Rebound Seizures During Rewarming Period

Rebound seizures during the rewarming period may be a significant clue for future seizure outcomes. Whether seizures are more likely to occur during rewarming after hypothermia, and if they are associated with abnormal outcomes, is yet to be investigated.

A new prespecified cohort study by Dr. Lina F. Chalak, MD, MSCS, and team revealed that higher odds of electrographic seizure during the rewarming phase after hypothermia were associated with an increased risk of death or disability at a 2-year follow-up.

The study suggests that oxygen-deprived newborns who undergo cooling therapy to protect their brains are at an elevated risk of seizures and brain damage during the rewarming period, which could be a precursor of disability or death.

The finding could lead to better ways to protect these vulnerable patients during an often overlooked yet critical period of cooling – or hypothermia – therapy.

The findings of this study are published in JAMA Neurology.

Study Objective

The objective of the study was to determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and if they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy.

Study Design

The study was a cohort study of infants enrolled in the Optimizing Cooling (OC) conducted from December 2011 to December 2013 with 2 years follow-up. Randomized infants underwent 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020. Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment of parameters. The primary outcome was seizure occurrence, and the secondary outcome was death and disability.

Results

• A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks.
• Interrater agreement (κ, 0.99) in the detection of seizures was found to be the best in the study. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03).
• Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B.
• The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center.

Dr. Chalak and team conveyed that findings of the study suggested that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years, highlighting the necessity of electroencephalography monitoring during rewarming in infants at risk.

Reference

Chalak LF, Pappas A, Tan S, et al. Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study. JAMA Neurol. Published online October 18, 2021. doi:10.1001/jamaneurol.2021.3723