Remote Monitoring for Seizures During Therapeutic Hypothermia in Neonates With Hypoxic-Ischemic Encephalopathy

Abstract

This cohort study evaluates electroencephalography characteristics in newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.

Key Points

Question

In a low- or middle-income country, what are the amplitude integrated electroencephalography characteristics in newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia?

Findings

In this multicenter cohort study of 872 infants, seizures were identified in 33.9% of infants, and 71.9% of seizures were electrographic only. Seizure onset was most frequent in the first 24 hours (74.6%); however, 11.5% had onset during rewarming.

Meaning

This large cohort study described brain monitoring characteristics in newborns with HIE, suggesting the feasibility and importance of a telehealth model and remote neuromonitoring approach in a low- or middle-income country.

Abstract

Importance

Neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently experience seizures, which are associated with adverse outcomes. Efforts to rapidly identify seizures and reduce seizure burden may positively change neurologic and neurodevelopmental outcomes.

Objective

To describe the onset, treatment, and evolution of seizures in a large cohort of newborns with HIE during TH assisted by a telehealth model and remote neuromonitoring approach.

Design, Setting, and Participants

This was a prospective, observational, multicenter cohort study performed between July 2017 and December 2021 in 32 hospitals in Brazil. Participants were newborns with HIE meeting eligibility criteria and receiving TH. Data were analyzed from November 2022 to April 2023.

Exposure

Infants with HIE receiving TH were remotely monitored with 3-channel amplitude-integrated electroencephalography (aEEG) including raw tracing and video imaging, and bedside clinicians received assistance from trained neonatologists and neurologists.

Main Outcomes and Measures

Data on modified Sarnat examination, presence, timing and seizure type, aEEG background activity, sleep-wake cycling, and antiepileptic drugs used were collected. Descriptive statistical analysis was used with independent t test, χ ², Mann-Whitney test, and post hoc analyses applied for associations.

Results

A total of 872 cooled newborns were enrolled; the median (IQR) gestational age was 39 (38-40) weeks, 518 (59.4%) were male, and 59 (6.8%) were classified as having mild encephalopathy by modified Sarnat examination, 504 (57.8%) as moderate, and 180 (20.6%) as severe. Electrographic seizures were identified in 296 newborns (33.9%), being only electrographic in 213 (71.9%) and clinical followed by electroclinical uncoupling in 50 (16.9%). Early abnormal background activity had a significant association with seizures. Infants with flat trace had the highest rate of seizures (58 infants [68.2%]) and the greatest association with the incidence of seizures (odds ratio [OR], 12.90; 95% CI, 7.57-22.22) compared with continuous normal voltage. The absence of sleep-wake cycling was also associated with a higher occurrence of seizures (OR, 2.22; 95% CI, 1.67-2.96). Seizure onset was most frequent between 6 and 24 hours of life (181 infants [61.1%]); however, seizure occurred in 34 infants (11.5%) during rewarming. A single antiepileptic drug controlled seizures in 192 infants (64.9%). The first line antiepileptic drug was phenobarbital in 294 (99.3%).

Conclusions and Relevance

In this cohort study of newborns with HIE treated with TH, electrographic seizure activity occurred in 296 infants (33.9%) and was predominantly electrographic. Seizure control was obtained with a single antiepileptic drug in 192 infants (64.9%). These findings suggest neonatal neurocritical care can be delivered at remote limited resource hospitals due to innovations in technology and telehealth.