Abstracts

Rationale: Infants with early life epilepsies (ELE, epilepsy onset at < 3 years old), are at risk for infantile epileptic spasms syndrome (IESS) – a rare epilepsy syndrome that poses risks of severe, long-term epilepsy and developmental comorbidities. Given increasing evidence to support effective management of neonatal and infantile focal seizures with sodium channel blocking agents (SCB), it is critical to understand whether SCB could increase risk of IESS for these infants. Historically, attempts to answer this question have been limited due to the rarity of ELE and IESS. Here, we use a large insurance claims database to evaluate data from the largest published cohort to date. Using this dataset, we established a cohort of ELE infants, defined as those who have anti-seizure medications (ASM) dispensed during 0-23mo of age.

Methods: Using the IBM® MarketScan® Research Databases, a cohort of ELE infants during 2016-2022, with and without SCB exposure prior to the onset of any epileptic spasms in the first 2y of life, was identified as detailed in Figure 1 below. A chi-squared analysis assessed for significant difference between IESS+ and IESS- in SCB-exposed and non-exposed infants. Cox regression analysis was then used to assess both whether probability of IESS, time to IESS, and probability to develop refractory epilepsy differed for SCB+ and – infants, with age, sex, seizure etiology, and number of anti-seizure medications as covariates.

Results: Infants with ELE (n=4180) who took SCBs were less likely to develop IESS than those not exposed to SCBs (odds ratio = 0.17, p-value < 2e-16). Among those exposed to SCBs, 40 (6.6%) developed the IESS, while 567 did not. In the SCBs non-exposure group, 508 (14.2%) developed the IESS, while 3065 did not. There was a statistically significant association between SCB treatment and the development of IESS in infants with ELE, X2(1, N = 4180) = 25.837, p-value = 3.715e-07. A logistic regression was performed to ascertain the impact of SCB treatment on the likelihood that infants with ELE develop IESS, controlling for age, sex, etiologies of seizure and epilepsy, and the number of ASMs per patient. Infants with ELE who took SCBs were less likely to develop IESS than those not exposed to SCBs (odds ratio = 0.08, p-value < 2e-16). Increasing number of ASMs was associated with an increased likelihood of developing IESS (odds ratio = 1.72, p-value = 3.10e-07). Etiology of epilepsy and presence of IESS were associated with an increased likelihood of developing refractory epilepsy. Increasing number of ASMs was associated with an increased likelihood of developing refractory epilepsy. Infants with ELE who took SCBs were more likely to have refractory epilepsy than those who were not on SCBs (odds ratio = 1.72, p-value = 3.10e-07).

Conclusions: In the largest cohort analyzed to date, SCB exposure does not increase the risk of developing IESS.

Funding: Maternal & Child Health Research Institute, Stanford University