Abstracts

Rationale: Up to two-thirds of neonates with acute symptomatic seizures have incomplete response to initial antiseizure medication (ASM). Indirect evidence suggests early treatment may lead to better seizure control. Pre-emptive, screening cEEG in high-risk neonates may facilitate earlier treatment, potentially improving treatment response. We examined whether cEEG monitoring strategy within the Neonatal Seizure Registry (NSR) -confirmatory cEEG vs. pre-emptive screening cEEG - was associated with improved response to initial treatment of EEG seizures. Methods: This 9 center cohort analysis from the NSR included neonates with acute symptomatic seizures due to an identified etiology. All had seizures confirmed on cEEG; this analysis excluded subjects with clinically diagnosed seizures prior to cEEG who had no subsequent seizures on cEEG. Neonates with cEEG indications of “clinical events suspicious for seizures” or “clinical events and encephalopathy” were classified as having confirmatory cEEG. Neonates with cEEG indications of “encephalopathy” or “paralysis” were classified as having pre-emptive screening cEEG. The primary outcome was successful response to initial treatment, defined as no seizures on cEEG >30 minutes after initial loading dose of ASM. Multivariable logistic regression analysis included: primary seizure etiology, 5 minute Apgar score, presence of multiple seizure etiologies, and hypothermia treatment. Descriptive statistics characterized groups. Exploratory three-level variable analysis compared subjects in the confirmatory cEEG group with and without phenobarbital (PB) administration prior to cEEG against subjects in the screening group. Results: 514 neonates were included; 353 (69%) had confirmatory cEEG and 161 (31%) had pre-emptive screening cEEG (Table). Neonates in the pre-emptive screening group had a higher proportion of successful treatment response as compared to neonates in the confirmatory group (39% versus 18%, respectively), as well as greater odds of successful treatment response after adjusting for covariates (adjusted OR 2.44, 95% CI: 1.45-4.11, p<0.01). In three-level analysis, neonates in the pre-emptive screening group also had a higher proportion of successful treatment response as compared to just those neonates in the confirmatory group without PB prior to cEEG (39% vs 29%), with greater odds of successful treatment response (adjusted OR 1.41, 95% CI: 0.73-2.5), although the effect was no longer significant (p=0.25). Neonates in the confirmatory cEEG group who received PB before cEEG had lowest rate of treatment success (9.7%); odds of treatment success were much higher in the pre-emptive screening group as compared to those in the confirmatory group who had received PB prior to cEEG (adjusted OR 5.26, 95% CI:2.63-10, p<0.01). Conclusions: Screening cEEG in neonates at high risk for seizures may facilitate improved initial ASM treatment response. A limitation of this study was that, because our outcome measure of seizure treatment response was defined by cEEG, our analysis did not include subjects who had no seizures on cEEG. We excluded neonates with clinical seizures that resolved prior to cEEG, and thus the confirmatory group may have included a higher proportion of neonates with more treatment-resistant seizures. Further work is needed to clarify the relationship between cEEG monitoring strategy, timing of ASM administration, and treatment response. Funding: Funding for this study was provided by PCORI (1507-31187), the Pediatric Epilepsy Research Foundation, the Stanford Maternal Child Health Research Institute, and NINDS (1K02NS102598).