Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis

IMPORTANCE: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are childhood-onset disorders that may persist into adulthood. Several studies have suggested that they may be associated with an increased risk of mortality; however, the results are inconsistent. OBJECTIVE: To assess the risk of mortality among persons with ASD or ADHD and their first-degree relatives. DATA SOURCES: A search of MEDLINE, Embase, Scopus, Web of Science, and PsycINFO (published from inception to April 1, 2021) was supplemented by searching reference lists of the retrieved articles. STUDY SELECTION: Cohort and case-control studies that reported mortality rate ratios (RRs) in persons with ASD or ADHD and/or their first-degree relatives compared with the general population or those without ASD/ADHD were included. DATA EXTRACTION AND SYNTHESIS: Screening, data extraction, and quality assessment were performed by at least 2 researchers independently. A random-effects model was used to meta-analyze individual studies and assessed heterogeneity (I(2)). MAIN OUTCOMES AND MEASURES: All-cause mortality in association with ASD or ADHD. Secondary outcome was cause-specific mortality. RESULTS: Twenty-seven studies were included, with a total of 642 260 individuals. All-cause mortality was found to be higher for persons with ASD (154 238 participants; 12 studies; RR, 2.37; 95% CI, 1.97-2.85; I(2), 89%; moderate confidence) and persons with ADHD (396 488 participants; 8 studies; RR, 2.13; 95% CI, 1.13-4.02; I(2), 98%; low confidence) than for the general population. Among persons with ASD, deaths from natural causes (4 studies; RR, 3.80; 95% CI, 2.06-7.01; I(2), 96%; low confidence) and deaths from unnatural causes were increased (6 studies; RR, 2.50; 95% CI, 1.49-4.18; I(2), 95%; low confidence). Among persons with ADHD, deaths from natural causes were not significantly increased (4 studies; RR, 1.62; 95% CI, 0.89-2.96; I(2), 88%; low confidence), but deaths from unnatural causes were higher than expected (10 studies; RR, 2.81; 95% CI, 1.73-4.55; I(2), 92%; low confidence). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that ASD and ADHD are associated with a significantly increased risk of mortality. Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups. The substantial heterogeneity between studies should be explored further.