Knowledge Synthesis Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Department of Medicine, University of Valencia/INCLIVA Health Research Institute and Centro de Investigación en Red de Salud Mental (CIBERSAM), Valencia, Spain.
JAMA Pediatr. 2022 Apr 1;176(4):e216401. doi: 10.1001/jamapediatrics.2021.6401. Epub 2022 Apr 4.
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.
To assess the risk of mortality among persons with ASD or ADHD and their first-degree relatives.
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.
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.
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).
All-cause mortality in association with ASD or ADHD. Secondary outcome was cause-specific mortality.
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).
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.
自闭症谱系障碍（ASD）和注意力缺陷/多动障碍（ADHD）是儿童期发病的疾病，可能会持续到成年。几项研究表明，它们可能与死亡率增加有关；然而，结果并不一致。
评估 ASD 或 ADHD 患者及其一级亲属的死亡风险。
对 MEDLINE、Embase、Scopus、Web of Science 和 PsycINFO（从成立到 2021 年 4 月 1 日）进行了检索，并补充了检索文章的参考文献列表。
纳入了报告 ASD 或 ADHD 患者及其一级亲属与普通人群或无 ASD/ADHD 患者相比死亡率率比（RR）的队列研究和病例对照研究。
至少有 2 名研究人员独立进行了筛选、数据提取和质量评估。使用随机效应模型对个体研究进行荟萃分析，并评估异质性（I2）。
与 ASD 或 ADHD 相关的全因死亡率。次要结局是病因特异性死亡率。
共纳入 27 项研究，共涉及 642260 名参与者。结果发现，ASD 患者（154238 名参与者；12 项研究；RR，2.37；95%CI，1.97-2.85；I2，89%；中度置信度）和 ADHD 患者（396488 名参与者；8 项研究；RR，2.13；95%CI，1.13-4.02；I2，98%；低置信度）的全因死亡率高于普通人群。在 ASD 患者中，自然原因导致的死亡（4 项研究；RR，3.80；95%CI，2.06-7.01；I2，96%；低置信度）和非自然原因导致的死亡（6 项研究；RR，2.50；95%CI，1.49-4.18；I2，95%；低置信度）增加。在 ADHD 患者中，自然原因导致的死亡并不显著增加（4 项研究；RR，1.62；95%CI，0.89-2.96；I2，88%；低置信度），但非自然原因导致的死亡高于预期（10 项研究；RR，2.81；95%CI，1.73-4.55；I2，92%；低置信度）。
本系统评价和荟萃分析发现，ASD 和 ADHD 与死亡率显著增加相关。了解这些关联的机制可能会导致针对高风险人群的预防可避免死亡的靶向策略。应进一步探讨研究之间的大量异质性。
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