Neonatal encephalopathy beyond hypoxic-ischemic etiology: experience of a Level III Neonatal Intensive Care Unit in the last decade

Neonatal encephalopathy (NE) is a condition of neurologic dysfunction with heterogeneous severity. The terms hypoxic-ischemic encephalopathy (HIE) and NE are often used interchangeably, although the differential diagnosis is vast. We aimed to evaluate the etiologies behind NE in newborns (NB) treated with therapeutic hypothermia (TH) for a presumed diagnosis of HIE. A retrospective analysis between January 2012 and July 2020 was conducted. Demographic data, information regarding pre-and perinatal factors, systemic dysfunction parameters, neuroimaging and neurologic sequelae were collected. A comparative analysis between the group considered with hypoxic-ischemic versus non-hypoxic-ischemic NE was performed. Forty-six NB were included. HIE was confirmed in 29 (63.0%) patients (group 1). There was no evidence of perinatal asphyxia in 17 (37.0%) patients (group 2). In the latter group, intracranial hemorrhage was the most frequent etiology (7; 15.2%), followed by infection (5; 10.9%). In group 1, there was a higher prevalence of emergency cesarean section (p = 0.013), clinical seizures at admission (p = 0.048) and a higher encephalopathy severity (p = 0.027). In this group, amplitude-integrated electroencephalogram improvement at 48 hours of TH was less frequent (p = 0.027) and major neurologic sequelae were more prevalent at 12 (p = 0.006) and 24 months (p = 0.041).HIE was the main cause of NE. Despite the clinical overlap, clinicians should recognize other etiologic factors beyond anoxic events. Our findings might help to prospectively differentiate between HIE and NE from different etiologies early after birth, ideally prior to initiation of TH, in the future.