Whole-Body Cooling for Birth Asphyxia in Term Infants

Perinatal cerebral hypoxia-ischemia injury is an important cause of death and
neurodevelopmental disability. Data from animal models suggest that brain cooling immediately
after injury is neuroprotective. Experience with total body cooling during surgery,
accidental near drownings, and one Phase I trial of term infants suggest that it is effective
and safe in children.

This large multicenter trial tested whether cerebral cooling initiated within 6 hours of
birth and continued for 72 hours would reduce the risk of death and moderate to severe
neurodevelopmental injury at 18-22 months corrected age. Infants at least 36 weeks gestation
with an abnormal blood gas within 1 hour of birth, or a history of an acute perinatal event
and a 10-min Apgar score <5, or continued need for ventilation were screened. Following a
neurological exam, those with moderate to severe encephalopathy were randomized to a 72-hour
period of total body cooling (cooling blanket, followed by slow re-warming). The study was
conducted in two phases: Phase I (20 infants) were examined for the safety of an esophageal
temperature of 34-35 C; Phase II (main trial, 200 infants) were evaluated for the safety and
efficacy of an esophageal temperature of 33-34 C. Cardio-respiratory, electroencephalograms
(EEGs), renal, metabolic, and hematologic status, and esophageal and abdominal skin
temperature were monitored during the 72 hours of intervention.

Neurodevelopmental outcome was assessed at 18-22 mos of age by masked certified examiners.
The outcome at 18-22 months showed that whole-body cooling reduces the risk of death or
moderate to severe disability in infants with hypoxic ischemic encephalopathy.

Surviving infants were assessed at 6-7 years (school age).

Inclusion Criteria:

- At least 36 weeks gestation

- Any blood gas (cord, postnatal) done within the first 60 minutes had a pH less than or
equal to 7.0

- Any blood gas (cord postnatal) done within the first 60 minutes had a base deficit
greater than or equal to 16 mEq/L

- All infants must have seizures or signs of moderate to severe encephalopathy before
randomization

Exclusion Criteria:

- Inability to randomize by 6 hours of age

- Presence of known chromosomal anomaly or major congenital anomaly

- Severe intrauterine growth restriction (weight less than 1800g)

- All blood gases done within the first 60 minutes had a pH less than 7.15 and a base
deficit less than 10 mEq/L

- Infants in extremis for whom no additional intensive therapy will be offered by
attending neonatologist

- Parents refuse consent

- Attending neonatologist refuses consent