Despite advances in neonatal care, moderate-to-severe acute perinatal HIE in late preterm and term infants remains a cause of mortality, neurological injury, and long-term neurodevelopmental disability. The current standard of care includes therapeutic hypothermia for 72 hours, but 40-50% of infants will die or suffer significant neurodevelopmental impairment. It has been shown that administration of hydrogen gas (H2) significantly diminishes ischemic injury in swine, and that H2 administration at the dose and duration proposed herein is well-tolerated in healthy adults. The purpose of this project is to test the feasibility and safety of H2 administration as an adjunct to therapeutic hypothermia in infants with HIE. Under exemption from informed consent, infants with severe, acute brain injury at birth will be randomized to standard therapy with or without the administration of 2% hydrogen in gases administered via the ventilator, non-invasive ventilation, or nasal cannula for 72 hours.

Inclusion Criteria:

1. Infants born ≥36 weeks gestation.

2. Any one of the following:

   1. sentinel event prior to delivery, such as uterine rupture, profound fetal bradycardia, or cord prolapse
   2. low Apgar scores (≤ 5 at 10 minutes of life)
   3. prolonged resuscitation at birth (chest compressions and/or intubation and/or mask ventilation at 10 minutes)
   4. severe acidosis (pH < 7.0 from cord or neonate blood gas within 60 minutes of birth)
   5. abnormal base excess (≤ -16 mEq/L from cord gas or neonate blood gas within 60 minutes of birth)

3. Moderate or severe encephalopathy present in the first 2 hours of life.

4. Intubated and mechanically ventilated at the time of enrollment.

Exclusion Criteria:

1. Enrollment in the opt-out program.
2. Presence of known cyanotic congenital heart disease.
3. Presence of known or suspected genetic/chromosomal syndrome or multiple congenital anomalies.
4. Presence of known congenital malformation that is expected to require urgent surgical intervention in the neonatal period, including congenital diaphragmatic hernia (CDH), gastroschisis, omphalocele, intestinal atresia, or imperforate anus.
5. Presence of antenatally diagnosed central nervous system malformation, including hemorrhage, hydrocephalus, or structural anomaly of the brain (eg. polymicrogyria).
6. Need for high frequency ventilation (HFV) at time of enrollment.
7. Patients receiving respiratory support via Drager Babylog ventilators.
8. Study enrollment and randomization after 2 hours of age