Rationale: Seizures in neonates are commonly caused by acute perinatal brain injury, and EEG monitoring is recommended by an ACNS guideline. However, questions remain regarding the contribution of neonatal seizures to long-term neurologic outcome. We addressed these questions in neonates enrolled in a randomized, controlled trial of bumetanide to treat neonatal seizures. Methods: Continuous video-EEG data (cvEEG) were collected for all enrolled neonates following the ACNS guideline, with a minimum of 48 hours of cvEEG following randomization. Neuropsychological testing, including the Bayley-III and Vineland-II, was administered at 17 to 31 months of age by study neuropsychologists blinded to treatment assignment. Seizure recurrence was determined by medical record review. SPSS Statistics-24 was used to examine the relationships between neonatal seizures and outcomes: Pearson correlation for total seizure burden and neuropsychological test scores, ANOVA for seizure etiology and test scores, Pearson Chi Square for seizure etiology and seizure recurrence, and logistic regression for total seizure burden and seizure recurrence. Results: Of 111 enrolled neonates, 82 (45 male) were included in the current analysis, with mean gestational age 39 weeks. The other 29 neonates were excluded by seizure etiology, neonatal death or loss to follow-up. Of those 82, 53 neonates had hypoxic-ischemic encephalopathy (65%), 18 had ischemic stroke (22%), and 11 had intracranial hemorrhage (13%). Most neonates (74%) had clinical and/or EEG-confirmed seizures, with a mean total seizure burden (TSB) of 2.6 minutes per hour (SD ±4.0). Neuropsychological testing was performed in 66 patients at a mean age of 20 months (±2.8). Mean composite scores were below expected for age for the Bayley-III: cognitive 95 (±15), language 91 (±16) and motor 93 (±16) and the Vineland-II: adaptive behavior 91 (±15), communication 90 (±16) and motor 93 (±21). Of the 61 patients with neonatal seizures, 12 (20%) had seizure recurrence. There was no statistically significant relationship between seizure etiology and developmental testing results or seizure recurrence. Interestingly, there was a statistically significant negative correlation between TSB and all Bayley-III and Vineland-II composite scores for cognition and language/communication, particularly the Bayley-III (cognitive R= -0.43, p=0.001) and Vineland-II communication scores (R= -0.40, p=0.007). TSB was not significantly associated with seizure recurrence. Conclusions: Neonates with acute perinatal brain injury enrolled in this trial had developmental scores in early childhood that were below expected values for age. Higher TSB correlated with worse developmental outcome, but not with later seizure recurrence. The lack of correlation with post-neonatal seizure recurrence may relate in part to young age at follow-up. The correlation between higher seizure burden and worse developmental outcome highlights the importance of EEG monitoring and effective seizure treatment. Further study is required to identify risk factors for later seizure recurrence and the magnitude of neonatal seizure burden that affects long-term neurologic outcome. Funding: Please list any funding that was received in support of this abstract.: National Institute of Neurological Disorders and Stroke R01 NS066929 Charles H. Hood Foundation Citizens United for Research in Epilepsy Harvard Catalyst, The Harvard Clinical and Translational Science Center (UL1 TR001102) National Institute of Health Translational Research Program, Boston Children's Hospital Mooney Family Initiative for Translational Studies in Rare Diseases, Boston Children's Hospital Tufts Clinical and Translational Science Institute (CTSI), UL1 TR001064
