ArticlePDF Available

Abstract and Figures

Background Mortality has been suggested to be increased in autism spectrum disorder (ASD).AimsTo examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability.Method Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27 122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2 672 185).ResultsDuring the observed period, 24 358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38-2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability.Conclusions Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.
Content may be subject to copyright.
Autism spectrum disorder (ASD) is a chronic childhood-onset
neurodevelopmental condition with detrimental effects on adaptive
functions throughout life.
1–3
The number of people with ASD
diagnoses has increased during the last decades although the
underlying reasons for this increase are not fully understood.
4
Both clinical
5,6
and population-based studies
1,7
have reported
poor long-term outcomes
8
regarding education, employment,
independent living and peer relations. A poor long-term outcome
has been observed in both low-functioning ASD (i.e. individuals
with ASD and a co-existing intellectual disability) and high-
functioning ASD (i.e. individuals with ASD and intellectual ability
in the average or above range). Psychiatric comorbidity is common
in individuals with ASD,
9–13
and especially low-functioning ASD
may be part of a known genetic syndrome (‘syndromic’ autism),
such as fragile X syndrome, Down syndrome or tuberous sclerosis.
14
Risk of premature mortality has been reported to be elevated
among individuals with ASD, compared with the general
population,
15–19
as well as compared with healthy cousin or
sibling controls.
20
To date, studies on mortality in ASD with
long-term follow-ups comprise two clinical cohorts
16–19
and two
population-based cohorts,
15,20
diagnosed with ASD as children.
Compared with mortality statistics from the general population
or general population controls, the risk of premature mortality
has been estimated to be twofold to 10-fold higher in the ASD
population. Characteristics of the previous studies on the outcome
of mortality in ASD are summarised in Table 1.
Based on the well-known association between ASD and medical
conditions (e.g. epilepsy),
21
and especially in individuals with low-
functioning ASD, it has been suggested that the excess mortality
in ASD may be related to the presence of comorbid medical
conditions and intellectual disability, rather than ASD per se.
20
However, the only study to date analysing differences in mortality
between individuals with low-functioning ASD and high-
functioning ASD did not identify significant between-group
differences in overall mortality.
17
In addition, in most previous
studies sample sizes have been too small to compare mortalities in
low-functioning and high-functioning ASD reliably. Thus, the
potentially moderating effect of intellectual disability in mortality
and causes of death in ASD remain unclear, and it has not been
possible to determine whether ASD per se carries an increased
mortality.
15
Gender is another possible moderator of excess mortality in
ASD. Relative to males, females with ASD have been reported to
have an elevated mortality risk.
15–20
However, there has been
considerable variation in the reported risk ratios ranging from
3.6 to 20.7 for females, whereas the risk ratios for males have
ranged between 1.6 and 7.9.
15–20
Large confidence intervals
(CIs) in some of the studies indicate imprecise estimations.
Large-scale studies are needed to explore the predictive role
of risk factors (such as comorbid intellectual disability or the
potential role of gender) for mortality in ASD. Moreover, access
to data from a large sample including a broad age range and a
substantial follow-up period is needed to study different causes
of death. On this point, most studies did not have adequate
statistical power to examine less frequent causes of death.
The population-based studies conducted to date have identified
such causes of death as associated medical conditions (including
epilepsy), as well as cardiovascular and respiratory deaths.
15,20
In a clinical cohort, a pattern of causes of death resembling that
of the background population was observed, with exception for
a very strong association for deaths associated with epilepsy.
16,17
The largest study on causes of death in ASD was based on a
clinical cohort including ambulatory Californians with autism.
18,19
Nevertheless, on excluding concomitant conditions such as cerebral
palsy, tuberous sclerosis and Down syndrome, the results showed
an elevated risk for several causes of death.
The aim of the current study was to analyse all-cause
and cause-specific mortality in ASD using nationwide Swedish
population-based registers. A further aim was to address the role
of intellectual disability and gender as possible moderators of
mortality and causes of death in ASD.
Method
Study design
We conducted a matched case cohort study.
1
Premature mortality in autism spectrum disorder
Tatja Hirvikoski, Ellenor Mittendorfer-Rutz, Marcus Boman, Henrik Larsson,
Paul Lichtenstein and Sven Bo
¨lte
Background
Mortality has been suggested to be increased in autism
spectrum disorder (ASD).
Aims
To examine both all-cause and cause-specific mortality in
ASD, as well as investigate moderating role of gender and
intellectual ability.
Method
Odds ratios (ORs) were calculated for a population-based
cohort of ASD probands (n= 27 122, diagnosed between 1987
and 2009) compared with gender-, age- and county of
residence-matched controls (n= 2 672 185).
Results
During the observed period, 24 358 (0.91%) individuals in the
general population died, whereas the corresponding figure
for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI
2.38–2.76). Cause-specific analyses showed elevated mortality
in ASD for almost all analysed diagnostic categories. Mortality
and patterns for cause-specific mortality were partly
moderated by gender and general intellectual ability.
Conclusions
Premature mortality was markedly increased in ASD owing to
a multitude of medical conditions.
Declaration of interest
None.
Copyright and usage
BThe Royal College of Psychiatrists 2015.
The British Journal of Psychiatry
1–7. doi: 10.1192/bjp.bp.114.160192
Study setting
Two nationwide population-based Swedish registers were linked:
the National Patient Register and the Cause of Death Register,
both held by the National Board of Health and Welfare. The data
were linked using the unique 10-digit personal identification
number used in registers for all Swedish residents, including
migrants with a residence permit. The National Patient Register
includes diagnoses for all in-patient treatment episodes for
psychiatric disorders in Sweden since 1973, as well as for
out-patients (including diagnostic assessments with no further
contact with psychiatric services) since 2001. The diagnoses are
coded according to the Swedish versions of the ICD by the World
Health Organization (WHO).
Study population
Individuals with ICD diagnosis codes for any ASD were identified
from the National Patient Register. The validity or diagnostic
accuracy of ASD diagnoses in Swedish health registries has been
shown to be good.
22
We first identified all individuals with an
ASD diagnosis in the National Patient Register between 1987
and 2009. The ICD-9
23
ASD diagnoses (1987–1996; 299xx) were
converted to corresponding ICD-10
24
diagnoses (1997 onwards)
using a conversion instrument provided by the Swedish National
Board of Health and Welfare. In the final cohort, the included
diagnoses were autism (F84.0), Asperger syndrome (F84.5),
atypical autism (F84.1) and pervasive developmental disorder –
not otherwise specified (F84.9), other childhood disintegrative
disorder (F84.3) and other pervasive developmental disorders
(F84.8). Diagnoses of Rett syndrome (F84.2) and overactive
disorder associated with mental retardation and stereotyped
movements (F84.4) were excluded, as these are no longer
considered core ASD diagnoses in current psychiatry (e.g. no
longer classified in DSM-5).
25
In Swedish clinical practice,
diagnostic assessment of ASD was rare before 1990 (less than
2% of the final study cohort) and a majority of the study cohort
(88.2%) was diagnosed after 2001, i.e. after inclusion of out-patient
data in the National Patient Register. The dichotomisation into
low-functioning ASD and high-functioning ASD groups was
based on the registered ICD codes for mental retardation. The
ICD-9 codes 317–319 were converted to the corresponding
ICD-10 diagnoses mild (F70), moderate (F71), severe (F72),
profound (F73), other (F78) and unspecified (F79) intellectual
disability. Thus, individuals with a co-existing intellectual disability
were classified as low-functioning ASD regardless of which ASD
diagnosis they had. The same type of classification strategy has
been applied in previous studies
26,27
based on high-functioning
ASD v. low-functioning ASD as two key categories for the
specification of ASD in DSM-5.
For each proband identified with ASD from the National
Patient Register, up to 100 controls were randomly selected from
the Total Population Register. The controls were alive at the time-
point of inclusion (when the case with ASD was registered the first
time) and were not diagnosed with ASD during the study period.
Controls were matched with cases by birth year, gender and
county of residence in the year when the matched cases received
their first ASD diagnosis.
Classification of the specific causes of death
ICD-9 codes for specific causes of death (for deaths during
1987–1996) were converted into corresponding ICD-10 diagnoses
(1997–2009) using the conversion instrument provided by the
National Board of Health and Welfare. The main causes of death
were grouped into the following categories (ICD-10 chapters and
codes are specified in the Appendix):
(a) Infections
(b) Neoplasms
(c) Endocrine
2
Hirvikoski et al
Table 1 A summary of study cohorts and main results from previous studies on mortality in ASD
Study Country
Total n
ASD
Diagnosis,
% of total
n
Mean age at
diagnosis
(range),
years
Mean
(years)
follow-up
[time period]
Observed
deaths
n
Expected
deaths in
general
population, n
Reported
risk ratio
(95% CI)
Separate
analyses for
HFASD/
LFASD
Risk ratio separately
for females/males
(CIs if given in the
original article)
Isager et al
16
Denmark 341 ASD
a
low-
functioning:
41.8%
9.5
(2–17)
23.7
[1960–1993]
12 6.2 SMR 1.9
(1.0–3.4)
Not
analysed
F: 3.61 (0.75–10.56)
M: 1.67 (0.76–3.18)
Mouridsen et al
17
Update of the cohort reported
in Isager et al
16
35.5
[1960–2006]
26: low-
functioning
12/143; high-
functioning
14/196
13.5 SMR 1.9
(1.3–2.8)
N
significant
differences
F: 4.01 (1.73–7.90)
M: 1.57 (0.93–2.48)
Shavelle et al
19
USA 13 111 ASD low-
functioning:
48.1%
8.5
(2–15)
14
[1983–1997]
202 84.2 SMR 2.4 Not
analysed
F: 5.5, M: 1.7
Pickett et al
18
Update of the cohort reported in
Shavelle et al
19
19
[1998–2002]
280 114.2 SMR 2.5 Not
analysed
F: 5.2, M: 2.3
Gillberg et al
15
Sweden 120 ASD low-
functioning:
80%
11 (4–18) 22.5
[1962–2008]
9 1.6 SMR 5.6
(2.5–10.5)
Not
analysed
F: 20.7, M:2.3
Bilder et al
20
USA 305 ASD low-
functioning:
64%
10.8 (1.4–
29.2)
25
[1982–2011]
29 Comparison
with
matched
population
controls
HRR 9.9
(5.7–17.2)
Not
analysed
F: 20.7 (6.2–69.2)
M: 7.9 (4.2–15.0)
ASD, autism spectrum disorder; SMR, standardised mortality ratio; HRR, hazard rate ratio; CI, confidence interval; F, female; M, male.
a. The previous Scandinavian diagnosis Borderline childhood psychosis was included as a proxy for Asperger syndrome.
IQ was tested in 60% of cases and in the rest of the cases was based on clinical assessments.
Mortality in autism spectrum disorders
(d) Mental and behavioural disorders
(e) Diseases of the nervous system
(f) Diseases of the circulatory system
(g) Diseases of the respiratory system
(h) Diseases of the digestive system
(i) Diseases of the genitourinary system
(j) Congenital malformations
(k) Symptoms, signs and abnormal findings not elsewhere classified
(l) External causes of morbidity and mortality: intentional self-
harm/suicide was analysed separately from other external
causes of death. X60-X84 in ICD-10 was combined with
undetermined suicide Y10-Y34 in ICD-10 and corresponding
codes from ICD-9. These codes were combined to limit the
temporal and geographic variation in the ascertainment. This
practice is common in research and reporting concerning
public health statistics.
28,29
A sensitivity analysis proved the
comparability of the two diagnostic groups. The combined
measure is referred to hereafter as suicide. In Other external
causes we included remaining X and Y diagnoses and V
diagnoses, as well as W diagnoses.
(m) Other causes of death: in this category we included chapters
with only a few cases (in total, 247 cases; 15 of these with
ASD) (for information on ICD chapters and codes, see
Appendix).
Statistical analyses
Conditional logistic regression analyses were performed and odds
ratios (ORs) with 95% CIs were calculated for all-cause and cause-
specific mortality in cases of an ASD diagnosis in the National
Patient Register (1987–2009). In the first step, the ORs were
calculated for the total ASD group, as well as separately for the
genders. In the second step, the ORs were calculated separately
for the low- and the high-functioning ASD groups (compared
with the matched controls). Analyses were performed stratified
for gender if the difference between the entire ASD group and
controls was significant (all other categories except Infections).
For the analysis of interaction (ASD6gender), an interaction
term was added as a covariate in the conditional logistic regression
analyses and significant interaction was tested with the partial
likelihood ratio test. If any cell included fewer than five cases at
any level of the analysis, that level was dropped and the data were
thus not shown. In the analyses of Mental and behavioural
disorders, ASD diagnoses as primary causes of death (n= 2) were
regarded as ill-defined causes of death and excluded. A partial
likelihood ratio test was also used to compare the fit of the null
model of diagnostic status (ASD or control) with the alternative
model (low-functioning ASD, high-functioning ASD or control).
Thus, if the data fitted the alternative model significantly better,
an interaction effect between low-functioning ASD and high-
functioning ASD was assumed and the null model was rejected.
The alpha level was set at P50.05. All statistical analyses were
planned a priori.
Ethical approval
The Regional Ethics Committee in Stockholm approved the study
(0229/939-31/5).
Results
Characteristics of the study sample are described in Table 2.
All-cause mortality
At the time of the follow-up, 24 358 persons (0.91%) in the
general population group had died, whereas the corresponding
figure in the ASD group was 706 (2.60%; Table 3).
Individuals with ASD had a 2.56-fold increased odds of
mortality compared with matched general population controls
(Table 3). Mortality was significantly elevated in both genders
relative to the general population (males: OR = 2.87; females
OR = 2.24), whereas the significant interaction effect indicated
higher mortality among males (Table 3). Moreover, all-cause
mortality was increased in both the low-functioning ASD
3
Table 2 Characteristics of the study groups
Control ASD in total Low-functioning ASD High-functioning ASD
ntotal (%) 2 672 185 27 122 6240 (23.01) 20 882 (76.99)
Females n(%) 840 962 (31.47) 8429 (31.08) 2032 (32.56) 6397 (30.63)
Males n(%) 1 831 223 (68.53) 18 693 (68.92) 4208 (67.44) 14 485 (69.37)
Age at first registered diagnosis, years:
mean (s.d.) median
N/A 19.83 (14.54) 16.49 (13.83)
12
20.83 (14.59)
17
ASD, autism spectrum disorder.
Table 3 Risk for all-cause mortality for the entire autism spectrum disorder (ASD) group, as well as separately for females and males,
and low-functioning ASD and high-functioning ASD groups
Controls
Number of deaths (%)
ASD OR (95% CI)
Number of deaths (%)
Low-functioning ASD OR (95% CI)
Number of deaths (%)
High-functioning ASD OR (95% CI)
Number of deaths (%)
Total 2.56 (2.38–2.76) 5.78** (4.94–6.75) 2.18 (2.00–2.38)
24 358 (0.91) 706 (2.60) 169 (2.71) 537 (2.57)
Females 2.24 (1.99–2.51) 8.52 (6.55–11.08) 1.88 (1.65–2.14)
11 693 (1.39) 296 (3.51) 61 (3.00) 235 (3.67)
Males 2.87* (2.60–3.16) 4.88 (4.02–5.93) 2.49 (2.22–2.80)
12 665 (0.69) 410 (2.19) 108 (2.57) 302 (2.08)
ASD, autism spectrum disorder; OR, odds ratio; CI, confidence interval.
*Partial likelihood ratio test for interaction effect ASD6gender, P= 0.001.
**Partial likelihood ratio test for model selection (low-functioning ASD/high-functioning ASD), P50.001.
Hirvikoski et al
(OR = 5.78) and the high-functioning ASD (OR = 2.18) groups,
compared with the general population. The excess mortality was
significantly higher in the low-functioning ASD group, as
indicated by the significance of the partial likelihood ratio test
(Table 3). Mortality was increased in both females (OR = 8.52)
and males (OR = 4.88) with low-functioning ASD, as well as in both
females (OR = 1.88) and males (OR = 2.49) with high-functioning
ASD, compared with controls of the same gender.
Individuals in the control group died at a mean age of 70.20
years (s.d. = 24.16, median = 80), whereas the corresponding
figure for the entire ASD group was 53.87 years (s.d. = 24.78,
median = 55), for low-functioning ASD 39.50 years (s.d. = 21.55,
median = 40) and high-functioning ASD 58.39 years
(s.d. = 24.01, median = 63) respectively. The time period between
registered ASD diagnosis and death (regardless of cause of death)
was on average 5.30 years (s.d. = 4.85) for low-functioning ASD
and 3.79 years (s.d. = 4.17) for the high-functioning ASD group.
Cause-specific mortality
Specific causes of death in the whole ASD group
Significantly elevated mortality was noted among individuals with
ASD in all analysed categories of specific causes of death except for
infections (Table 4). The ICD diagnoses including only a few
cases were combined and, also in this category, an excess mortality
of the ASD group was observed. The mortality was 1.5-fold to
eightfold increased compared with the general population (with
exception for congenital malformations (OR = 19.10); however,
the broad CIs indicate an imprecise estimation). ORs were highest
in cases of mortality because of diseases of the nervous system
(OR = 7.49) and because of suicide (OR = 7.55), in comparison
with matched general population controls.
Specific causes of death in low-functioning
v.
high-functioning ASD
In most of the specific causes of death (Mental and behavioural
disorders; Nervous system; Circulatory system; Respiratory
system; Digestive system; and Congenital malformations), the
low-functioning ASD group had higher mortality relative to the
high-functioning ASD group, although both groups had
significantly elevated mortality compared with the general
population controls (Table 4). The most common cause of death
in the low-functioning ASD group was epilepsy. In contrast, the
high-functioning ASD group had a significantly more elevated
suicide risk than the low-functioning ASD group, whereas, again,
both groups had an increased risk compared with controls. The
time period between registered ASD diagnosis and suicide was on
average 2.86 years (s.d. = 2.41) in the low-functioning ASD group
and 2.53 years (s.d. = 2.65) in the high-functioning ASD group.
Online Table DS1 specifies the most common subcategories of
the main causes of death for controls, the entire ASD group,
and low-functioning and high-functioning ASD groups.
Gender differences in specific causes of death
For most diagnostic categories, the pattern of mortality risk was
comparable in females and males with ASD. Nevertheless, males
with ASD had a higher relative risk than females of mortality
4
Table 4 Cause-specific mortality in relation to ASD and separately for low-functioning ASD and high-functioning ASD
a
Controls, n
of deaths (%)
ASD OR (95% CI)
nof deaths (%)
Low-functioning ASD
OR (95% CI), nof deaths (%)
High-functioning ASD
OR (95% CI), nof deaths (%)
Infections 1.83 (0.75–4.30) N/A N/A
245 (0.01) 5 (0.02)
Neoplasms 1.80 (1.46–2.23) 2.12 (1.25–3.61) 1.75 (1.39–2.21)
4493 (0.17) 88 (0.32) 14 (0.22) 74 (0.35)
Endocrine 3.70 (2.34–5.87) 8.89 (3.52–22.41) 3.07 (1.80–5.23)
474 (0.02) 19 (0.07) 5 (0.08) 14 (0.07)
Mental and behavioural
disorders
2.80 (1.94–4.03) 21.81** (12.20–39.00) 1.58 (0.96–2.59)
925 (0.03) 30 (0.11) 14 (0.22) 16 (0.08)
Nervous system 7.49 (5.78–9.72) 40.56** (26.82–61.33) 3.98 (2.76–5.74)
737 (0.03) 62 (0.23) 32 (0.51) 30 (0.14)
Circulatory system 1.49 (1.27–1.75) 4.61** (3.06–6.95) 1.33 (1.12–1.58)
8820 (0.33) 157 (0.58) 24 (0.38) 133 (0.64)
Respiratory system 2.68 (1.99–3.62) 13.92** (7.04–27.50) 2.17 (1.55–3.05)
1351 (0.05) 45 (0.17) 10 (0.16) 35 (0.17)
Digestive system 3.31 (2.25–4.87) 9.13* (4.42–18.87) 2.61 (1.65–4.12)
733 (0.03) 27 (0.10) 8 (0.13) 19 (0.09)
Genitourinary system 3.82 (2.13–6.84) N/A N/A
253 (0.01) 12 (0.04)
Congenital malformations 19.10 (11.94–30.55) 38.75* (20.39–73.64) 10.38 (4.98–21.61)
106 (<0.01) 21 (0.08) 13 (0.21) 8 (0.04)
Symptoms, signs and
abnormal findings, other 618 (0.02)
1.81 (1.06–3.08)
14 (0.05)
N/A N/A
Suicide 7.55 (6.04–9.44) 2.41 (1.14–5.11) 9.40** (7.43–11.90)
1094 (0.04) 83 (0.31) 7 (0.11) 76 (0.36)
External causes, other 1.67 (1.16–2.40) 1.53 (0.69–3.44) 1.71 (1.14–2.56)
1696 (0.06) 30 (0.11) 6 (0.10) 24 (0.11)
Other 5.84 (3.46–9.86) N/A N/A
232 (0.01) 15 (0.06)
ASD, autism spectrum disorder; OR, odds ratio; CI, confidence interval.
a. Missing data on primary cause of death (n= 2677, 50.5% in both groups) are not included in the analyses; N/A analyses were not performed owing to the low number of cases in
certain cells; partial likelihood ratio test for model selection (low-functioning ASD/high-functioning ASD).
*P50.01 (Digestive P= 0.009; Congenital malformations P= 0.007); **P50.001.
Mortality in autism spectrum disorders
owing to diseases of the nervous and circulatory systems. On the
other hand, females with ASD had higher relative mortality risk
than males in diseases owing to endocrine diseases, congenital
malformations and suicide (Table 5).
Discussion
In this large population-based study, we observed increased
mortality in individuals with ASD. Mortality was increased in
both low-functioning and high-functioning ASD, as well as in
both genders. However, the risk was particularly high for females
with low-functioning ASD. Patterns of specific causes of death
were somewhat different for low-functioning ASD compared with
high-functioning ASD.
The observed OR of 2.56 for ASD in relation to all-cause
mortality is in line with most of the previous clinical and
population-based mortality studies.
15–20
We found that increased
mortality in ASD was not limited to certain causes of death, such
as diseases of nervous system, but was elevated for all analysed
categories according to the ICD, apart from infectious diseases.
In most previous studies, the samples have been too small
and/or selected to adequately analyse the role of intellectual
disability regarding mortality in ASD. Therefore, we performed all
analyses comparing low-functioning ASD and high-functioning
ASD groups. Based on the well-known association of low-
functioning ASD with several medical conditions, the higher
mortality in low-functioning ASD than in high-functioning ASD
was expected.
21
In approximately 10% of cases, ASD
(predominantly low-functioning ASD) is part of a known genetic
syndrome,
14
which may be associated with both intellectual
disability and many of the comorbid diseases. Opposing results
from the only previous study focusing on differences in mortality
between low-functioning ASD and high-functioning ASD,
17
the
current study showed increased mortality in mental and
behavioural disorders, diseases of nervous, circulatory,
respiratory and digestive systems, as well as congenital
malformations in the low-functioning ASD group compared with
the high-functioning ASD group. However, our results clearly
indicated that mortality was elevated across a multiplicity of
causes of death in ASD as a whole, including high-functioning
ASD. Thus, our results add to the accumulating evidence
indicating that ASD accounts for substantial health loss across
the lifespan.
30
Suicide was the only specific cause of death showing a higher
risk in high-functioning ASD compared with low-functioning
ASD. High-functioning ASD often presents with co-existing
psychiatric disorders.
9–13
In a recent study,
31
high prevalence of
suicidal ideation and suicide attempts was reported among
individuals with Asperger syndrome. Suicidality was increased
5
Table 5 Cause-specific mortality analysed separately for females and males
a
Control females
nof deaths (%)
ASD females OR (95% CI)
nof deaths (%)
Control males
nof deaths (%)
ASD males OR (95% CI)
nof deaths (%)
Neoplasms 1.83 (1.33–2.50) 1.79 (1.34–2.38)
2047 40 2446 48
(0.24) (0.47) (0.13) (0.26)
Endocrine 5.70* (3.25–9.99) 2.11 (0.94–4.73)
214 13 260 6
(0.03) (0.15) (0.01) (0.03)
Mental and behavioural disorders 2.53 (1.58–4.05) 3.31 (1.85–5.92)
614 18 311 12
(0.07) (0.21) (0.02) (0.06)
Nervous system 5.29 (3.50–7.99) 10.19* (7.27–14.29)
405 24 332 38
(0.05) (0.28) (0.02) (0.20)
Circulatory system 1.10 (0.86–1.40) 2.02*** (1.64–2.49)
5071 66 3749 91
(0.60) (0.78) (0.21) (0.49)
Respiratory system 3.24 (2.18–4.79) 2.16 (1.36–3.42)
692 26 659 19
(0.08) (0.31) (0.04) (0.10)
Digestive system 2.78 (1.52–5.07) 3.81 (2.31–6.29)
352 11 381 16
(0.04) (0.13) (0.02) (0.09)
Congenital malformations 33.86* (18.04–63.56) 11.07 (5.30–23.13)
38 13 68 8
(50.01) (0.15) (<0.01) (0.04)
Suicide 13.05** (8.73–19.50) 6.28 (4.79–8.23)
213 27 881 56
(0.03) (0.32) (0.05) (0.30)
External causes, other 2.32 (1.27–4.22) 1.44 (0.91–2.26)
445 11 1251 19
(0.05) (0.13) (0.07) (0.10)
Other 4.89 (2.39–9.99) 7.49 (3.46–16.21)
145 8 87 7
(0.02) (0.09) (<0.01) (0.04)
ASD, autism spectrum disorder; OR, odds ratio; CI, confidence interval.
a. Missing data on primary cause of (n= 2677, 50.5% in both groups) are not included in the analyses; partial likelihood ratio test for interaction effect (ASD gender).
*P50.05 (Endocrine P= 0.039; Nervous system P= 0.014; Congenital malformations P= 0.021); **P50.01 (Suicide P= 0.004); ***P50.001.
Hirvikoski et al
in, but not limited to, individuals with Asperger syndrome and a
history of depression.
31
In addition to psychiatric comorbidity,
individuals with high-functioning ASD may have psychological
vulnerability, such as social disengagement, which may increase
the risk of suicide.
32
Analysis of moderators and mediators of
suicidal behaviours in individuals with ASD is an important area
of future research, and should not only focus on risk factors but
also resilience. Individuals with ASD may lack many of the
protective factors that could decrease the risk of suicide, such as
a supportive social network,
32
good coping skills
33
and overall life
satisfaction.
34
The risk of suicide may also be reduced by
therapeutic and supportive contacts.
32
However, in individuals
with ASD, difficulties in social interaction and communication
(i.e. core symptoms of ASD) may seriously reduce the ability to
seek and receive help and treatment. This may not only apply to
help regarding psychological well-being but also somatic illness.
A large Swedish nationwide register-based study
35
has
indicated lower levels of somatic healthcare quality for psychiatric
patients than for the general population. Thus, higher avoidable
mortality
36
in psychiatric patients suggests that the medical care
for physical disorders provided to psychiatric patients is less
effective than in the general population. A recent systematic
review
30
stressed the public health and policy implications of
the substantial burden of ASD across the lifespan. Given that most
individuals living with ASD today are adults, the support and
interventions need to extend beyond paediatric and early
education. Similarly, our findings may indicate a continuous need
for improvement in public health and medical care for individuals
with ASD. For instance, on average, age at initial diagnosis in the
current sample was rather high in both low-functioning ASD and
high-functioning ASD groups, and the time interval between ASD
diagnosis and death was relatively short (3–5 years for overall
mortality, but under 3 years regarding suicide as cause of death).
However, the present study is unable to differentiate whether
increased mortality in ASD is because of shortcomings in care
provision, increased general biological vulnerability, or both.
Previous studies have reported higher mortality in females
with ASD than males with ASD.
15–20
Our results were in line with
the previous studies in the low-functioning ASD group. However,
we also observed opposite gender-specific mortality risk patterns
among individuals with low-functioning ASD compared with
high-functioning ASD. Among individuals with high-functioning
ASD, females had a somewhat lower mortality risk than males.
However, in the low-functioning ASD group, females had a higher
risk than males. Thus, in the entire ASD group, females with low-
functioning ASD seemed to be an especially vulnerable group in
which the mortality risk was nine times higher than in the general
population control group.
Strengths and limitations
The strengths of this population-based register study include
the large study population with high statistical power and the
good validity of Swedish registers.
22
Consequently, we had the
opportunity to analyse mortality even in less frequent causes of
death for both low-functioning ASD and high-functioning ASD,
as well as in both genders. Weaknesses of the present study include
exclusive reliance on the National Patient Register for case
ascertainment, leading to a selected and perhaps severely affected
sample by only including individuals with ASD who had been in
contact with clinical psychiatry services. This selection bias may be
particularly relevant for individuals diagnosed before the year
2001 (i.e. before contact with out-patient psychiatric care services
was included in the National Patient Register). However, after the
year 2001 (88.2% in current data) all individuals having received
an ASD diagnosis are registered in the National Patient Register
because of the diagnostic assessment per se, i.e. also in cases with
no further contact with psychiatric services. Another limitation is
that this study did not in detail examine comorbidity for other
ICD diagnoses than developmental intellectual disability.
Future studies may highlight the likely possibility of psychiatric
comorbidity moderating or mediating mortality in ASD. Finally,
the generalisability of the present study is limited by the fact that
healthcare is organised differently in different countries. Our
results may not be fully generalisable for countries with very
different healthcare systems.
Clinical implications
Our observation of excess cause-specific mortality in individuals
with ASD may signify a generally increased biological vulnerability
in ASD, as well as insufficient awareness, diagnoses and treatment
of comorbid diseases within the healthcare system. As the
mortality risk was increased for a number of different causes of
death, a better knowledge of ASD appears to be desirable in all
medical specialties. Health- and lifestyle-related issues may be a
future focus for interventions directed at individuals with ASD
and their significant others. Moreover, individuals with ASD
may need support in communicating their symptoms and
developing their skills in seeking help and treatment for problems
involving psychological well-being or somatic health.
In summary, we observed markedly increased premature
mortality in ASD owing to a multitude of medical conditions.
The risk was particularly high for females with low-functioning
ASD. However, individuals with high-functioning ASD had a high
risk for suicide. Adequate and coordinated medical care for
individuals with ASD and research into the phenomenon should
be a target for a considerably broader audience of medical
specialties than psychiatry and neurology.
Tatja Hirvikoski, PhD, Department of Women’s and Children’s Health, Pediatric
Neuropsychiatry Unit, Center for Neurodevelopmental Disorders at Karolinska
Institutet (KIND), Karolinska Institutet, Stockholm, Sweden and Habilitation and
Health, Stockholm County Council, Sweden; Ellenor Mittendorfer-Rutz, PhD,
Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska
Institutet, Stockholm, Sweden; Marcus Boman, BSc, Henrik Larsson, PhD,
Paul Lichtenstein, PhD, Department of Medical Epidemiology and Biostatistics,
Karolinska Institutet, Stockholm, Sweden; Sven Bo
¨lte, PhD, Department of Women’s
and Children’s Health, Pediatric Neuropsychiatry Unit, Center for Neurodevelopmental
Disorders at Karolinska Institutet (KIND), Karolinska Institutet, Stockholm and Division
of Child and Adolescent Psychiatry, Stockholm County Council, Sweden
Correspondence: Tatja Hirvikoski, PhD/Neuropsychologist, Center for
Neurodevelopmental Disorders at Karolinska Institutet (KIND), CAP Research
Center, Ga
¨vlegatan 22B, SE-11330 Stockholm, Sweden. Email:
Tatja.Hirvikoski@ki.se
First received 9 Nov 2014, final revision 22 Dec 2014, accepted 15 Jan 2015
Funding
The study was funded by the regional agreement on medical training and clinical research
(ALF) between Stockholm County Council and Karolinska Institutet (grants no. 20120419 and
20130630, Tatja Hirvikoski), Karolinska Institutet in cooperation with the Stockholm County
Council (KI/SLL, 2008:9, Sven Bo
¨lte), the Swedish Research Council (grant no. 523-2009-7054,
Sven Bo
¨lte) and the Swedish Research Council in cooperation with the Swedish Research
Council for Health, Working Life and Welfare, Vinnova and FORMAS (cross-disciplinary
research programme concerning children’s and youth’s mental health, grant no.
259-2012-24, Sven Bo
¨lte).
Acknowledgements
We express our gratitude to psychiatrist Berit Lagerheim for providing us with an overview
of Swedish clinical practice from 1980s onwards in diagnostic assessment of ASD and
other neurodevelopmental disorders. We would also thank MD/Professor in psychiatry Jussi
Jokinen for information on clinical aspects of ICD causes of death codes registration.
6
Mortality in autism spectrum disorders
Appendix
ICD-10 chapters and codes used as a basis for
categorisation of causes of death in current study
Chapter I: Infections (ICD codes A00-B99)
Chapter II: Neoplasms (C00-D48)
Chapter IV: Endocrine, nutritional and metabolic diseases (E00-E99)
Chapter V: Mental and behavioural disorders (F00-F99)
Chapter VI: Diseases of the nervous system (G00-G99)
Chapter IX: Diseases of the circulatory system (I00-I99)
Chapter X: Diseases of the respiratory system (J00-J99)
Chapter XI: Diseases of the digestive system (K00-K99)
Chapter XIV: Diseases of the genitourinary system (N00-N99)
Chapter XVII: Congenital malformations (Q00-Q99)
Chapter XVIII: Symptoms, signs, and abnormal findings not elsewhere
classified (R00-R99)
Chapter XX: External causes of morbidity and mortality (V01-Y98)
Other causes of death
: In this category, we included chapters with only a
few cases chapter III (D50-D89, diseases of the blood and blood-forming
organs and certain disorders involving the immune mechanism); chapter
VII (H00-H59, diseases of the eye and adnexa); chapter VIII (H60-H95,
diseases of the ear and mastoid process); chapter XII (L00-L99, diseases
of the skin and subcutaneous tissue); chapter XIII (M00-M99, diseases of
the musculoskeletal system and connective tissue); chapter XV (O00-O99,
pregnancy, childbirth and/or obstetric causes); chapter XVI (P00-P96, certain
conditions originating in the perinatal period).
References
1Billstedt E, Gillberg IC, Gillberg C. Autism after adolescence: population-based
13- to 22-year follow-up study of 120 individuals with autism diagnosed in
childhood. J Autism Dev Disord 2005; 35: 351–60.
2Howlin P, Moss P, Savage S, Rutter M. Social outcomes in mid- to later
adulthood among individuals diagnosed with autism and average nonverbal
IQ as children. J Am Acad Child Adolesc Psychiatry 2013; 52: 572–81.
3Pinborough-Zimmerman J, Bakian AV, Fombonne E, Bilder D, Taylor J,
McMahon WM. Changes in the administrative prevalence of autism spectrum
disorders: contribution of special education and health from 2002–2008.
J Autism Dev Disord 2012; 42: 521–30.
4Wazana A, Bresnahan M, Kline J. The autism epidemic: fact or artifact?
J Am Acad Child Adolesc Psychiatry 2007; 46: 721–30.
5Cederlund M, Hagberg B, Billstedt E, Gillberg IC, Gillberg C. Asperger
syndrome and autism: a comparative longitudinal follow-up study more than
5 years after original diagnosis. J Autism Dev Disord 2008; 38: 72–85.
6Howlin P, Goode S, Hutton J, Rutter M. Adult outcome for children with
autism. J Child Psychol Psychiatry 2004; 45: 212–29.
7Gillberg C, Steffenburg S. Outcome and prognostic factors in infantile autism
and similar conditions: a population-based study of 46 cases followed
through puberty. J Autism Dev Disord 1987; 17: 273–87.
8Bo
¨lte S, de Schipper E, Robison JE, Wong VC, Selb M, Singhal N, et al.
Classification of functioning and impairment: the development of ICF core
sets for autism spectrum disorder. Autism Res 2014; 7: 167–72.
9Caamano M, Boada L, Merchan-Naranjo J, Moreno C, Llorente C, Moreno D,
et al. Psychopathology in children and adolescents with ASD without mental
retardation. J Autism Dev Disord 2013; 43: 2442–9.
10 Hofvander B, Delorme R, Chaste P, Nyden A, Wentz E, Stahlberg O, et al.
Psychiatric and psychosocial problems in adults with normal-intelligence
autism spectrum disorders. BMC Psychiatry 2009; 9: 35.
11 Lichtenstein P, Carlstrom E, Rastam M, Gillberg C, Anckarsater H. The
genetics of autism spectrum disorders and related neuropsychiatric
disorders in childhood. Am J Psychiatry 2010; 167: 1357–63.
12 Lugnegard T, Hallerback MU, Gillberg C. Psychiatric comorbidity in young
adults with a clinical diagnosis of Asperger syndrome. Res Dev Disabil 2011;
32: 1910–7.
13 Skokauskas N, Gallagher L. Psychosis, affective disorders and anxiety in
autistic spectrum disorder: prevalence and nosological considerations.
Psychopathology 2010; 43: 8–16.
14 Persico AM, Napolioni V. Autism genetics. Behav Brain Res 2013; 251:
95–112.
15 Gillberg C, Billstedt E, Sundh V, Gillberg IC. Mortality in autism: a prospective
longitudinal community-based study. J Autism Dev Disord 2010; 40: 352–7.
16 Isager T, Mouridsen SE, Rich B. Mortality and causes of death in pervasive
developmental disorders. Autism 1999; 3: 7–16.
17 Mouridsen SE, Bronnum-Hansen H, Rich B, Isager T. Mortality and causes of
death in autism spectrum disorders: an update. Autism 2008; 12: 403–14.
18 Pickett JA, Paculdo DR, Shavelle RM, Strauss DJ. 1998–2002 update on
ˆCauses of death in autism¤. J Autism Dev Disord 2006; 36: 287–8.
19 Shavelle RM, Strauss DJ, Pickett J. Causes of death in autism. J Autism Dev
Disord 2001; 31: 569–76.
20 Bilder D, Botts EL, Smith KR, Pimentel R, Farley M, Viskochil J, et al. Excess
mortality and causes of death in autism spectrum disorders: a follow up of
the 1980s Utah/UCLA autism epidemiologic study. J Autism Dev Disord 2013;
43: 1196–204.
21 Woolfenden S, Sarkozy V, Ridley G, Coory M, Williams K. A systematic review
of two outcomes in autism spectrum disorder – epilepsy and mortality. Dev
Med Child Neurol 2012; 54: 306–12.
22 Idring S, Rai D, Dal H, Dalman C, Sturm H, Zander E, et al. Autism spectrum
disorders in the Stockholm Youth Cohort: design, prevalence and validity.
PLoS ONE 2012; 7: e41280.
23 World Health Organization. ICD-9: International Statistical Classification of
Diseases and Related Health Problems. WHO, 1978.
24 World Health Organization. ICD-10: The ICD-10 Classification of Mental and
Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. WHO,
1992.
25 American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders, 5th edn (DSM-5). APA, 2013.
26 Idring S, Magnusson C, Lundberg M, Ek M, Rai D, Svensson AC, et al. Parental
age and the risk of autism spectrum disorders: findings from a Swedish
population-based cohort. Int J Epidemiol 2014; 43: 107–15.
27 Magnusson C, Rai D, Goodman A, Lundberg M, Idring S, Svensson A,
et al. Migration and autism spectrum disorder: population-based study.
Br J Psychiatry 2012; 201: 109–15.
28 Lager A, Berlin M, Heimerson I, Danielsson M. Young people’s health: Health
in Sweden: The National Public Health Report 2012. Chapter 3. Scand J Public
Health 2012; 40: 42–71.
29 Mittendorfer-Rutz E, Rasmussen F, Wasserman D. Restricted fetal growth
and adverse maternal psychosocial and socioeconomic conditions as risk
factors for suicidal behaviour of offspring: a cohort study. Lancet 2004; 364:
1135–40.
30 Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T, Scott JG. The
epidemiology and global burden of autism spectrum disorders. Psychol Med
2014: 11: 1–13.
31 Cassidy S, Bradley P, Robinson J, Allison C, McHugh M, Baron-Cohen S.
Suicidal ideation and suicide plans or attempts in adults with Asperger’s
syndrome attending a specialist diagnostic clinic: a clinical cohort study.
Lancet Psychiatry 2014; 1: 142–7.
32 Fowler JC. Suicide risk assessment in clinical practice: pragmatic guidelines
for imperfect assessments. Psychotherapy 2012; 49: 81–90.
33 Oquendo MA, Dragatsi D, Harkavy-Friedman J, Dervic K, Currier D, Burke AK,
et al. Protective factors against suicidal behavior in Latinos. J Nerv Ment Dis
2005; 193: 438–43.
34 Chioqueta AP, Stiles TC. The relationship between psychological buffers,
hopelessness, and suicidal ideation: identification of protective factors.
Crisis 2007; 28: 67–73.
35 Bjorkenstam E, Ljung R, Burstrom B, Mittendorfer-Rutz E, Hallqvist J,
Weitoft GR. Quality of medical care and excess mortality in psychiatric
patients – a nationwide register-based study in Sweden. BMJ Open 2012;
2: e000778.
36 Rutstein DD, Berenberg W, Chalmers TC, Child CG, III, Fishman AP, Perrin EB.
Measuring the quality of medical care. A clinical method. N Engl J Med 1976;
294: 582–8.
7
Hirvikoski et al. Premature mortality in autism spectrum disorder. Br J Psychiatry (doi:
10.1192/bjp.bp.114.160192)
Table DS1.Three most common subcategories of specific causes of death(not specified if <5
individuals in the ASD groups).
Controls
ASD
HF ASD
Neoplasms
(C00-D48)
Neoplasm of
bronchus and
lung
; prostate;
breast
Neoplasm of breast
Neoplasm of
pancreas
Mesothelioma
Neoplasm of
pancreas
Mesothelioma
Nervous
system (G00-
G99)
Stroke
Alzheimer's
disease
Systemic
atrophies
Epilepsy
Epilepsy
Stroke
Circulatory
(I00-I99)
Ischemic
heart diseases
Heart failure
Atrial
fibrillation
and flutter
Ischemic heart
diseases
diseases
Ischemic heart
diseases
Respiratory
(J00-J99)
Pneumonia
Chronic
obstructive
pulmonary
disease
Emphysema
Pneumonia
Chronic obstructive
pulmonary disease
Pneumonia
Chronic
obstructive
pulmonary
disease
10.1192/bjp.bp.114.160192
published online November 5, 2015 Access the most recent version at DOI: BJP
Bölte
Tatja Hirvikoski, Ellenor Mittendorfer-Rutz, Marcus Boman, Henrik Larsson, Paul Lichtenstein and Sven
Premature mortality in autism spectrum disorder
Material
Supplementary http://bjp.rcpsych.org/content/suppl/2015/10/26/bjp.bp.114.160192.DC1.html
Supplementary material can be found at:
References http://bjp.rcpsych.org/content/early/2015/10/22/bjp.bp.114.160192#BIBL
This article cites 0 articles, 0 of which you can access for free at:
permissions
Reprints/ permissions@rcpsych.ac.ukwrite to
To obtain reprints or permission to reproduce material from this paper, please
P<P Published online 2015-11-05T00:05:17-08:00 in advance of the print journal.
to this article at
You can respond /letters/submit/bjprcpsych;bjp.bp.114.160192v1
from
Downloaded The Royal College of PsychiatristsPublished by on November 10, 2015http://bjp.rcpsych.org/
digital object identifier (DOIs) and date of initial publication. theindexed by PubMed from initial publication. Citations to Advance online articles must include
final publication). Advance online articles are citable and establish publication priority; they are
appeared in the paper journal (edited, typeset versions may be posted when available prior to
Advance online articles have been peer reviewed and accepted for publication but have not yet
http://bjp.rcpsych.org/site/subscriptions/ go to: The British Journal of PsychiatryTo subscribe to
... Suicide has a significant impact on individuals, families, and society; in Australia suicide and the associated mental health impacts cost the economy in excess of AUD $51 billion annually (Productivity Commission, 2019). Compared to people in the general population, people with a diagnosis of Autism Spectrum Disorder (ASD; henceforth 'autism') 1 are at increased risk of suicide behaviour, including thoughts of suicide (ideation), planning for suicide, non-fatal suicide attempt, and death by suicide Hirvikoski et al., 2016;Kirby et al., 2019). In this chapter we provide a detailed overview of the current knowledge concerning suicide behaviour in autistic people, ...
... There is robust evidence of increased risk of suicidal behaviour in the autistic population, with suicide rates ranging from 0.17% to 0.4% (Hirvikoski et al., 2016;Kirby et al., 2019;Kõlves et al., 2021). In a large population-based study from Sweden, Hirvikoski et al. (2016) reported a sevenfold increased risk of premature death by suicide amongst autistic people compared to the general population. ...
... There is robust evidence of increased risk of suicidal behaviour in the autistic population, with suicide rates ranging from 0.17% to 0.4% (Hirvikoski et al., 2016;Kirby et al., 2019;Kõlves et al., 2021). In a large population-based study from Sweden, Hirvikoski et al. (2016) reported a sevenfold increased risk of premature death by suicide amongst autistic people compared to the general population. In a large cohort study from Denmark, Kõlves et al. (2021) reported a 3-fold higher rate of both suicide attempt and suicide in the autistic sample. ...
Chapter
Full-text available
People who are diagnosed with Autism Spectrum Disorder (ASD) are at increased risk of suicidal behaviour compared to the general population; recent population-based studies demonstrate a three- to sevenfold increased risk of premature death by suicide. This chapter provides an overview of: (a) the current literature regarding risk and prevalence of suicide behaviour in autism; (b) the role of intellectual disability/intellectual developmental disorder in suicide in autism; (c) correlates, risk and protective factors; (d) dimensional constructs of suicide, including autistic traits; (e) current approaches to suicide assessment, including potential modifications; and (f) suicide prevention and service access. We consider these topics by drawing on state-of-the-art research, the perspective of lived experience, and consideration of the potential impacts of major events such as the coronavirus (COVID-19) pandemic.
... Even modest weight gain after the age of 18 years increases the risk of coronary heart disease and type 2 diabetes mellitus irrespective of initial bodyweight 13 . Autism spectrum disorder is associated with reduced life expectancy and premature mortality [14][15][16] . The standardized mortality ratio for circulatory causes of death in a cohort of individuals with ASD from California compared to the general population is 2.3 15 . ...
... The standardized mortality ratio for circulatory causes of death in a cohort of individuals with ASD from California compared to the general population is 2.3 15 . Similarly, the risk of death due to a circulatory cause was increased by 1.5 times in individuals with ASD in a Swedish population study 16 . While the cause of excess mortality remains unknown, the health conditions associated with excess bodyweight including cardiovascular disease, the leading cause of death in the United States (U.S.) 17 , are likely major contributors. ...
Article
Full-text available
Adults with autism spectrum disorder (ASD) are at risk for excess bodyweight and hypertension, yet the prevalence of and clinical predictors for these health conditions remain unknown. The objective of this study was to assess the prevalence of overweight, obesity, and hypertension in a large clinical sample of adults with a confirmed diagnosis of ASD and to examine potential clinical predictors. This retrospective chart review study included adult subjects (≥ 20 years) with ASD who had been seen within the past 5 years at a multidisciplinary developmental disorders clinic. Data collected from the electronic health record included age, sex, race and ethnicity, cognitive ability, language ability, body mass index (BMI), hypertension, and use of second generation antipsychotic medications (SGAs). Of 622 adults with a confirmed diagnosis of ASD potentially eligible for the study, 483 (78%) had one or more notes in their records from the past 5 years. Those with recent notes were 23% female, 89% White, and had a mean (SD) age of 28.1 (7.1) years. Overall prevalence estimates for adults represented by this predominantly male, White, and young clinical sample were 28% (95% CI 24%, 32%) for overweight (BMI 25–29.9 kg/m2), 35% (95% CI 31%, 40%) for obesity (≥ 30 kg/m2), and 11% (95% CI 9%, 15%) for hypertension. Controlling for age and sex, intellectual disability (ID) was significantly associated with BMI (p = 0.003) but not hypertension (p = 0.69); those with moderate or more severe ID had a mean BMI that was 2.26 kg/m2 (95% CI 0.96, 3.57) lower than those with no ID. Controlling for age and sex, neither language ability, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) subtype of autism, nor past or current use of SGAs were significantly associated with BMI or hypertension. The study identified a high prevalence of overweight and obesity in adults with ASD consistent with the prevalence of these medical comorbidities in the U.S. population.
... 5 Autistic people have a two to three decades' decreased life expectancy and heightened all-cause and injury mortality. 6 Atypical eating behaviours are common in those with ASC, with the most frequent being limited food preferences, food texture hypersensitivity, pica, and other unusual patterns, such as eating only one brand of food. Atypical eating behaviours are more common in ASC than in other developmental disabilities and occurrence may be as high as 70.5%. ...
... Kõlves et al. (2021) also found higher rates of suicide attempt and suicide among those with highfunctioning ASD only. This finding is consistent with other studies (see Hirvikoski et al., 2016Hirvikoski et al., , 2020Lai et al., 2011). ...
Article
Julian Assange is an Australian national and the founder of WikiLeaks, a nonprofit organization that publishes news leaks and classified information provided by anonymous whistle-blowers. In May 2019, a United States federal grand jury returned an 18-count criminal indictment against Assange. If convicted, Assange could face up to 10 years of incarceration for each Espionage Act (1917) charge and up to 5 years for conspiracy to access a government computer network. Due to Assange’s current physical location in the United Kingdom, the United States has requested extradition. However, to date, there has been limited scholarly discussion of the relationship between Assange’s autism spectrum disorder (ASD) diagnosis and his potential extradition and lengthy pretrial or postconviction imprisonment in the United States. This article explores the psychiatric submissions from Assange and the United States in light of available evidence on ASD and the risk of suicide among people who are imprisoned. The analysis will focus on common misperceptions about ASD, the particularly detrimental impacts of the prison environment on individuals with ASD, the varying opinions of Assange’s ASD diagnosis, and the importance of considering Assange’s risk of suicide in the context of ASD. From a human rights and individual fairness perspective, a complete understanding of the significance of these issues which does not minimize a diagnosis of ASD is paramount for Assange and any future case with similar elements.
... Only about a quarter of the individuals with autism and an average intelligence level live independently in the US, while the rest remain with their families to late adulthood or beyond [9]. Premature mortality in individuals with ASD and ID is higher than those without ID [10,11]. Therefore, low cognition function affects ASD symptoms and reduces the quality of life of these individuals. ...
Article
Full-text available
Background Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. Methods We enrolled 1019 ASD preschoolers aged 2–7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. Results Based on general developmental quotient (GQ) < 70, 68.4% of the preschoolers with ASD had a developmental delay (DD), rated mild in 32.7% of them. The highest DD rate (> 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55–69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. Conclusions Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. Trial registration ChiCTR2000031194, registered on 03/23/2020.
... Most epidemiological studies report an overabundance of metabolic comorbidities, often secondary to obesity and a sedentary lifestyle . Less is known for adult long-term health and for the causes of elevated mortality, that are sadly seen in this population (Hirvikoski et al. 2016). Social and psychogenic causes (e.g., elevated anxiety or reduced access to medical assistance) are difficult to disentangle from an underlying endocrine pathology. ...
Thesis
Autism is a neurodevelopmental condition that is more frequently diagnosed in males than females. To explain this, in 2014, the prenatal sex steroid theory was proposed. This extended the fetal testosterone theory, published in 2004. The prenatal sex steroid theory proposes that exposure to higher levels of prenatal sex steroids (e.g., prenatal androgens and estrogens) that are on average higher in male fetuses are associated with higher likelihood for autism and elevated autistic traits. This background literature is reported in Chapter 1. In this thesis, eight novel studies are reported that test and extend the prenatal sex steroid theory by investigating perinatal factors related to sex differences in physiology. Study 1 (described in Chapter 2) reports a case-control analysis of steroid levels in the amniotic fluid of males who were later diagnosed as autistic, linked with the Danish Biobank (n = 98 cases, n = 177 controls). This included univariate analyses of both prenatal androgens and estrogens, as well as the aromatisation ratio. All estrogens, but not testosterone, on average were elevated in autistic males. Study 2 (described in Chapter 3) reports a prospective cohort study (the Cambridge Ultrasound and Pregnancy [CUSP] study) of pregnant women and their infants in Cambridge (n=219), who were assessed for their autistic traits during pregnancy and late infancy. Steroid hormone levels were assessed in maternal serum. Estradiol levels correlated with both maternal autistic traits and the male infants’ autistic traits, but there was no correlation with female infants’ autistic traits. Study 3 (described in Chapter 4) reports a large prospective cohort study in Rotterdam (Generation-R) that studied the levels of placental function markers in maternal serum (n=3469), their sex differences in the general population, their association with both autistic traits in childhood (assessed using the Social Responsiveness Scale - SRS), and with likelihood for autism in males. Male-like patterns in placental angiogenic markers, high placental growth factor (PlGF) and low soluble fms-like tyrosine kinase-1 (sFlt-1) levels, respectively correlated with higher autistic traits in females and an autism diagnosis in males. Chapter 5 describes Studies 4, 5, and 6, all based on a longitudinal cohort, the Cambridge Human Infant Longitudinal Development [CHILD] Study. This included prenatal (n=41) and postnatal (n=27) brain MRI imaging and salivary testosterone measurements during mini-puberty. Study 4 found that both male and female infants experienced transient increases in testosterone postnatally (2 to 6 months), but this did not correlate to their autistic traits at 18 months. Study 5 focused on total brain volume and surface area in infancy, as well as rate of brain growth perinatally, all of which correlated negatively with the infant’s autistic traits. Study 6 found that this was driven by low volume in regions that show sex differences and are involved in face recognition. Chapter 6 describes two genetic studies, which found that autism-related genetic variance (rare and common variance respectively) overlaps with X-linked genes that show sex differences in the placenta (Study 7) and correlates with the genetics for early age of menarche (Study 8). Chapter 7 brings all of the findings from Studies 1 to 8 together to draw conclusions and consider limitations and future directions. Based on these analyses, I then propose a new theory on the role of the placenta in mediating sex differences in human perinatal development and autism.
... We find it particularly surprising that the mortality studies published over the past few years received very little attention in recommendations for clinical research. [54][55][56][57][58] We need clinical research to tackle the problem of harmful pseudoscientific treatments, mapping their use and effects on mental and physical health, as well as improving awareness among clinicians and carers. 59 We need more research on assisted and augmented communication and supported decision making in the context of clinical work and care. ...
Article
‘Neurodiversity’ is a term used to describe people with neurological variation; this includes people with autism, dyspraxia, dyslexia and attention deficit hyperactivity disorder. Studies have shown an increased prevalence of malocclusion and dental trauma in people with these conditions. Unfortunately, a lack of understanding around such neurological differences can create barriers when accessing orthodontic care. The aim of this article is to raise awareness around the subject and to suggest reasonable adjustments to practice which may subsequently be used by the orthodontic team to improve the patient experience. CPD/Clinical Relevance: Recognition of neurodiversity and the need to make reasonable adjustments to orthodontic care may aid compliance and improve outcomes in this group of patients.
Article
Autism spectrum disorder (ASD) is an increasingly prevalent diagnosis characterized by impairment of social communication and behavioral regulation. Children with ASD seek care more frequently in the emergency department (ED) than their neurotypical peers and the approach to medical evaluation of this population requires heightened attention to a variety of factors. Communication with caregivers, attention to environmental stimulation, identification of accommodation needs, and understanding frequently associated medical conditions are important considerations in ED encounters. Gastrointestinal problems, seizure disorders, and metabolic disease are common causes for ED presentation in children with ASD. A high index of suspicion for underlying medical issues must be maintained, even when children with ASD present primarily for behavioral concerns. Autism spectrum disorder (ASD) is an increasingly prevalent diagnosis characterized by impairment of social communication and behavioral regulation. Children with ASD seek care more frequently in the emergency department (ED) than their neurotypical peers and the approach to medical evaluation of this population requires heightened attention to a variety of factors. Communication with caregivers, attention to environmental stimulation, identification of accommodation needs, and understanding frequently associated medical conditions are important considerations in ED encounters. Gastrointestinal problems, seizure disorders, and metabolic disease are common causes for ED presentation in children with ASD. A high index of suspicion for underlying medical issues must be maintained, even when children with ASD present primarily for behavioral concerns.
Article
Full-text available
Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.
Article
Full-text available
Background: Asperger’s syndrome in adulthood is frequently associated with depression, but few studies have explored the lifetime experience of self-reported suicidal ideation and suicide plans or attempts in this clinical group. We aimed to assess this prevalence in a clinical cohort of patients in the UK. Method: In a clinical cohort study, we undertook a retrospective analysis of clinical survey data from adults newly diagnosed with Asperger’s syndrome at a specialist diagnostic clinic between Jan 23, 2004, and July 8, 2013, in England. Patients completed a self-report questionnaire before clinical assessment, recording lifetime experience of depression, suicidal ideation, and suicide plans or attempts, along with self-reported measures of autistic traits and empathy. We compared the rate of suicidal ideation in the sample with published rates of suicidal ideation in the general population and other clinical groups. We also assessed associations between depression, autistic traits, empathy, and likelihood of suicidal ideation and suicide plans or attempts. Findings: 374 adults (256 men and 118 women) were diagnosed with Asperger’s syndrome in the study period. 243 (66%) of 367 respondents self-reported suicidal ideation, 127 (35%) of 365 respondents self-reported plans or attempts at suicide, and 116 (31%) of 368 respondents self-reported depression. Adults with Asperger’s syndrome were significantly more likely to report lifetime experience of suicidal ideation than were individuals from a general UK population sample (odds ratio 9•6 [95% CI 7•6–11•9], p<0•0001), people with one, two, or more medical illnesses (p<0•0001), or people with psychotic illness (p=0•019). Compared with people diagnosed with Asperger’s syndrome without depression, people with Asperger’s syndrome and depression were more likely to report suicidal ideation (p<0•0001) and suicide plans or attempts (p<0•0001). Interpretation: Our findings lend support to anecdotal reports of increased rates of suicidal ideation in adults with Asperger’s syndrome, and depression as an important potential risk factor for suicidality in adults with this condition. Because adults with Asperger’s syndrome often have many risk factors for secondary depression (e.g., social isolation or exclusion, and unemployment), our findings emphasise the need for appropriate service planning and support to reduce risk in this clinical group.
Article
Full-text available
The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID). The sample consisted of 417 303 Swedish children born 1984-2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD. Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63-1.89] at ages 40-45. For fathers, compared with the median age of 32 years, the OR for ages 55-59 was 1.39 (1.29-1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40-45 (≥97.2th percentile) had an estimated 18.63 (95% CI: 17.25-20.01) ASD cases per 1000 births, whereas fathers aged 55-59 (≥99.7th percentile) had 16.35 (95% CI: 15.11-17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers ≤35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID. We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.
Article
Full-text available
Given the variability seen in Autism Spectrum Disorder (ASD), accurate quantification of functioning is vital to studying outcome and quality of life in affected individuals. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive, universally accepted framework for the description of health-related functioning. ICF Core Sets are shortlists of ICF categories that are selected to capture those aspects of functioning that are most relevant when describing a person with a specific condition. In this paper, the authors preview the process for developing ICF Core Sets for ASD, a collaboration with the World Health Organization and the ICF Research Branch. The ICF Children and Youth version (ICF-CY) was derived from the ICF and designed to capture the specific situation of the developing child. As ASD affects individuals throughout the life span, and the ICF-CY includes all ICF categories, the ICF-CY will be used in this project ("ICF(-CY)" from now on). The ICF(-CY) categories to be included in the ICF Core Sets for ASD will be determined at an ICF Core Set Consensus Conference, where evidence from four preparatory studies (a systematic review, an expert survey, a patient and caregiver qualitative study, and a clinical cross-sectional study) will be integrated. Comprehensive and Brief ICF Core Sets for ASD will be developed with the goal of providing useful standards for research and clinical practice and generating a common language for functioning and impairment in ASD in different areas of life and across the life span. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Article
Full-text available
The present chapter discusses trends in public health among 16-24-year-olds - young people who are poised precariously between childhood and adulthood. The group includes upper-secondary school pupils and young people who have gone on to higher education or work. Along with the rest of the population, young people have benefited from the development of postwar health and welfare policies and programs. Since the 1990s, however, the health of young people - particularly their mental health - has not shown the same general improvement as that of other age groups. Since health status surveys began at the end of the 1980s, the proportion of young people aged 16-24 who suffer from anxiousness, nervousness and anxiety (angst) has increased. In 1988-1989, 9 per cent of women and 4 per cent of men reported experiencing feelings of anxiousness, nervousness or anxiety. In 2004-2005, the percentage had risen to 30 per cent among women and 14 per cent among men. This increase not only subsumes self-reported complaints such as anxiousness, nervousness and anxiety; it has also become more common for young people to be hospitalised with depression and states of anxiety. The percentage of 20-24-year-old men and women who were hospitalised with depression more than doubled between 1990 and 2010, and in the 16-19 age group, hospitalisation have become eight times as frequent among women and four times among men. Hospitalisation as a result of suicide attempts or other self-destructive behaviour rose significantly among women 16-24-year-olds from the beginning of the 1990s until 2007, but has since declined. Although the number of suicide attempts was also rising among young men, twice as many women as men are hospitalised for suicide attempts in 2010. Accidents and suicides are the most common causes of death among young people. Approximately a quarter of all women and men who died between the ages of 16 and 24 committed suicide, while 27 per cent of women and 40 per cent of men died in accidents. Suicide among young people was more frequent in the 1970s than in the 1990s. Suicide is twice as frequent among men as women. In the last decade, the number of suicides has declined in several age groups. However, this does not apply to young women and men. Rather, the tendency appears to be towards a slight increase in the number of suicides in this age group. However, it is difficult to assess the trend in suicides among young people in view of the relatively small number of cases and the fairly large 'random' variations from one year to the next. Although suicide is a frequent cause of death among people aged 16-24, it is less common than in older age groups. According to self-reported data, alcohol consumption among 15-16-year-old girls and boys rose in the second half of the 1990s. However, it has declined in recent years. Alcohol consumption among upper-secondary school pupils has declined among men, and is largely unchanged among women. More young people are being hospitalised with alcohol poisoning today than at the beginning of the 1990s. Hospitalisation for this condition has since increased more among women than men, and is now equally common in both sexes. The number of alcohol-related deaths among men has also risen in the 2000s. The figures for women, however, have remained unchanged. It has also become more common for young people to be hospitalised for narcotic drug use. Deaths caused by drug abuse also increased significantly in the 1990s, particularly among men, but have declined in the 2000s. Significantly more men than women are hospitalised or die as a result of drug abuse. The overall rise in the number of deaths caused by accidents or by alcohol and narcotics abuse together with a small increase in the number of suicides have led to a slight increase in the mortality rate among men aged 16-24 since the mid-1990s. But deaths among young people are still uncommon; an average of approximately 120 women and 300 men in the 16-24 age group die each year. Significantly more women than men feel they suffer from impaired mental wellbeing. The disparities are greatest among young people aged 16-19. Of these, 29 per cent of young women and 7 per cent of young men reported having problems with anxiousness, nervousness and anxiety in 2004-2005. Impaired mental wellbeing is on the increase in every category of young people, irrespective of family circumstances, country of birth, labour market status, parents' socioeconomic status, etc. However, the increase varies in size from group to group, and in the severity of the complaint. Among 16-19-year-olds, anxiousness, nervousness and anxiety occur most frequently among people who neither study nor work. However, this is a relatively small group. Most young people in this category study. What has mainly accounted for the increase in the number of complaints in this age group over the past 20 years is the threefold rise in the number of problems among female teenage school pupils. The growing prevalence of anxiousness, nervousness and anxiety has been most evident in the 20-24 age group, with women students being the most commonly affected. However, a significantly growing number of male students also suffer from these problems. Women aged between 20 and 24 and men who are largely gainfully employed have fewer issues than students. It is unclear why mental health issues have become more frequent among young people. The fact that living conditions for young people have changed considerably may be one explanation. At present, the number of full-time job opportunities for compulsory and upper-secondary school leavers is significantly lower than it was 20 years ago. Many may be pursuing further studies although they would prefer to work. Moreover, those that do find jobs face poorer working conditions. While more young people are studying compared with earlier generations, many more are also inactive, i.e. they neither work, study, do military service nor work in the home. However, it is unclear how these changes are affecting people's mental health. It is also unclear why the gender disparities are so significant and why they are greater in the 16-19 age group than among 20-24-year-olds.
Article
Background: Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs. Method: A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010. Results: In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000. Conclusions: ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.
Article
In the present study, we rediagnosed and followed a clinical sample of 341 children with related pervasive developmental disorders for an average of 24 years (current mean age of 31 years; range 14-48 years). Twelve patients had died. For the whole group crude mortality was 3.5 percent (95 percent Confidence Interval 1.8-6.1 percent). The standardized mortality ratio was 1.9 (95 percent Confidence Interval 1.0-3.4). For the diagnostic subgroups crude mortality was: infantile autism 3.4 percent, autistic-like conditions 3.4 percent, borderline childhood psychosis 2.5 percent and disintegrative psychosis 15.4 percent. Mortality was related to intelligence in a U-shaped fashion, with both severe retardation and normal intelligence being associated with a relatively high risk of death. The distribution between natural causes and unnatural causes of death (accidents, suicide) resembled the pattern seen in a background population of adolescents and younger adults. Five of the 12 deaths were related to epilepsy.
Article
Objective: To describe current social functioning in a clinical sample of 60 adults with autism (mean age = 44 years) who were all of average nonverbal IQ (70+) when first diagnosed (mean age = 6.75 years). Method: Outcome measures included standardized diagnostic and cognitive assessments and questionnaires on social functioning. Child and adult variables related to current outcomes were explored. Results: All individuals continued to meet criteria for autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R), but severity of autism symptoms declined over time. Nevertheless, only 10 individuals (17%) were rated as having a "good" or "very good" outcome; the majority (60%) were assessed as having "poor" or "very poor" outcomes. The strongest predictor of adult outcome was the Reciprocal Social Interaction domain score on the ADI at diagnostic confirmation. Change over time was further examined in a subgroup (n = 44) previously assessed 20 years ago earlier (mean age = 26 years). Although severity of autism had continued to decrease during the adult period, social outcomes were poorer than in younger adulthood. Conclusions: In this cohort of adults first diagnosed with autism, on average, 37 years previously, social inclusion remains very limited, despite general improvements in autism symptomatology with age. Whether these findings will be replicated in future generations of children with autism, who now have the benefits of earlier diagnosis and wider access to specialist provision, needs to be the focus of further longitudinal research.
Article
This study analyzes subclinical psychopathology in children and adolescents with autism spectrum disorders (ASD) without mental retardation with no comorbid disorder, assessed by an extensive general psychopathology interview. The K-SADS-PL was administered to a group of 25 patients with ASD (mean age = 12.80 ± 2.86 years) and 25 healthy controls (mean age 12.52 ± 2.86 years). Significant differences were found between patients with ASD and controls for the domains of: depressive disorder, anxiety separation disorder, agoraphobia and specific phobias, obsessive compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). In patients without a comorbid disorder, we found a profile of subclinical disturbances that suggest high risk for comorbid psychiatric conditions derived from the presence of subthreshold symptomatology.
Article
This study's purpose was to investigate mortality among individuals with autism spectrum disorders (ASD) ascertained during a 1980s statewide autism prevalence study (n = 305) in relation to controls. Twenty-nine of these individuals (9.5 %) died by the time of follow up, representing a hazard rate ratio of 9.9 (95 % CI 5.7-17.2) in relation to population controls. Death certificates identified respiratory, cardiac, and epileptic events as the most common causes of death. The elevated mortality risk associated with ASD in the study cohort appeared related to the presence of comorbid medical conditions and intellectual disability rather than ASD itself suggesting the importance of coordinated medical care for this high risk sub-population of individuals with ASD.