{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:26:50Z","timestamp":1792985210858,"version":"4.5.0"},"reference-count":69,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE:<\/jats:title>\n                    <jats:p>To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>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 &amp;lt;5, pH &amp;lt;7.00 or base deficit \u226515, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1542\/peds.2016-0191","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T08:36:43Z","timestamp":1462264603000},"source":"Crossref","is-referenced-by-count":190,"title":["High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial"],"prefix":"10.1542","volume":"137","author":[{"given":"Yvonne W.","family":"Wu","sequence":"first","affiliation":[{"name":"Departments of Neurology,"},{"name":"Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit M.","family":"Mathur","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeun","family":"Chang","sequence":"additional","affiliation":[{"name":"Departments of Neurology and"},{"name":"Neonatology, Children\u2019s National Health Systems, Washington, District of Columbia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"McKinstry","sequence":"additional","affiliation":[{"name":"Radiology, Washington University School of Medicine, St Louis, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Mulkey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis E.","family":"Mayock","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisa P.","family":"Van Meurs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando F.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan A.","family":"Comstock","sequence":"additional","affiliation":[{"name":"Biostatistics, University of Washington, Seattle, Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Juul","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Msall","sequence":"additional","affiliation":[{"name":"Section of Developmental and Behavioral Pediatrics, Department of Pediatrics, University of Chicago Medicine, Comer Children\u2019s Hospital, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia L.","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Glass","sequence":"additional","affiliation":[{"name":"Departments of Neurology,"},{"name":"Pediatrics, and"},{"name":"Epidemiology and Biostatistics, University of California, San Francisco, 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