Anesthesia Neurodevelopmental Impact in Congenital Scoliosis Children

Long-term Effect of General Anesthesia Before School Age on Neurodevelopment in Children With Congenital Scoliosis

In the past, a large number of animal studies have suggested that anesthesia exposure has potential neurotoxic effects, resulting in persistent cognitive and behavioral deficits. At present, there is still a lack of sufficient clinical research evidence to prove whether anesthesia exposure has long-term effects on neurodevelopment. The existing clinical research data suggests that a single short-time anesthesia exposure in young children does not affect long-term neurodevelopmental outcomes. Early onset scoliosis, including congenital scoliosis, is a type of scoliosis deformity that occurs before the age of 10. Posterior scoliosis correction surgery is one of the common treatment. There is currently no research indicating the impact of early single or multiple long-duration anesthesia exposure on the neurological development of children with congenital scoliosis. The aim of this study is to determine the long-term effect of general anesthesia exposure on neurocognitive function and behavior in children with congenital scoliosis, in order to provide reference for related clinical work.

Study Overview

• Status: Recruiting
• Conditions: General Anesthetics Toxicity
• Intervention / Treatment: Procedure: General anesthesia

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Lulu Ma, Dr.; Phone Number: 0086-10-13811049619; Email: malulu@pumch.cn
• Study Contact Backup: Name: Ziyi Dai, Dr.; Phone Number: 0086-10-18611703606; Email: daiziyi@pumch.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Lulu Ma, Dr.; Phone Number: 0086-010-13811049619; Email: malulu@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Children diagnosed with congenital scoliosis

Description

Inclusion Criteria:

• Diagnosed with congenital scoliosis
• 6-16 years old at the time of assessment

Exclusion Criteria:

• Cognitive impairment caused by congenital, traumatic or other reasons;
• Existence of mental or psychological disorders;
• There are factors that may affect neurological development, including any known central nervous system disease, neurological injury, or history of neonatal asphyxia;
• Unable to cooperate with cognitive function tests;
• The child is unable to communicate in Chinese.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Unexposed; Children unexposed to general anesthesia before school age (<=6y)
Singly exposed; Children singly exposed to general anesthesia before school age (<=6y)	Procedure: General anesthesia; General anesthesia including inhaled and intravenous
Multiply exposed; Children multiply exposed to general anesthesia before school age (<=6y)	Procedure: General anesthesia; General anesthesia including inhaled and intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
full-scale intelligence quotient, FSIQ	Measured by Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV)	At the time of collecting baseline demographic data

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBCL Total score, CBCL Internalizing score, CBCL Externalizing score	Measured by Child Behavior Checklist (CBCL)	Within six months of WISC-IV assessment
Verbal Comprehension Index (VCI), Perceptual Reasoning/Organization Index (PRI/POI)	Measured by Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV)	At the time of collecting baseline demographic data
SDQ total difficulties score, SDQ internalizing problems score, SDQ externalizing problems score, SDQ prosocial behavior score	Measured by Strengths and Difficulties Questionnaire (SDQ)	Within six months of WISC-IV assessment

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Lulu Ma, Dr., Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Zaccariello MJ, Frank RD, Lee M, Kirsch AC, Schroeder DR, Hanson AC, Schulte PJ, Wilder RT, Sprung J, Katusic SK, Flick RP, Warner DO. Patterns of neuropsychological changes after general anaesthesia in young children: secondary analysis of the Mayo Anesthesia Safety in Kids study. Br J Anaesth. 2019 May;122(5):671-681. doi: 10.1016/j.bja.2019.01.022.
• Brambrink AM, Back SA, Riddle A, Gong X, Moravec MD, Dissen GA, Creeley CE, Dikranian KT, Olney JW. Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain. Ann Neurol. 2012 Oct;72(4):525-35. doi: 10.1002/ana.23652.
• Zhang H, Du L, Du Z, Jiang H, Han D, Li Q. Association between childhood exposure to single general anesthesia and neurodevelopment: a systematic review and meta-analysis of cohort study. J Anesth. 2015 Oct;29(5):749-57. doi: 10.1007/s00540-015-2030-z. Epub 2015 May 23.
• Ruiz G, Torres-Lugo NJ, Marrero-Ortiz P, Guzman H, Olivella G, Ramirez N. Early-onset scoliosis: a narrative review. EFORT Open Rev. 2022 Aug 4;7(8):599-610. doi: 10.1530/EOR-22-0040.
• Istaphanous GK, Ward CG, Nan X, Hughes EA, McCann JC, McAuliffe JJ, Danzer SC, Loepke AW. Characterization and quantification of isoflurane-induced developmental apoptotic cell death in mouse cerebral cortex. Anesth Analg. 2013 Apr;116(4):845-54. doi: 10.1213/ANE.0b013e318281e988. Epub 2013 Mar 4.
• Briner A, De Roo M, Dayer A, Muller D, Habre W, Vutskits L. Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis. Anesthesiology. 2010 Mar;112(3):546-56. doi: 10.1097/ALN.0b013e3181cd7942.
• Baky FJ, Milbrandt TA, Flick R, Larson AN. Cumulative Anesthesia Exposure in Patients Treated for Early-Onset Scoliosis. Spine Deform. 2018 Nov-Dec;6(6):781-786. doi: 10.1016/j.jspd.2018.05.001.
• Zhang Q, Peng Y, Wang Y. Long-duration general anesthesia influences the intelligence of school age children. BMC Anesthesiol. 2017 Dec 19;17(1):170. doi: 10.1186/s12871-017-0462-8.
• Lin T, Meng Y, Ji Z, Jiang H, Shao W, Gao R, Zhou X. Extent of Depression in Juvenile and Adolescent Patients with Idiopathic Scoliosis During Treatment with Braces. World Neurosurg. 2019 Jun;126:e27-e32. doi: 10.1016/j.wneu.2019.01.095. Epub 2019 Jan 29.
• McCann ME, de Graaff JC, Dorris L, Disma N, Withington D, Bell G, Grobler A, Stargatt R, Hunt RW, Sheppard SJ, Marmor J, Giribaldi G, Bellinger DC, Hartmann PL, Hardy P, Frawley G, Izzo F, von Ungern Sternberg BS, Lynn A, Wilton N, Mueller M, Polaner DM, Absalom AR, Szmuk P, Morton N, Berde C, Soriano S, Davidson AJ; GAS Consortium. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019 Feb 16;393(10172):664-677. doi: 10.1016/S0140-6736(18)32485-1. Epub 2019 Feb 14.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Spinal Curvatures; Scoliosis; Anesthesia and Analgesia; Anesthesia; Anesthesia, General
• Other Study ID Numbers: S-K1093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that underlie results in a publication
• IPD Sharing Time Frame: starting 1 year after the results are published
• IPD Sharing Access Criteria: IPD is available on appropriate request from the Principle Investigator by email
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No