Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial
dc.contributor.author | Laptook, Abbot R. | |
dc.contributor.author | Shankaran, Seetha | |
dc.contributor.author | Tyson, Jon E. | |
dc.contributor.author | Munoz, Breda | |
dc.contributor.author | Bell, Edward F. | |
dc.contributor.author | Goldberg, Ronald N. | |
dc.contributor.author | Parikh, Nehal A. | |
dc.contributor.author | Ambalavanan, Namasivayam | |
dc.contributor.author | Pedroza, Claudia | |
dc.contributor.author | Pappas, Athina | |
dc.contributor.author | Das, Abhik | |
dc.contributor.author | Chaudhary, Aasma S. | |
dc.contributor.author | Ehrenkranz, Richard A. | |
dc.contributor.author | Hensman, Angelita M. | |
dc.contributor.author | Van Meurs, Krisa P. | |
dc.contributor.author | Chalak, Lina F. | |
dc.contributor.author | Hamrick, Shannon E. G. | |
dc.contributor.author | Sokol, Gregory M. | |
dc.contributor.author | Walsh, Michele C. | |
dc.contributor.author | Poindexter, Brenda B. | |
dc.contributor.author | Faix, Roger G. | |
dc.contributor.author | Watterberg, Kristi L. | |
dc.contributor.author | Frantz, Ivan D., III | |
dc.contributor.author | Guillet, Ronnie | |
dc.contributor.author | Devaskar, Uday | |
dc.contributor.author | Truog, William E. | |
dc.contributor.author | Chock, Valerie Y. | |
dc.contributor.author | Wyckoff, Myra H. | |
dc.contributor.author | McGowan, Elisabeth C. | |
dc.contributor.author | Carlton, David P. | |
dc.contributor.author | Harmon, Heidi M. | |
dc.contributor.author | Brumbaugh, Jane E. | |
dc.contributor.author | Cotten, C. Michael | |
dc.contributor.author | Sánchez, Pablo J. | |
dc.contributor.author | Hibbs, Anna Maria | |
dc.contributor.author | Higgins, Rosemary D. | |
dc.contributor.author | Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network | |
dc.contributor.department | Pediatrics, School of Medicine | en_US |
dc.date.accessioned | 2018-05-22T18:53:46Z | |
dc.date.available | 2018-05-22T18:53:46Z | |
dc.date.issued | 2017-10-24 | |
dc.description.abstract | Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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). Main Outcomes and Measures: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results: 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. Conclusions and Relevance: 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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Laptook, A. R., Shankaran, S., Tyson, J. E., Munoz, B., Bell, E. F., Goldberg, R. N., … Higgins, R. D. (2017). 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, 318(16), 1550–1560. http://doi.org/10.1001/jama.2017.14972 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/16231 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Medical Association | en_US |
dc.relation.isversionof | 10.1001/jama.2017.14972 | en_US |
dc.relation.journal | JAMA | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Bayes theorem | en_US |
dc.subject | Developmental disabilities | en_US |
dc.subject | Gestational age | en_US |
dc.subject | Hypothermia, Induced | en_US |
dc.subject | Hypoxia-Ischemia, Brain | en_US |
dc.subject | Infant, Newborn | en_US |
dc.subject | Pregnancy complications | en_US |
dc.title | Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial | en_US |
dc.type | Article | en_US |