| Summary: | 博士 === 中山醫學大學 === 醫學研究所 === 102 === Background: Postnatal exposure to anesthetics causes neural apoptosis and degeneration in animals, but results from studies conducted on humans were discordant. Though some genes seem to contribute to susceptibility of neurodevelopmental disorders, other factors like perinatal insults and exposure to neurotoxic agents may also play important roles in gene-environmental interaction. Previous studies did not provide any information of the relationship between neurobehavioural disorders and anesthesia exposure in Asian children. We conducted two retrospective matched-cohort studies in Taiwan to investigate the association of early life anesthesia exposure with risk of attention deficit/hyperactivity disorder (ADHD) and autistic disorder.
Materials and Methods: Data were depicted from the National Health Insurance Research Database of Taiwan. Study I. Children born between 2001/01/01 and 2005/12/31 were included. Each child with general anesthesia exposure before three years of age was matched to four unexposed children. Proportional hazards regression was used to assess the association of anesthesia exposure with risk of ADHD. Study II. Children born between 2001/01/01 and 2007/12/31 were included. Each child with anesthesia exposure before two years of age was matched to four unexposed children. Proportional hazards regression was used to assess the association of anesthesia exposure with risk of developing autistic disorder. For both studies, the observation were concluded on 2010/12/31. Additional analyses were also made based on cumulative exposure number and age at the time of the first exposure.
Results: Study I. This matched-cohort comprised of 16,465 children, among which 3,293 were exposed to general anesthesia before three years of age. The adjusted hazard ratio of developing ADHD was 1.06 (95% CI: 0.86,1.31) for general anesthesia exposure. The adjusted hazard ratio of developing ADHD for single and multiple exposures was1.11 (95% CI: 0.88, 1.41) and 0.96 (95% CI: 0.71,1.31 ), respectively. No trend of increasing risk was noted based on age at the time of first exposure.
Study II. There were 5,197 children who were exposed to general anesthesia before the age of two. The 1:4 matched controls comprised 20,788 children. There were no differences in incidence of autistic disorder between the exposed group (0.96%) and the unexposed controls (0.89%). (P = .62) Cox proportional hazards regression showed that the hazard ratio of exposure to general anesthesia was 0.93 (95% confidence interval: 0.57, 1.53) after adjusting for potential confounders. Age at the first exposure did not influence the risk of autistic disorder. No relationship was noted between the total number of exposures and risk of autistic disorder.
Conclusions: Exposure to general anesthesia before three years of age did not increase the risk of ADHD. Exposure to general anesthesia before the age of two were not associated with development of autistic disorder.
No relationship could be identified between age at the first exposure or number of exposure and the risk of developing ADHD or autistic disorder.
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