Tuesday, June 26, 2018

Topiramate and necrotizing enterocolitis in preterm infants

Courchia B, Kurtom W, Pensirikul A, Del-Moral T, Buch M. Topiramate for Seizures in Preterm Infants and the Development of Necrotizing Enterocolitis. Pediatrics. 2018 Jun 14. pii: e20173971. doi: 10.1542/peds.2017-3971. [Epub ahead of print]

Neonatal seizures represent a significant health burden on the term and preterm neonatal population and are linked to poor long-term neurodevelopmental outcomes. Currently, there are no US Food and Drug Administration-approved antiepileptic drugs for neonates, and authors of the medical literature have yet to reach a consensus on the most adequate approach to neonatal seizures. Topiramate is readily used in the adult and older pediatric population for the management of migraines and partial-onset seizures. Topiramate continues to gain favor among pediatric neurologists who often recommend this medication as a third-line treatment of neonatal seizures. We report our recent experience with 4 preterm neonates, born between 2015 and 2017, who developed radiographic signs of necrotizing enterocolitis after receiving topiramate for seizures. Each was given oral topiramate for the treatment of electrographic and clinical seizures and developed the subsequent diagnosis of necrotizing enterocolitis, with abdominal distention, hemoccult-positive stools, and radiographic signs of intestinal distention and pneumatosis. More research regarding the risk factors of topiramate use in premature infants is needed.

Writing in Pediatrics, online June 14, the authors note the lack of consensus on how to treat neonatal seizures and that in cases of uncontrolled seizures, adding topiramate to therapy with two antiepileptic drugs is "controversial." Nonetheless, they point out, topiramate is commonly recommended by pediatric neurologists as a tertiary medication in neonates.

Corresponding author Dr. Benjamin Courchia told Reuters Health by e-mail, "We are concerned by articles reporting a significant increase in the use of topiramate for neonatal seizure in preterm infants."

He called the lack of scientific evidence in favor of topiramate use "striking" and said the authors hope their report, in addition to spurring further research, will "give clinicians pause, to weigh the risks and benefits of prescribing a medication without adequate data regarding safety and efficacy in premature infants."

His team notes that although gastrointestinal side effects of topiramate in adults had been described, "The temporal association between the usage of topiramate and NEC has not been reported previously."

In addition, the researchers believe theirs is the only report of topiramate use in premature infants for the treatment of seizures.

The infants were all managed at Holtz Children's Hospital, Miami, between 2015 and 2017. All 10 infants (half female) were born at less than 37 weeks gestation. Birth weights ranged from 440 g to 2,100 g.

The authors noted that the 40% incidence of NEC in this case series contrasted with their hospital's baseline NEC rate of 5.8% over about the same period. 

They also cautioned that because these neonates had multiple risk factors for NEC, the association with topiramate use might not have been causal.

"Seizures are more common in the neonatal period than in any other time throughout life" and are associated with poor outcome, Dr. Ronit Pressler, a consultant in clinical neurophysiology at Great Ormond Street Hospital for Children, London, told Reuters Health in an email.


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