Association of early childhood constipation with the risk of autism spectrum disorder in Taiwan: Real-world evidence from a nationwide population-based cohort study.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental problem that presents with limited interests, repetitive behaviors, and deficits in reciprocal communication and social interactions. Mounting evidence indicates that an imbalanced gut microbiota contributes to autism Methods: We identified 12,935 constipated children aged 3 years or younger from the National Health Insurance Research Database (NHIRD) in Taiwan from 1997 to 2013. Non-constipated children were also selected from the database and propensity score matching of age, gender, and underlying comorbidities was conducted with a ratio of 1:1. Kaplan-Meier analysis was applied to determine different levels of constipation severity and cumulative incidence of autism. Subgroup analysis was also applied in this study. Results: The incidence rate of ASD was 12.36 per 100,000 person-months in the constipation group, which was higher than the rate of 7.84 per 100,000 person-months noted in the non-constipation controls. Constipated children had a significantly higher risk of autism when compared to the non-constipation group (crude relative risk = 1.458, 95% CI = 1.116-1.904; adjusted hazard ratio = 1.445, 95% CI = 1.095-1.907).Moreover, among constipated children, a higher number of laxative prescriptions, male gender, constipation during infancy, and atopic dermatitis were significantly associated with higher risks of ASD when compared to the non-constipation group. Conclusion: Constipation in early childhood was correlated with a significantly increased risk of ASD. Clinicians should pay attention to the possibility of ASD in constipated children. Further research is necessary to study the possible pathophysiological mechanisms of this association.