Neonate Rewarming Tied to Increased Electrographic Seizure Risk

(Reuters Health) – Neonates with hypoxic ischemic encephalopathy who are treated with hypothermia have an increased risk of seizures during rewarming, and those seizures are associated with greater death and disability at 2 years, a new study suggests.

Researchers examined data on 120 newborns at a mean gestational age of 39 weeks who were randomized to receive either 72 hours (n=66) or 120 hours (n=54) of cooling as an intervention for hypoxic ischemic encephalopathy. The primary endpoint was electrographic evidence of seizures during the 12 hours prior to rewarming compared with the first 12 hours of rewarming.

Compared with the 12 hours prior to rewarming, infants had significantly greater seizure risk during the first 12 hours of treatment for both 72-hour rewarming (odds ratio 2.7) and 120-hour rewarming (OR 3.2).

At ages 18-22 months, the infants who experienced seizures during rewarming had a significantly higher risk of mortality or severe disability (OR 1.7) in adjusted analysis that accounted for baseline clinical encephalopathy and seizures as well as treatment center.

“The presence of higher odds of seizures during rewarming that are associated with death and disability at two years is a new and important finding,” said lead study author Dr. Lina Chalak, a professor of pediatrics and psychiatry and director of the Neonatal Neurological Intensive Care and Fetal and Neonatal Neurology Fellowship Program at the University of Texas Southwestern Medical Center in Dallas.

“The underlying mechanisms are likely related to impaired auto-regulation with hemodynamic mismatch between oxygen delivery and metabolic demands during rewarming which precipitates seizures,” Dr. Chalak said by email.

These results suggest that there’s a significantly elevated risk of seizures during the rewarming period, most of which typically go unnoticed if not monitored with EEG or amplitude compressed EEG, Dr. Chalak added.

For infants randomized to a 72-hour rewarming period, 27% experienced seizures during the first 12 hours of rewarming, compared with 14% in the 12 hours prior to initiation of rewarming.

For infants randomized to a 120-hour rewarming period, 21% experienced seizures during the first 12 hours of rewarming, compared with 10% in the 12 hours prior to treatment initiation.

These outcomes add to the evidence that faster rewarming may carry more risks for infants, the study team concludes in JAMA Neurology.

One limitation of the study is that the researchers didn’t use continuous EEG monitoring, which is the gold standard for detecting electrographic seizures, the authors note. The researchers also lacked hemodynamic assessments to confirm any underlying mechanisms for seizures such as a mismatch in oxygen delivery and consumption, they point out.

However, the results underscore the importance of monitoring these infants for seizures, Dr. Chalak said.

“This study is telling us that there’s an untapped opportunity to improve care for these babies during rewarming by recommending EEG monitoring a standard part of the rewarming protocol,” Dr. Chalak said. “Monitoring during both cooling and rewarming can help protect these young patients’ brains from further insults while they heal.”

SOURCE: JAMA Neurology, online October 18, 2021.

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