Original ArticleRole of Intravenous Levetiracetam for Acute 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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