{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:52:18Z","timestamp":1791921138517,"version":"4.3.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Children with complex congenital heart disease (CHD) are at high risk of brain lesions both before and after cardiac surgery. Preoperative brain injury reflects foetal and perinatal brain development and represents an independent predictor of neurodevelopmental outcome. This study aimed to characterize preoperative brain lesions and their correlation with clinical course and neurodevelopmental outcomes in children with complex CHD. The secondary objective was to compare findings between syndromic and non-syndromic patients, as preoperative brain injury in syndromic children remains underreported. A single-centre cohort study was performed at the University of Padova, Italy, involving children with complex CHD who underwent preoperative brain MRI between January 2020 and October 2024. Patients were categorized based on the presence or absence of a known or suspected genetic syndrome. Neurological and neurodevelopmental evaluations were conducted pre- and postoperatively, and at 6- and 18-months follow-up. Among 54 enrolled patients, 21 (39%) had a suspected or confirmed genetic syndrome. Preoperative brain lesions were present in 24 children (44%), including 16\/33 (48%) non-syndromic and 8\/21 (38%) syndromic patients (OR 0.65 [0.21\u20131.94],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.5708). Arterial ischemic stroke was the most common lesion (20%), followed by subdural haemorrhage (11%), cerebral sinovenous thrombosis (9%), and white matter injury (6%). Despite similar lesion rates, syndromic children showed more complicated perinatal histories and greater neurodevelopmental impairment, particularly in motor and language domains.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusion<\/jats:italic>\n                    :\u00a0Syndromic children with CHD do not have higher rates of preoperative brain injury but remain at greater neurodevelopmental risk. Further studies are warranted to confirm these findings.\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td colspan=\"2\">\n                              <jats:bold>What is Known:<\/jats:bold>\n                              \u2022\n                              <jats:italic>Children with complex congenital heart disease (CHD) are at high risk for preoperative brain injury and neurodevelopmental impairment.<\/jats:italic>\n                              \u2022\n                              <jats:italic>Syndromic children with CHD are often excluded from neurodevelopmental studies.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td colspan=\"2\">\n                              <jats:bold>What is New:<\/jats:bold>\n                              \u2022\n                              <jats:italic>Preoperative brain lesions (44%), mainly arterial ischemic stroke (20%), are frequent in our cohort of syndromic and non-syndromic children with complex CHD.<\/jats:italic>\n                              \u2022\n                              <jats:italic>Syndromic children with CHD do not show increased rates of preoperative brain injury compared to non-syndromic children, but remain a population at higher neurodevelopmental risk.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-026-07437-w","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:44:13Z","timestamp":1790664253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative brain injury and neurodevelopmental outcomes in syndromic and non-syndromic children with complex congenital heart disease: a single-centre cohort study"],"prefix":"10.1007","volume":"185","author":[{"given":"Chiara","family":"Paolin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Ancona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mezzalira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Di Salvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Padalino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Scattolin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimiro","family":"Vida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Sartori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Manara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"issue":"5","key":"7437_CR1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1002\/pd.6292","volume":"43","author":"FT Lee","year":"2023","unstructured":"Lee FT, Sun L, Freud L, Seed M (2023) A guide to prenatal counseling regarding neurodevelopment in congenital heart disease. Prenat Diagn 43(5):661\u2013673. https:\/\/doi.org\/10.1002\/pd.6292","journal-title":"Prenat Diagn"},{"issue":"9","key":"7437_CR2","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1161\/CIRCULATIONAHA.120.052436","volume":"143","author":"M Seed","year":"2021","unstructured":"Seed M, Miller SP (2021) A life-course approach to the neurodevelopmental trajectory of congenital heart disease. Circulation 143(9):892\u2013894. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.120.052436","journal-title":"Circulation"},{"issue":"4","key":"7437_CR3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00431-025-06085-w","volume":"184","author":"X Zhang","year":"1990","unstructured":"Zhang X, Feng Y, Ren J, Jin X, Li J, Hou Y et al (1990) Global, regional, and national burden of congenital heart disease, 1990-2021: a systematic analysis for the global burden of disease study 2021. Eur J Pediatr 184(4):253. https:\/\/doi.org\/10.1007\/s00431-025-06085-w","journal-title":"Eur J Pediatr"},{"issue":"5","key":"7437_CR4","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1007\/s00431-023-05419-w","volume":"183","author":"N Derridj","year":"2024","unstructured":"Derridj N, Calderon J, Bonnet D, Khoshnood B, Monier I, Guedj R (2024) Neurodevelopmental outcomes of preterm and growth-restricted neonate with congenital heart defect: a systematic review and meta-analysis. Eur J Pediatr 183(5):1967\u20131987. https:\/\/doi.org\/10.1007\/s00431-023-05419-w","journal-title":"Eur J Pediatr"},{"issue":"1","key":"7437_CR5","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.clp.2015.11.012","volume":"43","author":"B Latal","year":"2016","unstructured":"Latal B (2016) Neurodevelopmental outcomes of the child with congenital heart disease. Clin Perinatol 43(1):173\u2013185. https:\/\/doi.org\/10.1016\/j.clp.2015.11.012","journal-title":"Clin Perinatol"},{"issue":"1","key":"7437_CR6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/s1071-9091(99)80042-4","volume":"6","author":"A Majnemer","year":"1999","unstructured":"Majnemer A, Limperopoulos C (1999) Developmental progress of children with congenital heart defects requiring open heart surgery. Semin Pediatr Neurol 6(1):12\u201319. https:\/\/doi.org\/10.1016\/s1071-9091(99)80042-4","journal-title":"Semin Pediatr Neurol"},{"issue":"6","key":"7437_CR7","doi-asserted-by":"publisher","first-page":"e2615885","DOI":"10.1001\/jamanetworkopen.2026.15885","volume":"9","author":"M Seed","year":"2026","unstructured":"Seed M, Ilardi D, Rofeberg V, Ortinau C, Goldberg C, Reichle G et al (2026) Early neurodevelopmental outcomes in children with congenital heart disease. JAMA Netw Open 9(6):e2615885. https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.15885","journal-title":"JAMA Netw Open"},{"issue":"1","key":"7437_CR8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/chd.12322","volume":"11","author":"T Alsaied","year":"2016","unstructured":"Alsaied T, Marino BS, Esbensen AJ, Anixt JS, Epstein JN, Cnota JF (2016) Does congenital heart disease affect neurodevelopmental outcomes in children with Down syndrome? Congenit Heart Dis 11(1):26\u201333. https:\/\/doi.org\/10.1111\/chd.12322","journal-title":"Congenit Heart Dis"},{"issue":"23","key":"7437_CR9","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1016\/j.jacc.2023.09.824","volume":"82","author":"K Phillips","year":"2023","unstructured":"Phillips K, Callaghan B, Rajagopalan V, Akram F, Newburger JW, Kasparian NA (2023) Neuroimaging and neurodevelopmental outcomes among individuals with complex congenital heart disease. J Am Coll Cardiol 82(23):2225\u20132245. https:\/\/doi.org\/10.1016\/j.jacc.2023.09.824","journal-title":"J Am Coll Cardiol"},{"key":"7437_CR10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.xjon.2023.11.018","volume":"17","author":"JG Reitz","year":"2024","unstructured":"Reitz JG, Zurakowski D, Kuhn VA, Murnick J, Donofrio MT, d\u2019Udekem Y et al (2024) Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease. JTCVS Open 17:229\u2013247. https:\/\/doi.org\/10.1016\/j.xjon.2023.11.018","journal-title":"JTCVS Open"},{"issue":"9","key":"7437_CR11","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1136\/archdischild-2021-323132","volume":"107","author":"FJ Alablani","year":"2022","unstructured":"Alablani FJ, Chan HSA, Beishon L, Patel N, Almudayni A, Bu\u2019Lock F et al (2022) Paediatric brain MRI findings following congenital heart surgery: a systematic review. Arch Dis Child. 107(9):818\u201325. https:\/\/doi.org\/10.1136\/archdischild-2021-323132","journal-title":"Arch Dis Child."},{"issue":"11","key":"7437_CR12","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.3174\/ajnr.A7328","volume":"42","author":"R Stegeman","year":"2021","unstructured":"Stegeman R, Feldmann M, Claessens NHP, Jansen NJG, Breur JMPJ, De Vries LS et al (2021) A uniform description of perioperative brain MRI findings in infants with severe congenital heart disease: results of a European collaboration. AJNR Am J Neuroradiol 42(11):2034\u20132039. https:\/\/doi.org\/10.3174\/ajnr.A7328","journal-title":"AJNR Am J Neuroradiol"},{"issue":"1","key":"7437_CR13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/uog.12526","volume":"43","author":"A Khalil","year":"2014","unstructured":"Khalil A, Suff N, Thilaganathan B, Hurrell A, Cooper D, Carvalho JS (2014) Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis: brain abnormalities and neurodevelopmental delay in CHD. Ultrasound Obstet Gynecol 43(1):14\u201324. https:\/\/doi.org\/10.1002\/uog.12526","journal-title":"Ultrasound Obstet Gynecol"},{"issue":"7","key":"7437_CR14","doi-asserted-by":"publisher","first-page":"e025516","DOI":"10.1161\/JAHA.122.025516","volume":"12","author":"DJ Licht","year":"2023","unstructured":"Licht DJ, Jacobwitz M, Lynch JM, Ko T, Boorady T, Devarajan M et al (2023) Impaired maternal\u2010fetal environment and risk for preoperative focal white matter injury in neonates with complex congenital heart disease. J Am Heart Assoc 12(7):e025516. https:\/\/doi.org\/10.1161\/JAHA.122.025516","journal-title":"J Am Heart Assoc"},{"issue":"11","key":"7437_CR15","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1161\/CIRCULATIONAHA.113.002453","volume":"128","author":"AM Herskind","year":"2013","unstructured":"Herskind AM, Almind Pedersen D, Christensen K (2013) Increased prevalence of congenital heart defects in monozygotic and dizygotic twins. Circulation 128(11):1182\u20131188. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.113.002453","journal-title":"Circulation"},{"issue":"7","key":"7437_CR16","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00431-026-07189-7","volume":"185","author":"F Lu","year":"2026","unstructured":"Lu F, Liu Y, Lu S, Ma S, Zhu M, Yang F et al (2026) Cortical structure alterations in toddlers with different severities of congenital heart disease: a cross-sectional study. Eur J Pediatr 185(7):537. https:\/\/doi.org\/10.1007\/s00431-026-07189-7","journal-title":"Eur J Pediatr"},{"issue":"3","key":"7437_CR17","doi-asserted-by":"publisher","first-page":"e214569","DOI":"10.1212\/WNL.0000000000214569","volume":"106","author":"C Kim","year":"2026","unstructured":"Kim C, Chetan D, Kazazian V, Alzamil J, Chau V, Seed M et al (2026) Prevalence of ischemic brain injury in neonates with congenital heart disease: a systematic review and meta-analysis. Neurology 106(3):e214569. https:\/\/doi.org\/10.1212\/WNL.0000000000214569","journal-title":"Neurology"},{"issue":"155","key":"7437_CR18","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.57187\/s.4466","volume":"2","author":"W Knirsch","year":"2025","unstructured":"Knirsch W, De Silvestro A, Steger C, Rathke V, Weber R, Von Rhein M et al (2025) Serial cerebral magnetic resonance imaging before and after birth in patients with complex congenital heart disease - a prospective, multicentre observational study. Swiss Med Wkly 2(155):4466. https:\/\/doi.org\/10.57187\/s.4466","journal-title":"Swiss Med Wkly"},{"issue":"8","key":"7437_CR19","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.3174\/ajnr.A3903","volume":"35","author":"M Brossard-Racine","year":"2014","unstructured":"Brossard-Racine M, Du Plessis AJ, Vezina G, Robertson R, Bulas D, Evangelou IE et al (2014) Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease. AJNR Am J Neuroradiol 35(8):1593\u20131599. https:\/\/doi.org\/10.3174\/ajnr.A3903","journal-title":"AJNR Am J Neuroradiol"},{"issue":"1","key":"7437_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pediatrneurol.2007.04.001","volume":"37","author":"AR Paciorkowski","year":"2007","unstructured":"Paciorkowski AR, Greenstein RM (2007) When is enlargement of the subarachnoid spaces not benign? A genetic perspective. Pediatr Neurol 37(1):1\u20137. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2007.04.001","journal-title":"Pediatr Neurol"},{"issue":"12","key":"7437_CR21","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1161\/STROKEAHA.122.039492","volume":"53","author":"AF Bonthrone","year":"2022","unstructured":"Bonthrone AF, Stegeman R, Feldmann M, Claessens NHP, Nijman M, Jansen NJG et al (2022) Risk factors for perioperative brain lesions in infants with congenital heart disease: a European collaboration. Stroke 53(12):3652\u20133661. https:\/\/doi.org\/10.1161\/STROKEAHA.122.039492","journal-title":"Stroke"},{"key":"7437_CR22","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.70391","author":"J Liu","year":"2026","unstructured":"Liu J, Baral VR, Ereno IL, Zainal KA, Ong J, Chua JS et al (2026) Predictive ability of the Hammersmith Neonatal Neurological Examination for identifying severe neurodevelopmental impairment in infants born very preterm. Dev Med Child Neurol. https:\/\/doi.org\/10.1111\/dmcn.70391","journal-title":"Dev Med Child Neurol"},{"issue":"2","key":"7437_CR23","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0022-3476(99)70016-8","volume":"135","author":"L Haataja","year":"1999","unstructured":"Haataja L, Mercuri E, Regev R, Cowan F, Rutherford M, Dubowitz V et al (1999) Optimality score for the neurologic examination of the infant at 12 and 18 months of age. J Pediatr 135(2):153\u2013161. https:\/\/doi.org\/10.1016\/S0022-3476(99)70016-8","journal-title":"J Pediatr"},{"issue":"4","key":"7437_CR24","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/ejcts\/ezt422","volume":"45","author":"S Bertholdt","year":"2014","unstructured":"Bertholdt S, Latal B, Liamlahi R, Pretre R, Scheer I, Goetti R et al (2014) Cerebral lesions on magnetic resonance imaging correlate with preoperative neurological status in neonates undergoing cardiopulmonary bypass surgery. Eur J Cardiothorac Surg 45(4):625\u2013632. https:\/\/doi.org\/10.1093\/ejcts\/ezt422","journal-title":"Eur J Cardiothorac Surg"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07437-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-026-07437-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07437-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:36:46Z","timestamp":1791920206000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-026-07437-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":24,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["7437"],"URL":"https:\/\/doi.org\/10.1007\/s00431-026-07437-w","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"30 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the local hospital Research Board at the University of Padova (Protocol ID 3142\/AO\/14).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from the parents or legal guardians of all individual participants included in the study.","order":2,"name":"Ethics","label":"Consent to participate and to publish","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"782"}}