# Cooling treatment (therapeutic hypothermia) for HIE

Intervention · id `maternal:therapeutic-hypothermia` · Maternal & Newborn Atlas · release `c7fb95f1d15a7d13` (public)

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Also called: Whole-body cooling; Therapeutic hypothermia

Browse, life stage: Newborn  
Browse, care area: Newborn care  

## In plain language

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.

## 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.

## Claims, with the population each applies to

## 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.

### 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.

- Category: Effect
- Evidence stage: Interventional
- Certainty: Certainty not assessed
- Applies to: 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.
- 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
- Source problem: a cited source is corrected. Check the sources before relying on this claim.
- Sources:
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Findings, sentence 4. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: Primary outcome result.
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Methods, sentences 1 to 7. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: Design, population, treatment and primary outcome.
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Findings, sentences 2 and 3. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: Numbers recruited, assigned and with primary outcome data.
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Interpretation, sentence 1. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: The authors' interpretation.
  5. Background: Correction to Lancet Glob Health 2021; 9: e1273-85 (HELIX trial report) (Publication, edition PubMed record (PMID 34450042, no abstract) and the PMC open-access text of the correction (PMC8636277), dated 24 August 2021.) <https://pmc.ncbi.nlm.nih.gov/articles/PMC8636277/>
     Locator: Body, correction text. Retrieved 2026-10-14T19:48:32Z. Source state: Current. Snapshot hash: b5f28d719494fcbcacc399433970b4c07aac0f89edcdeab3e8428428294ee818.
     How it applies: The published correction to the HELIX report.

### 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.

- Category: Safety
- Evidence stage: Interventional
- Certainty: Certainty not assessed
- Applies to: 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.
- 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
- Source problem: a cited source is corrected. Check the sources before relying on this claim.
- Sources:
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Findings, sentences 5 to 7. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: Deaths and adverse events.
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Interpretation, sentences 1 and 2. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: The authors' conclusion on death and on offering cooling.
  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, 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.) <https://doi.org/10.1016/S2214-109X(21)00264-3>
     Locator: Abstract, Findings, sentence 2. Retrieved 2026-10-14T18:24:01Z. Source state: Corrected. Snapshot hash: 5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f.
     How it applies: Number of infants recruited.
  4. Background: Correction to Lancet Glob Health 2021; 9: e1273-85 (HELIX trial report) (Publication, edition PubMed record (PMID 34450042, no abstract) and the PMC open-access text of the correction (PMC8636277), dated 24 August 2021.) <https://pmc.ncbi.nlm.nih.gov/articles/PMC8636277/>
     Locator: Body, correction text. Retrieved 2026-10-14T19:48:32Z. Source state: Current. Snapshot hash: b5f28d719494fcbcacc399433970b4c07aac0f89edcdeab3e8428428294ee818.
     How it applies: The published correction to the HELIX report.

## 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.

### 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.

- Category: Effect
- Evidence stage: Interventional
- Certainty: Certainty not assessed
- Applies to: 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.
- 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
- Sources:
  1. Supports: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMcps050929>
     Locator: Abstract, RESULTS, sentences 4 to 6. Retrieved 2026-10-14T18:24:01Z. Source state: Current. Snapshot hash: 57ed1ee99cddf1334683d6aca7c0231f9d6f7be3169b8b704c6dc4650d655de7.
     How it applies: Primary outcome, deaths and disability.
  2. Background: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMcps050929>
     Locator: Abstract, METHODS, sentences 1 to 4. Retrieved 2026-10-14T18:24:01Z. Source state: Current. Snapshot hash: 57ed1ee99cddf1334683d6aca7c0231f9d6f7be3169b8b704c6dc4650d655de7.
     How it applies: Population, treatment and primary outcome.
  3. Background: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMcps050929>
     Locator: Abstract, RESULTS, sentence 1. Retrieved 2026-10-14T18:24:01Z. Source state: Current. Snapshot hash: 57ed1ee99cddf1334683d6aca7c0231f9d6f7be3169b8b704c6dc4650d655de7.
     How it applies: Number eligible and assigned.
  4. Background: Whole-Body Cooling for Birth Asphyxia in Term Infants (Registry, edition ClinicalTrials.gov API v2 record, last update posted 2019-03-22.) <https://clinicaltrials.gov/study/NCT00005772>
     Locator: protocolSection.armsInterventionsModule.armGroups\[0\].description. Retrieved 2026-10-14T18:23:55Z. Source state: Current. Snapshot hash: 4b3d3e9e0dbfbb5108f8defa668641bb850a84ad5a9b90c266b874a54eb07b8d.
     How it applies: The registry describes the cooling arm as 96 hours.

## Connected pages

- NICHD trial: fewer deaths or disability in US units: Brain injury from lack of oxygen around birth (HIE) (`maternal:hypoxic-ischaemic-encephalopathy`) [a claim, not a settled fact; see claim `maternal:claim-nichd-cooling-death-or-disability` and its context]
- HELIX: no reduction in death or disability in South Asia: Brain injury from lack of oxygen around birth (HIE) (`maternal:hypoxic-ischaemic-encephalopathy`) [a claim, not a settled fact; see claim `maternal:claim-helix-death-or-disability` and its context]
- HELIX: more deaths with cooling in South Asia: Brain injury from lack of oxygen around birth (HIE) (`maternal:hypoxic-ischaemic-encephalopathy`) [a claim, not a settled fact; see claim `maternal:claim-helix-death` and its context]
- Filed under this front: Newborn support: warmth, breathing, feeding (`maternal:front-newborn-support`)
- Investigated in: HELIX trial (cooling in low- and middle-income countries) (`maternal:helix-trial`)
- Investigated in: NICHD whole-body cooling trial for birth asphyxia (`maternal:nichd-whole-body-cooling-trial`)

## Provenance

Content hash: 24c52741177bb2a076fe4ed8bdde532089774048b87ceda33188dc3213b7f044
Last substantive edit: 2026-10-14
Evidence last checked: Not recorded