Caffeine for Hypoxic Ischemic Encephalopathy

Participant Inclusion Criteria: Infants who meet all the following criteria are eligible for enrollment as study participants: 1. Liveborn infants ≥36 weeks 2. Birth weight ≥1800 grams 3. Meets physiologic criteria for moderate to severe HIE, defined as meeting either of the following two criteria: 1. Criterion #1: Severe acidosis, defined as an umbilical cord sample or neonatal serum sample within one hour after birth demonstrating any of following criteria: * pH \<7.0; or * Base Deficit ≥16 mmol/L; or * Lactate \>8 mmol/L. 2. Criterion #2: Participant must meet all of the following three criteria: i. Moderate acidosis, defined as an umbilical cord sample or neonatal serum sample within one hour after birth demonstrating any of following criteria: * POC pH 7.0-7.15; or * Base Deficit 10.0-15.9 mmol/L; or * Lactate 6-8 mmol/L. ii. Evidence of an acute perinatal event (i.e., placental abruption, intrapartum hemorrhage, cord prolapse, severe fetal heart rate abnormality, uterine rupture). iii. Any of the following criteria: * 10-minute Apgar \<5; or * Need for assisted ventilation initiated at birth and continued for ≥10 minutes 4. Meets neurologic criteria for moderate to severe HIE, defined as a physical exam conducted between one and six hours after birth that meets either of the following criteria: 1. Moderate to severe encephalopathy in at least three out of six modified Sarnat categories (level of consciousness, spontaneous activity, muscle tone, posture, primitive reflexes, autonomic function); or 2. A clinical diagnosis of seizure in the first six hours after birth. Participant Exclusion Criteria: Infants who meet any of the following criteria are not eligible for enrollment as study participants: 1. Home births 2. Infants who cannot be enrolled, randomized and receive study medication within 6 hours post-delivery 3. Infants with a recognized major congenital anomaly or genetic syndrome that would affect their neurodevelopment. 4. Infants for whom medical care will not be provided based on the severity of their condition or any other condition that would preclude participation per clinical judgement. 5. Infant has received therapeutic hypothermia or there is a clinical plan to initiate active or passive hypothermia for the infant. 6. Infants who will be unavailable to complete follow-up visits. 7. Infants who have received caffeine after delivery. 8. Infants whom the health care team deem ineligible for the study based on likelihood to receive caffeine outside of the study protocol. 9. Enrollment in another trial that will impact participation in this trial.