The incidence of diagnosed autism spectrum disorders in Finland
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SUSANNA HINKKA-YLI-SALOMÄKI, P. NINA BANERJEE, MIKA GISSLER, KATJA M. LAMPI, RAIJA VANHALA, ALAN S. BROWN, ANDRÉ SOURANDER
Hinkka-Yli-Salomäki S, Banerjee PN, Gissler M, Lampi KM, Vanhala R, Brown AS, Sourander A. The incidence of diagnosed autism spectrum disorders in Finland. Nord J Psychiatry 2014;68:472–480. Background: Previous reports indicate an increase in incidence of autism spectrum disorders (ASD). Aims: First, to assess the incidence of diagnosed ASD in children born between 1996 and 1998, based on nationwide inpatient and outpatient register information. Second, to investigate the incidence rate over time of diagnosed ASD and specifically childhood autism, Asperger’s syndrome and pervasive developmental disorder (PDD-NOS) in children born between 1987 and 1998. Methods: This is population-based cohort study with children born in Finland between 1 January 1987 and 31 December 2005; a total of more than 1.2 million children. Children were identified in the Finnish Hospital Discharge Register, and the reported diagnoses were based on the International Statistical Classification of Diseases (ICD-10, ICD-9). Results: The annual incidence rate of diagnosed ASD based on inpatient and outpatient register data was 53.7 per 10,000 (95% CI 50.4–57.2). Incidence was 82.6 per 10,000 in boys and 23.6 per 10,000 in girls, yielding a sex ratio (boys:girls) of 3.5:1. We report an eightfold increase in the incidence rates in children of diagnosed ASD and specifically in childhood autism, Asperger’s syndrome and PDD-NOS and born between 1987 and 1992 based on inpatient register information. Conclusions: Increased awareness of ASD, more precise diagnostic criteria and changes in practice for diagnosing autism may have had a substantial effect on the increased incidence of inpatient treated ASD cases from 1987 to 1992. Between 1992 and 1998, the incidence rate based on inpatient and outpatient service use remained rather stable. • Autism, Autism spectrum disorders, Epidemiology, Incidence, Register study. André Sourander, M.D., Department of Child Psychiatry, University of Turku, Itäinen Pitkäkatu 1/Varia, 20014 Turku, Finland, E-mail: [email protected]; Accepted 24 October 2013.
A
utism spectrum disorders (ASD) are characterized by impaired communication, social interaction, restricted interests and repetitive behaviours. Although there have been several studies conducted on the epidemiology of ASD, including childhood autism, Asperger’s syndrome and other pervasive developmental disorders/ pervasive developmental disorder—unspecified, uncertainty about the frequency of ASD occurrence remains (1–6). The reported continually rising prevalence, the proportion of individuals in a population who suffer from an ASD, and incidence, the number of new ASD cases occurring in a population over a period of time, is hypothesized to be related to changes in study methodology and diagnostic criteria, diagnostic switching from other developmental disorders to ASD, improved diagnostic accuracy, increase in services available and increased awareness among lay and professional public, as well as growing acceptance that ASD can coexist with
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a range of other conditions (3–9). In addition to these probable causes, we are unable to exclude the possibility of a true increase for ASD (3, 4). To fulfil the criteria for childhood autism, the symptoms of abnormal functioning in social interaction and communication, and restricted, repetitive behaviour must occur. Furthermore, the symptoms must be evident prior to age 3; although an “atypical autism” diagnosis can be specified if symptoms develop after age 3 (10). However, according to studies by Mandell et al. (11), CDC (12) and Shattuck et al. (13), the median age of diagnosis is much later—after 4 or 5 years of age. A recent review by Daniels et al. (14) reported an encouraging finding that the age of diagnosis of ASD is decreasing over time nevertheless. Shared characteristics of ASD and intellectual disability may complicate the diagnosis of a child presenting with ASD (15). We therefore calculated median age at diagnosis in the present study. DOI: 10.3109/08039488.2013.861017
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A diagnosis of Asperger’s disorder is warranted only when there is impaired social interaction, stereotyped or repetitive behaviour, whereas language development and cognitive functions remain intact (10). However, deficits in pragmatic language are common in Asperger’s syndrome. The diagnostic category of PDD-NOS, “other pervasive developmental disorder” and “pervasive developmental disorder, unspecified” pooled together is assigned when some but not all diagnostic criteria are met for the one of the other disorders on the spectrum (10). Symptoms of PDD-NOS typically include multiple developmental delays and the phenotype exhibits significant variation between the children with PDD-NOS. Diagnosis also depends on the available resources, cultural norms and values in a particular region (16). A further complicating matter is the issue of diagnostic practices changing over time, with both the Diagnostic and Statistical Manual (DSM), and International Classification of Diseases (ICD) narrowing and broadening case criteria at different points (17). The prevalence of ASD is estimated to range from 0.3% to 1.8% (18–25). Two studies reported even higher prevalence estimates of ASD, namely Kim et al. in 2011 (26) reached the prevalence estimate of 2.6% in one South Korean community and Roelfsema et al. in 2011 (27) estimated the prevalence as high as 2.3% in one region of the Netherlands. While prevalence data are important in the planning of healthcare services, incidence data are critical to examining the relationship between aetiological factors and ASD and estimating individual risk of acquiring ASD as well as studying historical trends in ASD frequency. In the majority of publications on the epidemiology of ASD, existing cases in the population are not distinguished from the number of new cases occurring in the population, and each report as a whole are presented as prevalence studies. As Fombonne et al. (19) points out, both prevalence and incidence estimates will be inflated when case definition is broadened and case ascertainment is improved. A review of the few incidence studies of ASD that have been conducted around the world is presented in Table 1. The incidence rate of ASD in children is estimated to range from 5.3 to 22.8 per 10,000 per year in Europe (28–33), from 5.5 to 9.8 per 10,000 in Asia (34–36), from 1.4 to 5.8 per 10,000 in Australia (37, 38) and 52.0 per 10,000 in North America (17, 39–41). This variation in incidence across the globe may be due to differences in study periods and methods of case ascertainment as well as ages of children included in the studies. In addition, factors hypothesized to be creating the appearance of changing incidence over time, such as changes in diagnostic criteria between the times of the studies and improved diagnostic accuracy, are not usually accounted for. NORD J PSYCHIATRY·VOL 68 NO 7·2014
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Aims The first aim of the study was to examine the incidence rate of all diagnosed ASD subtypes based on ICD-10 classification (Table 2) in children born in 1996–1998 from inpatient and outpatient register information. The Finnish Hospital Discharge Register (FHDR) covers all somatic and psychiatric hospitals, inpatient wards of local health centres, military wards, prison hospitals and private hospitals. Since 1998, the FHDR has also covered all outpatient care in public hospitals. Hence, by including children born between 1996 and 1998, we were able to study both the children who received diagnoses as inpatients and as outpatients by age of 10. The second aim was to examine the incidence rates separately for the three most common ASD subtypes, childhood autism (F84.0), Asperger’s syndrome (F84.5) and PDD-NOS (F84.8–9) in children born between 1987 and 1998 based on inpatient register information. Since the collection of outpatient register information in Finland began in 1998, we were able to include only the inpatient information in the incidence estimates for the second aim. We hypothesized that, as in other populations, the annual incidence rate of these diagnosed ASD subtypes has increased over time in Finland.
Materials and Methods Ethics The present study is part of the Finnish Prenatal study in Autism and Autism Spectrum Disorders (FIPS-A) (42) and it is authorized by the Ministry of Social Affairs and Health of Finland (STM/2593/2008) with the approval from the ethics committee of the hospital district of Southwest Finland and the National Institute for Health and Welfare, and approved by the New York State Psychiatric Institute Institutional Review Board.
Study population The National Institute for Health and Welfare is a Finnish research and development institute that compiles and maintains several nationwide registers with comprehensive databases of health and welfare statistics. For this study, the Finnish Medical Birth Register (FMBR) and the Finnish Hospital Discharge Register (FHDR) were used. The FMBR includes comprehensive and standardized data on pregnancy, the prenatal period, and the neonatal period up to age 7 days on all births in Finland. The FMBR was established in 1987 with the primary purpose of collecting statistical data for research, development and provision of maternity care, obstetrics services, and the care of newborn infants. Extensive review of the virtually complete data, including cross-checking with the Population Register Centre (live births), and Cause-ofDeath Register at Statistics Finland (still births and infant
473
474 DSM-III, DSM-IV ICD-10 DSM-III-R; DSM-IV
DSM DSM-IV
⬍ 10
⬍9 ⬍9
Israel (1989–1993)
Western Australia (1983–1999) New South Wales and Western Australia (1999–2000)
5–7
⬍ 10 ⬍5 ⬍ 12 ⬍5
⬍4 ⬍7
China (1986–2005) Japan (1988–1996)
*Population size estimated. †Incidence rate. ‡Cumulative incidence. §Unclear (either incidence rate or cumulative incidence).
Williams et al. (2005) (38)
Davidovitch et al. (2001) (36) Australia Nassar et al. (2009) (37)
Asia Wong & Hui (2008) (34) Honda et al. (2005) (35)
Finland
Kielinen et al. (2000) (32)
(1988–2001) (1993–1998) (1988–1993) (1991–1996)
UK UK UK UK
ICD-10 ASD; Childhood autism ICD-8 (1971–1993), ASD ICD-10 (1994–2000) ASD Childhood autism Childhood autism ADI, ICD-10, DSM-III ASD or DSM-IV ICD-10 ASD
⬍ 10 ⬍ 10
Denmark (1995–2004) Denmark (1971–2000)
ASD
ASD
Childhood autism
ASD ASD; childhood autism
Childhood autism Childhood autism
DSM-IV DSM-IV
⬍ 21 ⬍ 21
ASD Childhood autism
Diagnostic group
MN, USA (1976–1997) MN, USA (1976–1997)
Diagnostic criteria
ICD-9 ICD-9
Age ⬍ 10 ⬍5
Country
Canada (1998–2004) CA, USA (1990–2006)
Smeeth et al. (2004) (29) Jick et al. (2003) (33) Kaye et al. (2001) (30) Powell et al. (2000) (31)
North America Burstyn et al. (2010) (39) Hertz-Picciotto & Delwiche (2009) (17) Barbaresi et al. (2005) (41) Barbaresi et al. (2009) (40) Europe Atladóttir et al. (2007) (28) Lauritsen et al. (2004) (10)
Reference
Table 1. Population-based studies of incidence of autism spectrum disorders (ASD).
–
982
26
645 278; 158
63
272 129 305 77
1860; 714 485
54 40
1138 3011
Cases
Incidence
–
419,917
26,000*
1,174,322 31,426
5.8†
1.4†
10†
5.5† 9.8‡; 5.6‡
WA Register for Autism Spectrum Disorders Active surveillance and WA Register for Autism Spectrum Disorders
Computerized public hospital database Inpatient and outpatient psychiatric facilities Children’s inpatient and outpatient psychiatric facilities
Patient registers of hospitals in Oulu and Lapland 27,572
22.8‡
Danish National Psychiatric Registry Danish National Psychiatric Registry UK General Practice Research Database UK General Practice Research Database UK General Practice Research Database Child Development Centre Records
50.8‡; 17.1‡ 7.1†
4.5† 3.3†
Alberta Perinatal Health Program California Department of Developmental Services Research identified, record review Clinical diagnosis
Case ascertainment
514,945 5.3† 43,000 30§ 3,092,742 1.0† 13.1† 58,779*
407,118 682,397
120,000* 121,212*
218,890 52.0† 2,678,019 11.2†
Population
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Table 2. Number of births (incident cases) with any diagnosed autism spectrum disorder (ASD).
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Diagnosis
Average number of incident cases*
Childhood autism (F84.0) Total Boys Girls Atypical autism (F84.1) Total Boys Girls Rett’s syndrome (F84.2) Total Boys Girls Other childhood disintegrative disorder (F84.3) Total Boys Girls Overactive disorder associated with mental retardation and stereotyped movements (F84.4) Total Boys Girls Asperger’s syndrome (F84.5) Total Boys Girls Other pervasive developmental disorders (F84.8) Total Boys Girls Pervasive developmental disorder, unspecified (F84.9) Total Boys Girls Autism spectrum disorders (ASD) (F84.0–9) Total Boys Girls
Incident rate per 10,000 children (95% CI)
Sex ratio (boys: girls) (95% CI) 3.0 (2.3–4.0)
84 64 20
14.3 (12.7–16.2) 21.3 (18.5–24.6) 7.1 ( 5.5–9.1)
16 12 4
2.7 ( 2.0–3.5) 4.0 ( 2.9–5.5) 1.3 ( 0.7–2.3)
2 – 2
0.3 ( 0.2–0.8) – 0.7 ( 0.3–1.5)
6 4 2
1.0 ( 0.6–1.6) 1.3 ( 0.8–2.3) 0.6 ( 0.2–1.4)
3.3 (1.6–6.2)
–
2.3 (0.8–6.5)
– 1 1 –
0.1 ( 0.0–0.5) 0.2 ( 0.1–0.9) –
95 80 14
16.1 (14.3–18.1) 26.8 (23.6–30.4) 5.0 ( 3.7–6.7)
46 35 10
7.8 ( 6.6–9.2) 11.8 ( 9.7–14.2) 3.6 ( 2.5–5.1)
67 51 16
11.4 ( 9.9–13.1) 17.1 (14.6–20.0) 5.4 ( 4.1–7.2)
316 248 68
53.7 (50.4–57.2) 82.6 (76.8–88.7) 23.6 (20.6–27.1)
5.4 (3.9–7.4)
3.3 (2.2–4.9)
3.1 (2.3–4.4)
3.5 (3.0–4.1)
Figures presented by sex and incidence rate per 10,000 children with 95% confidence interval averaged over birth cohorts 1996–1998 in Finland. *Mean of the number of incident cases in 1996, 1997 and 1998 (data by year available from the author at request).
deaths), indicated that less than 0.1% of the births are missing (43, 44). The register includes personal identity codes of mothers and live-born children that can be used to link the subjects across all of the databases in the study. The FHDR was established in the 1960s and computerized data with complete personal identity code (PID) are available from 1969 to the present. All medical diagnoses, based on ICD are included in the FHDR. The registration routines are standardized across Finland. As noted above, since 1998, the FHDR has covered also all outpatient care in public hospitals. All data used in the study from these registers were linked using the child’s PID. The PID is a means of identification that is more specific than a name and is unique for each person. The code remains unchanged NORD J PSYCHIATRY·VOL 68 NO 7·2014
throughout the person’s lifetime with the very rare cases of sex-change and misuse of personal identity code when a new code can be issued. The Finnish PID is issued to Finnish citizens born in or outside Finland on the basis of a birth certificate, and for permanent residents of Finland. Parents of a newborn child born in Finland need not take any special measures to obtain a code for the child, as the PID is automatically issued when the child’s birth is registered in the FMBR.
Identification of children with ASD diagnosis As the first aim of the study was to examine the incidence rate of diagnosed ASD and its diagnostic subtypes in children younger than 10 years and born in 1996–1998, we identified all subjects born in those
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years and receiving any diagnostic code of F84x based on ICD-10 during the period of 1 January 1996–31 December 2007. In the incidence rate calculation, we included births (incident cases) with later diagnosed ASD. Median age at diagnosis for ASD and its three most common subtypes was calculated to form the sample for the study. The follow-up time for children was therefore defined as less than 10 years. We calculated also the median age at diagnosis for ASD and its three most common subtypes in the sample for the incidence study to show the changes in median values and quartile ranges between the whole sample and the sample for the incidence study. We used the FHDR as our data source, and we were able to use both inpatient and outpatient register information. The identified ASD cases registered during the follow-up belonged to one of the following subtypes: childhood autism (F84.0), atypical autism (F84.1), Rett’s syndrome (F84.2), other childhood disintegrative disorder (F84.3), overactive disorder associated with mental retardation and stereotyped movements (F84.4), Asperger’s syndrome (F84.5) and other pervasive developmental disorders/pervasive developmental disorder—unspecified, PDD (F84.8–9). Cases receiving either a diagnosis of “other pervasive developmental disorder or “pervasive developmental disorder, unspecified” were pooled together, and they are referred to as “PDD-NOS”. As the second aim of the study was to examine the incidence rates separately for diagnosed childhood autism, diagnosed Asperger’s syndrome and diagnosed PDD-NOS in children younger than 10 years and born between 1 January 1987 and 31 December 1998, we identified from the FHDR all subjects born in that period and receiving any diagnostic code of 299x (ICD-9, in 1987–1995) or F84x (ICD-10, 1996–2007) between 1 January 1987 and 31 December 2007. In the incidence rate calculation, we included births (new incident cases) with diagnosed ASD. Also here we included the diagnostic inpatient FHDR information from children younger than 10 years. The majority of cases were diagnosed with the ICD-10 while only 19 cases (0.4%) were diagnosed with the ICD-9. Since the most recent registry diagnosis of ASD was used for classification, these 19 cases represent a group of individuals without ASD diagnoses registered after 1996. Even though in Finland, equal access to both primary and specialized healthcare services is available to all citizens in Finland free of charge, it is unknown how complete information the FHDR contains. In a diagnostic validation study, it was demonstrated that 96% of registry-based childhood autism diagnoses fulfilled the diagnostic criteria of the Autism Diagnostic Interview-Revised (ADI-R) (45). However, these data do not ensure validation of other ASD subgroups.
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Statistical methods Incidence rates and the corresponding 95% confidence intervals (CIs) of diagnosed ASD in children born in 1996–1998 based on inpatient and outpatient register information were estimated with a Poisson-regression model, assuming a Poisson error distribution. The number of diagnosed children born in Finland was divided by the number of the yearly birth cohorts, based on data from the FMBR. In addition, the sex ratio and reported 95% CIs were estimated with a Poisson-regression model in which the CIs were computed using the delta method (46). The incidence rates of diagnosed ASD and its subgroups of childhood autism, Asperger’s syndrome and PDD-NOS in children born in 1987–1998 based on inpatient register information were also calculated with a Poisson-regression model. Incidence rates are presented per 10,000 live born children. Statistical analyses were performed with SAS software (Version 9.3, SAS Institute, Cary, NC, USA). In testing, we used two-sided P-values at a 0.05 significance level.
Results Among children in the whole sample, born between 1 January 1987 and 31 December 2005, the median age of ASD was 7 years (quartile range 5–10; range 0–20). As each ASD varies considerably in typical age of clinical presentation, the estimated median age at diagnosis for childhood autism was 4 years (quartile range 3–7; range 0–20) and for Asperger’s syndrome and PDD-NOS the median ages were 9 years (7–12; 1–20) and 7 years (5–10; 0–19), respectively. As noted in the Methods, in the sample for the incidence study we restricted the age range to cases younger than 10 years. The median age of ASD in this sample was 6 years (quartile range 4–8). The estimated median ages at diagnosis for childhood autism, Asperger’s syndrome and PDD-NOS were 4 years (quartile range 3–5), 7 years (6–8) and 6 years (4–8), respectively. An average of 316 children born in 1996–1998, 78% boys and 22% girls, were given an ASD diagnosis before the age of 10. The estimates of incidence rate per year and their 95% CIs for each disorder are summarized in Table 2. The annual incidence rate of diagnosed ASD including all F84.0–9 diagnostic subgroups was 53.7 per 10,000 children (95% CI 50.4–57.2). The results revealed clear differences in incidence rate by sex. Diagnosed ASD diagnoses were 3.5 times more likely in boys than in girls (82.6 vs. 23.6 per 10,000). The incidence rate of childhood autism was 3 times greater in boys than in girls (21.3 vs. 7.1 per 10,000) whereas Asperger’s syndrome was 5.4 times higher in boys than in girls (26.8 vs. 5.0 per 10,000). PDD-NOS (F84.8 and F84.9 combined) was over 3 times more NORD J PSYCHIATRY·VOL 68 NO 7·2014
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cases were identified over each successive birth cohort from 1987 to 1998. Statistically significant increases (all P ⬍ 0.001) were found in the incidence rates from 1987 to 1998 for any diagnosed ASD and the three specific disorders, childhood autism, Asperger’s syndrome and PDD-NOS. There was an eightfold increase, from 3.0 to 24.1 per 10,000 (P ⬍ 0.001), in the overall ASD incidence between 1987 and 1992 (the mid-point of our study period of hospital-based incidence). No statistically significant difference (P ⫽ 0.96) was found when comparing the incidence rate of diagnosed ASD in 1992 (24.1 per 10,000) to 1998 (24.3 per 10,000). Significantly increased incidence rates of each specific diagnosed disorders of ASD (childhood autism, Asperger’s
(a) 35
Incidence, per 10 000
30 25 20 15 10 5 0 1987
1988
1989
1990 F84.0-9
1991
1992
F84.0
1993
1994
F84.5
1995
1996
1997
1998
1996
1997
1998
F84.8-9
(b) 50 45 40 Incidence, per 10 000
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likely in boys than in girls (28.9 vs. 9.0 per 10,000). The incidence rates of the remaining ASD subgroups, atypical autism, Rett’s syndrome, other childhood disintegrative disorder and overactive disorder associated with mental retardation and stereotyped movements, were clearly smaller, varying from 0.1 to 2.7 per 10,000 children under age 10. Between 1987 and 1998, there were 1524 of 752,512 (0.002%) children diagnosed with ASD before age 10. The diagnosis was performed in an inpatient setting, and of these 79% were boys and 21% were girls. Figure 1(a–b) illustrates the incidence rates of any diagnosed ASD, childhood autism, Asperger’s syndrome and PDD-NOS based on inpatient register information. New
AUTISM AND AUTISM SPECTRUM DISORDERS
35 30 25 20 15 10 5 0 1987
1988
1989
1990
1991
1992
1993
1994
1995
F84.0-9 boys
F84.0 boys
F84.5 boys
F84.8-9 boys
F84.0-9 girls
F84.0 girls
F84.5 girls
F84.8-9 girls
Fig. 1. Incidence rate (per 10,000) of diagnosed autism spectrum disorders (ASD, F84.0–9) and subtypes of childhood autism (F84.0), Asperger’s syndrome (F84.5) and pervasive developmental disorder, not otherwise unspecified (PDD-NOS; F84.8–9) in (a) children and (b) boys and girls separately. Information based on inpatient register information. New cases identified over each successive birth cohort from 1987 to 1998. NORD J PSYCHIATRY·VOL 68 NO 7·2014
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syndrome and PDD-NOS) were observed between 1987 and 1992, but not between 1992 and 1998 except for Asperger’s syndrome where there was a significant decrease from 5.2 to 2.8 per 10,000 (P ⫽ 0.039).
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Discussion The first aim of the study was to examine the incidence of diagnosed ASD and its subtypes, based on inpatient and outpatient register information. The annual incidence rate of diagnosed ASD was 53.7 per 10,000 children under age 10 and born between 1 January 1996 and 31 December 1998. This incidence rate is similar to the study by Burstyn et al. (39), which reported incidence rate of 52 per 10,000 children under age 10 in Canada. However, earlier studies reported much lower incidences; for example, in a study from 2005, reported an incidence rate of 4.5 per 10,000 children in the USA (41). Approximately 19 of 10,000 children per year were diagnosed with PDD-NOS. Among the diagnostic subtypes, PDD-NOS had a higher incidence than Asperger’s syndrome with approximately 16 of 10,000 children younger than 10 years and childhood autism had the third highest incidence of 14.3 per 10,000 children. Other subtypes were rare; less than 3 per 10,000 children per year. Bienvenu et al. (47) in 2006 reported an incidence rate of Rett’s syndrome of 0.7 per 10,000 girls born between 1996 and 1998 in France, which is the same as in our study. Similar to our findings, all the ASD subgroups except Rett’s syndrome have been reported to be more common in boys than in girls. The second aim of the study was to examine changes in incidence rates of diagnosed ASD and its three most common subtypes in children born from 1987–1998 and with diagnoses from the inpatient hospital-based register. As the information on outpatient care was available only from 1998 onwards, we were able to include only the inpatient register data. There was a dramatic increase, from 3 to 24 per 10,000 children, in the incidence of overall diagnosed ASD from 1987 to 1992. Between 1992 and 1998, the incidence rate remained rather stable varying from 22.5 to 30.7 per 10,000 children. This is in contrast to reports from the USA: Wazana et al. (9) concluded that ASD is more common than estimated 20 years ago and King & Bearman reported constant increases in children with autism between 1992 and 2005 (48). There are many potential explanations for the marked increases in the observed incidence of diagnosed ASD. Our findings most likely represent broadening of the diagnostic criteria, improved diagnostic accuracy, diagnostic switching from other developmental disabilities to ASD, changes in study methodology, an increase in services available, increased awareness among educational and clinical professionals and growing acceptance that
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autism can coexist with a range of other conditions. However, this conclusion does not necessarily rule out the possibility of a true rise in incidence. In Finland, knowledge among paediatricians, child neurologists and child psychiatrists about autism, its neurobiological background and rehabilitation programmes increased in the late 1980s. At the same time, the first children with Asperger’s syndrome were also diagnosed (Dr. Raija Vanhala, M.D., specialist in child neurology in Finland, through personal communication). ICD-10 was adopted in Finland in 1995. In the beginning of the 1990s, there were a number of research projects initiated to study the diagnosis of ASD in Finland. Moreover, large training programmes were implemented, and steps were taken to further develop rehabilitation programmes for children with ASD and their families. The first units in special schools for autistic children were established in the early 1990s. This may have been at least partly responsible for the increase in the number of children diagnosed with ASD as the ASD diagnosis was a prerequisite for the children to be enrolled in rehabilitation programmes and special schooling. Further evidence for increased awareness of, and services, for autism is the establishment of the Finnish Society for Autism in 1986 (49). The Society is a member of the Finnish Association for Autism and Asperger’s Syndrome that was founded in 1997 (50). The Association serves individuals with ASD and their families by increasing knowledge and understanding of the difficulties caused by ASD, and by developing the quality and improving the availability of services that support education, housing and everyday life. All the above may have paved the way for our findings where, for example, highest incidence rates of Asperger’s syndrome were found for the birth cohorts 1991 to approximately 1995 with a mean age of diagnosis of 9 years meaning that many children with Asperger’s syndrome were diagnosed in the calendar years 2000–2004. The strengths of the study include its national, population-based coverage. Finland has an efficient healthcare system including mandatory and fully covered visits to well-baby clinics for 0–6-year-olds and school healthcare centres for 7–16-year-olds. This implies that a vast majority of all ASD cases were ascertained by the FHDR, which is a national, scientifically validated highquality register based on a standardized diagnostic ICDcoding system and diagnostic reporting procedures. There are a few limitations in the present study. First, despite our claims of measuring incidence over time, we have limited the study to register information available. Mainly it is not known who is missing from the register. Studies that have systematically screened the population have identified many more children with ASD than previously expected. Therefore, without doing a full population screen and validation of the diagnoses, the NORD J PSYCHIATRY·VOL 68 NO 7·2014
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conclusions of this study are also limited to examining trends in identified or diagnosed ASDs. Second, the ASD sample for the analysis of time trends from 1987–1998 is based only on inpatient register data. Hence, the incidence rates over this time interval could have differed if the outpatient register data were also included. Third, we relied upon the FMBR to identify the ASD cases; hence, those cases who were born outside of Finland and who immigrated soon after birth are excluded from the data. However, because Finland’s immigration rate is very small (annual rate only 0.1–0.2%) compared with other countries in Europe this is unlikely to have substantially biased the results (51, 52). Acknowledgements—We acknowledge the contribution of Jarna Lindroos and Pyry Kantanen for assistance in manuscript preparation.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This study was supported by Autism Speaks, USA, by National Institute of Mental Health, USA, grant 1K02-MH65422, and by National Institute of Environmental Health Sciences, USA, grant 1R01ES019004.
References 1. Coury DL, Nash PL. Epidemiology and etiology of autistic spectrum disorders difficult to determine. Pediatr Ann 2003;32:696–700. 2. Fombonne E. The epidemiology of autism: A review. Psychol Med 1999;29:769–86. 3. Rutter M. Incidence of autism spectrum disorders: Changes over time and their meaning. Acta Paediatr 2005;94:2–15. 4. Fombonne E. Epidemiological surveys of autism and other pervasive developmental disorders: An update. J Autism Dev Disord 2003;33:365–82. 5. Blaxill MF. What’s going on? The question of time trends in autism. Public Health Rep 2004;119:536–51. 6. Fombonne E. Is there an epidemic of autism? Pediatrics 2001;107:411–12. 7. Rosenberg RE, Daniels AM, Law JK, Law PA, Kaufmann WE. Trends in autism spectrum disorder diagnoses: 1994–2007. J Autism Dev Disord 2009;39:1099–111. 8. Maenner MJ, Durkin MS. Trends in the prevalence of autism on the basis of special education data. Pediatrics 2010;126:e1018–25. 9. Wazana A, Bresnahan M, Kline J. The autism epidemic: Fact or artifact? J Am Acad Child Adolesc Psychiatry 2007;46:721–30. 10. Lauritsen MB, Pedersen CB, Mortensen PB. The incidence and prevalence of pervasive developmental disorders: A Danish population-based study. Psychol Med 2004;34:1339–46. 11. Mandell DS, Morales KH, Xie M, Lawer LJ, Stahmer AC, Marcus SC. Age of diagnosis among Medicaid-enrolled children with autism, 2001–2004. Psychiatr Serv 2010;61:822–9. 12. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators, Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, United States, 2012. MMWR Surveill Summ 2012;61:1–19. 13. Shattuck PT, Durkin M, Maenner M, Newschaffer C, Mandell DS, Wiggins L et al. Timing of identification among children with an autism spectrum disorder: Findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry 2009;48:474–83.
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14. Daniels AM, Mandell DS. Explaining differences in age at autism spectrum disorder diagnosis: A critical review. Autism 2013. Epub 2013 Jun 20. 15. Beglinger LJ, Smith TH. A review of subtyping in autism and proposed dimensional classification model. J Autism Dev Disord 2001;31:411–22. 16. Kawamura Y, Takahashi O, Ishii T. Reevaluating the incidence of pervasive developmental disorders: Impact of elevated rates of detection through implementation of an integrated system of screening in Toyota, Japan. Psychiatry Clin Neurosci 2008;62:152–9. 17. Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009;20:84–90. 18. Elsabbagh M, Divan G, Koh YJ, Kauchali S, Marcin C, Montiel-Nava C et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res 2012;5:160–79. 19. Fombonne E, Quirke S, Hagen A. Prevalence and interpretation of recent trends in rates of pervasive developmental disorders. MJM 2009;12:99–107. 20. Gal G, Abiri L, Reichenberg A, Gabis L, Gross R. Time trends in reported autism spectrum disorders in Israel, 1986–2005. J Autism Dev Disord 2012;42:428–31. 21. Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: The Special Needs and Autism Project (SNAP). Lancet 2006;368:210–15. 22. Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C. Prevalence of autism in a US metropolitan area. JAMA 2003;289:49–55. 23. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators, Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, United States, 2009. MMWR Surveill Summ 2009;58:1–20. 24. Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: The Special Needs and Autism Project (SNAP). Lancet 2006;368:210–15. 25. Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE et al. Prevalence of autism-spectrum conditions: UK school-based population study. Br J Psychiatry 2009;194:500–9. 26. Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 2011;168:904–12. 27. Roelfsema MT, Hoekstra RA, Allison C, Wheelwright S, Brayne C, Matthews FE et al. Are autism spectrum conditions more prevalent in an information-technology region? A schoolbased study of three regions in the Netherlands. J Autism Dev Disord 2012;42:734–9. 28. Atladóttir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Time trends in reported diagnoses of childhood neuropsychiatric disorders: A Danish cohort study. Arch Pediatr Adolesc Med 2007;161:193–8. 29. Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG. et al. Rate of first recorded diagnosis of autism and other pervasive developmental disorders in United Kingdom general practice, 1988 to 2001. BMC Medicine 2004;2:39. 30. Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: A time trend analysis. BMJ 2001;322:460–3. 31. Powell JE, Edwards A, Edwards M, Pandit BS, Sungum-Paliwal SR, Whitehouse W. Changes in the incidence of childhood autism and other autistic spectrum disorders in preschool children from two areas of the West Midlands, UK. Dev Med Child Neurol 2000;42:624–8. 32. Kielinen M, Linna SL, Moilanen I. Autism in Northern Finland. Eur Child Adolesc Psychiatry 2000;9:162–7. 33. Jick H, Kaye JA, Black C. Changes in risk of autism in the U.K. for birth cohorts 1990–1998. Epidemiology 2003;14:630–2. 34. Wong VC, Hui SL. Epidemiological study of autism spectrum disorder in China. J Child Neurol 2008;23:67–72. 35. Honda H, Shimizu Y, Imai M, Nitto Y. Cumulative incidence of childhood autism: A total population study of better accuracy and precision. Dev Med Child Neurol 2005;47:10–18.
479
Nord J Psychiatry Downloaded from informahealthcare.com by Deakin University on 03/13/15 For personal use only.
S HINKKA-YLI-SALOMÄKI ET AL. 36. Davidovitch M, Holtzman G, Tirosh E. Autism in the Haifa area—an epidemiological perspective. Isr Med Assoc J 2001;3:188–9. 37. Nassar N, Dixon G, Bourke J, Bower C, Glasson E, de Klerk N et al. Autism spectrum disorders in young children: Effect of changes in diagnostic practices. Int J Epidemiol 2009;38:1245–54. 38. Williams K, Glasson EJ, Wray J, Tuck M, Helmer M, Bower CI et al. Incidence of autism spectrum disorders in children in two Australian states. Med J Aust 2005;182:108–11. 39. Burstyn I, Sithole F, Zwaigenbaum L. Autism spectrum disorders, maternal characteristics and obstetric complications among singletons born in Alberta, Canada. Chronic Dis Can 2010;30: 125–34. 40. Barbaresi WJ, Colligan RC, Weaver AL, Katusic SK. The incidence of clinically diagnosed versus research-identified autism in Olmsted County, Minnesota, 1976–1997: Results from a retrospective, population-based study. J Autism Dev Disord 2009;39:464–70. 41. Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. The incidence of autism in Olmsted County, Minnesota, 1976–1997: Results from a population-based study. Arch Pediatr Adolesc Med 2005;159:37–44. 42. Lampi KM, Banerjee PN, Gissler M, Hinkka-Yli-Salomaki S, Huttunen J, Kulmala U et al. Finnish prenatal study of autism and autism spectrum disorders (FIPS-A): Overview and design. J Autism Dev Disord 2011;41:1090–6. 43. Gissler M, Shelley J. Quality of data on subsequent events in a routine Medical Birth Register. Med Inform Internet Med 2002;27:33–8. 44. Teperi J. Multi method approach to the assessment of data quality in the Finnish Medical Birth Registry. J Epidemiol Community Health 1993;47:242–7. 45. Lampi KM, Sourander A, Gissler M, Niemela S, Rehnstrom K, Pulkkinen E et al. Brief report: Validity of Finnish registry-based diagnoses of autism with the ADI-R. Acta Paediatr 2010;99: 1425–8.
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46. Oehlert GW. A note on the delta method. Am Stat 1992;46:27–9. 47. Bienvenu T, Philippe C, De Roux N, Raynaud M, Bonnefond JP, Pasquier L et al. The incidence of Rett syndrome in France. Pediatr Neurol 2006;34:372–5. 48. King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol 2009;38:1224–34. 49. The Finnish Society for Autism. http://www.suomenautismiyhdistys. com. Accessed 23 Apr 2013 50. The Finnish Association for Autism and Asperger’s Syndrome. http://www.autismiliitto.fi/liitto/in_english. Accessed 23 Apr 2013 51. Statistics Finland. http://www.stat.fi/index_en.html. Accessed 23 Apr 2013 52. Eurostat. http://epp.eurostat.ec.europa.eu/statistics_explained/ index.php/Migration_and_migrant_population_statistics. Accessed 23 Apr 2013 Susanna Hinkka-Yli-Salomäki, Department of Child Psychiatry, University of Turku, Turku, Finland. P. Nina Banerjee, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA. Mika Gissler, Department of Child Psychiatry, University of Turku, Turku, Finland; Information Department, National Institute for Health and Welfare, Helsinki, Finland, and Nordic School of Public Health, Gothenburg, Sweden. Katja M. Lampi, Department of Child Psychiatry, University of Turku, Turku, Finland. Raija Vanhala, Department of Child Neurology, Helsinki University Central Hospital, Helsinki, Finland. Alan S. Brown, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA and Department of Child Psychiatry, University of Turku, Turku, Finland. André Sourander, Department of Child Psychiatry, University of Turku, Turku, Finland, and Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, NY, USA.
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SUSANNA HINKKA-YLI-SALOMÄKI, P. NINA BANERJEE, MIKA GISSLER, KATJA M. LAMPI, RAIJA VANHALA, ALAN S. BROWN, ANDRÉ SOURANDER
Hinkka-Yli-Salomäki S, Banerjee PN, Gissler M, Lampi KM, Vanhala R, Brown AS, Sourander A. The incidence of diagnosed autism spectrum disorders in Finland. Nord J Psychiatry 2014;68:472–480. Background: Previous reports indicate an increase in incidence of autism spectrum disorders (ASD). Aims: First, to assess the incidence of diagnosed ASD in children born between 1996 and 1998, based on nationwide inpatient and outpatient register information. Second, to investigate the incidence rate over time of diagnosed ASD and specifically childhood autism, Asperger’s syndrome and pervasive developmental disorder (PDD-NOS) in children born between 1987 and 1998. Methods: This is population-based cohort study with children born in Finland between 1 January 1987 and 31 December 2005; a total of more than 1.2 million children. Children were identified in the Finnish Hospital Discharge Register, and the reported diagnoses were based on the International Statistical Classification of Diseases (ICD-10, ICD-9). Results: The annual incidence rate of diagnosed ASD based on inpatient and outpatient register data was 53.7 per 10,000 (95% CI 50.4–57.2). Incidence was 82.6 per 10,000 in boys and 23.6 per 10,000 in girls, yielding a sex ratio (boys:girls) of 3.5:1. We report an eightfold increase in the incidence rates in children of diagnosed ASD and specifically in childhood autism, Asperger’s syndrome and PDD-NOS and born between 1987 and 1992 based on inpatient register information. Conclusions: Increased awareness of ASD, more precise diagnostic criteria and changes in practice for diagnosing autism may have had a substantial effect on the increased incidence of inpatient treated ASD cases from 1987 to 1992. Between 1992 and 1998, the incidence rate based on inpatient and outpatient service use remained rather stable. • Autism, Autism spectrum disorders, Epidemiology, Incidence, Register study. André Sourander, M.D., Department of Child Psychiatry, University of Turku, Itäinen Pitkäkatu 1/Varia, 20014 Turku, Finland, E-mail: [email protected]; Accepted 24 October 2013.
A
utism spectrum disorders (ASD) are characterized by impaired communication, social interaction, restricted interests and repetitive behaviours. Although there have been several studies conducted on the epidemiology of ASD, including childhood autism, Asperger’s syndrome and other pervasive developmental disorders/ pervasive developmental disorder—unspecified, uncertainty about the frequency of ASD occurrence remains (1–6). The reported continually rising prevalence, the proportion of individuals in a population who suffer from an ASD, and incidence, the number of new ASD cases occurring in a population over a period of time, is hypothesized to be related to changes in study methodology and diagnostic criteria, diagnostic switching from other developmental disorders to ASD, improved diagnostic accuracy, increase in services available and increased awareness among lay and professional public, as well as growing acceptance that ASD can coexist with
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a range of other conditions (3–9). In addition to these probable causes, we are unable to exclude the possibility of a true increase for ASD (3, 4). To fulfil the criteria for childhood autism, the symptoms of abnormal functioning in social interaction and communication, and restricted, repetitive behaviour must occur. Furthermore, the symptoms must be evident prior to age 3; although an “atypical autism” diagnosis can be specified if symptoms develop after age 3 (10). However, according to studies by Mandell et al. (11), CDC (12) and Shattuck et al. (13), the median age of diagnosis is much later—after 4 or 5 years of age. A recent review by Daniels et al. (14) reported an encouraging finding that the age of diagnosis of ASD is decreasing over time nevertheless. Shared characteristics of ASD and intellectual disability may complicate the diagnosis of a child presenting with ASD (15). We therefore calculated median age at diagnosis in the present study. DOI: 10.3109/08039488.2013.861017
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A diagnosis of Asperger’s disorder is warranted only when there is impaired social interaction, stereotyped or repetitive behaviour, whereas language development and cognitive functions remain intact (10). However, deficits in pragmatic language are common in Asperger’s syndrome. The diagnostic category of PDD-NOS, “other pervasive developmental disorder” and “pervasive developmental disorder, unspecified” pooled together is assigned when some but not all diagnostic criteria are met for the one of the other disorders on the spectrum (10). Symptoms of PDD-NOS typically include multiple developmental delays and the phenotype exhibits significant variation between the children with PDD-NOS. Diagnosis also depends on the available resources, cultural norms and values in a particular region (16). A further complicating matter is the issue of diagnostic practices changing over time, with both the Diagnostic and Statistical Manual (DSM), and International Classification of Diseases (ICD) narrowing and broadening case criteria at different points (17). The prevalence of ASD is estimated to range from 0.3% to 1.8% (18–25). Two studies reported even higher prevalence estimates of ASD, namely Kim et al. in 2011 (26) reached the prevalence estimate of 2.6% in one South Korean community and Roelfsema et al. in 2011 (27) estimated the prevalence as high as 2.3% in one region of the Netherlands. While prevalence data are important in the planning of healthcare services, incidence data are critical to examining the relationship between aetiological factors and ASD and estimating individual risk of acquiring ASD as well as studying historical trends in ASD frequency. In the majority of publications on the epidemiology of ASD, existing cases in the population are not distinguished from the number of new cases occurring in the population, and each report as a whole are presented as prevalence studies. As Fombonne et al. (19) points out, both prevalence and incidence estimates will be inflated when case definition is broadened and case ascertainment is improved. A review of the few incidence studies of ASD that have been conducted around the world is presented in Table 1. The incidence rate of ASD in children is estimated to range from 5.3 to 22.8 per 10,000 per year in Europe (28–33), from 5.5 to 9.8 per 10,000 in Asia (34–36), from 1.4 to 5.8 per 10,000 in Australia (37, 38) and 52.0 per 10,000 in North America (17, 39–41). This variation in incidence across the globe may be due to differences in study periods and methods of case ascertainment as well as ages of children included in the studies. In addition, factors hypothesized to be creating the appearance of changing incidence over time, such as changes in diagnostic criteria between the times of the studies and improved diagnostic accuracy, are not usually accounted for. NORD J PSYCHIATRY·VOL 68 NO 7·2014
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Aims The first aim of the study was to examine the incidence rate of all diagnosed ASD subtypes based on ICD-10 classification (Table 2) in children born in 1996–1998 from inpatient and outpatient register information. The Finnish Hospital Discharge Register (FHDR) covers all somatic and psychiatric hospitals, inpatient wards of local health centres, military wards, prison hospitals and private hospitals. Since 1998, the FHDR has also covered all outpatient care in public hospitals. Hence, by including children born between 1996 and 1998, we were able to study both the children who received diagnoses as inpatients and as outpatients by age of 10. The second aim was to examine the incidence rates separately for the three most common ASD subtypes, childhood autism (F84.0), Asperger’s syndrome (F84.5) and PDD-NOS (F84.8–9) in children born between 1987 and 1998 based on inpatient register information. Since the collection of outpatient register information in Finland began in 1998, we were able to include only the inpatient information in the incidence estimates for the second aim. We hypothesized that, as in other populations, the annual incidence rate of these diagnosed ASD subtypes has increased over time in Finland.
Materials and Methods Ethics The present study is part of the Finnish Prenatal study in Autism and Autism Spectrum Disorders (FIPS-A) (42) and it is authorized by the Ministry of Social Affairs and Health of Finland (STM/2593/2008) with the approval from the ethics committee of the hospital district of Southwest Finland and the National Institute for Health and Welfare, and approved by the New York State Psychiatric Institute Institutional Review Board.
Study population The National Institute for Health and Welfare is a Finnish research and development institute that compiles and maintains several nationwide registers with comprehensive databases of health and welfare statistics. For this study, the Finnish Medical Birth Register (FMBR) and the Finnish Hospital Discharge Register (FHDR) were used. The FMBR includes comprehensive and standardized data on pregnancy, the prenatal period, and the neonatal period up to age 7 days on all births in Finland. The FMBR was established in 1987 with the primary purpose of collecting statistical data for research, development and provision of maternity care, obstetrics services, and the care of newborn infants. Extensive review of the virtually complete data, including cross-checking with the Population Register Centre (live births), and Cause-ofDeath Register at Statistics Finland (still births and infant
473
474 DSM-III, DSM-IV ICD-10 DSM-III-R; DSM-IV
DSM DSM-IV
⬍ 10
⬍9 ⬍9
Israel (1989–1993)
Western Australia (1983–1999) New South Wales and Western Australia (1999–2000)
5–7
⬍ 10 ⬍5 ⬍ 12 ⬍5
⬍4 ⬍7
China (1986–2005) Japan (1988–1996)
*Population size estimated. †Incidence rate. ‡Cumulative incidence. §Unclear (either incidence rate or cumulative incidence).
Williams et al. (2005) (38)
Davidovitch et al. (2001) (36) Australia Nassar et al. (2009) (37)
Asia Wong & Hui (2008) (34) Honda et al. (2005) (35)
Finland
Kielinen et al. (2000) (32)
(1988–2001) (1993–1998) (1988–1993) (1991–1996)
UK UK UK UK
ICD-10 ASD; Childhood autism ICD-8 (1971–1993), ASD ICD-10 (1994–2000) ASD Childhood autism Childhood autism ADI, ICD-10, DSM-III ASD or DSM-IV ICD-10 ASD
⬍ 10 ⬍ 10
Denmark (1995–2004) Denmark (1971–2000)
ASD
ASD
Childhood autism
ASD ASD; childhood autism
Childhood autism Childhood autism
DSM-IV DSM-IV
⬍ 21 ⬍ 21
ASD Childhood autism
Diagnostic group
MN, USA (1976–1997) MN, USA (1976–1997)
Diagnostic criteria
ICD-9 ICD-9
Age ⬍ 10 ⬍5
Country
Canada (1998–2004) CA, USA (1990–2006)
Smeeth et al. (2004) (29) Jick et al. (2003) (33) Kaye et al. (2001) (30) Powell et al. (2000) (31)
North America Burstyn et al. (2010) (39) Hertz-Picciotto & Delwiche (2009) (17) Barbaresi et al. (2005) (41) Barbaresi et al. (2009) (40) Europe Atladóttir et al. (2007) (28) Lauritsen et al. (2004) (10)
Reference
Table 1. Population-based studies of incidence of autism spectrum disorders (ASD).
–
982
26
645 278; 158
63
272 129 305 77
1860; 714 485
54 40
1138 3011
Cases
Incidence
–
419,917
26,000*
1,174,322 31,426
5.8†
1.4†
10†
5.5† 9.8‡; 5.6‡
WA Register for Autism Spectrum Disorders Active surveillance and WA Register for Autism Spectrum Disorders
Computerized public hospital database Inpatient and outpatient psychiatric facilities Children’s inpatient and outpatient psychiatric facilities
Patient registers of hospitals in Oulu and Lapland 27,572
22.8‡
Danish National Psychiatric Registry Danish National Psychiatric Registry UK General Practice Research Database UK General Practice Research Database UK General Practice Research Database Child Development Centre Records
50.8‡; 17.1‡ 7.1†
4.5† 3.3†
Alberta Perinatal Health Program California Department of Developmental Services Research identified, record review Clinical diagnosis
Case ascertainment
514,945 5.3† 43,000 30§ 3,092,742 1.0† 13.1† 58,779*
407,118 682,397
120,000* 121,212*
218,890 52.0† 2,678,019 11.2†
Population
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Table 2. Number of births (incident cases) with any diagnosed autism spectrum disorder (ASD).
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Diagnosis
Average number of incident cases*
Childhood autism (F84.0) Total Boys Girls Atypical autism (F84.1) Total Boys Girls Rett’s syndrome (F84.2) Total Boys Girls Other childhood disintegrative disorder (F84.3) Total Boys Girls Overactive disorder associated with mental retardation and stereotyped movements (F84.4) Total Boys Girls Asperger’s syndrome (F84.5) Total Boys Girls Other pervasive developmental disorders (F84.8) Total Boys Girls Pervasive developmental disorder, unspecified (F84.9) Total Boys Girls Autism spectrum disorders (ASD) (F84.0–9) Total Boys Girls
Incident rate per 10,000 children (95% CI)
Sex ratio (boys: girls) (95% CI) 3.0 (2.3–4.0)
84 64 20
14.3 (12.7–16.2) 21.3 (18.5–24.6) 7.1 ( 5.5–9.1)
16 12 4
2.7 ( 2.0–3.5) 4.0 ( 2.9–5.5) 1.3 ( 0.7–2.3)
2 – 2
0.3 ( 0.2–0.8) – 0.7 ( 0.3–1.5)
6 4 2
1.0 ( 0.6–1.6) 1.3 ( 0.8–2.3) 0.6 ( 0.2–1.4)
3.3 (1.6–6.2)
–
2.3 (0.8–6.5)
– 1 1 –
0.1 ( 0.0–0.5) 0.2 ( 0.1–0.9) –
95 80 14
16.1 (14.3–18.1) 26.8 (23.6–30.4) 5.0 ( 3.7–6.7)
46 35 10
7.8 ( 6.6–9.2) 11.8 ( 9.7–14.2) 3.6 ( 2.5–5.1)
67 51 16
11.4 ( 9.9–13.1) 17.1 (14.6–20.0) 5.4 ( 4.1–7.2)
316 248 68
53.7 (50.4–57.2) 82.6 (76.8–88.7) 23.6 (20.6–27.1)
5.4 (3.9–7.4)
3.3 (2.2–4.9)
3.1 (2.3–4.4)
3.5 (3.0–4.1)
Figures presented by sex and incidence rate per 10,000 children with 95% confidence interval averaged over birth cohorts 1996–1998 in Finland. *Mean of the number of incident cases in 1996, 1997 and 1998 (data by year available from the author at request).
deaths), indicated that less than 0.1% of the births are missing (43, 44). The register includes personal identity codes of mothers and live-born children that can be used to link the subjects across all of the databases in the study. The FHDR was established in the 1960s and computerized data with complete personal identity code (PID) are available from 1969 to the present. All medical diagnoses, based on ICD are included in the FHDR. The registration routines are standardized across Finland. As noted above, since 1998, the FHDR has covered also all outpatient care in public hospitals. All data used in the study from these registers were linked using the child’s PID. The PID is a means of identification that is more specific than a name and is unique for each person. The code remains unchanged NORD J PSYCHIATRY·VOL 68 NO 7·2014
throughout the person’s lifetime with the very rare cases of sex-change and misuse of personal identity code when a new code can be issued. The Finnish PID is issued to Finnish citizens born in or outside Finland on the basis of a birth certificate, and for permanent residents of Finland. Parents of a newborn child born in Finland need not take any special measures to obtain a code for the child, as the PID is automatically issued when the child’s birth is registered in the FMBR.
Identification of children with ASD diagnosis As the first aim of the study was to examine the incidence rate of diagnosed ASD and its diagnostic subtypes in children younger than 10 years and born in 1996–1998, we identified all subjects born in those
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years and receiving any diagnostic code of F84x based on ICD-10 during the period of 1 January 1996–31 December 2007. In the incidence rate calculation, we included births (incident cases) with later diagnosed ASD. Median age at diagnosis for ASD and its three most common subtypes was calculated to form the sample for the study. The follow-up time for children was therefore defined as less than 10 years. We calculated also the median age at diagnosis for ASD and its three most common subtypes in the sample for the incidence study to show the changes in median values and quartile ranges between the whole sample and the sample for the incidence study. We used the FHDR as our data source, and we were able to use both inpatient and outpatient register information. The identified ASD cases registered during the follow-up belonged to one of the following subtypes: childhood autism (F84.0), atypical autism (F84.1), Rett’s syndrome (F84.2), other childhood disintegrative disorder (F84.3), overactive disorder associated with mental retardation and stereotyped movements (F84.4), Asperger’s syndrome (F84.5) and other pervasive developmental disorders/pervasive developmental disorder—unspecified, PDD (F84.8–9). Cases receiving either a diagnosis of “other pervasive developmental disorder or “pervasive developmental disorder, unspecified” were pooled together, and they are referred to as “PDD-NOS”. As the second aim of the study was to examine the incidence rates separately for diagnosed childhood autism, diagnosed Asperger’s syndrome and diagnosed PDD-NOS in children younger than 10 years and born between 1 January 1987 and 31 December 1998, we identified from the FHDR all subjects born in that period and receiving any diagnostic code of 299x (ICD-9, in 1987–1995) or F84x (ICD-10, 1996–2007) between 1 January 1987 and 31 December 2007. In the incidence rate calculation, we included births (new incident cases) with diagnosed ASD. Also here we included the diagnostic inpatient FHDR information from children younger than 10 years. The majority of cases were diagnosed with the ICD-10 while only 19 cases (0.4%) were diagnosed with the ICD-9. Since the most recent registry diagnosis of ASD was used for classification, these 19 cases represent a group of individuals without ASD diagnoses registered after 1996. Even though in Finland, equal access to both primary and specialized healthcare services is available to all citizens in Finland free of charge, it is unknown how complete information the FHDR contains. In a diagnostic validation study, it was demonstrated that 96% of registry-based childhood autism diagnoses fulfilled the diagnostic criteria of the Autism Diagnostic Interview-Revised (ADI-R) (45). However, these data do not ensure validation of other ASD subgroups.
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Statistical methods Incidence rates and the corresponding 95% confidence intervals (CIs) of diagnosed ASD in children born in 1996–1998 based on inpatient and outpatient register information were estimated with a Poisson-regression model, assuming a Poisson error distribution. The number of diagnosed children born in Finland was divided by the number of the yearly birth cohorts, based on data from the FMBR. In addition, the sex ratio and reported 95% CIs were estimated with a Poisson-regression model in which the CIs were computed using the delta method (46). The incidence rates of diagnosed ASD and its subgroups of childhood autism, Asperger’s syndrome and PDD-NOS in children born in 1987–1998 based on inpatient register information were also calculated with a Poisson-regression model. Incidence rates are presented per 10,000 live born children. Statistical analyses were performed with SAS software (Version 9.3, SAS Institute, Cary, NC, USA). In testing, we used two-sided P-values at a 0.05 significance level.
Results Among children in the whole sample, born between 1 January 1987 and 31 December 2005, the median age of ASD was 7 years (quartile range 5–10; range 0–20). As each ASD varies considerably in typical age of clinical presentation, the estimated median age at diagnosis for childhood autism was 4 years (quartile range 3–7; range 0–20) and for Asperger’s syndrome and PDD-NOS the median ages were 9 years (7–12; 1–20) and 7 years (5–10; 0–19), respectively. As noted in the Methods, in the sample for the incidence study we restricted the age range to cases younger than 10 years. The median age of ASD in this sample was 6 years (quartile range 4–8). The estimated median ages at diagnosis for childhood autism, Asperger’s syndrome and PDD-NOS were 4 years (quartile range 3–5), 7 years (6–8) and 6 years (4–8), respectively. An average of 316 children born in 1996–1998, 78% boys and 22% girls, were given an ASD diagnosis before the age of 10. The estimates of incidence rate per year and their 95% CIs for each disorder are summarized in Table 2. The annual incidence rate of diagnosed ASD including all F84.0–9 diagnostic subgroups was 53.7 per 10,000 children (95% CI 50.4–57.2). The results revealed clear differences in incidence rate by sex. Diagnosed ASD diagnoses were 3.5 times more likely in boys than in girls (82.6 vs. 23.6 per 10,000). The incidence rate of childhood autism was 3 times greater in boys than in girls (21.3 vs. 7.1 per 10,000) whereas Asperger’s syndrome was 5.4 times higher in boys than in girls (26.8 vs. 5.0 per 10,000). PDD-NOS (F84.8 and F84.9 combined) was over 3 times more NORD J PSYCHIATRY·VOL 68 NO 7·2014
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cases were identified over each successive birth cohort from 1987 to 1998. Statistically significant increases (all P ⬍ 0.001) were found in the incidence rates from 1987 to 1998 for any diagnosed ASD and the three specific disorders, childhood autism, Asperger’s syndrome and PDD-NOS. There was an eightfold increase, from 3.0 to 24.1 per 10,000 (P ⬍ 0.001), in the overall ASD incidence between 1987 and 1992 (the mid-point of our study period of hospital-based incidence). No statistically significant difference (P ⫽ 0.96) was found when comparing the incidence rate of diagnosed ASD in 1992 (24.1 per 10,000) to 1998 (24.3 per 10,000). Significantly increased incidence rates of each specific diagnosed disorders of ASD (childhood autism, Asperger’s
(a) 35
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(b) 50 45 40 Incidence, per 10 000
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likely in boys than in girls (28.9 vs. 9.0 per 10,000). The incidence rates of the remaining ASD subgroups, atypical autism, Rett’s syndrome, other childhood disintegrative disorder and overactive disorder associated with mental retardation and stereotyped movements, were clearly smaller, varying from 0.1 to 2.7 per 10,000 children under age 10. Between 1987 and 1998, there were 1524 of 752,512 (0.002%) children diagnosed with ASD before age 10. The diagnosis was performed in an inpatient setting, and of these 79% were boys and 21% were girls. Figure 1(a–b) illustrates the incidence rates of any diagnosed ASD, childhood autism, Asperger’s syndrome and PDD-NOS based on inpatient register information. New
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35 30 25 20 15 10 5 0 1987
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Fig. 1. Incidence rate (per 10,000) of diagnosed autism spectrum disorders (ASD, F84.0–9) and subtypes of childhood autism (F84.0), Asperger’s syndrome (F84.5) and pervasive developmental disorder, not otherwise unspecified (PDD-NOS; F84.8–9) in (a) children and (b) boys and girls separately. Information based on inpatient register information. New cases identified over each successive birth cohort from 1987 to 1998. NORD J PSYCHIATRY·VOL 68 NO 7·2014
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syndrome and PDD-NOS) were observed between 1987 and 1992, but not between 1992 and 1998 except for Asperger’s syndrome where there was a significant decrease from 5.2 to 2.8 per 10,000 (P ⫽ 0.039).
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Discussion The first aim of the study was to examine the incidence of diagnosed ASD and its subtypes, based on inpatient and outpatient register information. The annual incidence rate of diagnosed ASD was 53.7 per 10,000 children under age 10 and born between 1 January 1996 and 31 December 1998. This incidence rate is similar to the study by Burstyn et al. (39), which reported incidence rate of 52 per 10,000 children under age 10 in Canada. However, earlier studies reported much lower incidences; for example, in a study from 2005, reported an incidence rate of 4.5 per 10,000 children in the USA (41). Approximately 19 of 10,000 children per year were diagnosed with PDD-NOS. Among the diagnostic subtypes, PDD-NOS had a higher incidence than Asperger’s syndrome with approximately 16 of 10,000 children younger than 10 years and childhood autism had the third highest incidence of 14.3 per 10,000 children. Other subtypes were rare; less than 3 per 10,000 children per year. Bienvenu et al. (47) in 2006 reported an incidence rate of Rett’s syndrome of 0.7 per 10,000 girls born between 1996 and 1998 in France, which is the same as in our study. Similar to our findings, all the ASD subgroups except Rett’s syndrome have been reported to be more common in boys than in girls. The second aim of the study was to examine changes in incidence rates of diagnosed ASD and its three most common subtypes in children born from 1987–1998 and with diagnoses from the inpatient hospital-based register. As the information on outpatient care was available only from 1998 onwards, we were able to include only the inpatient register data. There was a dramatic increase, from 3 to 24 per 10,000 children, in the incidence of overall diagnosed ASD from 1987 to 1992. Between 1992 and 1998, the incidence rate remained rather stable varying from 22.5 to 30.7 per 10,000 children. This is in contrast to reports from the USA: Wazana et al. (9) concluded that ASD is more common than estimated 20 years ago and King & Bearman reported constant increases in children with autism between 1992 and 2005 (48). There are many potential explanations for the marked increases in the observed incidence of diagnosed ASD. Our findings most likely represent broadening of the diagnostic criteria, improved diagnostic accuracy, diagnostic switching from other developmental disabilities to ASD, changes in study methodology, an increase in services available, increased awareness among educational and clinical professionals and growing acceptance that
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autism can coexist with a range of other conditions. However, this conclusion does not necessarily rule out the possibility of a true rise in incidence. In Finland, knowledge among paediatricians, child neurologists and child psychiatrists about autism, its neurobiological background and rehabilitation programmes increased in the late 1980s. At the same time, the first children with Asperger’s syndrome were also diagnosed (Dr. Raija Vanhala, M.D., specialist in child neurology in Finland, through personal communication). ICD-10 was adopted in Finland in 1995. In the beginning of the 1990s, there were a number of research projects initiated to study the diagnosis of ASD in Finland. Moreover, large training programmes were implemented, and steps were taken to further develop rehabilitation programmes for children with ASD and their families. The first units in special schools for autistic children were established in the early 1990s. This may have been at least partly responsible for the increase in the number of children diagnosed with ASD as the ASD diagnosis was a prerequisite for the children to be enrolled in rehabilitation programmes and special schooling. Further evidence for increased awareness of, and services, for autism is the establishment of the Finnish Society for Autism in 1986 (49). The Society is a member of the Finnish Association for Autism and Asperger’s Syndrome that was founded in 1997 (50). The Association serves individuals with ASD and their families by increasing knowledge and understanding of the difficulties caused by ASD, and by developing the quality and improving the availability of services that support education, housing and everyday life. All the above may have paved the way for our findings where, for example, highest incidence rates of Asperger’s syndrome were found for the birth cohorts 1991 to approximately 1995 with a mean age of diagnosis of 9 years meaning that many children with Asperger’s syndrome were diagnosed in the calendar years 2000–2004. The strengths of the study include its national, population-based coverage. Finland has an efficient healthcare system including mandatory and fully covered visits to well-baby clinics for 0–6-year-olds and school healthcare centres for 7–16-year-olds. This implies that a vast majority of all ASD cases were ascertained by the FHDR, which is a national, scientifically validated highquality register based on a standardized diagnostic ICDcoding system and diagnostic reporting procedures. There are a few limitations in the present study. First, despite our claims of measuring incidence over time, we have limited the study to register information available. Mainly it is not known who is missing from the register. Studies that have systematically screened the population have identified many more children with ASD than previously expected. Therefore, without doing a full population screen and validation of the diagnoses, the NORD J PSYCHIATRY·VOL 68 NO 7·2014
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conclusions of this study are also limited to examining trends in identified or diagnosed ASDs. Second, the ASD sample for the analysis of time trends from 1987–1998 is based only on inpatient register data. Hence, the incidence rates over this time interval could have differed if the outpatient register data were also included. Third, we relied upon the FMBR to identify the ASD cases; hence, those cases who were born outside of Finland and who immigrated soon after birth are excluded from the data. However, because Finland’s immigration rate is very small (annual rate only 0.1–0.2%) compared with other countries in Europe this is unlikely to have substantially biased the results (51, 52). Acknowledgements—We acknowledge the contribution of Jarna Lindroos and Pyry Kantanen for assistance in manuscript preparation.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This study was supported by Autism Speaks, USA, by National Institute of Mental Health, USA, grant 1K02-MH65422, and by National Institute of Environmental Health Sciences, USA, grant 1R01ES019004.
References 1. Coury DL, Nash PL. Epidemiology and etiology of autistic spectrum disorders difficult to determine. Pediatr Ann 2003;32:696–700. 2. Fombonne E. The epidemiology of autism: A review. Psychol Med 1999;29:769–86. 3. Rutter M. Incidence of autism spectrum disorders: Changes over time and their meaning. Acta Paediatr 2005;94:2–15. 4. Fombonne E. Epidemiological surveys of autism and other pervasive developmental disorders: An update. J Autism Dev Disord 2003;33:365–82. 5. Blaxill MF. What’s going on? The question of time trends in autism. Public Health Rep 2004;119:536–51. 6. Fombonne E. Is there an epidemic of autism? Pediatrics 2001;107:411–12. 7. Rosenberg RE, Daniels AM, Law JK, Law PA, Kaufmann WE. Trends in autism spectrum disorder diagnoses: 1994–2007. J Autism Dev Disord 2009;39:1099–111. 8. Maenner MJ, Durkin MS. Trends in the prevalence of autism on the basis of special education data. Pediatrics 2010;126:e1018–25. 9. Wazana A, Bresnahan M, Kline J. The autism epidemic: Fact or artifact? J Am Acad Child Adolesc Psychiatry 2007;46:721–30. 10. Lauritsen MB, Pedersen CB, Mortensen PB. The incidence and prevalence of pervasive developmental disorders: A Danish population-based study. Psychol Med 2004;34:1339–46. 11. Mandell DS, Morales KH, Xie M, Lawer LJ, Stahmer AC, Marcus SC. Age of diagnosis among Medicaid-enrolled children with autism, 2001–2004. Psychiatr Serv 2010;61:822–9. 12. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators, Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, United States, 2012. MMWR Surveill Summ 2012;61:1–19. 13. Shattuck PT, Durkin M, Maenner M, Newschaffer C, Mandell DS, Wiggins L et al. Timing of identification among children with an autism spectrum disorder: Findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry 2009;48:474–83.
NORD J PSYCHIATRY·VOL 68 NO 7·2014
AUTISM AND AUTISM SPECTRUM DISORDERS
14. Daniels AM, Mandell DS. Explaining differences in age at autism spectrum disorder diagnosis: A critical review. Autism 2013. Epub 2013 Jun 20. 15. Beglinger LJ, Smith TH. A review of subtyping in autism and proposed dimensional classification model. J Autism Dev Disord 2001;31:411–22. 16. Kawamura Y, Takahashi O, Ishii T. Reevaluating the incidence of pervasive developmental disorders: Impact of elevated rates of detection through implementation of an integrated system of screening in Toyota, Japan. Psychiatry Clin Neurosci 2008;62:152–9. 17. Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009;20:84–90. 18. Elsabbagh M, Divan G, Koh YJ, Kauchali S, Marcin C, Montiel-Nava C et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res 2012;5:160–79. 19. Fombonne E, Quirke S, Hagen A. Prevalence and interpretation of recent trends in rates of pervasive developmental disorders. MJM 2009;12:99–107. 20. Gal G, Abiri L, Reichenberg A, Gabis L, Gross R. Time trends in reported autism spectrum disorders in Israel, 1986–2005. J Autism Dev Disord 2012;42:428–31. 21. Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: The Special Needs and Autism Project (SNAP). Lancet 2006;368:210–15. 22. Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C. Prevalence of autism in a US metropolitan area. JAMA 2003;289:49–55. 23. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators, Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, United States, 2009. MMWR Surveill Summ 2009;58:1–20. 24. Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: The Special Needs and Autism Project (SNAP). Lancet 2006;368:210–15. 25. Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE et al. Prevalence of autism-spectrum conditions: UK school-based population study. Br J Psychiatry 2009;194:500–9. 26. Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 2011;168:904–12. 27. Roelfsema MT, Hoekstra RA, Allison C, Wheelwright S, Brayne C, Matthews FE et al. Are autism spectrum conditions more prevalent in an information-technology region? A schoolbased study of three regions in the Netherlands. J Autism Dev Disord 2012;42:734–9. 28. Atladóttir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Time trends in reported diagnoses of childhood neuropsychiatric disorders: A Danish cohort study. Arch Pediatr Adolesc Med 2007;161:193–8. 29. Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG. et al. Rate of first recorded diagnosis of autism and other pervasive developmental disorders in United Kingdom general practice, 1988 to 2001. BMC Medicine 2004;2:39. 30. Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: A time trend analysis. BMJ 2001;322:460–3. 31. Powell JE, Edwards A, Edwards M, Pandit BS, Sungum-Paliwal SR, Whitehouse W. Changes in the incidence of childhood autism and other autistic spectrum disorders in preschool children from two areas of the West Midlands, UK. Dev Med Child Neurol 2000;42:624–8. 32. Kielinen M, Linna SL, Moilanen I. Autism in Northern Finland. Eur Child Adolesc Psychiatry 2000;9:162–7. 33. Jick H, Kaye JA, Black C. Changes in risk of autism in the U.K. for birth cohorts 1990–1998. Epidemiology 2003;14:630–2. 34. Wong VC, Hui SL. Epidemiological study of autism spectrum disorder in China. J Child Neurol 2008;23:67–72. 35. Honda H, Shimizu Y, Imai M, Nitto Y. Cumulative incidence of childhood autism: A total population study of better accuracy and precision. Dev Med Child Neurol 2005;47:10–18.
479
Nord J Psychiatry Downloaded from informahealthcare.com by Deakin University on 03/13/15 For personal use only.
S HINKKA-YLI-SALOMÄKI ET AL. 36. Davidovitch M, Holtzman G, Tirosh E. Autism in the Haifa area—an epidemiological perspective. Isr Med Assoc J 2001;3:188–9. 37. Nassar N, Dixon G, Bourke J, Bower C, Glasson E, de Klerk N et al. Autism spectrum disorders in young children: Effect of changes in diagnostic practices. Int J Epidemiol 2009;38:1245–54. 38. Williams K, Glasson EJ, Wray J, Tuck M, Helmer M, Bower CI et al. Incidence of autism spectrum disorders in children in two Australian states. Med J Aust 2005;182:108–11. 39. Burstyn I, Sithole F, Zwaigenbaum L. Autism spectrum disorders, maternal characteristics and obstetric complications among singletons born in Alberta, Canada. Chronic Dis Can 2010;30: 125–34. 40. Barbaresi WJ, Colligan RC, Weaver AL, Katusic SK. The incidence of clinically diagnosed versus research-identified autism in Olmsted County, Minnesota, 1976–1997: Results from a retrospective, population-based study. J Autism Dev Disord 2009;39:464–70. 41. Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. The incidence of autism in Olmsted County, Minnesota, 1976–1997: Results from a population-based study. Arch Pediatr Adolesc Med 2005;159:37–44. 42. Lampi KM, Banerjee PN, Gissler M, Hinkka-Yli-Salomaki S, Huttunen J, Kulmala U et al. Finnish prenatal study of autism and autism spectrum disorders (FIPS-A): Overview and design. J Autism Dev Disord 2011;41:1090–6. 43. Gissler M, Shelley J. Quality of data on subsequent events in a routine Medical Birth Register. Med Inform Internet Med 2002;27:33–8. 44. Teperi J. Multi method approach to the assessment of data quality in the Finnish Medical Birth Registry. J Epidemiol Community Health 1993;47:242–7. 45. Lampi KM, Sourander A, Gissler M, Niemela S, Rehnstrom K, Pulkkinen E et al. Brief report: Validity of Finnish registry-based diagnoses of autism with the ADI-R. Acta Paediatr 2010;99: 1425–8.
480
46. Oehlert GW. A note on the delta method. Am Stat 1992;46:27–9. 47. Bienvenu T, Philippe C, De Roux N, Raynaud M, Bonnefond JP, Pasquier L et al. The incidence of Rett syndrome in France. Pediatr Neurol 2006;34:372–5. 48. King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol 2009;38:1224–34. 49. The Finnish Society for Autism. http://www.suomenautismiyhdistys. com. Accessed 23 Apr 2013 50. The Finnish Association for Autism and Asperger’s Syndrome. http://www.autismiliitto.fi/liitto/in_english. Accessed 23 Apr 2013 51. Statistics Finland. http://www.stat.fi/index_en.html. Accessed 23 Apr 2013 52. Eurostat. http://epp.eurostat.ec.europa.eu/statistics_explained/ index.php/Migration_and_migrant_population_statistics. Accessed 23 Apr 2013 Susanna Hinkka-Yli-Salomäki, Department of Child Psychiatry, University of Turku, Turku, Finland. P. Nina Banerjee, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA. Mika Gissler, Department of Child Psychiatry, University of Turku, Turku, Finland; Information Department, National Institute for Health and Welfare, Helsinki, Finland, and Nordic School of Public Health, Gothenburg, Sweden. Katja M. Lampi, Department of Child Psychiatry, University of Turku, Turku, Finland. Raija Vanhala, Department of Child Neurology, Helsinki University Central Hospital, Helsinki, Finland. Alan S. Brown, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA and Department of Child Psychiatry, University of Turku, Turku, Finland. André Sourander, Department of Child Psychiatry, University of Turku, Turku, Finland, and Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, NY, USA.
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