Cited by 2,328Neonatal and fetal brain pathologyThermal Regulation in MedicineInfant Development and Preterm Care

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Cooling for newborns with hypoxic ischaemic encephalopathy

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Jacobs, Susan E, Berg, Marie, Hunt, Rod, Tarnow-Mordi, William O, Inder, Terrie E, Davis, Peter G·2013·Cochrane Database of Systematic Reviews

DOI 10.1002/14651858.cd003311.pub3PMC PMC7003568

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Abstract

BACKGROUND: Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae without adverse effects. OBJECTIVES: To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and clinically important side effects. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomised controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012. SELECTION CRITERIA: We included randomised controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). MAIN RESULTS: We included 11 randomised controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68 to 0.83); typical RD -0.15, 95% CI -0.20 to -0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5 to 10) (8 studies, 1344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64 to 0.88), typical RD -0.09 (95% CI -0.13 to -0.04); NNTB 11 (95% CI 8 to 25) (11 studies, 1468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63 to 0.94), typical RD -0.13 (95% CI -0.19 to -0.07); NNTB 8 (95% CI 5 to 14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia. AUTHORS' CONCLUSIONS: There is evidence from the 11 randomised controlled trials included in this systematic review (N = 1505 infants) that therapeutic hypothermia is beneficial in term and late preterm newborns with hypoxic ischaemic encephalopathy. Cooling reduces mortality without increasing major disability in survivors. The benefits of cooling on survival and neurodevelopment outweigh the short-term adverse effects. Hypothermia should be instituted in term and late preterm infants with moderate-to-severe hypoxic ischaemic encephalopathy if identified before six hours of age. Further trials to determine the appropriate techniques of cooling, including refinement of patient selection, duration of cooling and method of providing therapeutic hypothermia, will refine our understanding of this intervention.

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Authors: Jacobs, S. E., Berg, M., Hunt, R., Tarnow-Mordi, W. O., Inder, T. E., & Davis, P. G.
Affiliations: Royal Women's Hospital (AU)
University of Vermont Medical Center (US)
Royal Children's Hospital (AU)
Westmead Hospital (AU)
St. Louis Children's Hospital (US)
ORCID: Berg, Marie
Hunt, Rod
Inder, Terrie E
Davis, Peter G
Venue: Cochrane Database of Systematic Reviews
Publisher: Wiley
Published: 2013-01-31
Volume: 2013
Issue: 3
Pages: CD003311-CD003311
ISSN: 1361-6137 (ISSN-L)
1465-1858
DOI: 10.1002/14651858.cd003311.pub3
PMC: PMC7003568
OpenAlex: W1830337612
Cited by: 2,328
References: 150
Citations by year: 2026: 44 · 2025: 142 · 2024: 190 · 2023: 179 · 2022: 191 · 2021: 231 · 2020: 157 · 2019: 132 · 2018: 162 · 2017: 155 · 2016: 138 · 2015: 142 · 2014: 107 · 2013: 65
FWCI: 21.42
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cochrane Database of Systematic Reviews (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
Keywords: therapeutic hypothermia, hypoxic-ischemic encephalopathy, neonates, intrapartum asphyxia, neurodevelopmental disorders, neonatal mortality, term infants, late preterm infants, neuroprotection, neonatal resuscitation, hypothermia duration
MeSH terms: Asphyxia Neonatorum, Developmental Disabilities, Humans, Hypothermia, Induced, Infant, Infant, Newborn, Infant, Premature, Randomized Controlled Trials as Topic, Hypoxia-Ischemia, Brain, Term Birth

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