / Q000145:classification / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D007231:Infant, Newborn; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D019957:Motor Skills Disorders / Q000209:etiology; D065886:Neurodevelopmental Disorders / Q000209:etiology; D009483:Neuropsychological Tests; D012720:Severity of Illness Index
chemical_list: D004921:Erythropoietin