Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)

Inclusion Criteria:

Eligibility will be determined in a stepped process:

   1. All infants with a gestational age ≥ 36 weeks will be screened for study entry if they
   are admitted to the NICU with a diagnosis of fetal acidosis, perinatal asphyxia,
   neonatal depression or encephalopathy.

   2. Infants will be eligible if:

      - They have a pH ≤ 7.0 or a base deficit ≥ 16m mEq/ L on umbilical cord or any
      postnatal sample within 1 hour of age.

      - If, during this interval, they have a pH between 7.01 and 7.15, a base deficit is
      between 10 and 15.9 mEq/L, or a blood gas is not available, AND they have an
      acute perinatal event AND either a 10-minute Apgar score ≤ 5 or assisted
      ventilation initiated at birth and continued for at least 10 minutes.

   3. Once these criteria are met, eligible infants will have a standardized neurological
   examination performed by a certified physician examiner. Infants will be candidates
   for the study when encephalopathy or seizures are present. For this study,
   encephalopathy is defined as the presence of 1 or more signs in 3 of the following 6
   categories:

      - Level of consciousness: lethargy, stupor or coma;

      - Spontaneous activity: decreased, absent;

      - Posture: distal flexion, decerebrate;

      - tone: hypotonia, flaccid or hypertonia, rigid;

      - Primitive reflexes: a) suck, weak, absent; b) Moro, incomplete, flaccid;

      - Autonomic nervous system: a) pupils: constricted, unequal, skew deviation or non
      reactive to light; b) heart rate: bradycardia, variable heart rate or c)
      respiration: periodic breathing, apnea.

Eligible infants from multiple births will be enrolled in the same arm of the study.

Exclusion Criteria:

   - Inability to randomize by 6 hours of age

   - Major congenital abnormality

   - Major chromosomal abnormality (including Trisomy 21),

   - Severe growth restriction (≤ 1800gm birth weight),

   - Infant is moribund and will not receive any further aggressive treatment,

   - Refusal of consent by parent

   - Refusal of consent by attending neonatologist

   - Infants with a core temperature < 33.5°C for > 1 hour at the time of screening by the
   research team would not be eligible for the study.