Effect of neonatal seizure burden and etiology on the long-term outcome: data from a randomized, controlled trial

Abstract

Background: Neonatal seizures are common, but the impact of neonatal seizures on long-term neurologic outcome remains unclear. We addressed this question by analyzing data from an early-phase controlled trial of bumetanide to treat neonatal seizures.

Methods: Neonatal seizure burden was calculated from continuous video-EEG data. Neurologic outcome was determined by standardized developmental tests and post-neonatal seizure recurrence.

Results: Of 111 enrolled neonates, 43 were randomized to treatment or control groups. There were no differences in neurologic outcome between treatment and control groups. A subgroup analysis was performed for 84 neonates with acute perinatal brain injury (57 HIE, 18 stroke, 9 ICH), most of whom (70%) had neonatal seizures. There was a significant negative correlation between seizure burden and developmental scores (p<0.01). Associations between seizure burden and developmental scores were stronger in HIE and stroke groups compared with ICH (p<0.05).

Conclusion: Bumetanide showed no long-term beneficial or adverse effects, as expected based on treatment duration versus duration of neonatal seizures. For neonates with perinatal brain injury, higher neonatal seizure burden correlated significantly with worse developmental outcome, particularly for ischemic versus hemorrhagic brain injury. These data highlight the need for further investigation of the long-term effects of both neonatal seizure severity and etiology.

Keywords: Bumetanide; Hypoxic ischemic encephalopathy; Intracranial hemorrhage; Neonatal seizures; Stroke.

Figure 1.

Study subject groupings. Algorithm demonstrating distribution of seizure etiologies among trial subjects

Figure 2.

Developmental psychological composite scores (Bayley-III and Vineland-II) and neonatal seizure burden for subjects with acute perinatal brain injury (HIE, stroke, or ICH).

Figure 3.

Receiver operating characteristic curves for normal versus abnormal outcome and (A) seizure burden in min/hr and (B) seizure burden in total seizure minutes. Sensitivity = true positive rate. (1-specificity) = false positive rate.