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Original Investigation |

Association of Psychiatric and Neurologic Comorbidity With Mortality Among Persons With Autism Spectrum Disorder in a Danish Population

Diana E. Schendel, PhD1,2,3; Morten Overgaard, MSc4; Jakob Christensen, MD5; Lene Hjort, MD1,6; Meta Jørgensen, MD6; Mogens Vestergaard, MD7; Erik T. Parner, MSc(Stat), PhD4
[+] Author Affiliations
1Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
2Department of Economics and Business, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark
3Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
4Department of Public Health, Section for Biostatistics, Aarhus University, Aarhus, Denmark
5Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
6Regional Centre for Child and Adolescent Psychiatry, Aarhus University Hospital, Risskov, Aarhus, Denmark
7Department of Public Health, Section for General Medicine and Research Unit for General Practice, Aarhus University, Aarhus, Denmark
JAMA Pediatr. 2016;170(3):243-250. doi:10.1001/jamapediatrics.2015.3935.
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Importance  Increased mortality has been reported among persons with autism spectrum disorder (ASD), especially among those who also have the comorbid condition of epilepsy or intellectual disability. The effects of psychiatric and neurologic comorbidity on mortality among persons with ASD have not been rigorously examined in large, population-based studies.

Objective  To investigate the mortality patterns among persons with ASD overall and to assess the associations of comorbid mental, behavioral, and neurologic disorders with mortality among persons with ASD.

Design, Setting, and Participants  Longitudinal cohort study of children born in Denmark during the period from 1980 to 2010 who were alive at 1.5 years of age and followed up through 2013. This population-based sample of children (N = 1 912 904) was identified via linkage between the Danish Civil Registration Service and the Danish Medical Birth Register using a unique 10-digit identifier assigned to all live births and new residents in Denmark. Children were followed up for diagnoses of ASD (International Classification of Diseases, Eighth Revision [ICD-8] codes 299.00, 299.01, 299.02, and 299.03 and ICD-10 codes F84.0, F84.1, F84.5, F84.8, and F84.9) and other mental/behavioral disorders (ICD-8 codes 290-315 and ICD-10 codes F00-F99) in the Danish Psychiatric Central Research Register and for diagnoses of neurologic disorders (ICD-8 codes 320-359 and ICD-10 codes G00-G99) in the Danish National Patient Register. Data analysis was performed in December 2014.

Main Outcomes and Measures  Deaths and causes of death among cohort members were identified via the Danish Civil Registration Service and the Danish Cause of Death Register, respectively. Regressions analyses were performed using Cox regression.

Results  Of the 1 912 904 persons included in our study, 20 492 (1.1%) had ASD (15 901 [77.6%] were male). Of the 20 492 persons with ASD, 68 died (0.3%) (57 of 68 [83.8%] had comorbid mental/behavioral or neurologic disorders). The adjusted hazard ratio (aHR) for overall mortality was 2.0 (95% CI, 1.5-2.8) for ASD. The aHRs for ASD-associated mortality among cohort members who did not have neurologic (2.0 [95% CI, 1.4-3.0]) or other mental/behavioral disorders (1.7 [95% CI, 1.0-3.1]) were similar. The co-occurrence of ASD added no additional mortality risk for persons with neurologic (aHR, 0.7 [95% CI, 0.4-1.3]) or mental/behavioral disorders (aHR, 0.8 [95% CI, 0.5-1.2]) compared with persons with these disorders and no ASD.

Conclusions and Relevance  The mortality risk was 2-fold higher through young adulthood for persons with ASD than for persons without ASD, although mortality affected only 0.3% of persons with ASD. The mechanisms underlying ASD-associated mortality may be mediated through or shared with neurologic or mental/behavioral disorders, thereby providing insights into their potential neurobiological links. Health care professionals and family members should recognize the importance of these disorders with regard to the mortality risk for persons with ASD.

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Estimated Cumulative Incidence Curves of All-Cause Mortality by Age Among Persons With or Without Autism Spectrum Disorder (ASD)
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