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Randomized Controlled Trial
. 2021 Dec 1;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

Rod W Hunt  1   2   3   4   5 , Helen G Liley  6   7 , Deepika Wagh  8 , Rachel Schembri  9 , Katherine J Lee  9   10 , Andrew D Shearman  6 , Samantha Francis-Pester  2 , Koert deWaal  11   12 , Jeanie Y L Cheong  2   13   14 , Monika Olischar  15 , Nadia Badawi  4   16 , Flora Y Wong  1   3   5 , David A Osborn  17   18 , Victor Samuel Rajadurai  19 , Peter A Dargaville  20   21 , Bevan Headley  22 , Ian Wright  23 , Paul B Colditz  7   24 ; Newborn Electrographic Seizure Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Effect of Treatment of Clinical Seizures vs Electrographic Seizures in Full-Term and Near-Term Neonates: A Randomized Clinical Trial

Rod W Hunt et al. JAMA Netw Open. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Drs Lee, Cheong, and Wong reported receiving grants from the National Health and Medical Research Council (NHMRC) during the conduct of the study. Dr Cheong reported receiving grants from NHMRC outside the submitted work. Dr Dargaville reported receiving personal fees from Chiesi Farmaceutici outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT 2010 Flow Diagram
aIncluded in the analysis of the primary outcomes.
See this image and copyright information in PMC

Comment in

References

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