Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014

J Perinatol. 2017 Mar;37(3):296-300. doi: 10.1038/jp.2016.206. Epub 2016 Nov 10.


Objective: Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period.

Study design: Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014.

Results: Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate.

Conclusions: Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.

Publication types

  • Multicenter Study

MeSH terms

  • Anticonvulsants / therapeutic use*
  • Child
  • Drug Utilization / statistics & numerical data
  • Drug Utilization / trends*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Intensive Care Units, Neonatal / statistics & numerical data*
  • Levetiracetam
  • Male
  • Phenobarbital / therapeutic use
  • Phenytoin / therapeutic use
  • Piracetam / analogs & derivatives
  • Piracetam / therapeutic use
  • Retrospective Studies
  • Seizures / drug therapy*
  • Seizures / epidemiology*
  • Texas / epidemiology


  • Anticonvulsants
  • Levetiracetam
  • Phenytoin
  • Phenobarbital
  • Piracetam