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

The DOI matches its Crossref record; 149 of the 150 references it cites were found in a registry or an index.

Cooling for newborns with hypoxic ischaemic encephalopathy

Open access
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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  1. Thayyil S Ayer M Guhan B Marlow N Jacobs I Costello A Whole body cooling using phase changing material in neonatal encephalopathy: a pilot randomised control trial. Proceedings of the Neonatal Society Autumn Conference; 2009 Nov 29; London London Neonatal Society 2009
  2. Filippi, Safety and efficacy of oral topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia: a pilot study of the Neonatal Neuroprotection of Asphyxiated Tuscan Infants (NeoNATI) Network, clinicaltrials.gov/show/NCT01241019
  3. Gunn, 2001, Is cerebral hypothermia a possible neuroprotective strategy after asphyxia in the premature fetus?, Pediatric Research, 49, 435A
  4. Pfister R Bingham P Carpenter J Horbar J Kenny M Inder T Hypothermia in practice, initial observations from the Vermont Oxford Network. Proceeding of the Pediatric Academic Society Conference. 2010 May 2; Vancouver E-PAS2010:26.32.5 2010
  5. The Nordic Cochrane Centre, The Cochrane Collaboration Review Manager (RevMan) 2011

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Metadata

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
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
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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