Childhood anaesthesia and autism risk: population and murine study

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.

Keywords: anaesthesia; autism; childhood; cohort study; murine model.

Graphical abstract

Figure 1

The impact of general anaesthesia on the cumulative incidence of autism Spectrum disorder in children: a Kaplan–Meier analysis. Statistical significance was determined using a stratified log-rank test (P < 0.001). GA, general anaesthesia; KM, Kaplan–Meier; No., number.