Cooling treatment (therapeutic hypothermia) for HIE

Cooling a baby's body to about 33.5 degrees C for 72 hours after birth to protect the brain. The 2005 US trial found fewer babies died or had disability. A 2021 trial in India, Sri Lanka and Bangladesh found no reduction in death or disability and more deaths with cooling. Which result applies depends on the setting.

Also called Whole-body cooling · Therapeutic hypothermia

Intervention
In this atlas

Overview

Technical summary

NICHD trial: death or moderate or severe disability 44% against 62% (risk ratio 0.72, 95% CI 0.54 to 0.95). HELIX: 50% against 47% (risk ratio 1.06, 95% CI 0.87 to 1.30), with deaths 42% against 31% (p=0.022); the authors concluded that cooling should not be offered in low-income and middle-income countries even where tertiary neonatal intensive care is available. Each claim keeps its own population and setting. The ClinicalTrials.gov record of the NICHD trial describes 96 hours of cooling and the paper 72 hours; both are kept.

About this intervention

Type: Procedure
Mechanism: Not reported

Claims and evidence

Context Infants of at least 36 weeks with moderate or severe encephalopathy in India, Sri Lanka and Bangladesh (HELIX trial)

Recipient: Newborn
Population: Infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 minutes of age or an Apgar score under 6 at 5 minutes (hospital births), or no crying by 5 minutes (home births). 408 infants were recruited: 202 to cooling and 206 to usual care.
Care setting: Seven tertiary neonatal intensive care units with facilities for invasive ventilation, cardiovascular support and 3 Tesla MRI.
Geography: India, Sri Lanka and Bangladesh
Life stage: Term and near-term newborns, randomised within 6 hours of birth
Gestational age: at least 36 weeks 0 days (252 days), measured at birth
Postnatal age: Not reported
Follow-up: The primary outcome was death or moderate or severe disability at 18 to 22 months.

Eligibility: 3 inclusion criteria; exclusion criteria not stated

Included: Born at or after 36 weeks of gestation
Moderate or severe neonatal encephalopathy
Need for continued resuscitation at 5 minutes, Apgar score under 6 at 5 minutes, or no crying by 5 minutes (home births)
Excluded: None stated

Effect Interventional Certainty not assessed

In the HELIX trial in India, Sri Lanka and Bangladesh, whole-body cooling to 33.5 degrees C for 72 hours did not reduce the combined outcome of death or moderate or severe disability at 18 to 22 months: 98 infants (50%) with cooling and 94 (47%) with usual care (risk ratio 1.06, 95% CI 0.87 to 1.30; p=0.55). The authors concluded that cooling did not reduce the combined outcome in low-income and middle-income countries.

Source problem. A cited source is corrected. Check the sources before relying on this claim.
Applies to Newborn
- Infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 minutes of age or an Apgar score under 6 at 5 minutes (hospital births), or no crying by 5 minutes (home births). 408 infants were recruited: 202 to cooling and 206 to usual care.
- Seven tertiary neonatal intensive care units with facilities for invasive ventilation, cardiovascular support and 3 Tesla MRI.
- India, Sri Lanka and Bangladesh
- Term and near-term newborns, randomised within 6 hours of birth
- Gestational age at least 36 weeks 0 days, measured at birth
- Postnatal age Not reported
Follow-up The primary outcome was death or moderate or severe disability at 18 to 22 months.
Certainty method
Not assessed

Limitations
Open-label trial in seven tertiary neonatal intensive care units; masking was not possible, though outcome assessors were masked. Primary outcome data were available for 195 of 202 infants in the cooling group and 199 of 206 in the control group. The result applies to this population and setting, and the NICHD trial in US units found a benefit, so the setting decides which claim applies. PubMed links a published correction (PMID 34450042, Lancet Global Health 2021, PMC8636277): it adds the list of HELIX consortium members to the article's appendix, and the correction notice describes no other change.

Last checked
Not recorded

Next evidence check due
Not scheduled
Sources and citations (5)
1. Supports Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Findings, sentence 4
  
  How it applies
  Primary outcome result.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
2. Background Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Methods, sentences 1 to 7
  
  How it applies
  Design, population, treatment and primary outcome.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
3. Background Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Findings, sentences 2 and 3
  
  How it applies
  Numbers recruited, assigned and with primary outcome data.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
4. Background Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Interpretation, sentence 1
  
  How it applies
  The authors' interpretation.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
5. Background Correction to Lancet Glob Health 2021; 9: e1273-85 (HELIX trial report)
  
  Publication · Elsevier (The Lancet Global Health 9(10):e1371) · Edition PubMed record (PMID 34450042, no abstract) and the PMC open-access text of the correction (PMC8636277), dated 24 August 2021. · DOI: 10.1016/S2214-109X(21)00397-1
  
  Locator
  Body, correction text
  
  How it applies
  The published correction to the HELIX report.
  
  Retrieved
  2026-10-14T19:48:32Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  b5f28d719494fcbcacc399433970b4c07aac0f89edcdeab3e8428428294ee818
  
  Reuse basis
  PMC8636277 states that it is open access under CC BY 4.0. Short quotation with attribution. The XML is committed as research/snapshots/mx-pmc-PMC8636277.xml.
Safety Interventional Certainty not assessed

In the HELIX trial more babies died with cooling than with usual care: 84 infants (42%) against 63 (31%; p=0.022), and 72 (36%) against 49 (24%; p=0.0087) during neonatal hospitalisation. The authors state that cooling significantly increased death alone and that it should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even where tertiary neonatal intensive care is available. Five serious adverse events were reported (three with cooling, two in the control group), and none were judged causally related to the intervention.

Source problem. A cited source is corrected. Check the sources before relying on this claim.
Applies to Newborn
- Infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 minutes of age or an Apgar score under 6 at 5 minutes (hospital births), or no crying by 5 minutes (home births). 408 infants were recruited: 202 to cooling and 206 to usual care.
- Seven tertiary neonatal intensive care units with facilities for invasive ventilation, cardiovascular support and 3 Tesla MRI.
- India, Sri Lanka and Bangladesh
- Term and near-term newborns, randomised within 6 hours of birth
- Gestational age at least 36 weeks 0 days, measured at birth
- Postnatal age Not reported
Follow-up The primary outcome was death or moderate or severe disability at 18 to 22 months.
Certainty method
Not assessed

Limitations
Death was a secondary finding of an open-label trial of 408 infants; the abstract prints the death counts without the group sizes beside them. The result is for the three South Asian countries studied. This record reports the finding as the trial reported it and does not extend it to other settings. PubMed links a published correction (PMID 34450042, Lancet Global Health 2021, PMC8636277): it adds the list of HELIX consortium members to the article's appendix, and the correction notice describes no other change.

Last checked
Not recorded

Next evidence check due
Not scheduled
Sources and citations (4)
1. Supports Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Findings, sentences 5 to 7
  
  How it applies
  Deaths and adverse events.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
2. Supports Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Interpretation, sentences 1 and 2
  
  How it applies
  The authors' conclusion on death and on offering cooling.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
3. Background Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
  
  Publication · The Lancet. Global health · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, plus the PMC Open Access full text (PMC8371331, CC BY 4.0). The Lancet Global Health version of record was not fetched. · Published 2021-08-03 · DOI: 10.1016/S2214-109X(21)00264-3 · PMID: 34358491 · PMCID: PMC8371331
  
  Locator
  Abstract, Findings, sentence 2
  
  How it applies
  Number of infants recruited.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Corrected
  
  Snapshot hash
  5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f
  
  Reuse basis
  The PMC article is licensed CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) and is committed at research/snapshots/mh-pmc-PMC8371331.xml. Attribution: Thayyil S et al., Lancet Glob Health 2021, doi:10.1016/S2214-109X(21)00264-3, via PMC (PMC8371331). The PubMed record snapshot keeps only the hash of its bytes. Short factual quotations under 25 words, with the citation.
4. Background Correction to Lancet Glob Health 2021; 9: e1273-85 (HELIX trial report)
  
  Publication · Elsevier (The Lancet Global Health 9(10):e1371) · Edition PubMed record (PMID 34450042, no abstract) and the PMC open-access text of the correction (PMC8636277), dated 24 August 2021. · DOI: 10.1016/S2214-109X(21)00397-1
  
  Locator
  Body, correction text
  
  How it applies
  The published correction to the HELIX report.
  
  Retrieved
  2026-10-14T19:48:32Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  b5f28d719494fcbcacc399433970b4c07aac0f89edcdeab3e8428428294ee818
  
  Reuse basis
  PMC8636277 states that it is open access under CC BY 4.0. Short quotation with attribution. The XML is committed as research/snapshots/mx-pmc-PMC8636277.xml.

Context Infants of at least 36 weeks with moderate or severe encephalopathy in US neonatal units (NICHD cooling trial)

Recipient: Newborn
Population: Infants of at least 36 weeks of gestation admitted at or before 6 hours of age with severe acidosis, or perinatal complications and resuscitation at birth, who had moderate or severe encephalopathy. Of 239 eligible infants, 102 were assigned to cooling and 106 to usual care.
Care setting: Hospitals of the NICHD Neonatal Research Network. The abstract says admitted to the hospital; ClinicalTrials.gov lists sites in the United States.
Geography: United States (ClinicalTrials.gov)
Life stage: Term and near-term newborns of at least 36 weeks, treated within the first 6 hours of life
Gestational age: at least 36 weeks 0 days (252 days), measured at birth
Postnatal age: Not reported
Follow-up: Neurodevelopmental outcome was assessed at 18 to 22 months of age.

Eligibility: 4 inclusion criteria; exclusion criteria not stated

Included: Gestational age of at least 36 weeks
Admitted at or before 6 hours of age
Severe acidosis, or perinatal complications with resuscitation at birth
Moderate or severe encephalopathy
Excluded: None stated

Effect Interventional Certainty not assessed

In the 2005 NICHD trial in infants of at least 36 weeks with moderate or severe encephalopathy, whole-body cooling to 33.5 degrees C for 72 hours lowered the combined outcome of death or moderate or severe disability at 18 to 22 months: 45 of 102 infants (44%) with cooling against 64 of 103 (62%) with usual care (risk ratio 0.72, 95% CI 0.54 to 0.95; P=0.01). Deaths alone were 24% against 37% (risk ratio 0.68, 95% CI 0.44 to 1.05; P=0.08), which was not statistically significant. The authors reported no increase in major disability among survivors.
Applies to Newborn
- Infants of at least 36 weeks of gestation admitted at or before 6 hours of age with severe acidosis, or perinatal complications and resuscitation at birth, who had moderate or severe encephalopathy. Of 239 eligible infants, 102 were assigned to cooling and 106 to usual care.
- Hospitals of the NICHD Neonatal Research Network. The abstract says admitted to the hospital; ClinicalTrials.gov lists sites in the United States.
- United States (ClinicalTrials.gov)
- Term and near-term newborns of at least 36 weeks, treated within the first 6 hours of life
- Gestational age at least 36 weeks 0 days, measured at birth
- Postnatal age Not reported
Follow-up Neurodevelopmental outcome was assessed at 18 to 22 months of age.
Certainty method
Not assessed

Limitations
Randomised comparison with usual care. The result applies to this population and setting. The same treatment was tested in India, Sri Lanka and Bangladesh in the HELIX trial, which found no reduction in death or disability and more deaths with cooling. The ClinicalTrials.gov record describes cooling for 96 hours and the paper 72 hours; both are kept. Only the abstract was read.

Last checked
Not recorded

Next evidence check due
Not scheduled
Sources and citations (4)
1. Supports Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy
  
  Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2005-10-13 · DOI: 10.1056/NEJMcps050929 · PMID: 16221780
  
  Locator
  Abstract, RESULTS, sentences 4 to 6
  
  How it applies
  Primary outcome, deaths and disability.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  57ed1ee99cddf1334683d6aca7c0231f9d6f7be3169b8b704c6dc4650d655de7
  
  Reuse basis
  PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.
2. Background Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy
  
  Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2005-10-13 · DOI: 10.1056/NEJMcps050929 · PMID: 16221780
  
  Locator
  Abstract, METHODS, sentences 1 to 4
  
  How it applies
  Population, treatment and primary outcome.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  57ed1ee99cddf1334683d6aca7c0231f9d6f7be3169b8b704c6dc4650d655de7
  
  Reuse basis
  PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.
3. Background Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy
  
  Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2005-10-13 · DOI: 10.1056/NEJMcps050929 · PMID: 16221780
  
  Locator
  Abstract, RESULTS, sentence 1
  
  How it applies
  Number eligible and assigned.
  
  Retrieved
  2026-10-14T18:24:01Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  57ed1ee99cddf1334683d6aca7c0231f9d6f7be3169b8b704c6dc4650d655de7
  
  Reuse basis
  PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.
4. Background Whole-Body Cooling for Birth Asphyxia in Term Infants
  
  Registry · U.S. National Library of Medicine (ClinicalTrials.gov) · Edition ClinicalTrials.gov API v2 record, last update posted 2019-03-22. · NCT: NCT00005772
  
  Locator
  protocolSection.armsInterventionsModule.armGroups[0].description
  
  How it applies
  The registry describes the cooling arm as 96 hours.
  
  Retrieved
  2026-10-14T18:23:55Z
  
  Source effective date
  2019-03-22
  
  Source state
  Current
  
  Snapshot hash
  4b3d3e9e0dbfbb5108f8defa668641bb850a84ad5a9b90c266b874a54eb07b8d
  
  Reuse basis
  Registry record. The raw API JSON is committed. The ClinicalTrials.gov terms page is rendered by JavaScript and its text was not read by a script, so the redistribution basis is unverified; any quotation stays short. The raw file is committed at research/snapshots/mh-ctgov-NCT00005772.json.

Clinical links

Each link reports what one cited claim says about one population. "Evaluated for" means studied, not shown to work. These links do not show that anything is effective or right for you.

Claim, not a settled fact NICHD trial: fewer deaths or disability in US units: Brain injury from lack of oxygen around birth (HIE) (Claimed to treat)
Applies to Newborn
- Infants of at least 36 weeks of gestation admitted at or before 6 hours of age with severe acidosis, or perinatal complications and resuscitation at birth, who had moderate or severe encephalopathy. Of 239 eligible infants, 102 were assigned to cooling and 106 to usual care.
- Hospitals of the NICHD Neonatal Research Network. The abstract says admitted to the hospital; ClinicalTrials.gov lists sites in the United States.
- United States (ClinicalTrials.gov)
- Term and near-term newborns of at least 36 weeks, treated within the first 6 hours of life
- Gestational age at least 36 weeks 0 days, measured at birth
- Postnatal age Not reported
Follow-up Neurodevelopmental outcome was assessed at 18 to 22 months of age.
In the 2005 NICHD trial in infants of at least 36 weeks with moderate or severe encephalopathy, whole-body cooling to 33.5 degrees C for 72 hours lowered the combined outcome of death or moderate or severe disability at 18 to 22 months: 45 of 102 infants (44%) with cooling against 64 of 103 (62%) with usual care (risk ratio 0.72, 95% CI 0.54 to 0.95; P=0.01). Deaths alone were 24% against 37% (risk ratio 0.68, 95% CI 0.44 to 1.05; P=0.08), which was not statistically significant. The authors reported no increase in major disability among survivors.
Limitations. Randomised comparison with usual care. The result applies to this population and setting. The same treatment was tested in India, Sri Lanka and Bangladesh in the HELIX trial, which found no reduction in death or disability and more deaths with cooling. The ClinicalTrials.gov record describes cooling for 96 hours and the paper 72 hours; both are kept. Only the abstract was read.
Claim, not a settled fact HELIX: no reduction in death or disability in South Asia: Brain injury from lack of oxygen around birth (HIE) (Evaluated for)
Applies to Newborn
- Infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 minutes of age or an Apgar score under 6 at 5 minutes (hospital births), or no crying by 5 minutes (home births). 408 infants were recruited: 202 to cooling and 206 to usual care.
- Seven tertiary neonatal intensive care units with facilities for invasive ventilation, cardiovascular support and 3 Tesla MRI.
- India, Sri Lanka and Bangladesh
- Term and near-term newborns, randomised within 6 hours of birth
- Gestational age at least 36 weeks 0 days, measured at birth
- Postnatal age Not reported
Follow-up The primary outcome was death or moderate or severe disability at 18 to 22 months.
In the HELIX trial in India, Sri Lanka and Bangladesh, whole-body cooling to 33.5 degrees C for 72 hours did not reduce the combined outcome of death or moderate or severe disability at 18 to 22 months: 98 infants (50%) with cooling and 94 (47%) with usual care (risk ratio 1.06, 95% CI 0.87 to 1.30; p=0.55). The authors concluded that cooling did not reduce the combined outcome in low-income and middle-income countries.
Source problem. A cited source is corrected. Check the sources before relying on this claim.
Limitations. Open-label trial in seven tertiary neonatal intensive care units; masking was not possible, though outcome assessors were masked. Primary outcome data were available for 195 of 202 infants in the cooling group and 199 of 206 in the control group. The result applies to this population and setting, and the NICHD trial in US units found a benefit, so the setting decides which claim applies. PubMed links a published correction (PMID 34450042, Lancet Global Health 2021, PMC8636277): it adds the list of HELIX consortium members to the article's appendix, and the correction notice describes no other change.
Claim, not a settled fact HELIX: more deaths with cooling in South Asia: Brain injury from lack of oxygen around birth (HIE) (Evaluated for)
Applies to Newborn
- Infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 minutes of age or an Apgar score under 6 at 5 minutes (hospital births), or no crying by 5 minutes (home births). 408 infants were recruited: 202 to cooling and 206 to usual care.
- Seven tertiary neonatal intensive care units with facilities for invasive ventilation, cardiovascular support and 3 Tesla MRI.
- India, Sri Lanka and Bangladesh
- Term and near-term newborns, randomised within 6 hours of birth
- Gestational age at least 36 weeks 0 days, measured at birth
- Postnatal age Not reported
Follow-up The primary outcome was death or moderate or severe disability at 18 to 22 months.
In the HELIX trial more babies died with cooling than with usual care: 84 infants (42%) against 63 (31%; p=0.022), and 72 (36%) against 49 (24%; p=0.0087) during neonatal hospitalisation. The authors state that cooling significantly increased death alone and that it should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even where tertiary neonatal intensive care is available. Five serious adverse events were reported (three with cooling, two in the control group), and none were judged causally related to the intervention.
Source problem. A cited source is corrected. Check the sources before relying on this claim.
Limitations. Death was a secondary finding of an open-label trial of 408 infants; the abstract prints the death counts without the group sizes beside them. The result is for the three South Asian countries studied. This record reports the finding as the trial reported it and does not extend it to other settings. PubMed links a published correction (PMID 34450042, Lancet Global Health 2021, PMC8636277): it adds the list of HELIX consortium members to the article's appendix, and the correction notice describes no other change.

Record details

Record id: maternal:therapeutic-hypothermia
Content hash: 24c52741177bb2a076fe4ed8bdde532089774048b87ceda33188dc3213b7f044