Abstract
<jats:p>Background: Suicide attempts (SA) are elevated in individuals with autism spectrum disorder (ASD), but population-level data characterizing how SA prevalence varies across demographic and clinical subgroups - at the scale and granularity needed to inform evidence-based risk stratification - have been largely unavailable. This study examines SA prevalence across sex, age group, psychiatric comorbidity type, and substance use disorder subtype in the largest real-world ASD cohort to date. Methods: We conducted a retrospective cross-sectional analysis using Epic Cosmos electronic health record data from 2,311,171 individuals with ASD identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, spanning 2016-2025. SA prevalence was calculated with Wilson score 95% confidence intervals. Modified Poisson regression with robust variance estimation was used to estimate adjusted prevalence ratios (aPRs) for sex, age group, and psychiatric comorbidity. Unadjusted prevalence ratios (uPRs) were calculated separately for individual comorbidity types and substance use disorder subtypes. Results: Overall SA prevalence was 1.7% (38,160 individuals). Females showed higher SA prevalence than males (2.9% vs. 1.2%; aPR 1.61, 95% CI 1.35-1.92). SA prevalence peaked in the 15-24 age group overall (aPR 5.14, 95% CI 3.62-7.29), with sex-stratified analyses revealing that females peaked earlier (15-24 years; aPR 4.33, 95% CI 4.23-4.43) than males (25-34 years; aPR 6.08, 95% CI 5.05-7.31) - a sex-specific divergence in the timing of peak SA prevalence not previously documented in ASD. Having at least one psychiatric comorbidity was associated with a 30-fold higher SA prevalence (aPR 30.56, 95% CI 26.03-35.89), with the effect stronger in females (aPR 36.54, 95% CI 31.04-43.01) than males (aPR 27.77, 95% CI 22.65-34.06). Among comorbidity subtypes, substance-related disorders showed the highest crude SA prevalence (16.9%; uPR 134.20, 95% CI 67.68-266.10). Subtype-level characterization revealed SA prevalence ranging from 19.7% to 24.3% across all five substance use disorder subtypes examined, with stimulant use disorder showing the highest unadjusted prevalence ratio of any subtype (uPR 196.11, 95% CI 100.63-382.20). Conclusion: SA prevalence in ASD is markedly elevated relative to the general population and varies meaningfully by sex, age, and comorbidity profile in clinically important ways. Females carry a disproportionate SA burden relative to males, with peak vulnerability arriving earlier in adolescence; males peak later in young adulthood and remain at elevated risk into midlife. Psychiatric comorbidity - particularly substance use disorders - is associated with the largest relative elevations in SA prevalence. These population-level estimates are directly applicable to EHR-based risk stratification models and can inform the development of ASD-specific clinical decision support tools that concentrate surveillance and intervention on those at demonstrably elevated risk, rather than applying uniform approaches across a heterogeneous population.</jats:p>