Functional Neurodevelopment, Epilepsy Risk Similar Regardless of ASM Discontinuation in Neonates


After propensity adjustment, there was no difference in the risk of epilepsy or age at epilepsy onset for infants whose ASM was discontinued vs maintained at hospital discharge.

Hannah C. Glass, MD

Hannah C. Glass, MD

Data from a comparative effectiveness study suggest that functional neurodevelopment and epilepsy risk both remain similar among children whose antiseizure medication (ASM) was discontinued compared to those whose was maintained at hospital discharge after resolution of acute symptomatic neonatal seizures.

Lead author Hannah C. Glass, MD, professor of neurology, Weill Institute for Neurosciences, University of California, San Francisco, and colleagues concluded that, “these results support discontinuation of ASM prior to hospital discharge for most infants with acute symptomatic neonatal seizures.” A total of 303 neonates with acute symptomatic seizures were included in the study, 194 (64%) of whom had ASM maintained at the time of hospital discharge. The investigators used Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 24 months, powered for propensity-adjusted noninferiority of early ASM discontinuation to assess functional neurodevelopment.

Among 270 children evaluated at 24 months, the median 24-month WIDEA-FS score was 164 (interquartile range [IQR], 136-175). Children whose ASM was discontinued prior to hospital discharge (101 of 270; 37%) had unadjusted total WIDEA-FS scores that were 4 points (2%; median score, 165 [IQR, 150-175]) higher than children whose ASM was maintained at discharge (169 of 270 [63%]; median score, 161 [IQR, 129-174]; P = .09).

READ MORE: Reevaluating Prevalence and Management of Generalized Epilepsy in Elders

Between the treatment duration groups, the proportion of children with impaired functional neurodevelopment at 24 months was not different (28% vs 37%; odds ratio [OR], 0.6 [95% CI, 0.4-1.1]; P = .11).

In total, 37 of 282 infants (13%) with data available developed epilepsy before age 24 months, including 5% (13 of 282) with infantile spasms. The epilepsy risk was similar between the groups, with an 11% risk observed for infants whose ASM was discontinued compared to a 14% risk for those whose ASM was maintained at the time of hospital discharge (OR, 0.8 [95% CI, 0.4-1.6]; P = .49).

The timing of epilepsy onset also did not differ between the groups (hazard ratio [HR], 0.8 [95% CI, 0.4-1.5]). After propensity adjustment, there was no difference in the risk of epilepsy (adjusted OR, 1.5 [95% CI, 0.7-3.4]; P = .32) or age at epilepsy onset (adjusted HR, 1.4 [95% CI, 0.7-2.9]; P = .37) for infants whose ASM was discontinued vs maintained at hospital discharge.

Gross Motor Function Classification System scores greater than or equal to 2 were observed in 16% of infants (43 of 270); however, similar to other outcomes, no difference between infants whose ASM was discontinued prior to vs maintained at hospital discharge was observed (13% vs 19%; OR, 0.6 [95% CI, 0.3-1.3]; P .18).

Among the neonates whose ASMs were maintained at the time of discharge, 131 of 194 (68%) had phenobarbital (Luminal; Bayer) monotherapy maintained, 25 of 194 (13%) had levetiracetam (Keppra; UCB Pharma) monotherapy maintained, and 38 of 194 (20%) had polytherapy maintained. Seizure cause was hypoxic-ischemic encephalopathy in 130 (43%), ischemic stroke in 79 (26%), intracranial hemorrhage in 55 (18%), or other acute brain injury in 39 (13%) infants, which included intracranial infection in 24, hypoglycemia with brain injury in 4, and uncategorized in 11. Phenobarbital was the first loading ASM for 90% of the infants included in the study.

NeurologyLive recently sat down with Solomon Moshe, MD, and Elissa Yozawitz, MD, who were part of the Neonatal Seizures Task Force, a group established by the International League Against Epilepsy, which published a report that tackled issues and ways to eliminate misdiagnosis of seizures in the neonatal stage. When asked about the greatest unmet needs in neonates, they claimed that there needs to be increased evidence towards treatment regimens among neonates, something that this study addressed further. Listen to their comments below.

Glass HC, Soul JS, Chang T, et al. Safety of early discontinuation of antiseizure medication after acute symptomatic neonatal seizures. JAMA Neurol. Published online May 24, 2021. doi: 10.1001/jamaneurol.2021.1437
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