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




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.


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.


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.

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Drs Bennett and Tolia had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Author contributions

Dr K. Ahmad conceptualized and designed the study, analyzed and interpreted the data, drafted the initial manuscript and approved the final manuscript as submitted.

Drs Desai, Clark and Tolia conceptualized and designed the study, analyzed and interpreted the data, critically reviewed and revised the manuscript and approved the final manuscript as written.

Dr Bennett carried out the data analyses, critically reviewed and revised the manuscript and approved the final manuscript as written.

Drs S. Ahmad and Ng designed the study, analyzed and interpreted the data, critically reviewed and revised the manuscript and approved the final manuscript as written.

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Correspondence to K A Ahmad.

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Competing interests

Y-T Ng is on the speakers’ bureau for Upsher-Smith Pharmaceuticals, UBC Pharma, Lundbeck Pharmaceuticals, Eisai Pharmaceuticals, Cyberonics, Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Zogenix Pharmaceuticals, has been a consultant for Mallinckrodt Pharmaceuticals and Eisai Pharmaceuticals and is an associate editor for Pediatric Neurology. VT has been a consultant for Chiesi USA. The other authors declare no conflict of interest.

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Ahmad, K., Desai, S., Bennett, M. et al. Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014. J Perinatol 37, 296–300 (2017).

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