Hypoxic-Ischemic Encephalopathy in Newborns: Pathophysiology, Early Identification, and Management

Hypoxic-ischemic encephalopathy (HIE) is a severe neurological condition resulting from impaired oxygen delivery and reduced cerebral blood flow to the neonatal brain during the perinatal period. It remains one of the leading causes of neonatal mortality and long-term neurodevelopmental disability worldwide, despite significant advances in obstetric and neonatal care. The pathophysiology of HIE is complex and evolves through a cascade of events beginning with primary energy failure, followed by secondary energy failure characterized by mitochondrial dysfunction, oxidative stress, inflammation, excitotoxicity, and delayed neuronal cell death. Early identification of affected neonates is critical, as timely intervention can significantly influence neurological outcomes. Diagnosis relies on a combination of clinical assessment, neuroimaging, particularly magnetic resonance imaging (MRI), and neurophysiological monitoring such as amplitude-integrated electroencephalography (aEEG), which aid in determining severity and prognosis. Therapeutic hypothermia has emerged as the cornerstone of neuroprotective treatment and has demonstrated improved survival and neurodevelopmental outcomes when initiated within the first six hours of life. Additional supportive strategies, including seizure control and meticulous metabolic and hemodynamic management, play an essential role in comprehensive care. This review summarizes the current understanding of the pathophysiology, diagnostic approaches, and management strategies of HIE in newborns, emphasizing the importance of early intervention and ongoing research into novel neuroprotective therapies aimed at improving long-term outcomes.