Premature Mortality in Individuals with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

Introduction: Autism Spectrum Disorder (ASD) may increase vulnerability to premature mortality, but the magnitude of risk and sex-specific differences remain unclear. Methods: A systematic search of PubMed, Web of Science, Scopus, and Google Scholar was conducted up to January 13, 2025. Studies comparing premature mortality risk between ASD and non-ASD populations were included. Pooled Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using I². Results: Six cohort studies (5,814,167 participants) were included. ASD was associated with a significantly increased risk of premature mortality (RR = 2.06; 95% CI: 1.44–2.69; I² = 97.1%). The risk was higher in females (RR = 3.41; 95% CI: 1.95–4.86; I² = 87.0%) than in males (RR = 2.33; 95% CI: 1.63–3.02; I² = 86.2%). Discussion: These findings confirm that ASD confers a more than twofold risk of premature death, with females disproportionately affected. The high heterogeneity reflects variations in causes of death (e.g., epilepsy, suicide) and study populations. Importantly, many contributing factors are potentially preventable through early comorbidity screening, integrated mental and physical healthcare, and psychosocial support. The elevated risk in females may stem from diagnostic delays and under-recognition of ASD. Clinicians and policymakers should prioritize proactive, life-course-oriented strategies to reduce this mortality gap. Conclusion: ASD is associated with substantially increased premature mortality, especially among females. Targeted prevention and improved healthcare access are urgently needed.