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 (I2). 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; I2, 89%; moderate confidence) and persons with ADHD (396 488 participants; 8 studies; RR, 2.13; 95% CI, 1.13-4.02; I2, 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; I2, 96%; low confidence) and deaths from unnatural causes were increased (6 studies; RR, 2.50; 95% CI, 1.49-4.18; I2, 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; I2, 88%; low confidence), but deaths from unnatural causes were higher than expected (10 studies; RR, 2.81; 95% CI, 1.73-4.55; I2, 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. This study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Drs Catalá-López and Tabarés-Seisdedos received funding from the Centro de Investigación Biomédica en Red de Salud Mental, Institute of Health Carlos III, and Generalitat Valencia. Dr Page received support from an Australian Research Council Discovery Early Career Researcher Award. Dr Hutton received support from a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network. Dr Ridao received support from the Spanish Health Services Research on Chronic Patients Network and Institute of Health Carlos III.