Journal article
Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial
JAMA : the journal of the American Medical Association, Vol.318(16), pp.1550-1560
10/24/2017
DOI: 10.1001/jama.2017.14972
PMCID: PMC5783566
PMID: 29067428
Abstract
Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours.
To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy.
A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size.
Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C).
The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization.
Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively.
Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.
clinicaltrials.gov Identifier: NCT00614744.
Details
- Title: Subtitle
- Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial
- Creators
- Abbot R Laptook - Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, Rhode IslandSeetha Shankaran - Department of Pediatrics, Wayne State University, Detroit, MichiganJon E Tyson - Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at HoustonBreda Munoz - Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaEdward F Bell - Department of Pediatrics, University of Iowa, Iowa CityRonald N Goldberg - Department of Pediatrics, Duke University, Durham, North CarolinaNehal A Parikh - Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioNamasivayam Ambalavanan - Division of Neonatology, University of Alabama at BirminghamClaudia Pedroza - Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at HoustonAthina Pappas - Department of Pediatrics, Wayne State University, Detroit, MichiganAbhik Das - Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, MarylandAasma S Chaudhary - Department of Pediatrics, University of Pennsylvania, PhiladelphiaRichard A Ehrenkranz - Department of Pediatrics, Yale University School of Medicine, New Haven, ConnecticutAngelita M Hensman - Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, Rhode IslandKrisa P Van Meurs - Lucile Packard Children's Hospital, Palo Alto, CaliforniaLina F Chalak - Department of Pediatrics, University of Texas Southwestern Medical Center, DallasAmir M Khan - Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at HoustonShannon E G Hamrick - Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, GeorgiaGregory M Sokol - Department of Pediatrics, Indiana University School of Medicine, IndianapolisMichele C Walsh - Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OhioBrenda B Poindexter - Department of Pediatrics, Indiana University School of Medicine, IndianapolisRoger G Faix - Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake CityKristi L Watterberg - University of New Mexico Health Sciences Center, AlbuquerqueIvan D Frantz III - Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MassachusettsRonnie Guillet - University of Rochester School of Medicine and Dentistry, Rochester, New YorkUday Devaskar - Department of Pediatrics, University of California, Los AngelesWilliam E Truog - University of Missouri Kansas City School of Medicine, Kansas CityValerie Y Chock - Lucile Packard Children's Hospital, Palo Alto, CaliforniaMyra H Wyckoff - Department of Pediatrics, University of Texas Southwestern Medical Center, DallasElisabeth C McGowan - Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, Rhode IslandDavid P Carlton - Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, GeorgiaHeidi M Harmon - Department of Pediatrics, Indiana University School of Medicine, IndianapolisJane E Brumbaugh - Department of Pediatrics, University of Iowa, Iowa CityC Michael Cotten - Department of Pediatrics, Duke University, Durham, North CarolinaPablo J Sánchez - Department of Pediatrics, Nationwide Children's Hospital, Columbus, OhioAnna Maria Hibbs - Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OhioRosemary D Higgins - Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.318(16), pp.1550-1560
- DOI
- 10.1001/jama.2017.14972
- PMID
- 29067428
- PMCID
- PMC5783566
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Grant note
- UG1 HD053109 / NICHD NIH HHS UG1 HD040689 / NICHD NIH HHS UG1 HD053089 / NICHD NIH HHS UG1 HD027851 / NICHD NIH HHS UG1 HD027904 / NICHD NIH HHS R01 NS102617 / NINDS NIH HHS UL1 TR001863 / NCATS NIH HHS UG1 HD087229 / NICHD NIH HHS UG1 HD027880 / NICHD NIH HHS
- Language
- English
- Date published
- 10/24/2017
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984093507202771
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