PMID- 38246187 OWN - NLM STAT- MEDLINE DCOM- 20240219 LR - 20240320 IS - 2352-4650 (Electronic) IS - 2352-4642 (Print) IS - 2352-4642 (Linking) VI - 8 IP - 3 DP - 2024 Mar TI - Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies. PG - 214-224 LID - S2352-4642(23)00296-1 [pii] LID - 10.1016/S2352-4642(23)00296-1 [doi] AB - BACKGROUND: Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome. METHODS: This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]). Infants were born at 36(+0) weeks of gestation with moderate or severe hypoxic-ischaemic encephalopathy and underwent therapeutic hypothermia with prolonged conventional video-electroencephalography (EEG) monitoring for 10 h or longer from the start of rewarming. Seizure burden characteristics were calculated based on electrographic seizures annotations: hourly seizure burden (minutes of seizures within an hour) and total seizure burden (minutes of seizures within the entire recording). We categorised infants into those with electrographic seizures during active cooling only, those with electrographic seizures during cooling and rewarming, and those without seizures. Neurodevelopmental outcomes were determined using the Bayley's Scales of Infant and Toddler Development, Third Edition (BSID-III), the Griffiths Mental Development Scales (GMDS), or neurological assessment. An abnormal outcome was defined as death or neurodisability at 2 years. Neurodisability was defined as a composite score of 85 or less on any subscales for BSID-III, a total score of 87 or less for GMDS, or a diagnosis of cerebral palsy (dyskinetic cerebral palsy, spastic quadriplegia, or mixed motor impairment) or epilepsy. FINDINGS: Of 263 infants recruited between Jan 1, 2011, and Feb 7, 2017, we included 129 infants: 65 had electrographic seizures (43 during active cooling only and 22 during and after active cooling) and 64 had no seizures. Compared with infants with seizures during active cooling only, those with seizures during and after active cooling had a longer seizure period (median 12 h [IQR 3-28] vs 68 h [35-86], p<0.0001), more seizures (median 12 [IQR 5-36] vs 94 [24-134], p<0.0001), and higher total seizure burden (median 69 min [IQR 22-104] vs 167 min [54-275], p=0.0033). Hourly seizure burden peaked at about 20-24 h in both groups, and infants with seizures during and after active cooling had a secondary peak at 85 h of age. When combined, worse EEG background (major abnormalities and inactive background) at 12 h and 24 h were associated with the seizure group: compared with infants with a better EEG background (normal, mild, or moderate abnormalities), infants with a worse EEG background were more likely to have seizures after cooling at 12 h (13 [54%] of 24 vs four [14%] of 28; odds ratio 7.09 [95% CI 1.88-26.77], p=0.0039) and 24 h (14 [56%] of 25 vs seven [18%] of 38; 5.64 [1.81-17.60], p=0.0029). There was a significant relationship between EEG grade at 12 h (four categories) and seizure group (p=0.020). High total seizure burden was associated with increased odds of an abnormal outcome at 2 years of age (odds ratio 1.007 [95% CI 1.000-1.014], p=0.046), with a medium negative correlation between total seizure burden and BSID-III cognitive score (r(S)=-0.477, p=0.014, n=26). INTERPRETATION: Overall, half of infants with hypoxic-ischaemic encephalopathy had electrographic seizures and a third of those infants had seizures beyond active cooling, with worse outcomes. These results raise the importance of prolonged EEG monitoring of newborn infants with hypoxic-ischaemic encephalopathy not only during active cooling but throughout the rewarming phase and even longer when seizures are detected. FUNDING: Wellcome Trust, Science Foundation Ireland, and the Irish Health Research Board. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Pavel, Andreea M AU - Pavel AM AD - INFANT Research Centre and Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. FAU - Rennie, Janet M AU - Rennie JM AD - Institute for Women's Health, University College London, London, UK. FAU - de Vries, Linda S AU - de Vries LS AD - Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. FAU - Mathieson, Sean R AU - Mathieson SR AD - INFANT Research Centre and Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. FAU - Livingstone, Vicki AU - Livingstone V AD - INFANT Research Centre and Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. FAU - Finder, Mikael AU - Finder M AD - Department of Neonatal Medicine, Karolinska University Hospital, Stockholm, Sweden; Division of Paediatrics, Department CLINTEC, Karolinska Institutet, Stockholm, Sweden. FAU - Foran, Adrienne AU - Foran A AD - Department of Neonatal Medicine, Rotunda Hospital, Dublin, Ireland. FAU - Shah, Divyen K AU - Shah DK AD - Royal London Hospital, London, UK; London School of Medicine and Dentistry, Queen Mary University of London, London, UK. FAU - Pressler, Ronit M AU - Pressler RM AD - Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Trust, London, UK. FAU - Weeke, Lauren C AU - Weeke LC AD - Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. FAU - Dempsey, Eugene M AU - Dempsey EM AD - INFANT Research Centre and Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. FAU - Murray, Deirdre M AU - Murray DM AD - INFANT Research Centre and Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. FAU - Boylan, Geraldine B AU - Boylan GB AD - INFANT Research Centre and Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. Electronic address: g.boylan@ucc.ie. CN - ANSeR Consortium LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 209325/Z/17/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Observational Study PT - Randomized Controlled Trial DEP - 20240118 PL - England TA - Lancet Child Adolesc Health JT - The Lancet. Child & adolescent health JID - 101712925 SB - IM MH - Infant, Newborn MH - Infant MH - Humans MH - *Hypoxia-Ischemia, Brain/complications/therapy MH - Seizures/therapy/diagnosis MH - Monitoring, Physiologic/methods MH - *Hypothermia, Induced MH - *Cerebral Palsy/complications PMC - PMC10864190 COIS- Declaration of interests We declare no competing interests. FIR - Pavlidis, Elena IR - Pavlidis E FIR - Kharoshankaya, Liudmila IR - Kharoshankaya L FIR - Marnane, Liam IR - Marnane L FIR - Lightbody, Gordon IR - Lightbody G FIR - O'Leary, Jackie IR - O'Leary J FIR - Murray, Mairead IR - Murray M FIR - Conway, Jean IR - Conway J FIR - Dwyer, Denis IR - Dwyer D FIR - Temko, Andrey IR - Temko A FIR - Kiely, Taragh IR - Kiely T FIR - Ryan, Anthony C IR - Ryan AC FIR - Mitra, Subhabrata IR - Mitra S FIR - Toet, Mona C IR - Toet MC FIR - Blennow, Mats IR - Blennow M FIR - Edqvist, Ingela IR - Edqvist I FIR - Pinnamaneni, Raga M IR - Pinnamaneni RM FIR - Colby-Milley, Jessica IR - Colby-Milley J FIR - Openshaw-Lawrence, Nicola IR - Openshaw-Lawrence N FIR - Kapellou, Olga IR - Kapellou O FIR - van Huffelen, Alexander C IR - van Huffelen AC EDAT- 2024/01/22 00:42 MHDA- 2024/02/19 06:44 PMCR- 2024/03/01 CRDT- 2024/01/21 18:53 PHST- 2023/06/30 00:00 [received] PHST- 2023/11/01 00:00 [revised] PHST- 2023/11/02 00:00 [accepted] PHST- 2024/02/19 06:44 [medline] PHST- 2024/01/22 00:42 [pubmed] PHST- 2024/01/21 18:53 [entrez] PHST- 2024/03/01 00:00 [pmc-release] AID - S2352-4642(23)00296-1 [pii] AID - 10.1016/S2352-4642(23)00296-1 [doi] PST - ppublish SO - Lancet Child Adolesc Health. 2024 Mar;8(3):214-224. doi: 10.1016/S2352-4642(23)00296-1. Epub 2024 Jan 18.