Association of Intellectual Disability With All-Cause and Cause-Specific Mortality in Sweden

This population-based cohort study evaluates the risks and prevalence of premature mortality in individuals with varying severity of intellectual disability in Sweden.


Introduction
Intellectual disability (ID) is a neurodevelopmental disorder characterized by substantial limitations on both intellectual ability and adaptive functioning; in most cases, these limitations lead to lifelong impairments and the need for support in many major life activities. 1 However, the nature and extent of these impairments vary greatly depending on the severity of the ID. Compared with the general population, those with ID have poor physical and mental health. [2][3][4] In addition, ID has been associated with shorter life expectancy of up to 2 decades and low mean age at death, 5,6 although the mortality discrepancy between those with ID and the general population has decreased in the past decades. 5 The increase in mean age at death in ID may illustrate the improvements in policies and practices, including the deinstitutionalization initiated in many high-income countries during the 1970s and 1980s that eventually led to the complete closure of large institutions in Sweden. 7 Living in the community instead of in congregate arrangements is generally associated with improved quality of life and several other outcomes, 8 but some studies have also indicated that limitations persist in accessing health care in community settings. 6,8 Therefore, studies into the health experiences of people with ID after deinstitutionalization are important to understanding the health challenges for people with ID in a contemporary welfare society.
The discrepancies in overall mortality risk in previous studies 5,6,[9][10][11][12][13][14][15] may be explained by methodological differences, such as sample selection, inclusion of narrow age ranges, and lack of matched control populations. Therefore, nationwide population-based studies with control individuals who are matched to individuals with different severity levels of ID are needed to increase the generalizability of the results. Furthermore, specific causes of death in mild ID compared with more severe ID (moderate to profound) have been identified as a knowledge gap in existing literature, 14 and studies of the factors associated with excess mortality [16][17][18][19][20][21][22] at different severity levels of ID are scarce. Moreover, some studies indicated that the overall mortality risk was generally higher among female individuals with ID, 5,6,9,11,14 but this observation was not confirmed in other studies. 13,15 The current scarcity of high-quality, population-based studies on mortality in individuals with ID may be inherent in the poor coverage of registries; for example, the Swedish National Patient Register (NPR) captures only a select minority of people with ID.
To examine premature mortality in individuals with ID, we performed a population-based study using nationwide health care and education registers in Sweden. We estimated the risk of premature all-cause, cause-specific, and potentially avoidable mortality, focusing on young adults with mild ID living in community settings.

Methods
This cohort study was approved by the Regional Ethical Review Board in Stockholm, Sweden. No patient consent was obtained because the work was a register-based epidemiological study. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Study Design and Setting
To conduct a population-based cohort study, we linked several nationwide population-based registers using the unique personal identification number that all Swedish residents have. Two registers were used to identify individuals with ID: the NPR and Halmstad University Register on Pupils With Intellectual Disability (HURPID).
The NPR applies diagnostic codes that are based on the Swedish versions of the International

Classification of Diseases, Eighth Revision (ICD-8); International Classification of Diseases, Ninth
Revision (ICD-9); and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). The NPR includes primary and secondary psychiatric diagnoses for inpatient care (from 1973 onward) and outpatient care (from 2001 onward), including a diagnostic assessment for ID without any further contact with psychiatric services. The HURPID is a national database of persons (n = 12 269) who graduated from an upper secondary school for students with intellectual disability (USSID) between January 1, 2001, andDecember 31, 2011. 23,24 Persons in the HURPID database are coded according to the USSID program they attended, 23 such as national programs (eg, special programs that focus on sports) and individual programs (eg, those that are adjusted for individual needs, such as vocational training and activity training). 25 Assignment to these USSID programs is based on the student's profile, which is created from psychological, pedagogical, medical, and social assessments. 26 Because activity training programs are adjusted for students with greater needs, most of the students who attend these programs have moderate to profound ID.

Study Cohorts
We created 2 cohorts: cohort 1 comprised young adults with mild ID, and cohort 2 comprised individuals with mild or moderate to profound ID. All individuals were followed up from their inclusion in the study until the end of the study period (December 31, 2013) or death, whichever occurred first.
To focus on the young adults with mild ID in the contemporary Swedish welfare society, we restricted cohort 1 to include individuals who were born between January 1, 1980, to December 31, 1991; alive at 18 years of age; and identified either from the NPR or the HURPID database (eFigure 1 in the Supplement). The categorization of ID from the NPR and the HURPID databases is depicted in eTable 1 in the Supplement, whereas the correspondence of the 2 registers is depicted in eTable 2 in the Supplement.
To enable a comparison to previous studies on mortality in ID, including all levels of ID severity and enrollment over a long period, we examined mortality in a second cohort from the NPR. In cohort 2, we included all individuals with ID diagnoses identified from 1969 to 2013 who were born between January 1, 1932, and December 31, 2013 (eFigure 1 in the Supplement). The categorization to mild vs moderate to profound ID is described in eTable 1 in the Supplement.
For each individual with ID, we identified 10 reference individuals who were matched from the Total Population Register 27 (135 410 for cohort 1, and 506 610 for cohort 2). The reference individuals were required to be free from ID; to be the same sex; to be born during the same calendar year; and to be alive and living in the same county in Sweden as the individuals with ID when they were first diagnosed, as recorded in the NPR, or when they finished the USSID (exact matching).

Outcomes and Confounding Factors
The primary outcome of the study was overall (all-cause) mortality, and the secondary outcomes were cause-specific mortality, categorized by the chapters in the ICD, 28 and potentially avoidable mortality 29 (defined in eTable 3 in the Supplement). The ICD diagnostic codes were extracted from the Cause of Death Register.
To analyze the role of possible confounding factors (described in eTable 1 in the Supplement), we conducted a series of analyses adjusted for (1) parental educational level using 3 data sources from Statistics Sweden; (2) congenital malformations, deformations, and chromosomal abnormalities; (3) epilepsy; (4) other coexisting neurodevelopmental disorders, such as autism spectrum disorder and/or attention-deficit/hyperactivity disorder; and (5) psychiatric comorbidity, such as depression and/or anxiety disorders.

Statistical Analysis
Conditional logistic regression analyses were conducted to calculate odds ratios (ORs) with 95% CIs for all-cause, cause-specific, and potentially avoidable mortality. Analyses for all-cause mortality were stratified by sex in cohort 1 and sex and level of ID in cohort 2. In addition to the crude OR analysis, we conducted a series of adjusted analyses to examine the potential role of possible confounding factors in separate models. Kaplan-Meier survival plots were drawn for the 2 cohorts and their matched reference cohorts and are shown in eFigure 2 in the Supplement.
All analyses were planned a priori. Data are not shown for any cell that included fewer than 5 individuals. We conducted the statistical analyses between June 1, 2020, and March 31, 2021, using SAS, version 9.4 (SAS Institute Inc).

Cohort 1: Young Adults With Mild ID
A total of 13 541 young adults with mild ID were included in cohort 1, whereas 135 410 individuals composed the matched reference cohort. The young adults in cohort 1 had a mean (SD) age at death of 24.53 (3.66) years and were composed of 7826 men (57.8%) and 5715 women (42.2%). The demographic data of cohort 1 are depicted in Table 1. During follow-up, 120 young adults with mild ID (0.9%) died (  Figure). In cohort 1, 55% of amenable mortality was attributed to epilepsy.  Table 3.

Cohort 2: Individuals With Mild or Moderate to Profound ID
Both the mild ID (OR, 6.21; 95% CI, 5.79-6.66) and the moderate to profound ID (OR, 13.15; 95% CI, 12.52-13.81) groups had an increased risk of premature mortality ( In cohort 2, individuals with mild ID or moderate to profound ID had significantly increased risk in all categories that could be analyzed, and the overall pattern of results showed generally higher risks in the moderate to profound ID group (

Discussion
This nationwide population-based cohort study suggests that health challenges remain for people with ID, including mild ID, in a contemporary Swedish welfare society. A large proportion of the excess risk for premature mortality in those with mild ID was classified as potentially treatable.
Expectedly, increased severity of ID was associated with considerably higher mortality risk. Common causes of death (neoplasms and diseases of the circulatory system) were more frequent among individuals with ID. Moreover, diseases of the nervous system, especially epilepsy, were frequently observed both as a cause of death and as a confounding factor in several cause-of-death categories.

All-Cause Mortality
We found an increased mortality risk in the 2 cohorts, including 2.86-fold risk in young adults with mild ID. These results are in line with those in other contemporary studies, although previous studies were mostly not stratified for ID severity level or only included small samples of mild ID. 5,[9][10][11]13,30,31    Nevertheless, these results suggest that, even in a modern egalitarian welfare society, health challenges remain for young adults with ID who took part in adjusted education.
Both syndromal ID and differences in life experiences (eg, living arrangements, community participation, and access to support) might play a role in the large differences in premature mortality among those with different ID severity levels (cohort 2). Thus, in accordance to a previous smaller study, 5 we observed a 15-year gap (almost 1 SD) in longevity in individuals with moderate to profound ID vs their matched reference cohort and a 5-year gap (one-third of an SD) between those with mild ID vs their matched reference cohort.
The large sample size and access to high-quality registries in this study allowed us to analyze several potential confounders. Similar to the findings in other studies, 5,6,9,11,14 female sex was associated with higher relative risk for overall mortality in cohorts 1 and 2 (vs same-sex reference individuals in the matched reference cohorts), whereas the observation of a similar proportion of deaths in both sexes in cohorts 1 and 2 was in line with the results of a recent study from Australia. 32 Moreover, confounders had only a limited association with all-cause mortality. Thus, we could not confirm in this study the recently reported higher mortality risk in socioeconomically disadvantaged people with ID 32 by using parental educational level as a proxy for socioeconomic status.

Cause-Specific Mortality
The risks of premature mortality in circulatory diseases and neoplasms were higher among people with ID compared with the matched reference cohorts. The current study does not explain the reasons for the increased risks; however, previous studies suggest a higher prevalence of risk factors, such as obesity, hypertension, and diabetes, among individuals with ID. 33 Despite the benefits of deinstitutionalization, challenges may exist pertaining to a lower restriction in living arrangement and an associated increase in behavioral factors, such as smoking, sedentary lifestyle, and poor diet. 8 Deaths attributed to nervous system diseases (eg, epilepsy) have consistently been found to be more prevalent among individuals with ID, 6,9,10,12,15 and the results were similar in this study.
Generally, epilepsy was indicated both as a major confounder in several categories for cohort 2 and as a common primary cause of death. National clinical guidelines for different ID severity levels that address multimorbidity and possibly avoidable deaths 6 are still lacking in Sweden. Similarly, improved primary care for people with ID that includes scheduled health checks 34 and health action plans remains to be implemented on a national level. To promote preventive health interventions and to reduce diagnostic overshadowing, which has been associated with late identification and treatment of ill health, educating the housing support staff may be needed. 35 We observed an increased risk of death from respiratory diseases (eg, pneumonitis from foods or fluids and pneumonia) in cohort 2, and this risk was higher among individuals with moderate to profound ID (ie, almost as common a cause of death as neoplasms), a finding that has been found in some 9,10,12,15 but not all 6 studies. Dysphagia (difficulties with eating, drinking, or swallowing) is common, especially in individuals with more severe levels of ID with coexisting motor impairment. 36 Dysphagia is associated with poor nutritional status, asphyxiation, respiratory infections, and premature mortality. 37 The identified knowledge gaps pertain to clinical management, including assessment, mealtime support, positioning, dietary modification, and well-being outcome. 36,37 In addition to respiratory diseases, we identified several cases that may be related to dysphagia among external causes of death (inhalation and ingestion of food that cause obstruction in the respiratory tract).
The moderate to profound group had a higher risk in several cause-of-death categories compared with the mild ID group in cohort 2. However, those with mild ID had a higher risk in the external cause-of-death category, an important topic for further research to better understand and prevent premature mortality attributed to external causes.

Potentially Avoidable Mortality
Among the young adults with mild ID (cohort 1), most deaths were attributed to potentially avoidable mortality, 29 with an especially high risk of death attributable to causes that were amenable to health care intervention, as has been previously suggested. 6,10 This obvious health challenge, which is indicative of persistent inequality in health care encounters for people with ID, is shown in the Figure. A high proportion (55%) of the amenable mortality among young adults with mild ID was associated with epilepsy.

Limitations
This study has several limitations. First, despite being widely included in available national registers, ID may remain unrecognized in some individuals. Moreover, given that the assignment to a specific USSID program is based on the individual functional profile, which is created from assessments by multiprofessional teams rather than specific ICD codes, some misclassification occurs, especially regarding individuals with moderate ID. Second, Sweden has a tax-funded health care system with universal access, and the generalizability of these results to other countries may be limited by societal differences in welfare policies, practices, and resources. 7,43 Third, we lacked information on the social network, an especially important health factor for individuals with ID. Family members and social networks may be advocates for pursuing their rights, supporting independent living, 44 and reducing loneliness, which may have an association with overall mortality. 45