036 - Anti-Seizure Medication Use in Neonates: Real World Evidence of Changing Treatment Patterns

Publication Number: 36.3854

Levon Utidjian, Childrens Hospital of Philadelphia, Wynnewood, PA, United States; Nicholas S. Abend, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, United States; Mitchell Maltenfort, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Kimberley Dickinson, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Dimitri Christakis, University of Washington School of Medicine, seattle, WA, United States; Charles Bailey, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Christopher B. Forrest, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Background: Seizures are the most common neurological emergencies in neonates, and prompt treatment may avoid long term adverse outcomes. The choice of anti-seizure medication (ASM) is challenging given limited clinical trials in this population. A recent multicenter, randomized, controlled clinical trial, NEOLEV2, showed phenobarbital was significantly more effective than levetiracetam in controlling seizures. Though published in 2020, it is unknown if real-world treatment of neonatal seizures reflects this new evidence.

Objective: Examine ASM treatment patterns in neonatal seizures for changes in real-world practice before and after the recent clinical trial results.

Design/Methods: We obtained data on ASMs administered to all hospitalized neonates (patients before 28 days of age) with a diagnosis for seizure and gestational age ≥35 weeks from 6 participating sites in PEDSnet, a national, multi-institutional research network of children’s hospitals. Administration was defined as the use of any ASM during the hospitalization where the index date (day first ASM given) was in the neonatal period. Our analysis was limited to non-benzodiazepine ASMs as benzodiazepines may be used for other clinical indications. Logistic regression was used to analyze changes in rates of ASM usage before and after 2020.

Results: Out of 285,489 patients hospitalized within 28 days of birth from 2010-2023, we identified a cohort of 3,726 neonates meeting inclusion criteria. This cohort (Table 1) was mostly term infants (74%) and male (58%). Figure 1 shows the rates of ASMs used, with percentages representing neonates receiving any of the ASMs each year. Figure 1A focuses on the three most used ASM: phenobarbital, levetiracetam, and fosphenytoin. In 2020, there is an inflection point showing increasing use of phenobarbital (OR 1.1/year, 95% confidence interval (CI) [0.97, 1.2], p = 0.17) and significantly decreasing use of levetiracetam (OR 0.83/year, 95% CI [0.75, 0.92], p = < 0.001). Fosphenytoin use also significantly increased after 2020 (OR 1.4/year, 95% CI [1.2, 1.6], p = < 0.001). Figure 1B shows less commonly used ASMs, with no single ASM having >10% usage in any year.

Conclusion(s): We demonstrated real-world practice changes after publication of NEOLEV2 trial in the treatment of neonatal seizures, with significantly decreasing levetiracetam use and increasing, though not significant, phenobarbital use. A significant increase in fosphenytoin use may indicate a role as an alternative to levetiracetam. This data demonstrates the ability to use a large real-world data research network like PEDSnet to detect changes in clinical practice.

Table 1. Description of Neonatal Cohort Receiving Anti-Seizure Medications


Figure 1. Patterns in Inpatient Administrations of Anti-Seizure Medications to Neonates from 2010-2023
Utidjian PAS abstract Figure 1.jpegFigure 1A on the left, the top 3 non-benzodiazepine anti-seizure medications (ASMs) administered. Figure 1B on the right, the other non- benzodiazepine ASMs administered.