Elsevier

Pediatric Neurology

Volume 49, Issue 5, November 2013, Pages 340-343
Pediatric Neurology

Original Article
Role of Intravenous Levetiracetam for Acute Seizure Management in Preterm Neonates

https://doi.org/10.1016/j.pediatrneurol.2013.05.008Get rights and content

Abstract

Background

Neonatal seizures are common in the first month of life and may impair neurodevelopmental outcome. Current antiepileptic drugs used in the treatment of neonatal seizures have limited efficacy and undesirable side effects. Intravenous levetiracetam is increasingly being used in the neonatal period to treat seizures. Presently, insufficient data about the efficacy and safety of intravenous levetiracetam in preterm neonates exist.

Methods

We retrospectively analyzed data from preterm neonates who were treated with intravenous levetiracetam at our institution between January 2007 and December 2011. Data were acquired from review of our institution's electronic medical record regarding patients who were treated with intravenous levetiracetam during the neonatal period (0 to 28 days) and were born at preterm gestation (<37 weeks).

Results

Twelve patients received a levetiracetam load of 25 to 50 mg/kg for neonatal seizures. Nine of 11 patients (82%) reached seizure cessation within 24 hours of receiving levetiracetam. No serious side effects were evident. Seven patients (59%) were discharged on oral levetiracetam alone, four patients (33%) were discharged on no oral antiepileptic drug, and one patient (8%) was discharged on levetiracetam and phenobarbital. Eleven of 12 patients were followed up to 6 months after receiving intravenous levetiracetam. Of these, six patients (55%) had achieved seizure freedom and been completely weaned off of all antiepileptic drugs. Three patients (27%) had achieved seizure freedom while still on oral levetiracetam.

Conclusions

Intravenous levetiracetam appears to be efficacious for seizure management in preterm neonates.

Introduction

Seizures affect one to four of 1000 live births in North America and are a major predictor of future adverse neurodevelopmental outcomes.1, 2 The incidence of seizures in preterm neonates is approximately 11 of 1000 live births, with clinical seizures occurring six times more often in preterm infants than term infants.3 Few medications have been studied and approved to treat neonatal seizures, and none has shown superior efficacy over another. With a high incidence of seizures refractory to currently approved antiepileptic drugs, a pressing need exists for alternative treatment choices in preterm neonates. The most common causes of neonatal seizures are hypoxic ischemic encephalopathy, intracranial hemorrhages, central nervous system infections, cerebral infarctions, and metabolic disturbances.1, 2, 3 The treatment of neonatal seizures often has limited efficacy and leads to deleterious adverse effects. The two antiepileptic drugs presently approved by the United States Food and Drug Administration (FDA) in the neonatal period—phenobarbital and phenytoin—demonstrate efficacy in less than 50% of cases and undesirable side effect profiles in major studies.4, 5, 6, 7, 8, 9 The benefits of alternative antiepileptic drugs are being recognized, and off-label use of antiepileptic drugs in children and neonates is increasing.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 An imperative need to investigate the use of newer antiepileptic drugs in preterm neonates exists.11, 12, 13, 14, 15, 16, 17, 18, 19

Levetiracetam is a pyrrolidine derivative antiepileptic drug chemically different from all previous antiepileptic drugs, with linear pharmacokinetics, renal metabolism, and minimal protein binding.10, 12, 27 Unlike phenobarbital, levetiracetam does not increase apoptosis in the developing brain in animal models.10, 28 Intravenous levetiracetam was approved by the FDA in August 2006 for use in patients older than 16 years of age. Oral levetiracetam was approved by the FDA in 2012 for use in partial-onset seizures in patients 1 month of age and older. Both intravenous and oral levetiracetam have been increasingly used off-label in pediatric and neonatal patients because of literature documenting efficacy and safety in adults, along with favorable reports in younger patients.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 Here, we report on our experience with intravenous levetiracetam in the management of seizures in preterm neonates.

Section snippets

Methods

Infants were eligible for inclusion if they were born at preterm gestational age (<37 weeks) and received their first dose of intravenous levetiracetam during the neonatal period (0 to 28 days of age). A retrospective electronic medical record review was conducted on all patients who met inclusion criteria between January 2007 and December 2011 at our institution. This study was approved by our institutional review board.

Results

We retrospectively analyzed 12 preterm neonates who had been treated with intravenous levetiracetam at our institution. The following variables were taken into consideration (Table).

Discussion

Our data suggest that intravenous levetiracetam can be used for acute seizure management in preterm neonates. Brain growth and development during the neonatal period is rapid, with physiological maturation of synapses in neurons occurring during this time. Thus, protection and prevention of significant adverse effects upon the developing brain is critical in this period. Seizures remain a common problem in the neonatal period and prompt recognition and treatment may help prevent abnormal

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