{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:12:47Z","timestamp":1784761967755,"version":"3.55.0"},"reference-count":48,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-A-062"],"award-info":[{"award-number":["2022-PUMCH-A-062"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,11,6]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Previous studies have indicated that exposure to anaesthetics has potential neurotoxic effects, particularly in cases of multiple and long-term general anaesthesia. However, there is currently no research exploring the relationship between early anaesthesia and neurological development in children with congenital scoliosis, who may require multiple surgical treatments. Herein, we present our design for a prospective longitudinal observational cohort study, assessing the long-term impact of general anaesthesia for surgery before school age on neurocognitive function and behaviour in children with congenital scoliosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      A dynamic cohort of children aged 6\u201316 years diagnosed with congenital scoliosis between July 2020 and December 2025 in the Department of Orthopaedic Surgery at a tertiary hospital will be enrolled, with an aim to include 150 patients. Detailed information about baseline characteristics, previous anaesthesia and surgery will be collected from medical records, parents or guardians. Neurodevelopment will be evaluated using the abbreviated version of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) for neurocognition, and parent-report Achenbach Child Behaviour Checklist and Strengths and Difficulties Questionnaire for neurobehaviour. Repeated measures will be performed during follow-up, with at least a 1-year interval from the previous assessment, whenever the participants are available. The primary outcome is the full-scale intelligence quotient estimated by the WISC-IV. A linear mixed effects model will be constructed, with exposure group\n                      <jats:bold>\u2014<\/jats:bold>\n                      categorised as none, single or multiple anaesthesia exposures based on all episodes of general anaesthesia for surgery before the age of 7 years\n                      <jats:bold>\u2014<\/jats:bold>\n                      as a fixed effect and subject-specific random effects intercept.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study was approved by the Institutional Review Board of Peking Union Medical College Hospital (S-K1093). Written informed consents will be obtained from the parents or guardians. The results of this research will be disseminated through peer-reviewed publications and conference presentations, and shared with paediatric surgical patients and their families who are concerned about the potential neurotoxicity of anaesthesia in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06315933\">NCT06315933<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-108845","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T05:40:22Z","timestamp":1764740422000},"page":"e108845","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Association between general anaesthesia exposure and neurodevelopment in children with congenital scoliosis at a Chinese tertiary hospital: study protocol for a prospective longitudinal observational cohort study"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06315933","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06315933","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-7899","authenticated-orcid":false,"given":"Ziyi","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-9003","authenticated-orcid":false,"given":"Yuelun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Peking Union Medical College Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"2026010703452128000_15.12.e108845.1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318281e988"},{"key":"2026010703452128000_15.12.e108845.2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23652"},{"key":"2026010703452128000_15.12.e108845.3","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bja.2020.10.015","article-title":"Infant isoflurane exposure affects social behaviours, but does not impair specific cognitive domains in juvenile non-human primates","volume":"126","author":"Neudecker","year":"2021","journal-title":"Br J Anaesth"},{"key":"2026010703452128000_15.12.e108845.4","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neuro.2018.11.005","article-title":"Early life exposure to extended general anesthesia with isoflurane and nitrous oxide reduces responsivity on a cognitive test battery in the nonhuman primate","volume":"70","author":"Talpos","year":"2019","journal-title":"Neurotoxicology"},{"key":"2026010703452128000_15.12.e108845.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32485-1"},{"key":"2026010703452128000_15.12.e108845.6","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002232"},{"key":"2026010703452128000_15.12.e108845.7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12871-017-0462-8","article-title":"Long-duration general anesthesia influences the intelligence of school age children","volume":"17","author":"Zhang","year":"2017","journal-title":"BMC Anesthesiol"},{"key":"2026010703452128000_15.12.e108845.8","doi-asserted-by":"crossref","unstructured":"Yang S , Andras LM , Redding GJ , et al . Early-Onset Scoliosis: A Review of History, Current Treatment, and Future Directions. Pediatrics 2016;137. doi:10.1542\/peds.2015-0709","DOI":"10.1542\/peds.2015-0709"},{"key":"2026010703452128000_15.12.e108845.9","doi-asserted-by":"crossref","first-page":"537","DOI":"10.2106\/JBJS.22.00277","article-title":"Retrospective Analysis of Associated Anomalies in 636 Patients with Operatively Treated Congenital Scoliosis","volume":"105","author":"Wu","year":"2023","journal-title":"J Bone Joint Surg Am"},{"key":"2026010703452128000_15.12.e108845.10","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.jspd.2018.05.001","article-title":"Cumulative Anesthesia Exposure in Patients Treated for Early-Onset Scoliosis","volume":"6","author":"Baky","year":"2018","journal-title":"Spine Deform"},{"key":"2026010703452128000_15.12.e108845.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2015.04.009"},{"key":"2026010703452128000_15.12.e108845.12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1530\/EOR-22-0040","article-title":"Early-onset scoliosis: a narrative review","volume":"7","author":"Ruiz","year":"2022","journal-title":"EFORT Open Rev"},{"key":"2026010703452128000_15.12.e108845.13","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l6459","article-title":"Does general anesthesia affect neurodevelopment in infants and children?","volume":"367","author":"McCann","year":"2019","journal-title":"BMJ"},{"key":"2026010703452128000_15.12.e108845.14","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2022.972025","article-title":"General anesthesia in children and long-term neurodevelopmental deficits: A systematic review","volume":"15","author":"Xiao","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"2026010703452128000_15.12.e108845.15","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/0883073816681257","article-title":"The Relationship of Exposure to Anesthesia on Outcomes in Children With Isolated Oral Clefts","volume":"32","author":"Conrad","year":"2017","journal-title":"J Child Neurol"},{"key":"2026010703452128000_15.12.e108845.16","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/27.2.121"},{"key":"2026010703452128000_15.12.e108845.17","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2022.17427","article-title":"Anesthetic Exposure During Childhood and Neurodevelopmental Outcomes: A Systematic Review and Meta-analysis","volume":"5","author":"Reighard","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2026010703452128000_15.12.e108845.18","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12014"},{"key":"2026010703452128000_15.12.e108845.19","doi-asserted-by":"crossref","first-page":"103724","DOI":"10.1016\/j.ajp.2023.103724","article-title":"Diagnostic efficiency and psychometric properties of CBCL DSM-oriented scales in a large sample of Chinese school-attending students aged 5-16","volume":"88","author":"Jiang","year":"2023","journal-title":"Asian J Psychiatr"},{"key":"2026010703452128000_15.12.e108845.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00127-009-0152-z"},{"key":"2026010703452128000_15.12.e108845.21","doi-asserted-by":"crossref","unstructured":"Wechsler D . Wechsler Intelligence Scales for Children. 4th edn. San Antonio, TX: Psychological Corporation, 2003.","DOI":"10.1037\/t15174-000"},{"key":"2026010703452128000_15.12.e108845.22","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199709000-00021"},{"key":"2026010703452128000_15.12.e108845.23","unstructured":"Achenbach TM , Rescorla LA . Manual for the ASEBA School-Age Forms & Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families, 2001."},{"key":"2026010703452128000_15.12.e108845.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.1997.tb01545.x"},{"key":"2026010703452128000_15.12.e108845.25","doi-asserted-by":"publisher","DOI":"10.1007\/s10802-010-9434-x"},{"key":"2026010703452128000_15.12.e108845.26","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.638259","article-title":"Health Behavior, Health-Related Quality of Life, and Mental Health Among Canadian Children: A Population-Based Cohort Study","volume":"8","author":"Wu","year":"2021","journal-title":"Front Nutr"},{"key":"2026010703452128000_15.12.e108845.27","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-200108000-00006"},{"key":"2026010703452128000_15.12.e108845.28","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0000000000000799"},{"key":"2026010703452128000_15.12.e108845.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedhc.2017.08.003"},{"key":"2026010703452128000_15.12.e108845.30","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1213\/ANE.0000000000005255","article-title":"Parental Psychosocial Factors Moderate Opioid Administration Following Children\u2019s Surgery","volume":"132","author":"Kain","year":"2021","journal-title":"Anesth Analg"},{"key":"2026010703452128000_15.12.e108845.31","doi-asserted-by":"crossref","unstructured":"Beck A , Steer R . Manual for Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation, 1996.","DOI":"10.1037\/t00742-000"},{"key":"2026010703452128000_15.12.e108845.32","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.56.6.893"},{"key":"2026010703452128000_15.12.e108845.33","doi-asserted-by":"publisher","DOI":"10.1023\/A:1019772628912"},{"key":"2026010703452128000_15.12.e108845.34","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.bja.2021.11.019","article-title":"Longitudinal assessment of cognitive function in young children undergoing general anaesthesia","volume":"128","author":"Shi","year":"2022","journal-title":"Br J Anaesth"},{"key":"2026010703452128000_15.12.e108845.35","doi-asserted-by":"publisher","DOI":"10.1097\/AAP.0b013e31823ebc74"},{"key":"2026010703452128000_15.12.e108845.36","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39335.541782.AD"},{"key":"2026010703452128000_15.12.e108845.37","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002047"},{"key":"2026010703452128000_15.12.e108845.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"2026010703452128000_15.12.e108845.39","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.6967"},{"key":"2026010703452128000_15.12.e108845.40","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/anae.12504","article-title":"The effects of general anaesthesia on memory in children: a comparison between propofol and sevoflurane","volume":"69","author":"Yin","year":"2014","journal-title":"Anaesthesia"},{"key":"2026010703452128000_15.12.e108845.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.01.027"},{"key":"2026010703452128000_15.12.e108845.42","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1111\/dmcn.14649","article-title":"Perinatal and childhood predictors of general cognitive outcome at 28 years in a very-low-birthweight national cohort","volume":"62","author":"Darlow","year":"2020","journal-title":"Dev Med Child Neurol"},{"key":"2026010703452128000_15.12.e108845.43","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-072779","article-title":"Gestational age at birth and cognitive outcomes in adolescence: population based full sibling cohort study","volume":"380","author":"Husby","year":"2023","journal-title":"BMJ"},{"key":"2026010703452128000_15.12.e108845.44","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-024-18309-z","article-title":"Associations of parental age at pregnancy with adolescent cognitive development and emotional and behavioural problems: a birth cohort in rural Western China","volume":"24","author":"Wan","year":"2024","journal-title":"BMC Public Health"},{"key":"2026010703452128000_15.12.e108845.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01130-0"},{"key":"2026010703452128000_15.12.e108845.46","doi-asserted-by":"crossref","first-page":"839473","DOI":"10.3389\/fped.2022.839473","article-title":"Participation in After-School Extracurricular Activities and Cognitive Ability Among Early Adolescents in China: Moderating Effects of Gender and Family Economic Status","volume":"10","author":"Pan","year":"2022","journal-title":"Front Pediatr"},{"key":"2026010703452128000_15.12.e108845.47","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2021.713668","article-title":"Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit","volume":"15","author":"Turner","year":"2021","journal-title":"Front Behav Neurosci"},{"key":"2026010703452128000_15.12.e108845.48","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1111\/anae.15980","article-title":"Neurodevelopmental effects of prenatal exposure to anaesthesia for maternal surgery: a systematic review and classification of the reported effect sizes","volume":"78","author":"Bleeser","year":"2023","journal-title":"Anaesthesia"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-108845","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:45:32Z","timestamp":1767786332000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-108845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":48,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,2]]},"published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1136\/bmjopen-2025-108845"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-108845","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]}}}