Journal article
Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up A Nested Multisite Cohort Study
JAMA neurology, Vol.78(12), pp.1484-1493
12/01/2021
DOI: 10.1001/jamaneurol.2021.3723
PMCID: PMC8524352
PMID: 34661629
Abstract
This cohort study evaluates whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy.
Importance Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce. Objective To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy. Design, Setting, and Participants This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020. Interventions Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity. Main Outcomes and Measures The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes. Results A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (kappa, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center. Conclusions and Relevance Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.
Question Are seizures more likely to occur during rewarming after hypothermia, and are they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy? Findings This cohort study reports higher odds of electrographic seizure during the rewarming phase after hypothermia associated with increased relative risk of death or disability at 2-year follow-up. Meaning Study findings support the American Clinical Neurophysiology Society's Guidelines for continuous electroencephalography monitoring of neonates with suspected perinatal asphyxia during hypothermia and further suggest that monitoring should be continued until normothermia is completed and seizure control is assured.
Details
- Title: Subtitle
- Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up A Nested Multisite Cohort Study
- Creators
- Lina F. Chalak - The University of Texas Southwestern Medical CenterAthina Pappas - Wayne State UniversitySylvia Tan - RTI InternationalAbhik Das - RTI InternationalPablo J. Sanchez - Nationwide Children's HospitalAbbot R. Laptook - Women & Infants Hospital of Rhode IslandKrisa P. Van Meurs - Lucile Packard Children's HospitalSeetha Shankaran - Wayne State UniversityEdward F. Bell - University of IowaAlexis S. Davis - Lucile Packard Children's HospitalRoy J. Heyne - The University of Texas Southwestern Medical CenterClaudia Pedroza - The University of Texas Health Science Center at HoustonBrenda B. Poindexter - Indiana UniversityKurt Schibler - Cincinnati Children's Hospital Medical CenterJon E. Tyson - The University of Texas Health Science Center at HoustonM. Bethany Ball - Lucile Packard Children's HospitalRebecca Bara - Wayne State UniversityCathy Grisby - Cincinnati Children's Hospital Medical CenterGregory M. Sokol - Indiana UniversityCarl T. D'Angio - University of RochesterShannon E. G. Hamrick - Emory University Hospital MidtownKevin C. Dysart - University of PennsylvaniaC. Michael Cotten - Duke UniversityWilliam E. Truog - Children's Mercy HospitalKristi L. Watterberg - University of New MexicoChristopher J. Timan - Nationwide Children's HospitalMeena Garg - University of California, Los AngelesWaldemar A. Carlo - University of Alabama at BirminghamRosemary D. Higgins - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA neurology, Vol.78(12), pp.1484-1493
- Publisher
- Amer Medical Assoc
- DOI
- 10.1001/jamaneurol.2021.3723
- PMID
- 34661629
- PMCID
- PMC8524352
- ISSN
- 2168-6149
- eISSN
- 2168-6157
- Number of pages
- 10
- Grant note
- 5R01NS102617 / Eunice Kennedy Shriver National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Language
- English
- Date published
- 12/01/2021
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984354159002771
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