(240) Association Between Maternal Anticholinergic Burden During Pregnancy and the Risk of Autism Spectrum Disorder: A Population-Based Cohort Study in Taiwan

Background: The prevalence of autism spectrum disorder (ASD) has significantly increased globally, including in Taiwan, over the last decade. Studies have suggested a potential relationship between decreased cholinergic status and the risk of ASD in children. However, limited evidence is available about the association between maternal anticholinergic burden and the risk of ASD in offspring.

Objectives: To evaluate the association between the gestational burden of anticholinergic activity and the risk of ASD in offspring.

Methods: We conducted a population-based retrospective cohort study using data from the National Health Insurance Research Database and the Taiwan Maternal and Child Health Database from 2004 to 2020. We included mothers with singleton pregnancies and assessed their anticholinergic burden during the second and third trimesters using the Anticholinergic Cognitive Burden (ACB) scale. Mothers were classified based on their ACB scores using a cut-off point of 3. The primary outcome was children’s ASD, followed from delivery until the occurrence of the outcome or until the offspring reached 18 years of age, or death, whichever came first. We applied a propensity score with fine stratification weighting approach to obtain two comparison groups with balanced covariates, including mothers’ and children’s characteristics. We compared children exposed to ACB scores of 3 or more with those exposed to scores less than 3. Hazard ratios with 95% confidence intervals were obtained using Cox proportional hazard models to evaluate the association between gestational anticholinergic burden and children’s ASD risk. Additionally, we also selected mothers with at least two offspring and conducted a sibling control analysis to examine the potential confounding effects from genetic or environmental factors.

Results: We identified 2,939,670 mother-child pairs in our study, of which 1,935,645 pairs were used for sibling comparison. We found that mothers with ACB scores of 3 or higher were associated with increased risks of ASD in their offspring compared to those with scores less than 3 (adjusted HR, 1.11; 95% CI, 1.09-1.12). However, this association was not observed in the sibling control analysis (HR, 0.94; 95% CI 0.87-1.01).

Conclusions: We found an association between an increased maternal anticholinergic burden during pregnancy and a higher risk of ASD in offspring when all measured covariates were controlled. However, the results from the sibling control analysis suggested that this association may be explained by genetic or environmental factors.