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Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates: A randomized clinical trial


Hunt, RW and Liley, HG and Wagh, D and Schembri, R and Lee, KJ and Shearman, AD and Francis-Pester, S and Dewaal, K and Cheong, JYL and Olischar, M and Badawi, N and Wong, FY and Osborn, DA and Rajadurai, VS and Dargaville, PA and Headley, B and Wright, I and Colditz, PB, Newborn Electrographic Seizure Trial Investigators, Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates: A randomized clinical trial, JAMA Network Open, 4, (12) pp. 1-12. ISSN 2574-3805 (2021) [Refereed Article]

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Copyright Statement

2021 Hunt RW et al. JAMA Network Open. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License (, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

DOI: doi:10.1001/jamanetworkopen.2021.39604


Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain.

Objective: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures.

Design, setting, and participants: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks' gestation or more and younger than 48 hours old. Data analysis was completed in April 2021.

Interventions: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated.

Main outcomes and measures: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years.

Results: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, -6.5 [95% CI, -1.2 to -11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score.

Conclusions and relevance: Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Paediatrics
Research Field:Neonatology
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Neonatal and child health
UTAS Author:Dargaville, PA (Professor Peter Dargaville)
ID Code:152232
Year Published:2021
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-08-15
Last Modified:2022-10-20
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