Characteristics of Neonates with Cardiopulmonary Disease Who Experience Seizures: A Multicenter Study

J Pediatr. 2022 Mar:242:63-73. doi: 10.1016/j.jpeds.2021.10.058. Epub 2021 Oct 30.


Objective: To compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease.

Study design: The Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease.

Results: We evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P < .001) and experience their first seizure later than those without cardiopulmonary disease (174 vs 21 hours of age, P < .001), but they had similar seizure exposure (many-recurrent electrographic seizures 39% vs 43%, P = .27). Phenobarbital was the primary initial antiseizure medication for both groups (90%), and both groups had similarly high rates of incomplete response to initial antiseizure medication administration (66% vs 68%, P = .75). Neonates with cardiopulmonary disease were discharged from the hospital later (hazard ratio 0.34, 95% CI 0.25-0.45, P < .001), although rates of in-hospital mortality were similar between the groups (hazard ratio 1.13, 95% CI 0.66-1.94, P = .64).

Conclusion: Neonates with and without cardiopulmonary disease had a similarly high seizure exposure, but neonates with cardiopulmonary disease were more likely to experience EEG-only seizures and had seizure onset later in the clinical course. Phenobarbital was the most common seizure treatment, but seizures were often refractory to initial antiseizure medication. These data support guidelines recommending continuous EEG in neonates with cardiopulmonary disease and indicate a need for optimized therapeutic strategies.

Keywords: ECMO; EEG monitoring; brain injury; congenital diaphragmatic hernia; congenital heart disease; neonatal neurocritical care; neonatal seizures.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anticonvulsants / therapeutic use
  • Electroencephalography
  • Epilepsy* / drug therapy
  • Humans
  • Infant, Newborn
  • Monitoring, Physiologic
  • Phenobarbital / therapeutic use
  • Seizures* / diagnosis
  • Seizures* / drug therapy
  • Seizures* / etiology


  • Anticonvulsants
  • Phenobarbital