Abstract Background Preclinical studies have shown that volatile anaesthetics, particularly sevoflurane, can disrupt neurodevelopment by inducing neuronal apoptosis, neuroinflammation and altered synaptic plasticity during critical periods of brain maturation. Whether these mechanisms translate into long‐term neurobehavioral risk in children remains uncertain. Aims To compare the long‐term risk of attention‐deficit/hyperactivity disorder (ADHD) following paediatric anaesthesia with sevoflurane versus propofol in a large, multinational real‐world cohort. Methods We conducted a large, multinational, retrospective cohort study using real‐world electronic health record data from more than 150 healthcare organisations across North America, Europe and Asia. Children and adolescents (0–18 years) who underwent a single surgical procedure under general anaesthesia between 2005 and 2025 were included. Patients with ADHD or multiple anaesthetic exposures were excluded. The primary exposure was sevoflurane versus propofol as the main anaesthetic. The primary outcome was new‐onset ADHD identified by International Classification of Diseases, Ninth or Tenth Revision codes after surgery. Propensity‐score matching (1:1), subgroup, sensitivity and positive/negative control analyses were performed to ensure robustness. Results Among 54 102 matched children (27 051 per group), the cumulative incidence of ADHD was 5.63% after sevoflurane and 2.95% after propofol, corresponding to incidence rates of 134.9 and 105.4 per 10 000 person‐years. Sevoflurane exposure was associated with a higher risk of ADHD (hazard ratio 1.21; 95% confidence interval 1.11–1.31; p < 0.001). Findings were consistent across subgroups and sensitivity analyses; mortality was rare and similar between groups. Conclusions In this multinational cohort, sevoflurane exposure during paediatric anaesthesia was associated with an increased long‐term risk of ADHD compared with propofol. These findings suggest that anaesthetic choice may have enduring neurobehavioral consequences and that prospective validation is warranted to guide safer paediatric anaesthesia practice.
Sun et al. (Wed,) studied this question.