{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:58:17Z","timestamp":1780451897516,"version":"3.54.1"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"02","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A.R.E.F. Onlus"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This retrospective, dual-center Italian study assessed the incidence, electroclinical characteristics, and risk factors for post-neonatal epilepsy among neonates with hypoxic\u2013ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). The study aims to better define the long-term risk factors for developing epilepsy or neurodevelopmental issues.<\/jats:p>\n                  <jats:p>We included neonates with HIE who underwent TH. Neurological examination and general movements were assessed before and after TH. Amplified-integrated EEGs (aEEG) or polygraphic EEGs (pEEG) were performed within 6\u2009hours of life; a pEEG was performed after TH (72\u2009hours to 10 days) and at 3, 9 to 12, and 24 months, and then yearly. Brain MRI was conducted within 30 days. The 24-month developmental outcome was evaluated using Griffiths Mental Development Scales. The median follow-up duration was 48 months. Epilepsy was classified according to ILAE criteria.<\/jats:p>\n                  <jats:p>We enrolled 159 patients: 15 (9.4%) developed epilepsy. Nine (5.6%) had onset before 24 months; three of them developed infantile epileptic spasm syndrome (IESS). Seizure onset was after 24 months in 6\/159 individuals (3.8%). At the last follow-up, all 15 patients had focal epilepsy. Global development was pathological in 11\/15 (10\/15 &lt;2SD; 1\/15 &lt;1SD). Risk factors for post-neonatal epilepsy included: MRI lesions involving the basal ganglia and thalamus (p\u2009&lt;\u20090.0001), severe HIE (p\u2009=\u20090.0008), and severe anomalies on the pEEG recorded pre-TH (p\u2009=\u20090.0032) and post-TH (p\u2009=\u20090.0071).<\/jats:p>\n                  <jats:p>Our study confirms that post-neonatal epilepsy is rare and generally well-controlled. MRI, HIE-3, and early pEEGs are key predictors. High-risk patients should be screened for IESS in the early months, and patients with electroclinical and neuroradiological risk factors should continue long-term neurological follow-up beyond 24 months.<\/jats:p>","DOI":"10.1055\/a-2781-6844","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T23:47:07Z","timestamp":1769730427000},"page":"107-115","source":"Crossref","is-referenced-by-count":1,"title":["Epilepsy and Neurodevelopment Outcomes 24 Months after Neonatal Hypoxic\u2013Ischemic Encephalopathy and Predictive Factors of Post-neonatal Epilepsy"],"prefix":"10.1055","volume":"57","author":[{"given":"Graziamaria","family":"Cicala","sequence":"first","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Ricca","sequence":"first","affiliation":[{"name":"Pediatric Unit, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'adulto, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2300-1514","authenticated-orcid":false,"given":"Maria","family":"Picilli","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rolleri","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Perulli","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Contaldo","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Veredice","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Quintiliani","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luigia","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Turrini","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Pede","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico Marco","family":"Romeo","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Bergonzini","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'adulto, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Lugli","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'adulto, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica Immacolata","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.seizure.2020.07.002","article-title":"Neonatal neuroimaging and neurophysiology predict infantile onset epilepsy after perinatal hypoxic ischemic encephalopathy","volume":"80","author":"P Nevalainen","year":"2020","journal-title":"Seizure"},{"issue":"08","key":"ref2","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.17219\/acem\/124437","article-title":"Methods for assessing the severity of perinatal asphyxia and early prognostic tools in neonates with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia","volume":"29","author":"W Walas","year":"2020","journal-title":"Adv Clin Exp Med"},{"issue":"03","key":"ref3","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1542\/neo.22-3-e148","article-title":"Neonatal encephalopathy: beyond hypoxic-ischemic encephalopathy","volume":"22","author":"J B Russ","year":"2021","journal-title":"Neoreviews"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s13760-020-01308-3","article-title":"Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future","volume":"120","author":"P Greco","year":"2020","journal-title":"Acta Neurol Belg"},{"issue":"01","key":"ref5","first-page":"9","article-title":"Ischemic conditioning and neonatal hypoxic ischemic encephalopathy: a literature review","volume":"1","author":"D Adstamongkonkul","year":"2017","journal-title":"Cond Med"},{"issue":"04","key":"ref7","doi-asserted-by":"crossref","first-page":"F267","DOI":"10.1136\/archdischild-2011-300716","article-title":"Cooling and seizure burden in term neonates: an observational study","volume":"97","author":"E Low","year":"2012","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"01","key":"ref8","first-page":"CD003311","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","volume":"2013","author":"S E Jacobs","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jpeds.2013.01.041","article-title":"Therapeutic hypothermia in neonatal hypoxic ischemic encephalopathy: electrographic seizures and magnetic resonance imaging evidence of injury","volume":"163","author":"P Srinivasakumar","year":"2013","journal-title":"J Pediatr"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpeds.2010.02.016","article-title":"Serial MRI and neurodevelopmental outcome in 9- to 10-year-old children with neonatal encephalopathy","volume":"157","author":"B JM van Kooij","year":"2010","journal-title":"J Pediatr"},{"issue":"05","key":"ref11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.braindev.2012.07.002","article-title":"EEG findings in cooled asphyxiated newborns and correlation with site and severity of brain damage","volume":"35","author":"E Briatore","year":"2013","journal-title":"Brain Dev"},{"issue":"02","key":"ref12","first-page":"150","article-title":"Brain cooling reduces the risk of postneonatal epilepsy in newborns affected by moderate to severe hypoxic-ischemic encephalopathy","volume":"73","author":"L Lugli","year":"2021","journal-title":"Minerva Pediatr (Torino)"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/dmcn.14331","article-title":"Impact of therapeutic hypothermia on infantile spasms: an observational cohort study","volume":"62","author":"F Abu Dhais","year":"2020","journal-title":"Dev Med Child Neurol"},{"issue":"07","key":"ref14","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1177\/0883073817698628","article-title":"Prediction of future epilepsy in neonates with hypoxic-ischemic encephalopathy who received selective head cooling","volume":"32","author":"T L McDonough","year":"2017","journal-title":"J Child Neurol"},{"issue":"10","key":"ref16","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/archneur.1976.00500100030012","article-title":"Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study","volume":"33","author":"H B Sarnat","year":"1976","journal-title":"Arch Neurol"},{"issue":"08","key":"ref17","first-page":"1194","article-title":"Polygraphic EEG can identify asphyxiated infants for therapeutic hypothermia and predict neurodevelopmental outcomes","volume":"9","author":"L Lugli","year":"2022","journal-title":"Children (Basel)"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"e459","DOI":"10.1542\/peds.2008-2190","article-title":"Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years","volume":"124","author":"D M Murray","year":"2009","journal-title":"Pediatrics"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/epi.16815","article-title":"The ILAE classification of seizures and the epilepsies: modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures","volume":"62","author":"R M Pressler","year":"2021","journal-title":"Epilepsia"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/epi4.13090","article-title":"Defining neonatal status epilepticus: a scoping review from the ILAE neonatal task force","volume":"10","author":"M L Nunes","year":"2025","journal-title":"Epilepsia Open"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1542\/peds.2007-0770","article-title":"Patterns of brain injury in neonates exposed to perinatal sentinel events","volume":"121","author":"A Okereafor","year":"2008","journal-title":"Pediatrics"},{"issue":"06","key":"ref22","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1111\/epi.18338","article-title":"Updated classification of epileptic seizures: position paper of the International League Against Epilepsy","volume":"66","author":"S Beniczky","year":"2025","journal-title":"Epilepsia"},{"issue":"06","key":"ref23","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/epi.17241","article-title":"International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions","volume":"63","author":"N Specchio","year":"2022","journal-title":"Epilepsia"},{"issue":"06","key":"ref24","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/epi.17239","article-title":"ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE Task Force on Nosology and Definitions","volume":"63","author":"S M Zuberi","year":"2022","journal-title":"Epilepsia"},{"key":"ref25","volume-title":"Griffiths Mental Development Scales: Extended Revised (GMDS-ER) Manual","author":"R Griffiths","year":"2001"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.clinph.2022.09.005","article-title":"Poor aEEG background recovery after perinatal hypoxic ischemic encephalopathy predicts postneonatal epilepsy by age 4 years","volume":"143","author":"J Nyman","year":"2022","journal-title":"Clin Neurophysiol"},{"issue":"11","key":"ref27","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1111\/epi.13914","article-title":"Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy","volume":"58","author":"X Liu","year":"2017","journal-title":"Epilepsia"},{"issue":"01","key":"ref28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.braindev.2008.04.001","article-title":"Development of epilepsy in newborns with moderate hypoxic-ischemic encephalopathy and neonatal seizures","volume":"31","author":"F Pisani","year":"2009","journal-title":"Brain Dev"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3389\/fneur.2020.00133","article-title":"Prognostic value of clinical tests in neonates with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: a systematic review and meta-analysis","volume":"11","author":"W Liu","year":"2020","journal-title":"Front Neurol"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.pediatrneurol.2004.11.005","article-title":"Postneonatal epilepsy following amplitude-integrated EEG-detected neonatal seizures","volume":"32","author":"M C Toet","year":"2005","journal-title":"Pediatr Neurol"},{"issue":"12","key":"ref31","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1111\/epi.16749","article-title":"Risk for infantile spasms after acute symptomatic neonatal seizures","volume":"61","author":"H C Glass","year":"2020","journal-title":"Epilepsia"},{"issue":"12","key":"ref32","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1111\/dmcn.13215","article-title":"Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy","volume":"58","author":"L Kharoshankaya","year":"2016","journal-title":"Dev Med Child Neurol"},{"issue":"11","key":"ref33","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.earlhumdev.2010.08.013","article-title":"Outcomes after central grey matter injury in term perinatal hypoxic-ischaemic encephalopathy","volume":"86","author":"M Martinez-Biarge","year":"2010","journal-title":"Early Hum Dev"},{"issue":"12","key":"ref34","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S1474-4422(06)70626-3","article-title":"Effects of seizures on developmental processes in the immature brain","volume":"5","author":"Y Ben-Ari","year":"2006","journal-title":"Lancet Neurol"},{"issue":"10","key":"ref35","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1111\/j.1528-1167.2010.02657.x","article-title":"Infantile spasms: a U.S. consensus report","volume":"51","author":"J M Pellock","year":"2010","journal-title":"Epilepsia"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.seizure.2020.12.023","article-title":"Seizures in the neonate: a review of etiologies and outcomes","volume":"85","author":"F Pisani","year":"2021","journal-title":"Seizure"},{"issue":"06","key":"ref37","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1212\/WNL.0b013e31820af91a","article-title":"Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia","volume":"76","author":"K B Nash","year":"2011","journal-title":"Neurology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"774828","DOI":"10.3389\/fped.2022.774828","article-title":"Etiologic classification of 541 infantile spasms cases: a cohort study","volume":"10","author":"P Peng","year":"2022","journal-title":"Front Pediatr"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejpn.2023.09.006","article-title":"Childhood-onset epilepsy in patients with dyskinetic cerebral palsy caused by basal ganglia and thalamic lesions","volume":"47","author":"S Nishimoto","year":"2023","journal-title":"Eur J Paediatr Neurol"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2781-6844.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:42:54Z","timestamp":1772602974000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2781-6844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":37,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2026,3,3]]},"published-print":{"date-parts":[[2026,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2781-6844","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]}}}