Neonatal Antiepileptic Medication Treatment Patterns: A Decade of Change

Abstract

Objective This article aims to describe the frequency and characteristics of anticonvulsant medication treatments initiated in the neonatal period. Study Design We analyzed a cohort of neonates with a seizure diagnosis who were discharged from institutions in the Pediatric Health Information System between 2007 and 2016. Adjusted risk ratios and 95% confidence intervals for characteristics associated with neonatal (≤ 28 days postnatal) anticonvulsant initiation were calculated via modified Poisson regression. Results A total of 6,245 infants from 47 institutions were included. There was a decrease in both phenobarbital initiation within the neonatal period (96.9 to 91.3%, p = 0.015) and continuation at discharge (90.6 to 68.6%, p <0.001). Levetiracetam (7.9 to 39.6%, p < 0.001) initiation within the neonatal period and continuation at discharge (9.4 to 49.8%, p < 0.001) increased. Neonates born at ≥ 37 weeks' gestation and those diagnosed with intraventricular hemorrhage, ischemic/thrombotic stroke, other hemorrhagic stroke, and hypoxic ischemic encephalopathy (HIE) had a higher probability of anticonvulsant administration. The most prevalent diagnosis was HIE (n = 2,223, 44.4%). Conclusion Phenobarbital remains the most widely used neonatal seizure treatment. Levetiracetam is increasingly used as a second line therapy. Increasing levetiracetam use indicates a need for additional study to determine its effectiveness in reducing seizure burden and improving long-term outcomes.

Novel Therapeutics for Neonatal Seizures

“…Review of American hospital data from the Pediatric Health Information System revealed that 97% of neonates treated for seizures received phenobarbital and this practice has been very consistent over time [24][25][26][27]. When antiseizure medications are prescribed to neonates at hospital discharge, phenobarbital is also the most commonly prescribed medication [27,28]. These data highlight the importance of phenobarbital in current treatment paradigms of neonatal seizures.…”

“…Levetiracetam is used less commonly than phenobarbital for the initial treatment of neonatal seizures. Over the past decade, use of levetiracetam increased from < 10% of all neonates with seizures to nearly 40%, surpassing the use of fosphenytoin/phenytoin [26,28]. Recent interest in levetiracetam is likely multifactorial and includes its availability for parenteral administration, relative safety profile, minimal drug interactions, likelihood of less adverse effects than phenobarbital on the newborn brain, and improved efficacy compared to phenobarbital in infantile epilepsy [49].…”

EBNEO Commentary: Safety of early discontinuation of anti‐seizure medication in neonates

“…3 Controversy exists in terms of the appropriate anticonvulsant for continuation at the time of discharge from the hospital. 4 The observational comparative effectiveness study by Glass et al demonstrates the safety of the discontinuation of ASM in neonates prior to discharge from the intensive care unit. There was no difference noted in neurodevelopment scores in neonates whose ASM was discontinued at discharge compared with those who had their seizure medication continued.…”

“…Current evidence is insufficient to determine the association of neonatal seizures and its impact on long‐term neurodevelopment 3 . Controversy exists in terms of the appropriate anticonvulsant for continuation at the time of discharge from the hospital 4 …”

A retrospective comparison of phenobarbital and levetiracetam for the treatment of seizures following cardiac surgery in neonates

“…Prior studies in neonates, including randomized controlled trials, have reported PHB efficacy of 40%‐50% for neonatal seizures, although success rates as high as 72% have been reported 14–17 . Levetiracetam (LEV) is a newer ASM increasingly used to treat neonatal seizures 18 . A small fraction of the administered dose is metabolized via nonhepatic pathways, whereas two‐thirds is excreted unchanged via the kidneys.…”