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Childhood anaesthesia and autism risk: population and murine study
Mingyang Sun1, Ningning Fu1, Ting Li1
1Department of Anesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan University People's Hospital, Zhengzhou, Henan 450003, China.
Insights
Early childhood exposure to general anesthesia is linked to a higher risk of autism spectrum disorder. Mouse studies show sevoflurane anesthesia induces autism-like behaviors and alters autism-related gene expression.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatrics
Background:
- Preclinical studies suggest early anesthesia exposure may affect infant brain development and behavior.
- Potential links exist between anesthesia and autism spectrum disorder (ASD) risk.
Purpose of the Study:
- To investigate the association between early childhood general anesthesia exposure and autism risk.
- To evaluate the impact of sevoflurane on autism-like behavior in a mouse model.
Main Methods:
- A population-based cohort study matched 7530 children exposed to general anesthesia with 7530 unexposed children.
- Mice exposed to sevoflurane on postnatal days 5-7 to assess autism-like behaviors and gene expression changes.
Main Results:
- Children exposed to general anesthesia had a 1.86-fold increased risk of autism (95% CI, 1.34-2.59).
- Sevoflurane exposure in mice induced autism-like behaviors and downregulated key autism-associated genes (e.g., SHANK3, ARID1B).
Conclusions:
- Early childhood general anesthesia exposure is associated with an increased risk of autism.
- Sevoflurane-induced autism-like behaviors in mice suggest a potential mechanistic link between anesthesia and autism development.
Abstract:
Early childhood exposure to general anaesthesia has been linked to potential changes in infant brain morphology and behaviour in preclinical studies, contributing to long-term behaviours associated with autism spectrum disorder. This study investigates the association between early childhood exposure to general anaesthesia and the risk of autism, using a population-based cohort study with matching for baseline characteristics and evaluates the effect of sevoflurane exposure on autism-like behaviour in mice, using the Taiwan Maternal and Child Health Database. Children aged 0-3 who received at least one exposure to general anaesthesia between 2004 and 2014 were matched 1:1 with children who were not exposed. Risk ratios and confidence intervals were used to assess the relationship between general anaesthesia and the occurrence of autism. Additionally, mice were exposed to sevoflurane for 2 h on postnatal days 5-7, and changes in behaviour related to autism were evaluated. Propensity score matching resulted in 7530 children in each group. The incidence rates (IRs) of autism were 11.26 and 6.05 per 100 000 person-years in the exposed and unexposed groups, respectively. The incidence ratio for autism following exposure to general anaesthesia was 1.86 (95% confidence interval, 1.34-2.59). In mice, sevoflurane exposure induced autism-like behaviours and led to the downregulation of high-risk autism genes, including ARID1B, GABRA5, GABRB3, GRIN2B, SHANK3 and SUV420H1. Early childhood exposure to general anaesthesia is associated with an increased risk of autism. Repeated exposure to sevoflurane in mice induces autism-like behaviours, suggesting a potential link between anaesthesia and the development of autism.
