Therapeutic hypothermia

Therapeutic hypothermia reduces death and severe disability in moderate-to-severe hypoxic-ischemic encephalopathy (HIE) when started within the first 6 hours of life in newborns of 36 weeks or more. This tool walks through the eligibility criteria of the 2026 American Academy of Pediatrics clinical report and returns a verdict with the reasoning, item by item.

How the decision is built

Block 0 checks gestational age and postnatal age: under 35 weeks or over 24 hours of life exclude; 35 completed weeks and the 6-to-24-hour window lead to a shared decision. Block A requires one criterion of peripartum hypoxia-ischemia, or both NICHD-pathway items when the blood gas is missing or borderline. Block B requires moderate-to-severe encephalopathy in at least 3 of the 6 categories of the modified Sarnat exam, or seizures. Block C records the aEEG as support only.

The five verdicts

Indicated: start hypothermia at 33.5 °C for 72 hours, rewarming at 0.5 °C/h. Shared decision: A and B satisfied but GA or window outside the trials. Individualized decision: encephalopathy present without evidence of hypoxia-ischemia, a scenario in which the report allows the therapy to be considered. Not indicated for now: no moderate-to-severe encephalopathy, reassess within the window. Not indicated: outside GA or window.

Example

Newborn at 39 weeks, 3 hours old, cord pH 6.95 and Apgar 4 at 10 minutes. Exam: lethargy, decreased activity, generalized hypotonia and weak Moro; posture and autonomic system normal. Block 0 complete, block A with 2 criteria, block B with 4 of 6 categories. Verdict: indicated. Start hypothermia or transfer immediately to a center that provides it.

Footnotes

1. Fig. 1 — decision algorithm for starting therapeutic hypothermia in the neonate with HIE. Ref. 1.
2. Fig. 1, note d, and Recommendation 3 — infants born between 35 0/7 and 35 6/7 weeks may be discussed case by case; equivocal data, with a discussion of risks and benefits with the family documented in the chart. Ref. 1.
3. Fig. 1, note e, and Recommendation 4 — starting between 6 and 24 h of life, in newborns who did not initially meet criteria or could not start within the first 6 h, may be considered after discussion with the parents or guardians about benefits and risks. It is uncertain whether this group benefits. Ref. 1.
4. Key Action Statement (Late Preterm) — therapeutic hypothermia is not recommended in infants born at less than 35 weeks of gestational age. Ref. 1.
5. Fig. 1 and Table 2 — documentation of peripartum hypoxia-ischemia used in the clinical trials: pH ≤ 7.00 or base deficit ≥ 16 mmol/L in cord blood or an arterial sample obtained in the first 60 min of life; Apgar ≤ 5 at 10 min; need for assisted ventilation started at birth and continued for ≥ 10 min. Ref. 1.
6. Fig. 1, note b — the NICHD Whole-Body Cooling trial included neonates without an available blood gas, or with pH 7.01–7.15, or base deficit 10–15.9 mmol/L in the first 60 min, provided they met two additional criteria: (1) an acute perinatal event supporting hypoxia-ischemia — late or variable decelerations, sustained fetal bradycardia < 80 bpm for > 15 min, cord prolapse, cord or uterine rupture, maternal trauma, hemorrhage or cardiorespiratory arrest — and (2) need for assisted ventilation at birth continued for 10 min or Apgar ≤ 5 at 10 min. Ref. 1.
7. Table 1 — moderate-to-severe encephalopathy criteria in 6 categories. The NICHD modified Sarnat exam makes the neonate a candidate when scoring moderate or severe in at least 3 of the 6 categories. Ref. 1.
8. Recommendation 2.ii and Fig. 1, note g — evidence of moderate-to-severe encephalopathy on neurologic examination (Table 1) or clinical or electrographic seizures is required. When there is moderate or severe encephalopathy and the biochemical and clinical criteria are borderline, with no other identifiable cause, the clinician may consider therapeutic hypothermia. Ref. 1.
9. Recommendation 1 and Key Action Statements — target temperature of 33.5 °C, started within the first 6 h of life and maintained for 72 h, followed by slow rewarming (0.5 °C/h). Ref. 1.
10. Fig. 1, notes a and i, Recommendations 6 and 7 — when HIE is suspected, passive cooling may be started by turning off the radiant warmer, which helps bring forward the start of therapy. Hyperthermia should be avoided in all cases, even when hypothermia is not provided. Centers offering hypothermia should have continuous neuromonitoring with EEG (preferred) or aEEG, neuroimaging and pediatric neurology consultation. Ref. 1.
11. Table 2 — only some trials (CoolCap, TOBY, neo.nEURO.network) used the aEEG as an inclusion criterion; NICHD, China and ICE did not. The eligibility criteria of the AAP Recommendations do not include the aEEG. Background pattern definitions: Ref. 2.

References

• Zanelli SA, Wusthoff CJ, Lucke AM, Kaufman DA; American Academy of Pediatrics, Committee on Fetus and Newborn; Section on Neurology. Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Clinical Report. Pediatrics. 2026;157(2):e2025073627. doi:10.1542/peds.2025-073627
• El-Dib M, de Vries LS. Neurophysiological Monitoring. In: Meijler G, Mohammad K, eds. Neonatal Brain Injury. Springer, Cham; 2024. doi:10.1007/978-3-031-55972-3_16 (open access, CC BY 4.0)
• Shankaran S, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574-84.

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