All-cause and cause-specific mortality among people with and without intellectual disabilities during the COVID-19 pandemic in the Netherlands: a population-based cohort study

Background Although high rates of COVID-19-related deaths have been reported for people with intellectual disabilities during the first 2 years of the pandemic, it is unknown to what extent the pandemic has impacted existing mortality disparities for people with intellectual disabilities. In this study, we linked a Dutch population-based cohort that contained information about intellectual disability statuses with the national mortality registry to analyse both cause-specific and all-cause mortality in people with and without intellectual disabilities, and to make comparisons with pre-pandemic mortality patterns. Methods This population-based cohort study used a pre-existing cohort that included the entire Dutch adult population (everyone aged ≥18 years) on Jan 1, 2015, and identified people with presumed intellectual disabilities through data linkage. For all individuals within the cohort who died up to and including Dec 31, 2021, mortality data were obtained from the Dutch mortality register. Therefore, for each individual in the cohort, information was available about demographics (sex and date of birth), indicators of intellectual disability, if any, based on chronic care and (social) services use, and in case of death, the date and underlying cause of death. We compared the first 2 years of the COVID-19 pandemic (2020 and 2021) with the pre-pandemic period (2015–19). The primary outcomes in this study were all-cause and cause-specific mortality. We calculated rates of death and generated hazard ratios (HRs) using Cox regression analysis. Findings At the start of follow-up in 2015, 187 149 Dutch adults with indicators of intellectual disability were enrolled and 12·6 million adults from the general population were included. Mortality from COVID-19 was significantly higher in the population with intellectual disabilities than in the general population (HR 4·92, 95% CI 4·58–5·29), with a particularly large disparity at younger ages that declined with increasing age. The overall mortality disparity during the COVID-19 pandemic (HR 3·38, 95% CI 3·29–3·47) was wider than before the pandemic (3·23, 3·17–3·29). For five disease groups (neoplasms; mental, behavioural, and nervous system; circulatory system; external causes; and other natural causes) higher mortality rates were observed in the population with intellectual disabilities during the pandemic than before the pandemic, and the pre-pandemic to during the pandemic difference in mortality rates was greater in the population with intellectual disabilities than in the general population, although relative mortality risks for most other causes remained within similar ranges compared with pre-pandemic years. Interpretation The impact of the COVID-19 pandemic on people with intellectual disabilities has been greater than reflected by COVID-19-related deaths alone. Not only was the mortality risk from COVID-19 higher in people with intellectual disabilities than in the general population, but overall mortality disparities were also further exacerbated during the first 2 years of the pandemic. For disability-inclusive future pandemic preparedness this excess mortality risk for people with intellectual disabilities should be addressed. Funding Dutch Ministry of Health, Welfare, and Sport and Netherlands Organization for Health Research and Development.


Introduction
People with intellectual disabilities generally have health disparities and barriers in accessing adequately tailored care, resulting in poor health outcomes and premature death. [1][2][3] Intellectual disabilities can be caused by a range of genetic, infectious, birth-related, or environmental factors, and are characterised by substantial cognitive impairment and limitations in adaptive behaviour with onset before adulthood, with an estimated prevalence of approximately 1·5% in high-income countries. [4][5][6] During the COVID-19 pandemic, people with intellectual disabilities were at a particular risk for poor health outcomes for at least three reasons. First, people with intellectual disabilities had an increased risk of contracting SARS-CoV-2. 7,8 Close encounters in care and social settings are common, especially within residential care facilities, and potentially low (health) literacy complicated complying with restrictive prevention measures, such as social distancing or wearing face masks. [9][10][11] Second, immunodeficiencies, generally poorer overall health, and health inequities put people with intellectual disabilities at a greater risk of serious illness and death from COVID-19 than people in the general population, particularly in the presence of a syndromic intellectual disability. 2,[12][13][14][15] Finally, COVID-19 might have exacerbated existing disparities for people with intellectual disabilities. 10,16 Mortality risks have always been greater for people with intellectual disabilities than for people in the general population. [17][18][19] These existing mortality disparities are associated with risk factors in people with intellectual disabilities (eg, multimorbidity and obesity 20 ) and factors related to provision of care and health services. 1,3,19 The COVID-19 pandemic disrupted routine provision of care, as residential facilities were closed for visitors during lockdowns, daytime and group activities were cancelled, and staff needed to spend more time on patients in isolation and quarantine. 21,22 High mortality rates from COVID-19 among people with intellectual disabilities have been reported, particularly for people with Down syndrome, and for residents of longterm care facilities. [23][24][25][26] However, to our knowledge, no evidence is available on the effect of the pandemic on mortality from all other causes excluding COVID-19 and the effect on existing mortality disparities between people with and without intellectual disabilities. Investigation of cause-specific mortality is pivotal for understanding the full impact the pandemic had on people with intellectual disabilities, but could also inform future public health policies. Although disability status information is essential for such investigations, this variable is not routinely available in surveillance systems set up to monitor COVID-19, nor is it part of standard mortality statistics. Therefore, data linkage at the population level is needed to combine information on disability status with causes of death. In this study, we linked a Dutch population-based cohort that contained information about intellectual disability statuses with the national mortality registry to analyse both cause-specific and all-cause mortality in people with and without intellectual disabilities, and to make comparisons with pre-pandemic mortality patterns.

Study design and population
This population-based cohort study used a pre-existing cohort that included the entire Dutch adult population (aged ≥18 years) on Jan 1, 2015, and identified people with presumed intellectual disabilities through data linkage. 27 For all individuals within the cohort who died up to and including Dec 31, 2021, mortality data were obtained from the Dutch mortality register. Therefore, for each individual in the cohort, information was available about demographics (sex and date of birth), indicators of intellectual disability, if any, based on chronic care and (social) services use, and in case of death, the date and underlying cause of death. The databases needed for this study were available for statistical and scientific research as non-public microdata within a secure, digital research

Research in context
Evidence before this study We searched PubMed for articles published in English from database inception up to Aug 11, 2022, using the following search terms: ("COVID" OR "coronavirus") AND ("intellectual disab*" OR "learning disab*") AND ("mortality" OR "death"). The search identified 76 articles, 22 of which reported primary data on COVID-19-related deaths. Most studies analysed data from the first epidemic waves only, and six studies included data from the start of the pandemic up to the first months of 2021. Outcomes mostly concerned COVID-19 case fatalities to identify risk factors and four studies included all-cause mortality to calculate excess mortality rates, but no studies specified cause-specific mortality from causes other than COVID-19. Existing studies showed a greater mortality risk for people with intellectual disabilities in general, and for certain subgroups (eg, those with Down syndrome or living in congregate settings) in particular. Studies that addressed excess mortality from COVID-19 showed an association with intellectual disability, among other factors.

Added value of this study
This population-based cohort study is the first, to our knowledge, to report cause-specific mortality for two complete years (2020 and 2021) since the start of the pandemic, providing robust evidence for increased mortality risks from COVID-19 for people with intellectual disabilities, and to specify to what extent other causes of death were affected. Our study showed that the full impact of the COVID-19 pandemic has been much greater than indicated by reported deaths due to COVID-19 alone. Existing mortality disparities between people with and without intellectual disabilities have been further widened compared with the period 2015-19.

Implications of all the available evidence
The health risks for people with intellectual disabilities warrant targeted policy making regarding protective measures for the current pandemic and future pandemic preparedness that go beyond the causative agent of a pandemic alone. This study shows the need for better monitoring of vulnerable populations, such as people with disabilities, who are at risk of otherwise being overlooked, with marked consequences. environment at Statistics Netherlands, the Dutch national statistics office. 28 The Radboud University Medical Center institutional ethics committee waived the need for ethics approval as this was a large-scale anonymous database study with posthumous investigation of mortality data (reference 2017-3921). We report our results in accordance with the STROBE statement. 29 The population with intellectual disabilities was determined by the presence of indicators of intellectual disability, as actual intellectual disability diagnoses are not saved in any national database. Indicators of intellectual disability consisted of a record in one of the national databases for chronic care or social services where "intellectual disability" was noted as a reason for calling upon one or more services. When service access was requested, an individual's intellectual disability diagnosis was verified, but information about the diagnosis was not included in service records. 27 This method identified individuals with presumed moderate to severe intellectual disabilities who either received residential intellectual disability care or non-residential intellectual disability-related chronic care, and individuals with mild intellectual disabilities who received support in the social domain. This method has been applied to other studies related to health and intellectual disability before, including investigation of mortality. 16,30 All individuals without indicators of intellectual disability were analysed as members of the general population.

Outcomes
The primary outcomes in this study were all-cause and cause-specific mortality. Dutch law prescribes mandatory notification of the cause of death. Forms specifying the cause and location of death are collected, processed, and coded by Statistics Netherlands. The disease or injury initiating the train of morbid events or fatal injury is recorded as the cause of death in the mortality registry using the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10). 31 COVID-19-related mortality was defined by the ICD-10 emergency codes for proven (U07.1) or suspected COVID-19 (not tested or virus not identified; U07.2). The database used for this study could contain only a single underlying cause of death.

Statistical analysis
Demographics were presented as frequencies (with percentages) or means (with SD). We reported the number of observed deaths in the population with intellectual disabilities and the general population and calculated mortality rates per 10 000 population per year (2015-2021). Crude mortality rates were calculated using the midperiod population size as the denominator. Agestandardised and sex-standardised mortality rates from the general population were applied to the population with intellectual disabilities to calculate expected deaths in this group. Relative mortality risks for the population with intellectual disabilities relative to the general population were expressed as hazard ratios (HRs) with 95% CIs for all-cause mortality and COVID-19-related mortality using Cox regression analysis to account for potential differences in survival time and to adjust for different distributions of age and sex in both groups. For the pre-pandemic period, follow-up time was from Jan 1, 2015, to time of death or Dec 31, 2019, and follow-up during the pandemic was calculated for all people alive on Jan 1, 2020, until time of death or Dec 31, 2021. Results were presented for the entire group, and for age and sex groups separately.
Specific causes of death other than those that were COVID-19-related were grouped into the same six umbrella categories as used by Statistics Netherlands, as follows: neoplasms; circulatory system; respiratory system; mental, behavioural, and nervous system; external (non-natural) causes; and other natural causes. 32 For each of these groups, we calculated mortality rates and generated HRs to compare the population with intellectual disabilities with the general population for  the pre-pandemic (2015-19) and pandemic period (2020-21), with deaths from other causes being censored at the time of death. The frequency distribution of individual causes (specified by their three position ICD-10 code) within each of the six disease groups was compared before and during the pandemic using χ² tests. p<0·05 was considered to indicate a statistically significant difference. All analyses were done in SPSS version 25.0.

Role of the funding source
The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Results
At the start of follow-up in 2015, 187 149 Dutch adults with indicators of intellectual disability were enrolled in the cohort (1·45% intellectual disability prevalence; population with intellectual disabilities) and 12·6 million adults from the general population were included. The population with intellectual disabilities consisted of more male In both the population with intellectual disabilities (460 [60·1%] of 765 people) and the general population (20 826 [54·0%] of 38 580 people) men were overrepresented among COVID-19-related deaths, but the relative risk for COVID-19-related mortality was higher for women with intellectual disabilities (HR 6·16, 95% CI 5·50-6·90) than for men with intellectual disabilities (4·33, 3·94-4·75;  The COVID-19-related mortality disparity between the population with intellectual disabilities and the general population was highest at young ages and declined with increasing age (table 3). Compared with before the pandemic, the death rate during the pandemic increased more in the population with intellectual disabilities (120·7 deaths per 10 000 people per year vs 151·2 deaths per 10 000 people per year) than in the general population (117·1 deaths per 10 000 people per year vs 134·4 deaths per 10 000 people per year), resulting in a higher HR during the pandemic (HR 3·38 95% CI 3·29-3·47) than before the pandemic (3·23, 95% CI 3·17-3·29; table 2). The frequency distribution of deaths from major individual causes within each disease category is included in the appendix (pp 1-2).
For five disease groups (neoplasms; mental, behavioural, and nervous system; circulatory system; external causes; and other natural causes) higher mortality rates were observed in the population with intellectual disabilities during the pandemic than before the pandemic, and the pre-pandemic to during the pandemic difference in mortality rates was greater in the population with intellectual disabilities than in the general population, despite the younger mean age of the population with intellectual disabilities compared to the general population (table 3). However, a significantly higher HR for the population with intellectual disabilities relative to the general population was only observed for external causes (table 3).
Notable changes in specific causes of death in the population with intellectual disabilities included an increase in deaths due to poorly defined cancers (cancer of unknown primary-C80; and unknown or uncertain behaviour-D37-D48), fewer deaths due to pneu monia (J18), more accidental falls (W19), more deaths related to diabetes (E100-E14), and fewer deaths from Down syndrome (Q90; appendix pp 1-2). In both groups, more deaths were coded with R99 (other illdefined and unspecified causes of mortality) during the pandemic than before.

Discussion
In this study, we analysed mortality patterns among Dutch adults with intellectual disabilities within the first two calendar years (2020 and 2021) of the COVID-19 pandemic and compared them with pre-pandemic patterns. The overall mortality disparity between people with and without intellectual disabilities during the pandemic was wider than before. Mortality due to COVID-19 was almost five times higher than in the general population, and particularly high for young people with intellectual disabilities compared with people in the same age groups in the general population. Disparities for causes of death other than COVID-19 were also further widened, indicating the impact of the COVID-19 pandemic for people with intellectual disabilities has been greater than what is reflected by the number of COVID-19 deaths alone.
Several studies in multiple countries have shown increased mortality risks for people with intellectual disabilities due to COVID-19. 24,33,34 Intellectual disabilities has even been identified to be one of the largest independent risk factors-besides age-for COVID-19related mortality in the USA. 8 Yet, to our knowledge, our study is one of the first to report these findings across the full first 2-year span of the pandemic with national registry data. This knowledge improves the understanding of the origin of the observed disparities between people with intellectual disabilities and the general population, and the need to address them when designing policies for future pandemics.
During the pandemic, we also observed an increase in deaths among people with intellectual disabilities for causes other than COVID-19, including related to certain types of cancer, diabetes, and accidental falls. Although the available data do not provide information about the context and circumstances at the time of death, these  Data are mean (SD) or n (%), unless otherwise indicated. Population size and age were determined on Jan 1, 2020. HRs are adjusted for age and sex, and compare the population with intellectual disabilities with the general population. Counts less than ten are not shown because of the privacy risk. *Expected deaths are calculated with sex and age group standardised rates from the general population; counts are rounded up to nearest whole and presented with 95% prediction intervals. †Denominators are the totals in the entire group row. is not yet possible in the Netherlands. Similarly, the decline in some other causes of death during the pandemic, such as respiratory or congenital diseases (eg, Down syndrome), is likely to be explained by the fact that those at high risk of dying from these causes were also at a high risk of dying from COVID-19. During the pandemic, this mechanism might have even reduced the phenomenon of miscoding deaths in populations with intellectual disabilities, where intellectual disability or Down syndrome is incorrectly listed as the underlying cause of death in circumstances where the actual cause is not readily apparent. 35,36 This study has two important implications. First, the study underlines the need for attention in public health policies and clinical practice for the vulnerability of people with disabilities. Availability of more and betterquality routine data about people with disabilities might have improved disability-inclusive communication and availability of personal protective measures in disability care during the COVID-19 pandemic. From a broader perspective, better-quality data can provide evidence for decision making, policies, and development of guidelines. [37][38][39] Second, there is a clear need for improved infrastructure for the public health monitoring of highrisk groups. Monitoring COVID-19-related mortality is part of population surveillance in the Netherlands, as in many other countries. However, the disproportionate effect of the pandemic on people with intellectual disabilities only became visible after databases were linked for this study and, thus, in retrospect. Alternative registries have been developed, also in the Netherlands, but were often restricted in timeperiod, outcomes, or study sample. 15 Although real-time data were unavailable to inform the public health response, this alternative registry provided the evidence needed to prioritise people with intellectual disabilities for COVID-19 vaccination in the Netherlands. 15 As many decisions in public health are data driven, a disability-inclusive data infrastructure is required for more timely insights and a quicker response towards those in need of action. 37,38 Mortality data are among the best available sources of public health information for such an approach, as they provide information about current health problems, including preventable and treatable causes, suggest persistent patterns of disparities in specific populations, and show trends over time. An example of a tailored monitoring programme is the Learning (Intellectual) Disabilities Mortality Review programme in England. 3,40 Lessons from this programme could contribute to service improvements locally and nationally, but also show the need for specific attention from policy and research, and a dedicated infrastructure.
A major strength of this study is the population coverage, with information on demographics, disability status, and mortality. For all registered deaths, a cause was submitted, although that reason could be labelled as unknown or unspecified, mostly coded as "other illdefined and unspecified deaths (R99)", which appeared more frequently in both our study groups during the COVID-19 pandemic than before the pandemic. Increased workload during the pandemic might have caused an increase in erroneous death certificates being submitted. Potentially, some of these deaths could also have been unidentified COVID-19 cases; this is especially likely in the first months of 2020, when testing capacities were constrained. However, the overall impact of unknown or unspecified coding on outcomes is small; although the proportion of unknown or unspecified causes of deaths was increased, as part of the total number of deaths the proportion was low.
Information about disability status was limited by the fact that it was obtained from secondary sources from Dutch national long-term care and social services, and provided no information about intellectual disability causes, as such information is unavailable in any Dutch population database. Yet, the information available represents the most comprehensive population-based database on intellectual disability available in the Netherlands, and the intellectual disability prevalence determined in this database aligned with international prevalence estimates. 4,5,27 Furthermore, accurate classification of intellectual disabilities was supported by the fact that intellectual disability-specific causes of death almost exclusively appeared in the population with intellectual disabilities. This indiciates that despite people with intellectual disabilities in this study being identified through systems exclusive to the Netherlands, groups of similar individuals would be identified in other countries with different health systems and social services. A further limitation is that the applied participant identifcation method provided no information about ethnicity or other sociodemographic characteristics that might have interacted with the outcomes in this study.
In conclusion, COVID-19 disproportionally affected people with intellectual disabilities, but the impact of the pandemic was larger than shown by COVID-19 deaths alone. With an increase in deaths from causes other than COVID-19, existing mortality disparities between the population with intellectual disabilities and the general population were further widened. The health risks for people with intellectual disabilities warrant targeted policy making regarding protective measures for current and future pandemics, and critical evaluation of the access for these individuals to health care in general. For this purpose, better infrastructure for disability-inclusive public health data is needed.