Birth · Newborn
Therapeutic Hypothermia Eligibility
Therapeutic hypothermia (cooling) eligibility checker per NICHD 2005 / TOBY 2008 / NICE NG237 criteria. Cooling within 6 hours of birth reduces death/disability by ~25 % in moderate-severe HIE.
Last reviewed 25 May 2026
Therapeutic hypothermia — eligibility
Neonatal cooling for HIE
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Perinatal depression (need ≥ 1)
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pH
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Encephalopathy (need Sarnat II/III OR Thompson > 7)
Sarnat stage
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Enter the criteria to check cooling eligibility.
Educational tool only — not medical advice. Therapeutic hypothermia is a NICU-level intervention requiring trained teams. Cooling reduces death/disability by ~25 % in moderate-severe HIE (Jacobs 2013 Cochrane); strict adherence to eligibility criteria is essential — cooling outside criteria (mild HIE, preterm, late presentation) has not been shown to benefit and may harm.
What does this mean?
Therapeutic hypothermia is one of the highest-evidence interventions in neonatology — cooling babies to 33.5 °C for 72 hours reduces death or major disability by ~25 % in moderate-to-severe HIE (Jacobs 2013 Cochrane meta-analysis, > 1,500 babies). Mechanism: mild hypothermia slows the secondary “reperfusion injury” cascade (excitotoxicity, free-radical damage, apoptosis) that unfolds over hours after the initial hypoxic-ischaemic insult. The 6-hour window matters — cooling started later is less effective. Strict eligibility (term ≥ 36 wk, evidence of perinatal depression, moderate/severe encephalopathy by Sarnat or Thompson) is essential because cooling outside criteria has not been shown to help and may harm (e.g. mild HIE — TOBY-Xe COOLPROP showed no benefit, possibly worse neurodevelopment). Whole-body and head cooling are equivalent. Rewarm slowly (≤ 0.5 °C/h). MRI day 5–7 predicts long-term outcome.
Introduction
Therapeutic hypothermia (cooling) is the standard of care for moderate-to-severe neonatal hypoxic-ischaemic encephalopathy (HIE). Cooling to 33.5 °C for 72 hours, initiated within 6 hours of birth, reduces the combined endpoint of death and major neurodisability by approximately 25 % (Jacobs 2013 Cochrane, 1,505 infants pooled).
Eligibility criteria (NICHD / TOBY / NICE)
ALL of the following must be met:
- Gestational age ≥ 36 weeks.
- Age ≤ 6 hours postnatally.
- Evidence of perinatal depression — any one of:
- Apgar score ≤ 5 at 10 minutes
- Need for ongoing resuscitation at 10 minutes
- Cord arterial pH < 7.0
- Base deficit ≥ 16 mmol/L
- Moderate or severe encephalopathy — Sarnat Stage II or III, OR Thompson HIE Score > 7.
The cooling protocol
- Core temperature target: 33.5 °C (range 33.0-34.0).
- Duration: 72 hours.
- Whole-body cooling (servo-controlled cooling mattress) OR selective head cooling.
- Continuous rectal or oesophageal temperature monitoring.
- Sedation usually required (morphine; pancuronium avoided).
- Rewarming gradually: ≤ 0.5 °C per hour.
- EEG / aEEG monitoring throughout for seizure detection.
The 6-hour window
The 6-hour window is critical. The secondary energy-failure phase of HIE — apoptotic cell death following the primary hypoxic event — begins around 6-15 hours after the insult. Cooling started during this window interrupts the cascade. Cooling started later is less effective; the 2017 Laptook trial (NEJM) of cooling at 6-24 hours suggested possible benefit but smaller effect size.
Outcomes
Cochrane meta-analysis (Jacobs 2013, 11 trials, 1,505 infants):
- Death or major neurodisability at 18 months: 60 % → 47 % with cooling (RR 0.75).
- NNT 7-8 to prevent one bad outcome.
- Moderate HIE NNT ~9; severe HIE NNT ~6 (background mortality higher).
- NO benefit (and possible harm) in mild HIE — eligibility criteria matter.
Side effects
- Thrombocytopenia (50-70 % — usually mild, resolves with rewarming).
- Hypotension (often needs inotrope support).
- Bradycardia (expected; heart rate drops 10-15 bpm at 33.5 °C).
- Subcutaneous fat necrosis (rare, characteristic).
- Prolonged QT interval.
- Glucose dysregulation.
- None of these contraindicates continuing cooling unless severe.
Limitations
- Cooling outside the 36+ week, ≤ 6 hour window is generally not recommended (insufficient evidence).
- Cooling does not benefit mild HIE.
- Some neonates deteriorate after cooling — cooling reduces but does not eliminate adverse outcomes.
- This is an educational checker; cooling decisions are made by neonatology teams in real-time.
Sources
- Shankaran S, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574-84. (NICHD)
- Azzopardi DV, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009;361:1349-58. (TOBY)
- Gluckman PD, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial (CoolCap). Lancet 2005;365:663-70.
- Jacobs SE, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013;1:CD003311.
- Laptook AR, et al. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy. JAMA 2017;318:1550-60.
- NICE. Hypoxic-ischaemic encephalopathy and neonatal encephalopathy (NG237).
Frequently asked questions
What is therapeutic hypothermia (cooling)?
Controlled lowering of an HIE neonate's core body temperature to 33.5 °C for 72 hours, started within 6 hours of birth. Whole-body cooling (mattress under the baby) is the most common approach; selective head cooling with a cap is an alternative. The mechanism — slowing brain metabolism during the secondary energy-failure phase of HIE, reducing apoptosis and inflammation — is well-established. Cooling reduces the combined endpoint of death/disability by ~25 % in moderate-severe HIE.
Who is eligible?
ALL of the following must be met (NICHD 2005 / TOBY 2008 / NICE NG237): GA ≥ 36 weeks; age ≤ 6 hours postnatally; evidence of perinatal depression (Apgar ≤ 5 at 10 min, OR need for resuscitation at 10 min, OR cord pH < 7.0, OR base deficit ≥ 16); moderate or severe encephalopathy (Sarnat Stage II or III, OR Thompson HIE Score > 7).
Why 6 hours?
Animal models and the human trial data show benefit declining sharply after 6 hours of life. The secondary energy-failure phase begins 6-15 hours after the initial hypoxic insult; cooling during this window seems to prevent the cascade of apoptosis and excitotoxicity. Cooling started later misses this window — although a 2017 trial (Laptook NEJM) suggested some benefit even at 6-24 hours, the effect size was smaller and confidence wider.
What are the cooling side effects?
Thrombocytopenia (50-70 % of cooled neonates — usually mild, resolves on rewarming), hypotension (often requires inotrope support), bradycardia (expected — heart rate drops ~10-15 bpm at 33.5 °C), subcutaneous fat necrosis (rare but characteristic), prolonged QT interval, hypoglycaemia or hyperglycaemia, increased intracranial pressure on rapid rewarming. All are managed in NICU; none typically contraindicate continuing cooling.
What about preterm infants?
Below 36 weeks gestation, cooling is generally NOT performed outside research protocols. The evidence base (NICHD / TOBY / CoolCap trials) excluded preterm infants. Cooling preterm infants raises specific risks (intraventricular haemorrhage, sepsis, fat necrosis) that may outweigh benefit. The PRECOOL feasibility study (2024) is looking at this question; results pending.
How is cooling delivered?
Whole-body cooling: neonate placed on a cooling blanket / mattress under servo-control of rectal or oesophageal temperature. Selective head cooling: cooling cap on the head with neonate at slight body cooling. Whole-body is more commonly used in the US/UK; selective head cooling more in some European centres. Outcomes are similar. The 72-hour cooling phase is followed by gradual rewarming at ≤ 0.5 °C per hour.
What's the outcome data?
Cochrane meta-analysis (Jacobs 2013, 11 trials, 1,505 infants): cooling reduced combined endpoint of death/major neurodisability at 18 months from 60 % to 47 % (relative risk 0.75). Number needed to treat (NNT) is 7-8 to prevent one bad outcome. Subgroup analysis: moderate HIE NNT ~9; severe HIE NNT ~6 but background mortality higher. Cooling does NOT improve outcomes in mild HIE (and may worsen — NTT could be net harmful).
What happens after cooling?
MRI brain at day 5-10 of life — pattern of injury (basal ganglia/thalamus, watershed, total brain) refines prognosis. EEG monitoring through the cooling and rewarming for seizures. Multi-disciplinary follow-up: paediatric neurology, developmental paediatrics, physiotherapy, speech and language therapy, family support. Long-term: 80 % of infants with normal MRI and Sarnat Stage II have normal neurodevelopment at 2 years; severe MRI changes correlate with cerebral palsy.