Rewarming after cooling therapy can trigger seizures in oxygen deprived newborns: JAMA

Newborns affected by hypoxic-ischemic encephalopathy are at risk of seizures during both the cooling and rewarming phases of hypothermia therapy, according to a multi-site study led by UT Southwestern researchers.

Published On 2021-10-21 03:30 GMT   |   Update On 2021-10-21 03:30 GMT

Credit: UT Southwestern Medical Center

Newborns affected by hypoxic-ischemic encephalopathy are at risk of seizures during both the cooling and rewarming phases of hypothermia therapy, according to a multi-site study led by UT Southwestern researchers.

Rebound seizures during rewarming period may be a significant clue for future seizure outcome. Are seizures more likely to occur during rewarming after hypothermia, and are 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 was associated with increased risk of death or disability at 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.


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

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 who underwent 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 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. Primary outcome was seizure occurrence and secondary outcome was death and disability.


The results of the study were

• 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 detection of seizures was found to be the best in 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, they highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.


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

Article Source : JAMA Neurology

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