JAMA Netw Open. 2021 Dec 01;4(12):e2139604. doi: 10.1001/jamanetworkopen.2021.39604.
Effect of Treatment of Clinical Seizures vs Electrographic Seizures in Full-Term and Near-Term Neonates: A Randomized Clinical Trial.
JAMA network open
Rod W Hunt, Helen G Liley, Deepika Wagh, Rachel Schembri, Katherine J Lee, Andrew D Shearman, Samantha Francis-Pester, Koert deWaal, Jeanie Y L Cheong, Monika Olischar, Nadia Badawi, Flora Y Wong, David A Osborn, Victor Samuel Rajadurai, Peter A Dargaville, Bevan Headley, Ian Wright, Paul B Colditz,
Affiliations
Affiliations
- Department of Paediatrics, Monash University, Melbourne, Australia.
- Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia.
- Monash Newborn, Monash Children's Hospital, Melbourne, Australia.
- Cerebral Palsy Alliance, University of Sydney, Sydney, Australia.
- Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, Australia.
- Mater Mother's Hospital, Brisbane, Australia.
- University of Queensland, Brisbane, Australia.
- Perth Children's Hospital, Perth, Australia.
- Clinical Epidemiology Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Australia.
- Department of Paediatrics, University of Melbourne, Melbourne, Australia.
- Department of Neonatal Medicine, John Hunter Children's Hospital, Newcastle, Australia.
- University of Newcastle, Callaghan, Australia.
- Neonatal Services, The Royal Women's Hospital, Melbourne, Australia.
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
- University Children's Hospital, Vienna, Austria.
- Grace Newborn Intensive Care, The Children's Hospital, Westmead, Australia.
- Newborn Medicine, Royal Prince Alfred Hospital, Sydney, Australia.
- University of Sydney, Sydney, Australia.
- Department of Neonatology, KK Women's and Children's Hospital, Singapore.
- Neonatal and Paediatric Intensive Care Unit, Royal Hobart Hospital, Hobart, Australia.
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
- Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, Australia.
- James Cook University, Cairns, Australia.
- Royal Brisbane and Women's Hospital, Brisbane, Australia.
PMID: 34919132
DOI: 10.1001/jamanetworkopen.2021.39604
Abstract
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.
TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12611000327987.
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