Neonatal encephalopathy and hypoxic-ischemic encephalopathy: the state of the art

Neonatal Encephalopathy (NE) remains a major cause of death and long-term severe disabilities, including epilepsy and cerebral palsy in term and near-term infants. The single most common cause is hypoxic-ischemic encephalopathy (HIE). However, there are many other potential causes, including infection, intracranial hemorrhage, stroke, brain malformations, metabolic disorders, and genetic causes. The appropriate management depends on both the specific cause and the stage of evolution of injury. Key tools to expand our understanding of the timing and causes of NE include aEEG, or even better, video EEG monitoring, neuro-imaging including cranial ultrasound and MRI, placental investigations, metabolic, biomarker, and genetic studies. This information is critical to better understand the underlying causes of NE. Therapeutic hypothermia improves outcomes after HIE, but there is still considerable potential to do better. Careful clinical and pre-clinical studies are needed to develop novel therapeutics and to help provide the right treatment at the right time for this high-risk population. IMPACT: Neonatal encephalopathy is complex and multifactorial. This review seeks to expand understanding of the causes, timing, and evolution of encephalopathy in newborns. We highlight key unanswered questions about neonatal encephalopathy.