Supplementary Information
We also studied a subsample of the total Swedish population, the Stockholm Youth Cohort
(SYC), for which ascertainment of ASD is based on national register data in addition to
regional register data from outpatient, specialist, and treatment centers in Stockholm County.
Consequently, while the total Swedish population sample is substantially larger, the SYC
subsample has better ASD ascertainment and subtype information regarding comorbid ID.
ASD case status as of December 31, 2011 was ascertained according to a validated casefinding approach covering all pathways to ASD diagnosis and care in Stockholm County,
described in detail elsewhere.1 In brief, ASD case status was described following ICD-9: 299,
ICD-10: F84, and DSM-IV: 299 classifications using: 1) the NPR; and regional registers
including; 2) the Habilitation Register; 3) the Clinical Database for Child and Adolescent
Psychiatry; 4) the VAL database recording all inpatient and outpatient health services usage
in Stockholm County since 1997. The presence of comorbid intellectual disability was based
on ICD-9: 317–319, ICD-10: F70–F79, and DSM-IV: 317–319 classifications and
supplemented with the Habilitation Register, which categorizes service recipients as having
autism with or without ID. Expert review of medical records for 177 ASD cases indicated that
96% were consistent with a diagnosis of ASD.1
The final SYC subsample consisted of 9 545 cases (2 361 with ID) matched to 80 986
controls (20 461 matched to an ID case), with case:control ratio varying from 1:2 to 1:10
(Supplementary Figure 1, Supplementary Table 1).
Statistical analysis
For the SYC sub-cohort, the outcome variable was stratified as ASD with and without ID and
the analyses (Models 1-3, as described in the main text) were repeated.
Results
In the SYC subsample, maternal diagnosis of PCOS was associated with higher odds of
ASD in the unadjusted model, though ORs were attenuated and confidence intervals
included one in the adjusted analyses (Supplementary Table 2). After stratifying the outcome
on the presence or absence of comorbid intellectual disability, we did not observe a striking
difference between the two diagnostic groups, though ORs were higher for ASD with ID
(Supplementary Table 2).
1
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(7).
Figures and tables for supplementary information
Supplementary Figure 1: Derivation of the analytical Stockholm Youth Cohort sample.
The Stockholm Youth Cohort
Residents in Stockholm, 0-17 years
old, born 1984-2011
N = 735 096
ASD cases N = 11 330
Case-Control sampling
10 sampled controls for every case
N = 11 330 ASD cases
N = 113 300 controls
Excluded
Not born in Sweden, born after
2007, adopted children, multiple
births, or matched to such cases
N = 1 659 ASD cases
N = 30 386 controls
Excluded
Missing covariate data, or matched
to such cases
N = 126 ASD cases
N = 1 928 controls
Analytical sample
Case:control ratio – 1:2 to 1:10
N = 9 545 ASD cases
N = 80 986 controls
Supplementary Table 1. Selected characteristics of birth cohorts 1984–2007 of the
Stockholm Youth Cohort.
Characteristic
ASD cases
(N = 9 545)
n (%)
Controls
(N = 80 986)
n (%)
Mother’s country of birth
Analysis
p
0.081
Sweden
7 345 (77.0)
61 668 (76.1)
Other
2 200 (23.0)
19 318 (23.9)
Mother
5 702 (59.7)
34 932 (43.1)
< 0.001
Father
3 670 (38.4)
22 894 (28.3)
< 0.001
Lowest quintile for family income
1 470 (15.4)
11 733 (14.5)
< 0.001
Parents with ≤ 9 years of schooling
1 712 (17.9)
12 865 (15.9)
< 0.001
Gestational Diabetes
127 (1.3)
755 (0.9)
< 0.001
Pre-eclampsia
374 (3.9)
2 406 (3.0)
< 0.001
Apgar score <7 at 5 minutes
138 (1.4)
779 (1.0)
< 0.001
94 (1.0)
649 (0.8)
Parental history of psychiatric care
Missing data
Gestational age
< 0.001
Preterm birth (<37 weeks)
651 (6.8)
3 715 (4.6)
Postterm birth (≥42 weeks)
800 (8.4)
6 550 (8.1)
Size for gestational age
< 0.001
Small for gestational age
388 (4.1)
1 976 (2.4)
Large for gestational age
391 (4.1)
2 518 (3.1)
Missing data
52 (0.5)
337 (0.4)
PCOS
67 (0.7)
389 (0.5)
0.004
Parental age at delivery (years)
Mean (SD)
Mean (SD)
p
Maternal
29.74 (5.5)
29.82 (5.2)
0.190
Paternal
32.76 (6.7)
32.75 (6.3)
0.874
Supplementary Table 2. Odds ratios (OR) and 95% confidence interval (CI) of maternal
PCOS and autism spectrum disorders in birth cohorts 1984–2007 in the Stockholm Youth
Cohort.
ASD
ASD without ID
ASD with ID
No PCOS
Maternal
PCOS
No PCOS
Maternal
PCOS
No PCOS
Maternal
PCOS
N Cases
(%)
9 478
(99.3)
67
(0.7)
7 135
(99.3)
49
(0.7)
2 343
(99.2)
18
(0.8)
N Controls
(%)
80 597
(99.5)
389
(0.5)
60 214
(99.5)
311
(0.5)
20 383
(99.6)
78
(0.4)
OR Model 1
(CI)
Ref.
1.46
(1.12 - 1.89)
Ref.
1.33
(0.98 - 1.80)
Ref.
1.95
(1.17 – 3.27)
OR Model 2
(CI)
Ref.
1.29
(0.99 – 1.68)
Ref.
1.18
(0.86 – 1.60)
Ref.
1.74
(1.04 – 2.93)
OR Model 3
(CI)
Ref.
1.26
(0.97 – 1.65)
Ref.
1.17
(0.86 – 1.59)
Ref.
1.62
(0.96– 2.75)
Model 1: Unadjusted.
Model 2: Adjusted for maternal age, paternal age, parental psychiatric history, household income,
parental education, and mother’s country of birth.
Model 3: Adjusted as above, with further adjustment for gestational diabetes, Apgar score at 5
minutes, gestational age, size for gestational age, and pre-eclampsia.