Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: A single center observational study

Objective: To examine the relationship between electrographic seizures and developmental outcome at 18 and 24 months in neonates with moderate and severe hypoxic-ischemic encephalopathy [HIE] treated with therapeutic hypothermia [TH].

Study design: 30 term infants with moderate-severe HIE treated with TH were enrolled prospectively from June 2012 to May 2018. All had continuous single channel amplitude integrated EEG (aEEG) monitoring for a minimum of 72 h and brain MR within 4 weeks. The aEEG was classified by severity of background and seizure burden. MR images were graded by the severity of injury. Outcome (defined abnormal in case of death, dyskinetic or spastic quadriplegic cerebral palsy, epilepsy, or Bayley III score < 85 in all three subscales or < 70 in any individual subscale) was assessed at 18 and 24 months.

Results: Seizures were recorded in 24 out of 30 [80 %] neonates and an abnormal outcome was observed in 7 [23 %] of infants. Patients with poor outcome had a statistically significant correlation with: high seizure burden (p = 0.0004), need for more than one antiepileptic drugs (p = 0.006), a persistent abnormal aEEG trace at 48 h (p = 0.0001) and moderate-severe brain injury at MRI (p = 0.0001). Moreover, infants with status epilepticus or frequent seizures reported a significantly association with abnormal MR imaging and poor outcome than patients with sporadic seizures (p = 0.0009).

Conclusion: The role of seizures in the pathogenesis of brain injury remains controversial. In our cohort the presence of seizures, per se, was not associated with abnormal outcome; however a high seizure burden as well as a persistent abnormal aEEG background pattern and MR lesions resulted significantly associated with poor prognosis.