High electroencephalographic seizure exposure is associated with unfavorable outcomes in neonates with hypoxic-ischemic encephalopathy

Purpose: Electroencephalographic seizures (ES) are common among neonates with hypoxic-ischemic encephalopathy (HIE), and they represent a treatable complication that might improve neurodevelopmental outcomes. We aimed to establish whether higher ES exposure was predictive of unfavorable outcomes while adjusting for other important clinical and electroencephalographic parameters. Methods: We performed a single-center, retrospective study of consecutive neonates with HIE managed with therapeutic hypothermia from June 2010 through December 2016. Neonates underwent continuous electroencephalographic (cEEG) monitoring during and after therapeutic hypothermia. Outcome measures included abnormal MRIs after rewarming and abnormal motor and language development. Results: Clinical data from the perinatal period were available for 116 neonates. Follow-up data were available for 93 of 116 (80%) neonates who survived to discharge, with a median follow-up period of 23 months (interquartile range 1236 months). Multivariate analysis demonstrated that high ES exposure (OR 5.2, 95% CI 1.3-21.2, p = 0.02) and moderate/severely abnormal EEG background (OR 8.3, 95% CI 1.6-43.9, p = 0.01) were independent predictors of abnormal motor development. High ES exposure was an independent predictor of abnormal language development (OR 4.2, 95% CI 1.1-15.9, p = 0.04). High ES exposure (OR 7.0, 95% CI 2.2-22.5, p = 0.01) and severe encephalopathy (OR 7.9, 95% CI 1.5-42.7, p = 0.02) were independent predictors of abnormal MRIs. Conclusions: Among neonates with HIE managed with therapeutic hypothermia, high ES exposure was the most important predictor of abnormal developmental and neuroimaging outcomes, even after adjustment for multiple clinical and EEG variables. Adequate identification and management of ES with judicious use of anti-seizure medications may optimize outcomes.