{ "release_id": "c7fb95f1d15a7d13", "id": "maternal:therapeutic-hypothermia", "owner": "maternal", "kind": "intervention", "slug": "therapeutic-hypothermia", "name": "Cooling treatment (therapeutic hypothermia) for HIE", "aliases": [ "Whole-body cooling", "Therapeutic hypothermia" ], "atlases": [ "maternal" ], "summary_plain": "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.", "summary_technical": "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.", "editorial_state": "draft", "last_substantive_edit": "2026-10-14", "last_evidence_check": null, "next_review_due": null, "identifiers": [], "navigation": { "maternal": { "life-stage": [ "newborn" ], "care-area": [ "newborn-care" ] } }, "payload": { "subtype": "procedure", "mechanism": null, "components": null }, "content_digest": "24c52741177bb2a076fe4ed8bdde532089774048b87ceda33188dc3213b7f044", "review": { "content_digest": "24c52741177bb2a076fe4ed8bdde532089774048b87ceda33188dc3213b7f044", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "claims": [ { "release_id": "c7fb95f1d15a7d13", "id": "maternal:claim-helix-death-or-disability", "owner": "maternal", "subject_entity_id": "maternal:therapeutic-hypothermia", "category": "effect", "statement": "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.", "context": { "id": "maternal:ctx-helix-neonatal-encephalopathy-south-asia", "label": "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_note": "Term and near-term newborns, randomised within 6 hours of birth", "life_stage_terms": { "maternal": [ "newborn" ] }, "gestational_age_min_days": 252, "gestational_age_max_days": null, "gestational_age_basis": "at_birth", "postnatal_age_min_days": null, "postnatal_age_max_days": null, "gestational_age_status": null, "postnatal_age_status": null, "followup_description": "The primary outcome was death or moderate or severe disability at 18 to 22 months.", "eligibility": { "inclusion": [ "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)" ], "exclusion": [] } }, "evidence_stage": "interventional", "certainty": "not_assessed", "certainty_method": null, "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.", "editorial_state": "draft", "checked_at": null, "next_review_due": null, "valid_from": null, "valid_to": null, "citations": [ { "evidence_role": "supports", "locator": "Abstract, Findings, sentence 4", "applicability_note": "Primary outcome result.", "snapshot": { "id": "maternal:pmc-pmc8371331-2026-10-14", "retrieved_at": "2026-10-14T18:24:01Z", "content_hash": "5fb8793f485155f0cf4e9262de19b2fd02566186ad18ce9305e17702f4cd5a4f", "source_effective_date": null, "public_archive_url": null, "source_state": "corrected" }, "source": { "id": "maternal:pubmed-10-1016-s2214-109x-21-00264-3", "source_type": "publication", "title": "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", "canonical_url": "https://doi.org/10.1016/S2214-109X(21)00264-3", "identifiers": [ { "scheme": "doi", "value": "10.1016/S2214-109X(21)00264-3", "normalized_value": "10.1016/s2214-109x(21)00264-3", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "34358491", "normalized_value": "34358491", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmcid", "value": "PMC8371331", "normalized_value": "PMC8371331", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2021-08-03", "publisher": "The Lancet. 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Short quotation with attribution. The XML is committed as research/snapshots/mx-pmc-PMC8636277.xml.", "public_text": "quote" } } ], "review": { "content_digest": "9d3c877698180c3bb29202556deb5c7991a0ae8339a745c32ab5ded60e08ce2e", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "api_path": "api/v1/claims/maternal--claim-helix-death-or-disability.json" }, { "release_id": "c7fb95f1d15a7d13", "id": "maternal:claim-helix-death", "owner": "maternal", "subject_entity_id": "maternal:therapeutic-hypothermia", "category": "safety", "statement": "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.", "context": { "id": "maternal:ctx-helix-neonatal-encephalopathy-south-asia", "label": "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_note": "Term and near-term newborns, randomised within 6 hours of birth", "life_stage_terms": { "maternal": [ "newborn" ] }, "gestational_age_min_days": 252, "gestational_age_max_days": null, "gestational_age_basis": "at_birth", "postnatal_age_min_days": null, "postnatal_age_max_days": null, "gestational_age_status": null, "postnatal_age_status": null, "followup_description": "The primary outcome was death or moderate or severe disability at 18 to 22 months.", "eligibility": { "inclusion": [ "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)" ], "exclusion": [] } }, "evidence_stage": "interventional", "certainty": "not_assessed", "certainty_method": null, "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. 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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.", "context": { "id": "maternal:ctx-nichd-cooling-term-hie-us", "label": "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. 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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. 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