A Randomized Trial of Targeted Temperature Management with Whole Body Hypothermia for Moderate and Severe Neonatal Encephalopathy in Premature Infants 33-35 Weeks Gestational Age-A Bayesian Study

This is a staged, prospective, randomized multicenter trial with qualifying infants randomized 1:1 to whole body hypothermia at 33.5 degrees Centigrade by esophageal temperature probe for 72 hours or to normothermia with steps to avoid hyperthermia of > 37.3 degrees Centigrade. The study will use the Cincinnati Sub-Zero Hyper-Hypothermia device. There will be surveillance for safety and adverse events within 108 hours of baseline(insertion of esophageal probe) and this will be compared with Bayesian techniques. There will be a cranial ultrasound done within 24 hours of baseline. A brain MRI will be done at 10-17 days of postnatal age. They infant will undergo interdisciplinary neurodevelopmental assessment at 18-22 months corrected age. The primary outcome using standard Neonatal Research Network criteria is death or moderate/severe disability at 18-22 months of age. Differences in study groups will be assessed for death up to 18-22 months of age only, cause of death, disability only, death or profound disability, severe disability and moderate disability only, survival with no impairment, each component of severe and moderate disability, differences in MRI findings, evolution of encephalopathy, seizures after intervention started, Bronchopulmonary dysplasia, necrotizing enterocolitis, culture-positive infection > 3 days, pulmonary hypertension, intracranial hemorrhage, esophageal probe injuries, metabolic abnormalities, treatments with vasopressors, steroids, oliguria, anuria, liver dysfunctions, coagulopathy, days of ventilation, receipt of ECMO, length of stay in the NICU.