Journal article
Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks' Gestation: A Randomized Clinical Trial
JAMA pediatrics, Vol.179(4), pp.396-406
04/01/2025
DOI: 10.1001/jamapediatrics.2024.6613
PMCID: PMC11851295
PMID: 39992674
Abstract
Hypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks' gestation. Trials of hypothermia for infants younger than 36 weeks' gestation are lacking.
To assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy.
This randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy at less than 6 hours after birth. Bayesian and intention-to-treat analyses were prespecified. The setting included 19 US Neonatal Research Network centers. Data were analyzed from March 2023 to November 2024.
Infants received unblinded targeted esophageal temperature management. Infants with hypothermia were maintained at 33.5 °C (acceptable 33-34 °C) for 72 hours and then rewarmed. Infants with normothermia were to be maintained at 37 °C (acceptable 36.5-37.3 °C).
Composite of death or disability (moderate or severe) at 18 to 22 months' corrected age adjusted for level of encephalopathy and center.
A total of 168 infants with hypothermia and normothermia were preterm (mean [SD] age, 34.0 [0.8] weeks' gestation and 34.1 [0.8] weeks' gestation, respectively), while 46 of 88 (52%) and 45 of 80 (56%) were male, respectively. Randomization occurred at mean (SD) 4.5 (1.2) hours and 4.5 (1.3) hours for the groups with hypothermia and normothermia, respectively. The primary outcome occurred in 29 of 83 infants (35%) with hypothermia and 20 of 69 infants (29%) with normothermia (adjusted relative risk [hypothermic/normothermic], 1.11; 95% credibility interval, 0.74-2.00), and death occurred in 18 of 88 infants (20%) with hypothermia and 9 of 78 infants (12%) with normothermia (adjusted relative risk, 1.38; 95% credibility interval, 0.79-2.85). Bayesian analysis with neutral prior indicated 74% probability of increased death or disability and 87% probability of increased death with hypothermia.
Among infants 33 to 35 weeks' gestation with hypoxic-ischemic encephalopathy, hypothermia at less than 6 hours' age did not reduce death or disability at 18 to 22 months' corrected age.
ClinicalTrials.gov Identifier: NCT01793129.
Details
- Title: Subtitle
- Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks' Gestation: A Randomized Clinical Trial
- Creators
- Roger G Faix - University of UtahAbbot R Laptook - Brown UniversitySeetha Shankaran - Wayne State UniversityBarry Eggleston - RTI InternationalDhuly Chowdhury - RTI InternationalRoy J Heyne - The University of Texas Southwestern Medical CenterAbhik Das - RTI InternationalClaudia Pedroza - The University of Texas Health Science Center at HoustonJon E Tyson - The University of Texas Health Science Center at HoustonCourtney Wusthoff - Lucile Packard Children's HospitalSonia L Bonifacio - Lucile Packard Children's HospitalPablo J Sánchez - Nationwide Children's HospitalBradley A Yoder - University of UtahMatthew M Laughon - University of North Carolina at Chapel HillDiana M Vasil - The University of Texas Southwestern Medical CenterKrisa P Van Meurs - Stanford UniversityMargaret M Crawford - Florida Gulf Coast UniversityShannon E G Hamrick - Children's Healthcare of AtlantaRosemary D Higgins - Florida Gulf Coast UniversityLina F Chalak - The University of Texas Southwestern Medical CenterBrenda B Poindexter - Cincinnati Children's Hospital Medical CenterRobin K Ohls - University of UtahTarah T Colaizy - University of IowaMichele E Hartley-McAndrew - University at Buffalo, State University of New YorkKevin Dysart - Children's Hospital of PhiladelphiaCarl T D'Angio - University of RochesterRonnie Guillet - University of RochesterStephen D Kicklighter - WakeMedWaldemar A Carlo - University of Alabama at Birmingham HospitalGregory M Sokol - Riley Hospital for ChildrenSara B DeMauro - University of PennsylvaniaAnna Maria Hibbs - Case Western Reserve UniversityC Michael Cotten - Duke University HospitalStephanie L Merhar - Cincinnati Children's Hospital Medical CenterRoopali V Bapat - Nationwide Children's HospitalHeidi M Harmon - University of IowaElizabeth Sewell - Children's Healthcare of AtlantaNathalie L Maitre - The Ohio State UniversityRicardo Mosquera - The University of Texas Health Science Center at HoustonGirija Natarajan - Wayne State UniversitySarah Winter - University of UtahKristen L Benninger - Nationwide Children's HospitalSusan R Hintz - Lucile Packard Children's HospitalMyriam Peralta-Carcelen - University of Alabama at Birmingham HospitalAbbey C Hines - Riley Hospital for ChildrenAndrea F Duncan - Children's Hospital of PhiladelphiaDeanne E Wilson-Costello - Case Western Reserve UniversityAndrea Trembath - University of North Carolina at Chapel HillWilliam F Malcolm - Duke University HospitalMichele C Walsh - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA pediatrics, Vol.179(4), pp.396-406
- DOI
- 10.1001/jamapediatrics.2024.6613
- PMID
- 39992674
- PMCID
- PMC11851295
- NLM abbreviation
- JAMA Pediatr
- ISSN
- 2168-6203
- eISSN
- 2168-6211
- Publisher
- AMER MEDICAL ASSOC
- Grant note
- National Institutes of Health: U10 HD27871, U10 HD53119, UG1 HD21364, UG1 HD21373, UG1 HD21385, UG1 HD27851, UG1 HD27853, UG1 HD27856, UG1 HD27880, UG1 HD27904, UG1 HD34216, UG1 HD36790, UG1 HD40492, UG1 HD40689, UG1 HD53089, UG1 HD53109, UG1 HD68244, UG1 HD68270, UG1 HD68278, UG1 HD68263, UG1 HD68284, UG1 HD87226, UG1 HD87229 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Center for Advancing Translational Sciences (NCATS): UL1 TR6, UL1 TR41, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR442, UL1 TR454, UL1 TR1117
This study was supported in part by grants U10 HD27871, U10 HD53119, UG1 HD21364, UG1 HD21373, UG1 HD21385, UG1 HD27851, UG1 HD27853, UG1 HD27856, UG1 HD27880,UG1 HD27904, UG1 HD34216, UG1 HD36790, UG1 HD40492, UG1 HD40689, UG1 HD53089, UG1 HD53109, UG1 HD68244, UG1 HD68270, UG1 HD68278, UG1 HD68263, UG1 HD68284, UG1 HD87226, UG1 HD87229) from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and grants (UL1 TR6, UL1 TR41, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR442, UL1 TR454, UL1 TR1117) from the National Center for Advancing Translational Sciences (NCATS), which provided grant support through cooperative agreements for the Neonatal Research Network. The National Institutes of Health, the NICHD, the National Center for Research Resources, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network's Preemie Hypothermia trial through cooperative agreements.
- Language
- English
- Electronic publication date
- 02/24/2025
- Date published
- 04/01/2025
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984793878102771
Metrics
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