People with autism spectrum disorder (ASD) or attention deficit-hyperactivity disorder (ADHD) have a higher risk of mortality, according to a systematic review and meta-analysis.
All-cause mortality was more than doubled in people with ASD (rate ratio [RR] 2.37, 95% CI 1.97-2.85, I2 89%) and in those with ADHD (RR 2.13, 95% CI 1.13-4.02, I2 98%), reported Ferrán Catalá-López, PhD, of the Institute of Health Carlos III in Madrid, and colleagues.
Among those with ASD, deaths from natural causes were increased (RR 3.80, 95% CI 2.06-7.01, I2 96%), as were deaths from unnatural causes (RR 2.50, 95% CI 1.49-4.18, I2 95%). For those with ADHD, deaths from natural causes were not significantly increased, but deaths from unnatural causes were higher than expected (RR 2.81, 95% CI 1.73-4.55, I2 92%).
“This systematic review and meta-analysis comprehensively assess for the first time, to our knowledge, the available evidence regarding the risk of mortality in persons with ASD or ADHD,” the authors wrote in JAMA Pediatrics.
“Higher mortality rates have been documented in the field of ASD for longer than they have in the field of ADHD, owing to the well-established higher risks for drowning, pedestrian-auto crashes, suicide, seizure disorders, and other medical conditions associated with ASD that can lead to a shorter life expectancy,” wrote Russell Barkley, PhD, of Virginia Commonwealth University School of Medicine in Richmond, and Geraldine Dawson, PhD, of Duke University School of Medicine in Durham, North Carolina, in a corresponding editorial.
One study in Denmark found that individuals with ASD had three times higher rates of attempted suicide and suicide compared with the general population, they noted. Other studies have also highlighted associations with substance use, eating disorders, and sleeping problems, among others.
ADHD itself is a comorbidity of ASD, Barkley and Dawson said. “It is possible that some of the risk for early mortality in individuals with ASD arises from its association with ADHD diagnosis.”
“The key message is that, in most cases, whether natural or unnatural, public health screening and prevention strategies could increase the lifespan and quality of life for individuals with these neurodevelopmental conditions,” they wrote. A recent randomized trial suggested that early intervention could reduce the severity of ASD symptoms in toddlers.
“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” Catalá-López and team wrote. They recommended that healthcare professionals routinely collect data on health outcomes related to ASD and ADHD.
Primary care physicians need to become more aware of the connection between ASD and ADHD diagnosis and early mortality, Barkley and Dawson echoed.
This systematic review and meta-analysis included 27 observational studies with a total of 642,260 individuals from 1988 to 2021 that reported mortality rate ratios in people with ASD or ADHD compared with either the general population or a population with no ASD or ADHD.
Fourteen studies on ASD included 206,162 participants, while 12 studies on ADHD included 433,761 participants. The median follow-up time for the studies was 16 years (range 3-33 years).
Females with ASD had higher mortality rates (RR 4.87, 95% CI 3.07-7.73, I2 91%) than males (RR 2.09, 95% CI 1.50-2.92, I2 94%). There were no such sex discrepancies in all-cause mortality for those with ADHD.
These “results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” Catalá-López and colleagues noted. They also acknowledged that most of the included studies were from Western countries.
This study was supported by the Institute of Health Carlos III and Generalitat Valenciana.
Catalá-López reported no disclosures. One co-author reported grants from the Spanish Ministry of Science, Spanish Ministry of Economy, European Commission Framework Program, IBM Research, Generalitat de Catalunya, and EuroHPC.
Barkley reported fees from Takeda Pharmaceutical, Medice Pharmaceutical, and AstraZeneca. Dawson reported fees from and a patent licensed to Apple, Inc.