J Autism Dev Disord DOI 10.1007/s10803-015-2486-6
ORIGINAL PAPER
Low but Increasing Prevalence of Autism Spectrum Disorders in a French Area from Register-Based Data Marit Maria Elisabeth van Bakel1 • Malika Delobel-Ayoub2,3 • Christine Cans4 Brigitte Assouline5 • Pierre-Simon Jouk6,7 • Jean-Philippe Raynaud2,3,8 • Catherine Arnaud2,3,9
•
Ó Springer Science+Business Media New York 2015
Abstract Register-based prevalence rates of childhood autism (CA), Asperger’s syndrome (AS) and other autism spectrum disorders (ASD) were calculated among children aged 7 years old of the 1997–2003 birth cohorts, living in four counties in France. The proportion of children presenting comorbidities was reported. 1123 children with ASD were recorded (M/F ratio: 4.1), representing an overall prevalence rate of 36.5/10,000 children (95 % CI 34.4–38.7): 8.8/10,000 for CA (95 % CI 7.8–9.9), 1.7/ 10,000 for AS (95 % CI 1.3–2.3) and 25.9/10,000 for other ASD (95 % CI 24.2–27.8). ASD prevalence significantly
& Marit Maria Elisabeth van Bakel [email protected] 1
Register for Severely Disabled Children and Perinatal Observatory (RHEOP), 23 Avenue Albert 1er de Belgique, 38000 Grenoble, France
2
INSERM U.1027, 330 Avenue de Grand Bretagne, 31000 Toulouse, France
3
Paul-Sabatier University, 31400 Toulouse, France
4
Themas Team, UMR 5525, Joseph Fourier University, Domaine de la Merci, 38706 Grenoble, France
5
Autism Resource Centre of the Rhone-Alpes Region, 3 rue de la Gare, 38521 St-Egreve, France
6
Department of Genetics and Procreation, University Hospital Grenoble, Avenue du Maquis du Gre´sivaudan, 38700 Grenoble, France
7
DYCTIM Team, UMR 5525 TIMC-IMAG, Joseph Fourier University Hospital, Domaine de la Merci, 38706 Grenoble, France
8
Department of Child Psychiatry, La Grave University Hospital, Place Lange, 31059 Toulouse, France
9
Department of Clinical Epidemiology, Purpan University Hospital, 31300 Toulouse, France
increased (p \ 0.0001) during the period under study. The proportion of children with an intellectual disability was 47.3 %, all other comorbidities were present in less than 5 % of the cases. Keywords Autism spectrum disorder Population register Prevalence Comorbidities
Introduction Individuals with autism all suffer from a triad of behavioural disorders with impairments in social interaction, developmental language and communication deficits, and rigid, repetitive behaviours, but not all persons show the same phenotypic features and to the same extent (Wing and Gould 1979). From the moment that Leo Kanner described the first individuals with infantile autism, diagnostic criteria and classifications of the disorder have continuously been evolving. This started with enlargement of the inclusion of individuals presenting several diagnostic features but not perfectly corresponding to the characteristics of the core autistic disorder, which are today altogether known under the umbrella term autism spectrum disorders. These changes in concepts of autism but also methodological artefacts (i.e. due to changes in classification, objectives and way of identification of cases), increased awareness, diagnostic substitution (Coo et al. 2008) or accretion (King and Bearman 2009), earlier diagnosis (Nassar et al. 2009), and possibly true rises in incidence due to changes in the risk factors in the society (Hultman et al. 2011; Pu et al. 2013; Sandin et al. 2012; Wing and Potter 2002), may have contributed to prevalence rates of up to 264 per 10,000 (Kim et al. 2011). In France, two registers ensure the surveillance of severe childhood
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neurodevelopmental disorders, among which ASD, in 7 year old children residing in geographically well defined areas. The French prevalence data have been communicated at the international level for the 1976–1985 (Fombonne et al. 1997) and the 1980–1993 birth cohorts (Guillem et al. 2006). We aimed to situate the prevalence data of ASD and related comorbidities of a French geographically restricted area among 7 year old children of the 1997–2003 birth cohorts within the internationally published data using populationbased register data, and to explain possible discrepancies.
Method Data Extraction The data from children born between 1997 and 2003, were extracted from the databases of the single two existing population-based registers in France actively monitoring severe childhood neurodevelopmental disabilities, i.e. the register called RHE31 covering the county of Haute-Garonne in the southwest of France (approximately 15,000 births per year), and the register called RHEOP covering three alpine counties in the southeast of France (the counties of Isere, Savoy and Upper-Savoy, together around 30,000 births per year). In spite of their distinct databases, these registers work in close collaboration and use the same definitions and criteria for including and describing children in their registers. Both registers routinely record all cases of autism spectrum disorders as well as children with cerebral palsy, intellectual disability, hearing loss and visual disability. Briefly, medical surveyors visited various sources where they collected information on children with a confirmed ASD diagnosis before their 8th birthday, and living in their 8th year of life in one of the above mentioned counties. These sources included all places contacted by families with children diagnosed with ASD, thus altogether covering the entire population. The main data source was the local public authority (Maison De´partementale des Personnes Handicape´es, MDPH) centralising all demands regarding financial allowances or educational support with regular or specialized schooling for children having widely varying disabilities. Financial and educational support are attributed independently from each other and concern children with all degrees of ASD severity, even the milder forms which benefit only from educational support at regular school. As from the first of April 2014 caregivers of children with an incapability [50 % are entitled to a monthly basic allowance of 130 € (183 US $). An additional monthly allowance (ranging from 98 € to 1103 €, or 137 US $ to 1554 US $) is granted if the child needs costly equipment or the assistance of an adult for daily tasks. The other sources were ASD
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diagnostic centres (CRAs), psychiatric day-care centres and centres for psychiatric outpatient care. On average, 1.5 sources per child were consulted. The age for registration was set at the year when the child turns eight, because in France school is compulsory for all children from age six and teachers play an important role in the referral of parents to a specialist for specific psychiatric assessments. We can reasonably assume that within 2 years all families concerned have had the time to register at the local public authorities to request for financial and/or educational support. Before collecting information, informed consent from 97 % of the parents was obtained. For the four MDPH, the informed consent of the parents of all children being registered was searched, independent whether their child was diagnosed an ASD or not. The surveyors collected information either by abstracting notes from medical records containing child psychiatrists’ diagnoses, or in case of doubt by direct contact with these qualified professionals. Registration was never based on any interpretation by surveyors. In addition, to assure consistent methods across surveyors, they are supervised along the whole procedure by the directors of the two registers. French psychiatrists traditionally based their diagnoses upon the clinical picture, but nowadays increasingly use specific tests or rely on CRA evaluations for ASD diagnosis. The CRAs particularly screen children whose diagnosis upon the clinical picture only is difficult. The surveyors subsequently coded the diagnoses according to the International Classification of Diseases, 10th edition (ICD10) (WHO 1993). The few diagnoses that were still expressed according to the definitions and concepts of the French classification of mental diseases (CFTMEA) were converted using a standardized table (Botbol and Portelli 2011). For the present study, we considered all ICD-10 codes on pervasive developmental disorders: F84.0 [childhood autism (CA)], F84.5 (Asperger’s syndrome, AS), and codes F84.1, F84.3, F84.8 and F84.9 (grouped into ‘other ASD’), except F84.2 (Rett syndrome) because of the fact that it will be removed from the ASD group in the upcoming 11th edition of the ICD and F84.4 (overactive disorder associated with mental retardation and stereotyped movements), because of its uncertain nosological validity. The medical files also contained results from various tests (cognitive, audio-, visual tests etc.) and information on educational and health care services. The presence of an intellectual disability (ID), cerebral palsy (CP), visual and hearing impairment, epilepsy, malformations, genetic syndromes and chromosomal aberrations was recorded. ID was measured as cognitive ability and classified according to the ICD-10 criteria into three levels: severe ID (IQ \ 50), mild ID (IQ = 50–69), and no ID (IQ C 70). Severe ID included those who could not be tested because of very low functioning. Diagnosis of ID was based on clinical assessment or based upon standardized cognitive
J Autism Dev Disord
tests (mainly Wechsler’s tests). Cerebral palsy was defined according to the SCPE definition (Cans et al. 2007), hearing impairment was defined as a loss of more than 70 dB of the best ear before correction, and visual impairment was defined as an acuity of less than 3/10 of the best eye after correction. The definition of epilepsy was having had at least two unprovoked seizures in life (excluding febrile and neonatal seizures). Both registers have obtained approval of the French national ethical committees for the treatment and processing of nominal data. Data Analysis Prevalence estimates and occurrence of comorbidities were calculated for each of the ASD categories defined above and for its combined figures. Prevalence estimates were expressed as the number of children with ASD per 10,000 children of the same age living in the same areas. The 95 % confidence intervals (95 % CI) were calculated over the whole period and for each category. Occurrence of comorbidities was expressed as proportions. Differences between groups were tested with the v2 test. Analyses on prevalence over time were done with the Cochran-Armitage test of STATA statistical package version 10 (StataCorp, College Station, TX, USA).
Results Over the period 1997–2003, 1123 children with ASD living at the age of 7 years in the area covered by the registers, were diagnosed (Table 1). The overall prevalence of ASD Table 1 Prevalence estimates of childhood autism, Asperger’s syndrome, other autism spectrum disorders and all autism spectrum disorders, 95 % CIs and sex-ratio in 7 year old children born between Generation
Reference populationa
was 36.5 per 10,000 (95 % CI = 34.4–38.7), and varied from 8.8 per 10,000 (95 % CI = 7.8–9.9) for CA, to 1.7 per 10,000 (95 % CI = 1.3–2.3) for AS, and 25.9 per 10,000 (95 % CI = 24.2–27.8) for other ASD. Prevalence was different across gender (p \ 0.001), i.e. 13.4 per 10,000 (95 % CI = 11.7–15.4) for girls and 59.0 per 10,000 (95 % CI = 55.1–63.0) for boys. Sex ratio was 4.1 (880 boys, 213 girls, 30 of unknown gender) for the total group, but varied significantly (p = 0.003) across ASD subgroups. There was a significant (p \ 0.0001) increase in overall prevalence from 26.2 per 10,000 (95 % CI = 21.6–31.5) in children born in 1997 to 41.3 per 10,000 (95 % CI = 35.6–47.7) in children born in 2003, which was also significant for the other ASD category (p \ 0.001), but not for the CA (p = 0.17) and AS (p = 0.49) categories. Table 2 shows the frequency and proportion of each of the comorbidities, genetic syndromes or chromosomal aberrations and malformations by autism subgroup. An ID (IQ \ 70) was present in 527 (46.9 %) children, of whom 31.7 % (n = 167) had a mild ID and 55.4 % (n = 292) a severe ID. For 12.9 % (n = 68) the exact ID level was not specified, but the IQ value was below 70. Children with CA presented more often an ID than children with other ASD (60.1 vs. 46.1 %, p = 0.03). By definition, none of the children with AS presented an ID. Epilepsy was present in 4.7 % of the cases (n = 53), and 3.4 % (n = 38) had both an ID and epilepsy. Among those having epilepsy, an ID was also present in 71.7 %, but inversely only 7.1 % of those having an ID suffered from epilepsy as well. In children without ID, only 2.5 % suffered from epilepsy. Cerebral palsy was diagnosed in 1.5 % (n = 17) of the children with ASD, visual and hearing impairments both in 0.8 % 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy
Number
Prevalence
CA
AS
Other ASD
All ASD
CA
AS
Other ASD
All ASD
95 % CI
1997
42,360
28
5
78
111
6.6
1.2
18.4
26.2
21.6–31.5
1998
42,724
33
5
107
145
7.7
1.2
25.0
33.9
28.6–40.0
1999
43,977
33
10
101
144
7.5
2.2
23.0
32.7
27.6–38.5
2000
44,275
42
8
122
172
9.5
1.8
27.6
38.8
33.3–45.1
2001
44,645
57
9
118
184
12.8
2.0
26.4
41.2
35.5–47.6
2002
44,742
46
10
125
181
10.3
2.2
27.9
40.5
34.8–46.8
2003 Total 95 % CI
45,028 30,7751
32 271
6 53
148 799
186 1123
7.1 8.8
1.3 1.7
32.6 25.9
41.3 36.5
35.6–47.7 34.4–38.7
1.3–2.3
24.2–27.8
7.8–9.9 Sex-ratio (m/f)
4.5
16.7
3.8
4.1
CA childhood autism, AS Asperger’s syndrome, ASD autism spectrum disorder a
Children of the same age, living in the same area
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J Autism Dev Disord Table 2 Presence of comorbidities, genetic syndromes and malformations in 7 year old children with autism spectrum disorders, born between 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy
Characteristic
CA n
Cerebral palsy
3
Intellectual disability (IQ \ 70)
163
Visual disability Hearing disability
AS %
n
%
Other ASD
All ASD
n
n
%
%
1.1
0
0
14
1.8
17
1.5
60.1
0
0
370
46.3
534
47.5
3
1.1
0
0
6
0.8
9
0.8
2
0.7
0
0
7
0.9
9
0.8
Epilepsy
15
5.5
2
3.8
36
4.5
53
4.7
Genetic syndrome or chromosomal aberration
5
1.8
0
0
20
2.5
25
2.2
Malformation
3
1.1
0
0
23
2.9
26
2.3
Table 3 Genetic and congenital syndromes, chromosomal aberrations and malformations in 7 year old children diagnosed with childhood autism, Asperger’s syndrome and other autism spectrum
disorders born between 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy
Anomalies
Syndromes and malformationsa
Chromosomal anomalies (n = 9)
Trisomy 21, trisomy 11, Klinefelter syndrome, William Beuren syndrome, Smith-Magenis syndrome, Angelman syndrome, complex chromosomal rearrangement (n = 2), chromosome 15 duplication (15q11)
Single gene disorders (n = 17)
Fragile X (n = 9), Bourneville syndrome (n = 2), Aase syndrome, faciodigitogenital syndrome, autosomal dominant polycystic kidney disease (n = 2), deafness due to connexin 26 anomaly, adenylosuccinase deficiency Agenesis of the corpus callosum (n = 4), microcephaly (n = 4), craniosynostosis (n = 3), cerebellar cyst, cerebellar malformation, Chiari type 1, periventricular nodular heterotopia
CNS anomalies without genetically identified anomalies (n = 15) Other anomalies (n = 14)
Heart malformation (2), Pierre Robin syndrome, cryptorchidism, pulmonary atresia, facial dysmorphy, congenital cataract, unilateral kidney agenesis, ureteral tract obstruction, abdominal cystic lymphangioma, coloboma of the eye, disorder of sex development, Duane retraction, congenital ptosis of right eye
a
One child has both a chromosomal anomaly and a malformation, one child has a single gene disorder and a malformation, one child has two single gene disorders and three children have two malformations
(n = 9) of the children. A syndrome (genetic or congenital) or chromosomal aberration was present in 2.2 % (n = 25) of the children (nine cases with X-fragile), and 2.3 % (n = 26) presented one or more malformations, both of which are detailed in Table 3. Gender differences were present for the proportion of ASD cases without ID (p = 0.001), as well as for the proportion of children with epilepsy (p = 0.003) and epilepsy in combination with ID (p = 0.002) (Table 4).
Discussion The average ASD prevalence rate in the presently studied 1997–2003 birth cohorts of children living at 7 years old in a French geographically restricted area comprising four counties was 36.5 per 10,000 children, which was higher than the previously published figures from France of 16.3 (Fombonne et al. 1997) and 22.2 (Guillem et al. 2006) per 10,000 children. However, compared to the global estimates calculated by Elsabbagh et al. (2012), including studies published since 2000, they still figure among the lowest prevalence values for both CA (17/10,000; range: 7.2–72.6)
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and total ASD (62/10,000; range: 30.0–116.1) (Elsabbagh et al. 2012). In Europe, the Swedish total ASD prevalence values of 50.2 per 10,000 for the 1999–2004 generations came closest to our figures (Atladottir et al. 2015), while at the global level only California showed similar prevalence rates for CA (Croen et al. 2002) and no other developed country showed similar values for total ASD. Part of the variation in prevalence across studies may be due to the population size, as estimates generally tend to be lower with increasing sample size (Elsabbagh et al. 2012). The present study included a large population of 1123 children with ASD, eligible from a population of 307,751 children, which is thus in favour of this explanation. Other possible explanations for the lower estimates found in this study include lack of exhaustiveness and representativeness, and different diagnostic and classification practices in France. Several arguments can be brought up against the lack of exhaustiveness: first, data were obtained through populationbased register activity, specifically collecting data on children with ASD, by actively collecting data from multiple sources. Guillem et al. (2000), using the capture-recapture
J Autism Dev Disord Table 4 Presence of comorbidities by gender in 7 year old children with autism spectrum disorders, born between 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy % Among boys (N = 880)
% Among girls (N = 213)
% Totala (N = 1123)
Male/female ratio
p value
Without ID
54.7
41.8
53.1
5.4
0.001
With ID (IQ \ 70) Mild ID (50 B IQ \ 70)
45.3 14.2
58.2 18.8
46.6 14.9
3.2 3.1
0.05 0.09
Severe ID (IQ \ 50)
24.9
33.3
26.0
3.1
0.06
6.3
6.1
6.1
4.2
0.4
ASD comorbidity Intellectual disability
Unspecified ID Epilepsy
3.9
8.9
4.7
1.8
0.004
Epilepsy and ID (IQ \ 70)
2.6
7.0
3.4
1.5
0.002
Anomalyb
4.2
5.6
4.4
3.1
0.39
CP, hearing- or visual disability
2.6
5.2
2.1
2.1
0.06
a
Including 30 children whose gender is unknown (26 are without ID, two with a mild ID and two with severe ID)
b
Including Genetic syndromes, chromosomal aberrations and malformations; Two children had both a genetic syndrome or chromosomal aberration and a malformation
method, showed that this way of proceeding resulted in highly exhaustive data for the RHEOP. Second, there is a strong incentive for parents to get their child known by the main source used by the registers, the county MDPH, as they play a very central role in the allocation of a wide range of services (including educational support for regular school) and they ensure substantial financial allowances to the families. Indeed, the number of parents that constituted a file at the MDPH increased over 70 % in 5 years. In rare cases, families ask for interventions without being registered at the MDPH. To ensure exhaustive coverage, cases were additionally searched for by extracting records from psychiatric day-care centres and centres for psychiatric outpatient care, which allowed to find 6 % of the children. Nevertheless, as our population was not systematically screened we may particularly have missed some of the milder types, i.e. those falling short of the strict diagnostic criteria for CA. The boundaries for inclusion are internationally still not well defined and it may be that the French psychiatrists who traditionally used the conceptually more conservative French classification for mental disorders of children and adolescents (CFTMEA), though having passed on to the ICD10, are still more conservative in diagnosing an ASD. Underestimation of the AS category in this population of 7 year old may also have contributed to the lower prevalence estimates, as diagnosis in these children occurs frequently only between 8 and 12 years (Howlin and Asgharian 1999). Our estimate of 1.7 per 10,000 was indeed in the lower range of the studies included in the review of Fombonne (2001) (range 0.3–48.4 per 10,000) (Fombonne 2001), and was more than ten times lower than the prevalence of 21.6 per 10,000 reported in an Icelandic
population of the same age (Saemundsen et al. 2013). Nevertheless, the influence on total prevalence is negligible as numbers in this category are relatively small compared to the whole group of children with ASD. Still another reason may be that the geographical areas covered by the registers are not representative for France. However, there are no particular arguments to support this hypothesis: the counties include both rural and urban areas and in spite of being separated by nearly 400 km, the two registers’ ASD prevalence rates were highly comparable (Delobel et al. 2012). Finally, some of the 3 % families that refused to participate may have had a child with an ASD diagnosis. In spite of these lower values, ASD prevalence values have risen in this French area, similarly to what has been observed at the global level. According to the reasons detailed below, changes in classification, diagnostic substitution, changing diagnostic procedures, improved service availability, better acceptance and awareness have probably each contributed to the increased prevalence rates, but we can neither draw any conclusion on their relative contributions nor on the impact of changing environmental risk factors, as this was beyond the scope of this study. The age of diagnosis was not available in our population, but in France the average age at diagnosis decreased significantly in recent decades (Saint-Georges et al. 2013) and may as well have contributed to increased prevalence values. Concerning changes in classification, as mentioned above, French children were in the past exclusively classified according to the French CFTMEA while for the current study nearly all children were directly classified according to the less conservative ICD10. Also, diagnostic substitution with ID may have played a role in this increase. Both disorders are defined by behavioural characteristics that
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have been subject to change over time and overlapping areas exists between ID and ASD. As a result, persons with ASD were easily overlooked in the past (Oeseburg et al. 2010). Indeed, it has been shown that as the rate of ASD diagnoses goes up, the rates of ID and learning disability diagnoses go down (Shattuck 2006). As the registers involved in this study also register children with severe ID (IQ \ 50), we looked upon these prevalence rates in the same period as the one considered in this study. Even though the overall prevalence of severe ID (associated or not with ASD) did not change in this period, a sharp decrease in prevalence was observed from 1997 to 1998, followed by a steady increase till the end of the period studied (data not shown). Even if the latter picture is incomplete because of the lack of data on mild ID, these data may indeed reflect a transition period in which increasing knowledge and tools for differential diagnosis of the two disorders seem to bear fruit. It is important to obtain both diagnoses, as persons with both ID and ASD have different needs from individuals having only one of the disorders. Concerning the changing diagnostic procedures, in France children are since 1998 increasingly referred to specialized Centers for Autism (CRAs) which use standardized tests for diagnosis, while in the past they were principally diagnosed upon clinical assessment, which is more subjective than the standardized diagnoses used at the CRAs (Bursztejn et al. 2011). This activity may thus have contributed to the increasing prevalence figures. Finally, the continuous increasing number of parents’ requesting support at the counties’ MDPH, suggests increased awareness and acceptance of having a child with ASD in the society, although the increased requests may evenly well be due to improved service availability. Association with Medical Disorders An ID (IQ \ 70) was present in 60.1 and 46.1 % of the children with CA and other ASD, respectively. These figures fall in the range of 25.7–70 % from previous studies reporting on ID (Fombonne 2009; Saemundsen et al. 2013). In the present study about 40 % of the children were tested cognitively, formal ID figures may therefore be slightly lower (Saemundsen et al. 2013). On the other hand, the proportion of children of the category ‘‘other ASD’’ having additionally an ID initially increased, and was steadily decreasing only since 2000 (data not shown) suggesting that an ID was overlooked in part of the children or that particularly children of the older generations, had received the wrong diagnostic label. The sex ratio (M/F) of children without ID was 5.1, which was higher than the ratio found in both the mild and severe ID categories (both 3.1), showing that the male–female profile differed across
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subgroups. Figures on epilepsy were lower (overall 4.7, 7.1 % in those with ID, 2.5 % in those without ID) as compared to the pooled prevalence values of 21.5 % in children with ID and 8 % in children without ID, calculated by Amiet et al. (2008), but were similar to the values described in a recent Icelandic study (Saemundsen et al. 2013). The age at registration could be responsible for this difference as epilepsy appears in the majority after the age of 10 years (Bolton et al. 2011). However, other factors also seem to influence, as the children in the Icelandic study were between 11 and 15 year old (Saemundsen et al. 2013). Like previous studies, epilepsy in our ASD group was associated more often to the female than the male gender, both in presence and absence of ID (Amiet et al. 2008; Saemundsen et al. 2013). In our population, ASD was associated in 2.2 % of the children with a known genetic cause, which is lower compared to literature estimates of 10–20 % (Betancur 2011). Fragile X syndrome, tuberous sclerosis, abnormalities of chromosome 15 involving the 15q11-13 region and deletions and duplication of 16p11 are currently considered probable causes for autism (Kumar and Christian 2009). Fragile X occurred in 0.8 % of our cases, while values probably lie between 2 and 8 % (Harris et al. 2008). Tuberous Sclerosis and duplication of the 15q11 region were detected in two and one of our cases (less than 0.5 % each), respectively, as compared to 2 % in the literature. None of our cases had abnormal findings for 16p11, while it was reported in 1 % of cases in the literature (Kumar and Christian 2009). The comparison of the presence of malformations is complicated, as it is not clearly defined what should be included. Congenital central nervous system malformations were reported in 2.2 % of the Icelandic children (Saemundsen et al. 2013), compared to 1.3 % in our children. The main reason of the lower values is most likely that the children in our study were not systematically screened for genetic syndromes and malformations. To conclude, ASD figures in the four French counties under study were among the lowest worldwide, but reflect well the current diagnostic practices of French psychiatrists. Nevertheless, continued surveillance of the rising prevalence is of public health importance, as early detection and adequate services contribute to better outcomes (Reichow et al. 2012). Conflict of interest All authors declare that they have no conflict of interest in relation to this study. Ethical Standards The study was carried out according to the French regulations of individual privacy. Parents who agreed to participate signed an informed consent form prior to inclusion of their child the study. The National Commission on Informatics and Liberties (CNIL) authorized the treatment and digitalization of the nominative data.
J Autism Dev Disord
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syndrome. American Journal of Mental Retardation, 113, 427–438. Howlin, P., & Asgharian, A. (1999). The diagnosis of autism and Asperger syndrome: Findings from a survey of 770 families. Developmental Medicine and Child Neurology, 41, 834–839. Hultman, C. M., Sandin, S., Levine, S. Z., Lichtenstein, P., & Reichenberg, A. (2011). Advancing paternal age and risk of autism: New evidence from a population-based study and a meta-analysis of epidemiological studies. Molecular Psychiatry, 16, 1203–1212. Kim, Y. S., Leventhal, B. L., Koh, Y. J., Fombonne, E., Laska, E., Lim, E. C., et al. (2011). Prevalence of autism spectrum disorders in a total population sample. American Journal of Psychiatry, 168, 904–912. King, M., & Bearman, P. (2009). Diagnostic change and the increased prevalence of autism. International Journal of Epidemiology, 38, 1224–1234. Kumar, R. A., & Christian, S. L. (2009). Genetics of autism spectrum disorders. Current Neurology and Neuroscience Reports, 9, 188–197. Nassar, N., Dixon, G., Bourke, J., Bower, C., Glasson, E., de Klerk, N., et al. (2009). Autism spectrum disorders in young children: Effect of changes in diagnostic practices. International Journal of Epidemiology, 38, 1245–1254. Oeseburg, B., Groothoff, J. W., Dijkstra, G. J., Reijneveld, S. A., & Jansen, D. E. (2010). Pervasive developmental disorder behavior in adolescents with intellectual disability and co-occurring somatic chronic diseases. Research in Developmental Disabilities, 31, 496–501. Pu, D., Shen, Y., & Wu, J. (2013). Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: A meta-analysis. Autism Research, 6, 384–392. Reichow, B., Barton, E. E., Boyd, B. A., & Hume, K. (2012). Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD). Cochrane Database Systematic Reviews, 10, CD009260. Saemundsen, E., Magnusson, P., Georgsdottir, I., Egilsson, E., Rafnsson, V. (2013). Prevalence of autism spectrum disorders in an Icelandic birth cohort. BMJ Open, 3(6), e002748. Saint-Georges, C., Guinchat, V., Chamak, B., Apicella, F., Muratori, F., & Cohen, D. (2013). Signes pre´coces d’autisme : d’ou` vienton ? Ou` va-t-on ? [Early signs of autism: Where have we been? Where are we going?]. Neuropsychiatrie Enfance et de l’Adolescence, 61, 400–408. Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., & Reichenberg, A. (2012). Advancing maternal age is associated with increasing risk for autism: A review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 51, 477–486. Shattuck, P. T. (2006). The contribution of diagnostic substitution to the growing administrative prevalence of autism in US special education. Pediatrics, 117, 1028–1037. WHO. (1993). International classification of diseases (10th revision ed.). Geneva, Switzerland: World Health Organization. Wing, L., & Gould, J. (1979). Severe impairments of social interaction and associated abnormalities in children: Epidemiology and classification. Journal of Autism and Developmental Disorders, 9, 11–29. Wing, L., & Potter, D. (2002). The epidemiology of autistic spectrum disorders: Is the prevalence rising? Mental Retardation and Developmental Disabilities Research Reviews, 8, 151–161.
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ORIGINAL PAPER
Low but Increasing Prevalence of Autism Spectrum Disorders in a French Area from Register-Based Data Marit Maria Elisabeth van Bakel1 • Malika Delobel-Ayoub2,3 • Christine Cans4 Brigitte Assouline5 • Pierre-Simon Jouk6,7 • Jean-Philippe Raynaud2,3,8 • Catherine Arnaud2,3,9
•
Ó Springer Science+Business Media New York 2015
Abstract Register-based prevalence rates of childhood autism (CA), Asperger’s syndrome (AS) and other autism spectrum disorders (ASD) were calculated among children aged 7 years old of the 1997–2003 birth cohorts, living in four counties in France. The proportion of children presenting comorbidities was reported. 1123 children with ASD were recorded (M/F ratio: 4.1), representing an overall prevalence rate of 36.5/10,000 children (95 % CI 34.4–38.7): 8.8/10,000 for CA (95 % CI 7.8–9.9), 1.7/ 10,000 for AS (95 % CI 1.3–2.3) and 25.9/10,000 for other ASD (95 % CI 24.2–27.8). ASD prevalence significantly
& Marit Maria Elisabeth van Bakel [email protected] 1
Register for Severely Disabled Children and Perinatal Observatory (RHEOP), 23 Avenue Albert 1er de Belgique, 38000 Grenoble, France
2
INSERM U.1027, 330 Avenue de Grand Bretagne, 31000 Toulouse, France
3
Paul-Sabatier University, 31400 Toulouse, France
4
Themas Team, UMR 5525, Joseph Fourier University, Domaine de la Merci, 38706 Grenoble, France
5
Autism Resource Centre of the Rhone-Alpes Region, 3 rue de la Gare, 38521 St-Egreve, France
6
Department of Genetics and Procreation, University Hospital Grenoble, Avenue du Maquis du Gre´sivaudan, 38700 Grenoble, France
7
DYCTIM Team, UMR 5525 TIMC-IMAG, Joseph Fourier University Hospital, Domaine de la Merci, 38706 Grenoble, France
8
Department of Child Psychiatry, La Grave University Hospital, Place Lange, 31059 Toulouse, France
9
Department of Clinical Epidemiology, Purpan University Hospital, 31300 Toulouse, France
increased (p \ 0.0001) during the period under study. The proportion of children with an intellectual disability was 47.3 %, all other comorbidities were present in less than 5 % of the cases. Keywords Autism spectrum disorder Population register Prevalence Comorbidities
Introduction Individuals with autism all suffer from a triad of behavioural disorders with impairments in social interaction, developmental language and communication deficits, and rigid, repetitive behaviours, but not all persons show the same phenotypic features and to the same extent (Wing and Gould 1979). From the moment that Leo Kanner described the first individuals with infantile autism, diagnostic criteria and classifications of the disorder have continuously been evolving. This started with enlargement of the inclusion of individuals presenting several diagnostic features but not perfectly corresponding to the characteristics of the core autistic disorder, which are today altogether known under the umbrella term autism spectrum disorders. These changes in concepts of autism but also methodological artefacts (i.e. due to changes in classification, objectives and way of identification of cases), increased awareness, diagnostic substitution (Coo et al. 2008) or accretion (King and Bearman 2009), earlier diagnosis (Nassar et al. 2009), and possibly true rises in incidence due to changes in the risk factors in the society (Hultman et al. 2011; Pu et al. 2013; Sandin et al. 2012; Wing and Potter 2002), may have contributed to prevalence rates of up to 264 per 10,000 (Kim et al. 2011). In France, two registers ensure the surveillance of severe childhood
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J Autism Dev Disord
neurodevelopmental disorders, among which ASD, in 7 year old children residing in geographically well defined areas. The French prevalence data have been communicated at the international level for the 1976–1985 (Fombonne et al. 1997) and the 1980–1993 birth cohorts (Guillem et al. 2006). We aimed to situate the prevalence data of ASD and related comorbidities of a French geographically restricted area among 7 year old children of the 1997–2003 birth cohorts within the internationally published data using populationbased register data, and to explain possible discrepancies.
Method Data Extraction The data from children born between 1997 and 2003, were extracted from the databases of the single two existing population-based registers in France actively monitoring severe childhood neurodevelopmental disabilities, i.e. the register called RHE31 covering the county of Haute-Garonne in the southwest of France (approximately 15,000 births per year), and the register called RHEOP covering three alpine counties in the southeast of France (the counties of Isere, Savoy and Upper-Savoy, together around 30,000 births per year). In spite of their distinct databases, these registers work in close collaboration and use the same definitions and criteria for including and describing children in their registers. Both registers routinely record all cases of autism spectrum disorders as well as children with cerebral palsy, intellectual disability, hearing loss and visual disability. Briefly, medical surveyors visited various sources where they collected information on children with a confirmed ASD diagnosis before their 8th birthday, and living in their 8th year of life in one of the above mentioned counties. These sources included all places contacted by families with children diagnosed with ASD, thus altogether covering the entire population. The main data source was the local public authority (Maison De´partementale des Personnes Handicape´es, MDPH) centralising all demands regarding financial allowances or educational support with regular or specialized schooling for children having widely varying disabilities. Financial and educational support are attributed independently from each other and concern children with all degrees of ASD severity, even the milder forms which benefit only from educational support at regular school. As from the first of April 2014 caregivers of children with an incapability [50 % are entitled to a monthly basic allowance of 130 € (183 US $). An additional monthly allowance (ranging from 98 € to 1103 €, or 137 US $ to 1554 US $) is granted if the child needs costly equipment or the assistance of an adult for daily tasks. The other sources were ASD
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diagnostic centres (CRAs), psychiatric day-care centres and centres for psychiatric outpatient care. On average, 1.5 sources per child were consulted. The age for registration was set at the year when the child turns eight, because in France school is compulsory for all children from age six and teachers play an important role in the referral of parents to a specialist for specific psychiatric assessments. We can reasonably assume that within 2 years all families concerned have had the time to register at the local public authorities to request for financial and/or educational support. Before collecting information, informed consent from 97 % of the parents was obtained. For the four MDPH, the informed consent of the parents of all children being registered was searched, independent whether their child was diagnosed an ASD or not. The surveyors collected information either by abstracting notes from medical records containing child psychiatrists’ diagnoses, or in case of doubt by direct contact with these qualified professionals. Registration was never based on any interpretation by surveyors. In addition, to assure consistent methods across surveyors, they are supervised along the whole procedure by the directors of the two registers. French psychiatrists traditionally based their diagnoses upon the clinical picture, but nowadays increasingly use specific tests or rely on CRA evaluations for ASD diagnosis. The CRAs particularly screen children whose diagnosis upon the clinical picture only is difficult. The surveyors subsequently coded the diagnoses according to the International Classification of Diseases, 10th edition (ICD10) (WHO 1993). The few diagnoses that were still expressed according to the definitions and concepts of the French classification of mental diseases (CFTMEA) were converted using a standardized table (Botbol and Portelli 2011). For the present study, we considered all ICD-10 codes on pervasive developmental disorders: F84.0 [childhood autism (CA)], F84.5 (Asperger’s syndrome, AS), and codes F84.1, F84.3, F84.8 and F84.9 (grouped into ‘other ASD’), except F84.2 (Rett syndrome) because of the fact that it will be removed from the ASD group in the upcoming 11th edition of the ICD and F84.4 (overactive disorder associated with mental retardation and stereotyped movements), because of its uncertain nosological validity. The medical files also contained results from various tests (cognitive, audio-, visual tests etc.) and information on educational and health care services. The presence of an intellectual disability (ID), cerebral palsy (CP), visual and hearing impairment, epilepsy, malformations, genetic syndromes and chromosomal aberrations was recorded. ID was measured as cognitive ability and classified according to the ICD-10 criteria into three levels: severe ID (IQ \ 50), mild ID (IQ = 50–69), and no ID (IQ C 70). Severe ID included those who could not be tested because of very low functioning. Diagnosis of ID was based on clinical assessment or based upon standardized cognitive
J Autism Dev Disord
tests (mainly Wechsler’s tests). Cerebral palsy was defined according to the SCPE definition (Cans et al. 2007), hearing impairment was defined as a loss of more than 70 dB of the best ear before correction, and visual impairment was defined as an acuity of less than 3/10 of the best eye after correction. The definition of epilepsy was having had at least two unprovoked seizures in life (excluding febrile and neonatal seizures). Both registers have obtained approval of the French national ethical committees for the treatment and processing of nominal data. Data Analysis Prevalence estimates and occurrence of comorbidities were calculated for each of the ASD categories defined above and for its combined figures. Prevalence estimates were expressed as the number of children with ASD per 10,000 children of the same age living in the same areas. The 95 % confidence intervals (95 % CI) were calculated over the whole period and for each category. Occurrence of comorbidities was expressed as proportions. Differences between groups were tested with the v2 test. Analyses on prevalence over time were done with the Cochran-Armitage test of STATA statistical package version 10 (StataCorp, College Station, TX, USA).
Results Over the period 1997–2003, 1123 children with ASD living at the age of 7 years in the area covered by the registers, were diagnosed (Table 1). The overall prevalence of ASD Table 1 Prevalence estimates of childhood autism, Asperger’s syndrome, other autism spectrum disorders and all autism spectrum disorders, 95 % CIs and sex-ratio in 7 year old children born between Generation
Reference populationa
was 36.5 per 10,000 (95 % CI = 34.4–38.7), and varied from 8.8 per 10,000 (95 % CI = 7.8–9.9) for CA, to 1.7 per 10,000 (95 % CI = 1.3–2.3) for AS, and 25.9 per 10,000 (95 % CI = 24.2–27.8) for other ASD. Prevalence was different across gender (p \ 0.001), i.e. 13.4 per 10,000 (95 % CI = 11.7–15.4) for girls and 59.0 per 10,000 (95 % CI = 55.1–63.0) for boys. Sex ratio was 4.1 (880 boys, 213 girls, 30 of unknown gender) for the total group, but varied significantly (p = 0.003) across ASD subgroups. There was a significant (p \ 0.0001) increase in overall prevalence from 26.2 per 10,000 (95 % CI = 21.6–31.5) in children born in 1997 to 41.3 per 10,000 (95 % CI = 35.6–47.7) in children born in 2003, which was also significant for the other ASD category (p \ 0.001), but not for the CA (p = 0.17) and AS (p = 0.49) categories. Table 2 shows the frequency and proportion of each of the comorbidities, genetic syndromes or chromosomal aberrations and malformations by autism subgroup. An ID (IQ \ 70) was present in 527 (46.9 %) children, of whom 31.7 % (n = 167) had a mild ID and 55.4 % (n = 292) a severe ID. For 12.9 % (n = 68) the exact ID level was not specified, but the IQ value was below 70. Children with CA presented more often an ID than children with other ASD (60.1 vs. 46.1 %, p = 0.03). By definition, none of the children with AS presented an ID. Epilepsy was present in 4.7 % of the cases (n = 53), and 3.4 % (n = 38) had both an ID and epilepsy. Among those having epilepsy, an ID was also present in 71.7 %, but inversely only 7.1 % of those having an ID suffered from epilepsy as well. In children without ID, only 2.5 % suffered from epilepsy. Cerebral palsy was diagnosed in 1.5 % (n = 17) of the children with ASD, visual and hearing impairments both in 0.8 % 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy
Number
Prevalence
CA
AS
Other ASD
All ASD
CA
AS
Other ASD
All ASD
95 % CI
1997
42,360
28
5
78
111
6.6
1.2
18.4
26.2
21.6–31.5
1998
42,724
33
5
107
145
7.7
1.2
25.0
33.9
28.6–40.0
1999
43,977
33
10
101
144
7.5
2.2
23.0
32.7
27.6–38.5
2000
44,275
42
8
122
172
9.5
1.8
27.6
38.8
33.3–45.1
2001
44,645
57
9
118
184
12.8
2.0
26.4
41.2
35.5–47.6
2002
44,742
46
10
125
181
10.3
2.2
27.9
40.5
34.8–46.8
2003 Total 95 % CI
45,028 30,7751
32 271
6 53
148 799
186 1123
7.1 8.8
1.3 1.7
32.6 25.9
41.3 36.5
35.6–47.7 34.4–38.7
1.3–2.3
24.2–27.8
7.8–9.9 Sex-ratio (m/f)
4.5
16.7
3.8
4.1
CA childhood autism, AS Asperger’s syndrome, ASD autism spectrum disorder a
Children of the same age, living in the same area
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J Autism Dev Disord Table 2 Presence of comorbidities, genetic syndromes and malformations in 7 year old children with autism spectrum disorders, born between 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy
Characteristic
CA n
Cerebral palsy
3
Intellectual disability (IQ \ 70)
163
Visual disability Hearing disability
AS %
n
%
Other ASD
All ASD
n
n
%
%
1.1
0
0
14
1.8
17
1.5
60.1
0
0
370
46.3
534
47.5
3
1.1
0
0
6
0.8
9
0.8
2
0.7
0
0
7
0.9
9
0.8
Epilepsy
15
5.5
2
3.8
36
4.5
53
4.7
Genetic syndrome or chromosomal aberration
5
1.8
0
0
20
2.5
25
2.2
Malformation
3
1.1
0
0
23
2.9
26
2.3
Table 3 Genetic and congenital syndromes, chromosomal aberrations and malformations in 7 year old children diagnosed with childhood autism, Asperger’s syndrome and other autism spectrum
disorders born between 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy
Anomalies
Syndromes and malformationsa
Chromosomal anomalies (n = 9)
Trisomy 21, trisomy 11, Klinefelter syndrome, William Beuren syndrome, Smith-Magenis syndrome, Angelman syndrome, complex chromosomal rearrangement (n = 2), chromosome 15 duplication (15q11)
Single gene disorders (n = 17)
Fragile X (n = 9), Bourneville syndrome (n = 2), Aase syndrome, faciodigitogenital syndrome, autosomal dominant polycystic kidney disease (n = 2), deafness due to connexin 26 anomaly, adenylosuccinase deficiency Agenesis of the corpus callosum (n = 4), microcephaly (n = 4), craniosynostosis (n = 3), cerebellar cyst, cerebellar malformation, Chiari type 1, periventricular nodular heterotopia
CNS anomalies without genetically identified anomalies (n = 15) Other anomalies (n = 14)
Heart malformation (2), Pierre Robin syndrome, cryptorchidism, pulmonary atresia, facial dysmorphy, congenital cataract, unilateral kidney agenesis, ureteral tract obstruction, abdominal cystic lymphangioma, coloboma of the eye, disorder of sex development, Duane retraction, congenital ptosis of right eye
a
One child has both a chromosomal anomaly and a malformation, one child has a single gene disorder and a malformation, one child has two single gene disorders and three children have two malformations
(n = 9) of the children. A syndrome (genetic or congenital) or chromosomal aberration was present in 2.2 % (n = 25) of the children (nine cases with X-fragile), and 2.3 % (n = 26) presented one or more malformations, both of which are detailed in Table 3. Gender differences were present for the proportion of ASD cases without ID (p = 0.001), as well as for the proportion of children with epilepsy (p = 0.003) and epilepsy in combination with ID (p = 0.002) (Table 4).
Discussion The average ASD prevalence rate in the presently studied 1997–2003 birth cohorts of children living at 7 years old in a French geographically restricted area comprising four counties was 36.5 per 10,000 children, which was higher than the previously published figures from France of 16.3 (Fombonne et al. 1997) and 22.2 (Guillem et al. 2006) per 10,000 children. However, compared to the global estimates calculated by Elsabbagh et al. (2012), including studies published since 2000, they still figure among the lowest prevalence values for both CA (17/10,000; range: 7.2–72.6)
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and total ASD (62/10,000; range: 30.0–116.1) (Elsabbagh et al. 2012). In Europe, the Swedish total ASD prevalence values of 50.2 per 10,000 for the 1999–2004 generations came closest to our figures (Atladottir et al. 2015), while at the global level only California showed similar prevalence rates for CA (Croen et al. 2002) and no other developed country showed similar values for total ASD. Part of the variation in prevalence across studies may be due to the population size, as estimates generally tend to be lower with increasing sample size (Elsabbagh et al. 2012). The present study included a large population of 1123 children with ASD, eligible from a population of 307,751 children, which is thus in favour of this explanation. Other possible explanations for the lower estimates found in this study include lack of exhaustiveness and representativeness, and different diagnostic and classification practices in France. Several arguments can be brought up against the lack of exhaustiveness: first, data were obtained through populationbased register activity, specifically collecting data on children with ASD, by actively collecting data from multiple sources. Guillem et al. (2000), using the capture-recapture
J Autism Dev Disord Table 4 Presence of comorbidities by gender in 7 year old children with autism spectrum disorders, born between 1997 and 2003 and living in the French counties Haute-Garonne, Isere, Savoy and Upper-Savoy % Among boys (N = 880)
% Among girls (N = 213)
% Totala (N = 1123)
Male/female ratio
p value
Without ID
54.7
41.8
53.1
5.4
0.001
With ID (IQ \ 70) Mild ID (50 B IQ \ 70)
45.3 14.2
58.2 18.8
46.6 14.9
3.2 3.1
0.05 0.09
Severe ID (IQ \ 50)
24.9
33.3
26.0
3.1
0.06
6.3
6.1
6.1
4.2
0.4
ASD comorbidity Intellectual disability
Unspecified ID Epilepsy
3.9
8.9
4.7
1.8
0.004
Epilepsy and ID (IQ \ 70)
2.6
7.0
3.4
1.5
0.002
Anomalyb
4.2
5.6
4.4
3.1
0.39
CP, hearing- or visual disability
2.6
5.2
2.1
2.1
0.06
a
Including 30 children whose gender is unknown (26 are without ID, two with a mild ID and two with severe ID)
b
Including Genetic syndromes, chromosomal aberrations and malformations; Two children had both a genetic syndrome or chromosomal aberration and a malformation
method, showed that this way of proceeding resulted in highly exhaustive data for the RHEOP. Second, there is a strong incentive for parents to get their child known by the main source used by the registers, the county MDPH, as they play a very central role in the allocation of a wide range of services (including educational support for regular school) and they ensure substantial financial allowances to the families. Indeed, the number of parents that constituted a file at the MDPH increased over 70 % in 5 years. In rare cases, families ask for interventions without being registered at the MDPH. To ensure exhaustive coverage, cases were additionally searched for by extracting records from psychiatric day-care centres and centres for psychiatric outpatient care, which allowed to find 6 % of the children. Nevertheless, as our population was not systematically screened we may particularly have missed some of the milder types, i.e. those falling short of the strict diagnostic criteria for CA. The boundaries for inclusion are internationally still not well defined and it may be that the French psychiatrists who traditionally used the conceptually more conservative French classification for mental disorders of children and adolescents (CFTMEA), though having passed on to the ICD10, are still more conservative in diagnosing an ASD. Underestimation of the AS category in this population of 7 year old may also have contributed to the lower prevalence estimates, as diagnosis in these children occurs frequently only between 8 and 12 years (Howlin and Asgharian 1999). Our estimate of 1.7 per 10,000 was indeed in the lower range of the studies included in the review of Fombonne (2001) (range 0.3–48.4 per 10,000) (Fombonne 2001), and was more than ten times lower than the prevalence of 21.6 per 10,000 reported in an Icelandic
population of the same age (Saemundsen et al. 2013). Nevertheless, the influence on total prevalence is negligible as numbers in this category are relatively small compared to the whole group of children with ASD. Still another reason may be that the geographical areas covered by the registers are not representative for France. However, there are no particular arguments to support this hypothesis: the counties include both rural and urban areas and in spite of being separated by nearly 400 km, the two registers’ ASD prevalence rates were highly comparable (Delobel et al. 2012). Finally, some of the 3 % families that refused to participate may have had a child with an ASD diagnosis. In spite of these lower values, ASD prevalence values have risen in this French area, similarly to what has been observed at the global level. According to the reasons detailed below, changes in classification, diagnostic substitution, changing diagnostic procedures, improved service availability, better acceptance and awareness have probably each contributed to the increased prevalence rates, but we can neither draw any conclusion on their relative contributions nor on the impact of changing environmental risk factors, as this was beyond the scope of this study. The age of diagnosis was not available in our population, but in France the average age at diagnosis decreased significantly in recent decades (Saint-Georges et al. 2013) and may as well have contributed to increased prevalence values. Concerning changes in classification, as mentioned above, French children were in the past exclusively classified according to the French CFTMEA while for the current study nearly all children were directly classified according to the less conservative ICD10. Also, diagnostic substitution with ID may have played a role in this increase. Both disorders are defined by behavioural characteristics that
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have been subject to change over time and overlapping areas exists between ID and ASD. As a result, persons with ASD were easily overlooked in the past (Oeseburg et al. 2010). Indeed, it has been shown that as the rate of ASD diagnoses goes up, the rates of ID and learning disability diagnoses go down (Shattuck 2006). As the registers involved in this study also register children with severe ID (IQ \ 50), we looked upon these prevalence rates in the same period as the one considered in this study. Even though the overall prevalence of severe ID (associated or not with ASD) did not change in this period, a sharp decrease in prevalence was observed from 1997 to 1998, followed by a steady increase till the end of the period studied (data not shown). Even if the latter picture is incomplete because of the lack of data on mild ID, these data may indeed reflect a transition period in which increasing knowledge and tools for differential diagnosis of the two disorders seem to bear fruit. It is important to obtain both diagnoses, as persons with both ID and ASD have different needs from individuals having only one of the disorders. Concerning the changing diagnostic procedures, in France children are since 1998 increasingly referred to specialized Centers for Autism (CRAs) which use standardized tests for diagnosis, while in the past they were principally diagnosed upon clinical assessment, which is more subjective than the standardized diagnoses used at the CRAs (Bursztejn et al. 2011). This activity may thus have contributed to the increasing prevalence figures. Finally, the continuous increasing number of parents’ requesting support at the counties’ MDPH, suggests increased awareness and acceptance of having a child with ASD in the society, although the increased requests may evenly well be due to improved service availability. Association with Medical Disorders An ID (IQ \ 70) was present in 60.1 and 46.1 % of the children with CA and other ASD, respectively. These figures fall in the range of 25.7–70 % from previous studies reporting on ID (Fombonne 2009; Saemundsen et al. 2013). In the present study about 40 % of the children were tested cognitively, formal ID figures may therefore be slightly lower (Saemundsen et al. 2013). On the other hand, the proportion of children of the category ‘‘other ASD’’ having additionally an ID initially increased, and was steadily decreasing only since 2000 (data not shown) suggesting that an ID was overlooked in part of the children or that particularly children of the older generations, had received the wrong diagnostic label. The sex ratio (M/F) of children without ID was 5.1, which was higher than the ratio found in both the mild and severe ID categories (both 3.1), showing that the male–female profile differed across
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subgroups. Figures on epilepsy were lower (overall 4.7, 7.1 % in those with ID, 2.5 % in those without ID) as compared to the pooled prevalence values of 21.5 % in children with ID and 8 % in children without ID, calculated by Amiet et al. (2008), but were similar to the values described in a recent Icelandic study (Saemundsen et al. 2013). The age at registration could be responsible for this difference as epilepsy appears in the majority after the age of 10 years (Bolton et al. 2011). However, other factors also seem to influence, as the children in the Icelandic study were between 11 and 15 year old (Saemundsen et al. 2013). Like previous studies, epilepsy in our ASD group was associated more often to the female than the male gender, both in presence and absence of ID (Amiet et al. 2008; Saemundsen et al. 2013). In our population, ASD was associated in 2.2 % of the children with a known genetic cause, which is lower compared to literature estimates of 10–20 % (Betancur 2011). Fragile X syndrome, tuberous sclerosis, abnormalities of chromosome 15 involving the 15q11-13 region and deletions and duplication of 16p11 are currently considered probable causes for autism (Kumar and Christian 2009). Fragile X occurred in 0.8 % of our cases, while values probably lie between 2 and 8 % (Harris et al. 2008). Tuberous Sclerosis and duplication of the 15q11 region were detected in two and one of our cases (less than 0.5 % each), respectively, as compared to 2 % in the literature. None of our cases had abnormal findings for 16p11, while it was reported in 1 % of cases in the literature (Kumar and Christian 2009). The comparison of the presence of malformations is complicated, as it is not clearly defined what should be included. Congenital central nervous system malformations were reported in 2.2 % of the Icelandic children (Saemundsen et al. 2013), compared to 1.3 % in our children. The main reason of the lower values is most likely that the children in our study were not systematically screened for genetic syndromes and malformations. To conclude, ASD figures in the four French counties under study were among the lowest worldwide, but reflect well the current diagnostic practices of French psychiatrists. Nevertheless, continued surveillance of the rising prevalence is of public health importance, as early detection and adequate services contribute to better outcomes (Reichow et al. 2012). Conflict of interest All authors declare that they have no conflict of interest in relation to this study. Ethical Standards The study was carried out according to the French regulations of individual privacy. Parents who agreed to participate signed an informed consent form prior to inclusion of their child the study. The National Commission on Informatics and Liberties (CNIL) authorized the treatment and digitalization of the nominative data.
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