Chapter 1: Global Autism Prevalence
Chapter 1: Global Autism Prevalence[1]
Research from the past fifty years has reported global differences in autism prevalence as well as an increase in autism prevalence over time. Many causes for these temporal and geographic autism prevalence patterns have been proposed; changes in diagnostic criteria for autism spectrum disorders, differences in study design and prevalence measuring methods, and increased recognition of autism-associated disorders are among a few. Although global differences in autism prevalence are apparent, epidemiological studies have found conflicting results on whether there are racial or ethnic disparities in autism prevalence [pic](47, 57, 94). Previous research has found significant differences in autism prevalence between countries with diverging racial compositions despite using measures to account for these previously listed potential causes for increase in autism prevalence (unpublished data by this author is this your JP? Generally not kosher to cite your own unpublished work. Seems like either you should cite published literature or include relevant results from your JP in your thesis. Remember that the JP is basically a term paper, whereas your thesis is an actual publication that goes to the PU library and is available to anyone in the world). While such research does not imply that ethnicity has a causal role in autism, it implies that ethnicity may play a role in the changing global and temporal patterns of autism prevalence. This thesis seeks to better understand whether differences in ethnicity are correlated with differences in autism prevalence as well as whether the genetic, cultural, and environmental aspects of ethnicity influence the global and temporal patterns of autism prevalence.
Ethnicity is a useful framework for categorizing individuals during the study of disease etiology because the term encompasses genetic, cultural and social, as well as environmental differences between groups of individuals. The goal of much public health research is to identify factors associated with the risk of obtaining a certain medical condition in individuals and populations and to use that information to develop effective prevention methods and treatments (66). Such risk factors can be directly associated with a disease, indirectly associated with a disease, or a combination of the two. For example, while tobacco smoking is directly associated with lung cancer, income is indirectly associated with a variety of conditions including cardiovascular disease (25, 95). Risk factors do not imply causal relationships and do not ensure that all members within the category are homogenous; rather, they serve as a starting point for further investigation when causal factors are unknown. Ethnicity is an example of one such risk factor (66). Many have argued that categorizations based on race and ethnicity are detrimental in scientific research because race has little or no biological basis, because such categorizations promote racist practices, and because racial and ethnic labels lead to inaccurate information on genetic relationships (7, 72). Researchers have also found that the terms “ethnicity” and “race” are frequently vaguely and unclearly defined by scientists in their studies, making them scientifically useless (66, 74).
While researchers have argued that genetic clustering is a superior method to determine biologically relevant information about ancestry, Risch argues that ethnicity is still a useful construct because ethnic classifications match genetic clustering extremely closely and because using ethnically heterogeneous study groups can confound results due to the genetic and social component of ethnicity. While some fear that categorizing disease risk based on ethnicity or race may lead to discrimination, failure to do so may result in the inability to identify causal disease factors more prevalent in certain populations and thus actually provide worse treatment for those groups (66). While unclear definitions of race and ethnicity do make scientific findings difficult to apply, it is far more detrimental to omit them completely because of this uncertainty. Ethnicity, as it is used in this work, will be taken to mean genetic, cultural, and environmental differences between individuals of different ancestry.
This work will study whether the identified potential genetic, cultural, and environmental causes of autism vary between different ethnic populations. After defining the global and temporal patterns of autism and reviewing how diagnostic methods can impact prevalence estimates, a systematic literature review will assess how these diagnostic methods are likely to influence prevalence trends over time in Asian, North American, and European populations. Next, the current genetic and neurological theories about the causes of autism will be evaluated. Analyses of the prevalence of various genetic mutations and morphological and anatomical abnormalities associated with autism in different ethnic populations will shed light on whether it is likely that ethnicity contributes to autism prevalence in a genetic and biological manner. A case study of autism in the Somali population in Minnesota will serve as a means to analyze both the effect of diagnostic criteria and of environments associated with particular ethnicities on reported autism prevalence levels. The current study from the Minnesota Department of Health on the increasing levels of autism prevalence in Minnesotan Somalis will be evaluated to determine if diagnostic substitution in Somali populations plays a significant role in increasing administrative prevalence of autism in Minnesotan Somalis. Likewise, the culture of the Somali population will be analyzed to determine if cultural factors are likely to contribute to the increasing prevalence of Somali autism. Combining these analyses should give an indication of both if and how ethnicity can contribute to different levels of reported prevalence of autism spectrum disorders.
The primary goal of this chapter is to introduce the patterns of global autism prevalence and evaluate whether diagnostic and other analytical methods used in determining autism prevalence are likely to contribute to the observed increase in autism prevalence. A systematic review of studies reporting autism prevalence from Japan, the United States, the United Kingdom, and Sweden published at similar times using similar diagnostic criteria were analyzed. Autistic disorder prevalence increases probably grammar-check whole thing at some point in all countries over time, with higher prevalence levels reported in Japanese studies than in similar studies from the United States, the United Kingdom, and Sweden. The impact of diagnostic criteria, study design, and prevalence of associated diseases on the observed temporal and geographic patterns of autism prevalence were further analyzed. Ultimately, this analysis allows one to determine if global differences in autism prevalence are likely to be caused by differences in diagnosis and study design in each nation. The final section of this chapter outlines how the rest of the work will seek to determine if the genetic, cultural, and environmental aspects of ethnicity are likely to contribute to the global patterns of autism prevalence described in this chapter.
Background
Phenotype
Autism is a pervasive development disorder (PDD) that develops during a child’s first three years of life, and is part of a spectrum of autistic disorders. The American Psychiatric Association lists five PDDS including autistic disorder, Asperger’s syndrome, Rett’s disorder, childhood disintegrative disorder (CDD), and pervasive developmental disorder not otherwise specified (PDDNOS) (11). Individuals with PDDs exhibit similar characteristics at different levels of severity. PDDS are distinguished amongst each other by differences in gender, regression, comprehension, language, and mental retardation. Autistic disorder, also known as classical autism or infantile autism, is associated with mental retardation and is characterized by stereotyped behavior, restricted interests and activities, and by deficits in social interaction, communication, and play (65). While individuals with Asperger’s syndrome exhibit the same stereotyped behaviors and social deficits as those with autism, they are not mentally retarded and have normal speech (65). Rett’s disorder, associated with mutations in the methyl CpG binding protein, occurs in girls only and is characterized by normal development and subsequent regression, stereotyped hand movements, language deficits, retardation, and microencephaly (6, 65). Individuals with CDD exhibit normal development and regress to autistic like symptoms between ages 2 and 10, while those with PDDNOS demonstrates autistic behavior that can not be classified into one of the above categories(65). All PDDs, excepting Rett’s disorder, are more often found in males than females with typical sex ratios of 3 or 4 to 1 (28, 52). Because of their similar behavioral characteristics, researchers believe that autistic disorder, Asperger’s syndrome, and PDDNOS constitute a spectrum of autistic disorders (ASD)(63).
Impaired social interaction, communication deficits, repetitive behaviors and interests, reduced cognition, and distinct sensorimotor behaviors are defining symptoms of autism. Since the autistic phenotype was first described by Leo Kanner in 1943, a wide range of characteristics associated with autistic individuals have been identified (43). Autistic children often have impaired social interactions because they have difficulty maintaining joint-attention what is this?, following another’s gaze, and vocalizing or smiling back at others. Social interactions are also limited because of problems with imitation, imaginative play, and non-verbal communication [pic](17, 54, 65). Communication deficits of autistic children include an inability to speak, difficulty comprehending other’s speech and gestures, and poor articulated, agrammatical, or sparse speech. In severe cases, autistic individuals exhibit verbal auditory agnosia, or an inability to understand language. Abnormal speech patterns such as reciting stereotype passages and delayed echolalia, the repetition of a previously heard phrase at a later time, are also observed (54, 65). This might be a place to mention previous classification of autism as a language disorder
Although autistic individuals have difficulty concentrating in social situations, they often focus for extended periods of time on repetitive ritualistic behavior and restricted interests. If an autistic individual is asked to stop such behaviors or interests, tantrums frequently ensue(54, 65). Although approximately 75% of children with autism are mentally retarded, a small amount of autistic individuals exhibit savantism, or exceptional musical, mathematical, visual-spatial, or other abilities. Autistic individuals also have limited creativity and a difficulty imagining what others are thinking (65). In addition to these cognitive deficits, autistic children exhibit stereotyped movements including flapping, rocking, tiptoeing and other postural abnormalities (54). Increased or decreased responses to sensory stimuli are also observed (69).
Although autism is typically diagnosed by age three, autistic individuals may exhibit the previously described symptoms as early as 18 months(68). Most autistic individuals exhibit continuous abnormal development; however, a quarter to a third develops normally and then regresses to autism[pic](53, 56). Although it is possible for communication deficits and repetitive behaviors to improve as a child ages, most autistic individuals retain the autistic phenotype and receive care in group homes as adults (54). Many other diseases, including tuberous sclerosis complex (TSC), Down Syndrome, and mental retardation, constitute “sydromic autism” as they share many autistic symptoms and are comorbid I realize everyone knows what this word means but I always want a definition at this point with ASD (77, 98).
Global Patterns In Autism Prevalence
Reported global prevalence of autistic disorder, excluding other spectrum disorders, has risen from 2 to 4 autistic individuals per 10,000 in 1966 to 60 autistic individuals per 10,000 today [pic](29, 92, 94). The first organized studies measuring the prevalence of autistic disorder were conducted in European and North American countries in the mid-1960’s and 1970’s. Studies from the United Kingdom, the United States, and Denmark reported the prevalence of autistic disorder to be between 2 to 4 autistic individuals per 10,000 with values ranging form 0.7 per 10,000 to 4.9 per 10,000 [pic](20, 55, 85, 93, 94). In the early and mid 1980’s studies expanded to include regions in Asia, such as Japan, as well as more regions in Europe, including Sweden, Ireland, and Germany. Studies from these countries reported similar levels of autistic disorder as the initial studies. By the late 80’s and early 1990’s, reported prevalence levels began to rise in the late 80’s and early 90’s (39, 94). Prevalence estimates from 1987 to 1996 in Japan, Canada, the United States, France, and Sweden ranged from 1.2 to 21.1 per 10,000. Most reported prevalence rates were between 8 to 14 autistic individuals per 10,000 however [pic](21, 38, 94). Global prevalence of autistic disorder rose even further in the late 1990’s and 2000’s. Reported prevalence reached values as high as 30.8, 40.0, and 60.0 autistic individuals per 10,000 in England, the United States, and Sweden respectively [pic](15, 18, 42).
In addition to exhibiting a temporal increase, autistic disorder prevalence has been observed to differ geographically. A recent meta-analysis by Williams et al. demonstrated that European and Scandinavian studies reported slightly higher rates of autistic disorder prevalence than the United States. Japan reported significantly higher prevalence rates that were 3.6 times those observed in North America, suggesting that geographic location is associated with reported prevalence of autistic disorder (92). Due to the scarcity of credible studies of autism prevalence from less developed areas of the world, temporal patterns in autism prevalence cannot be determined from these areas.
(generally you might need more paragraph breaks) Studies from less developed nations tend to report lower levels of autism prevalence, with a 2007 Chinese and 1992 Indonesian studies reporting rates of 16.1 and 12 autistic individuals per 10,000 respectively (91, 96). The only Israeli study reports incidence instead of prevalence what is the difference? What is prevalence, anyway?, with a value of 10 in 10,000 (24). Although Egypt does not report autism prevalence, it reports a prevalence of 29 in 10,000 individuals with a pervasive developmental disorder (26). Although the scarcity of credible studies from these areas makes it difficult to determine the specific geographic patterns of autistic disorder, these studies confirm that autism is a prevalent enough disorder to warrant significant attention worldwide.
Recent meta-analyses proposed that increasing autistic disorder prevalence is caused by changing diagnostic criteria, differences in study design, increased recognition of diseases associated with autistic disorder, increased awareness of autism spectrum disorders, or possible factors leading to a true increase in autism prevalence [pic](29, 92, 94). Since these factors are proposed to explain temporal changes in prevalence patterns, they may also account for geographic difference s in autistic disorder prevalence. Different definitions of autistic disorder have been used as diagnostic criteria have evolved fro the original Kanner criteria to the modern ADOS-G and ADI-R [pic](43, 50, 51). Meta-analyses suggested that broadening diagnostic criteria could increase the autistic disorder prevalence by allowing individuals to be classified as autistic who would not be under earlier criteria (92, 94). Such meta-analyses have also suggested that different aspects of study design including the screened population size, screening methods, screened children age, urbanization of area screen, and prospective/retrospective study nature, may lead to increasing reported prevalence of autistic disorder (92, 94). In addition to study design, increased recognition of autism-associated disorders, such as tuberous sclerosis and Down syndrome, may increase reported prevalence. Individuals with associated disorders are now more likely to be classified as autistic because of the disorder’s established linkage with autism. Increased awareness of autistic disorder by parents, medical professionals, and the general public may increase the prevalence levels by causing more children to be tested for autism (94).
Finally, environmental and genetic factors may cause actual increases in the numbers of autistic individuals over time of in different world regions. Researchers proposed actually no, this is all over – the original study was retracted that environmental factors including the measles, mumps, and rubella (MMR) vaccine and cable television ???, cause increased autism levels; however, little supporting evidence has been found (88) even worse, totally refuted. As twin and sibling studies have shown that autism is highly heritable genetic factors may significantly affect autism prevalence [pic](13, 14, 27). While genetic factors are not likely to explain temporal patterns of autism prevalence, they may explain geographic differences in autism prevalence. Note that consensus at this point is that autism is largely genetic – see twin studies. However, it is not true that genetics can account for the increased reported rate of autism, which is too fast to be accounted for by autism. Not enough time for selection or spread of genes to occur; also, why increases in all countries?
Methods for Assessing Autism: Diagnostic Criteria, Study Design, and Increased Recognition of Autistic Disorder Associated Diseases
Many researchers believe that the increasing global prevalence of autistic disorder is due to changes in the methods of assessing autistic disorder. Studies seeking to determine autism prevalence can vary by the autism diagnostic criteria and study design used as well as by whether disorders associated with autism are well recognized in the study population (94). A further examination of how these criteria influence autism prevalence will facilitate the systematic literature review of autism prevalence in Japan, United States, United Kingdom, and Sweden.
Diagnostic Criteria
Diagnostic criteria for autistic disorder have broadened from 1970 to the present by requiring fewer symptoms to be exhibited. In 1956, Kanner and Eisenberg published diagnostic criteria for ‘early infantile autism’ (autistic disorder) based on Kanner’s initial findings in 1943 (43). This diagnostic criteria emphasized the importance of “the presence of elaborately conceived rituals together with the characteristic aloneness” to identify autistic individuals (44). The combination of these two characteristics is very rare in autistic individuals because social isolation is generally characteristic or autistic children with extreme mental retardation while the planning of elaborate rituals requires extensive mental capacity (94). The Kanner and Eisenberg criteria also specifically required the absence of language or abnormal speech patterns including “delayed echolalia, pronominal reversal, literalness, and affirmation by repetition” for an ‘early infantile autism’ diagnosis (44). The Rutter criteria required onset before 30 months, impaired social behavior, delayed and abnormal language, and an “insistence on sameness,” with each feature described in detail. Like the Kanner criteria, the specific descriptions of each characteristic limited the individuals who could be classified as autistic (71, 94). The 1980 third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-II) broadened criteria for ‘infantile autism’ (autistic disorder) by emphasizing a “lack of responsiveness to other people,” “gross impairment in communicative skills,” and “bizarre responses to various aspects of the environment” as defining characteristics of autism; however, communication deficits were still specifically defined as “gross deficits in language development” as well as “immediate and delayed echolalia, metaphorical language [and] pronominal reversal” (10). The 1987 revised DSM-III (DSM-III-R) further broadened autistic diagnosis criteria because it required a patient to demonstrate eight trait total from three categories: “qualitative impairment in reciprocal social interactions,” “qualitative impairment in verbal and non-verbal communication, and in imaginative activity,” and “markedly restricted repertoire of activities and interests” (12). The 1994 DSM-IV and 2000 DSM-IV text revision (DSM-IV-TR) are identical in their autistic disorder definition. They define it even less specifically, requiring only six symptoms from “qualitative impairment in social interaction,” “qualitative impairments in communication,” and “restricted repetitive and stereotyped patterns of behaviors, interests, and activities” categories (9, 11). The 1992 International Classification of Diseases version 10 (ICD-10) criteria are broadest of all, only requiring “abnormal functioning in all three areas of social interaction, communication, and restricted repetitive behavior” (62). Unlike the Kanner and DSM-III criteria, DSM-III-R, DSM-IV, DSM-IV-TR, and ICD-10 criteria require deficits in verbal or nonverbal communication instead of the absence of language or abnormal patterns for diagnosis of autistic disorder (94). The broadening of diagnostic criteria, especially communication deficit criteria, could increase the number of children diagnosed with autistic disorder. The Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview – revised (ADI-R), are based on the DSM-IV and ICD-10 criteria, and are the most commonly administered tests today [pic](50, 51). While the ADOS is a set of clinical tests administered to patients suspected of autism assessing communication and physical deficits, the ADI-R is a set of questions given to a caregiver about the patient’s past and present communication, social development, and repetitive behaviors.
Autistic disorder diagnostic criteria also broadened from 1970 to the present by allowing a later diagnosis age. The Kanner and Eisenberg criteria required most symptoms to be “manifest within the first two years of life” (44). The DSM-III criteria require symptoms of ‘infantile autism’ to be demonstrated within the first 30 months (10). Although a specific age of onset for autistic disorder was not specified in DMS-III-R, DSM-IV, DSM-IV-TR, and ICD-10 criteria require only one of several autistic disorder symptoms to be demonstrated before three years of age [pic](9, 11, 12, 62). Increasing the age requirement for the demonstration of autistic symptoms is likely to increase the numbers of reported cases of autism because children have more time to develop autistic disorder symptoms.
From 1970 to the present, the addition of diagnostic criteria for PDDs other than autistic disorder to diagnostic manuals has reduced the likelihood that prevalence estimates are artificially high because of misclassification of PDDs as autistic disorder. Although the Kanner criteria distinguished ‘infantile autism’ from mental retardation and childhood schizophrenia, it did not divide ‘infantile autism’ into subcategories (43). While DSM-III also distinguished ‘infantile autism’ from mental retardation and schizophrenia, ‘infantile autism’ was considered a subtype of PDD along with child onset PDD and atypical PDD (10). DSM-III-R renamed ‘infantile autism’ ‘autistic disorder,’ and considered it a PDD along with PDD Not Otherwise Specified (PDDNOS) (12). DSM-IV and DSM-IV-TR defined Rett’s disorder, Childhood Disintegrative disorder, and Asperger’s disorder along with autistic disorder and PDD-NOS (9, 11). ICD-10 criteria also classifies a wide range of ASD’s including Childhood Autism, Atypical Autism, Rett’s syndrome, Other Childhood Disintegrative disorder, Asperger’s syndrome, and PDD unspecified (50, 62). While broadening autistic disorder diagnostic criteria may imply that prevalence levels should rise, specific criteria for diseases that exhibit autistic-like symptoms should ensure better specificity in autism diagnosis and lower autistic disorder prevalence by reducing misdiagnosis.
Studies applying multiple diagnostic criteria to the same population confirmed that prevalence rates for autistic disorder generally rise when newer diagnostic criteria are applied. The broadening of diagnostic criteria over time, rising age of diagnosis, and the addition of specific diagnostic criteria for disease with similar symptoms to autistic disorder should have competing effects on the reported prevalence of autistic disorder. Studying the autistic disorder prevalence of different diagnostic criteria in the same population should indicate which factors most influence prevalence rates. The overlapping autistic disorder diagnoses when ICD-10 and DSM-IV criteria are applied to the same population suggest that ICD-10 and DSM-IV criteria are comparable diagnostic criteria (87). European studies applying Kanner and DSM-IV/ICD-10 criteria to the same population found that Kanner criteria diagnosed 33 to 45% of the individuals identified by DSM-IV/ICD-10 criteria as having autistic disorder [pic](8, 42, 86, 94). An American study by Volkmar et al. applied DSM-II, DSM-III-R, and ICD-10 criteria to the same population. This study found that DSM-III reported slightly fewer cases of autistic disorder than both ICD-10 and DSM-III criteria (86). One cannot conclusively say that the Kanner criteria reports lower levels of autistic disorder than DSM-III because these diagnostic criteria have not been tested in the same population. The previously described studies suggest, however, that diagnostic criteria can be ordered from those which report the fewest cases to those which report the most cases in the following order: Kanner criteria, DSM-III, DSM-IV/ICD-10, and DSM-III-R. Meta-analyses have observed a significant association between changing diagnostic criteria and rising autistic disorder prevalence, supporting this conclusion (92, 94). Because newer diagnostic criteria does not always lead to higher autistic disorder prevalence, broadening diagnostic criteria, rising diagnostic age, and additional diagnostic criteria for diseases with autistic disorder-like symptoms may influence reported prevalence rates in different ways. Comparing studies from different countries conducted at similar times with the same diagnostic criteria will allow for a better evaluation of the role of diagnostic substitution in increasing autism prevalence.
Study Design
Previous meta-analyses have assessed how different aspects of study design contribute to reported prevalence of autistic disorder over time and between countries (92, 94). Screened population size, screening methods, screened children age, urbanization of area screened, and prospective/retrospective study nature can all potentially influence reported prevalence. A previous meta-analysis has found that studies with fewer than 50,000 individuals were significantly more likely to report higher levels of autism prevalence, suggesting that studies with smaller populations are more likely to report lower levels of prevalence. Studies using developmental checks to identify autistic children are more likely to have higher prevalence levels than those that used demographic and clinical information from state agencies (94). Age of children screened has been found to be associated with estimates of autism prevalence. Researchers have hypothesized that this is due to easier detection of autistic disorder in younger children. The same researchers have also found that urban areas are more likely than mixed urban/rural or rural areas to have high autism levels because these areas are more likely to have complete diagnostic records, specialized clinicians to diagnose autism, and higher response rates (92). Meta-analyses have shown that retrospective studies are more likely to report lower prevalence estimates than prospective studies. In a prospective study, populations are followed over time to identify cases; however, in a retrospective study, histories of exposure to certain factors are examined in individuals who have a certain condition. With higher amounts of confounding and bias, retrospective studies generally less reliable (94). Evaluating each aspect of study design during the systematic literature review will allow a better assessment of the potential causes of the observed prevalence patterns.
Increased Recognition of Autistic Disorder Associated Diseases
Higher levels of associated disease misdiagnosis may contribute to higher levels of autistic disorder prevalence. The theory hypothesis of diagnostic substitution states that increases in autistic disorder prevalence are caused by individuals being labeled autistic when in previous times they would be labeled with another associated disorder (75). Such associated disorders include Rett’s disorder, tuberous sclerosis complex (TSC), Down syndrome, and other neurological disorders (28). Additionally, if an individual is diagnosed with an associated disease, he or she may be more likely to be diagnosed with autism as well because of the known association. Countries with high amounts of diagnostic substitution are likely to have high autistic disorder prevalence with low prevalence of associated diseases. Examining the prevalence of such associated disorders in the systematic literature review will give a better picture of diagnostic substitution’s role in autism prevalence in each country.
Systematic Literature Review of Changing Global Autism Prevalence
This section seeks to evaluate if the previously discussed methods for assessing autism, including diagnostic criteria, study design, and increased recognition of autistic-disorder associated disease explain the geographic and temporal patterns of autism prevalence over the past fifty years in countries with consistently reported data. A systematic literature review analyzing how these factors influence reported levels of autism prevalence is performed using studies from the United States, Japan, United Kingdom, and Sweden. Previous research has shown that while temporal patterns of autistic disorder prevalence in Japan and the United States are likely to be influenced by changing diagnostic criteria and screened population size, geographic patterns of autistic disorder prevalence between these two countries are likely to be explained by differences in screened population size and misdiagnosis of diseases associated with autistic disorder (unpublished data by this author). This work is expanded to include the United Kingdom and Sweden in order to determine if similar conclusions hold for more ethnically homogenous, European populations. First, the geographic and temporal trends of autism prevalence are described in Japan, the United States, the United Kingdom, and Sweden. Diagnostic procedure, screened population size, screening methods, screened child age, urbanization of area screened, prospective/retrospective study nature, and prevalence of autism-associated diseases are assessed as potential explanations for these described prevalence trends. Studies with comparable publication dates and diagnostic criteria are analyzed together to allow for a controlled assessment of how these factors influence autistic disorder prevalence. The section concludes by comparing the findings regarding autistic disorder prevalence with those for autistic spectrum disorder prevalence from studies in United States, Japan, United Kingdom, and Sweden.
Japan, the United States, the United Kingdom, and Sweden were chosen for this systematic literature review because multiple studies measuring autistic disorder prevalence had been conducted from 1970 to the present, previous meta-analyses had found significant prevalence differences between different global regions, and the countries had different ethnic distributions. To study how diagnostic criteria, study design, and increased recognition of autism-associated diseases affect temporal patterns of autism prevalence, countries analyzed must have studies measuring prevalence at many difference time points. In Japan, autistic disorder prevalence studies have been conducted fairly consistently throughout the 1980’s, 1990’s, and 2000’s. American studies in the United States have been conducted through the 1970’s, 1980’s, and 2000’s. Studies in the United Kingdom have been conducted through the 1960’s, 1970’s, 1990’s, and 2000’s while Swedish studies have been conducted throughout the 1980’s and 1990’s. The overlapping timeframes of these studies make it possible to compare the temporal patterns of autistic disorder prevalence between the four countries. Since previous meta-analyses reported that regional differences explained 24% of all variance of autistic spectrum disorder prevalence, the potential causes of geographic differences in autism prevalence could be studied by analyzing Japanese, American, United Kingdom, and Swedish studies (92). Ethnic differences between the populations in Japan, the United States, the United Kingdom, and Sweden allows the possibility for the variations in genetics, culture, and environment associated with ethnicity to influence these prevalence patterns.
Studies in this systematic literature review satisfied specific inclusion criteria, and were analyzed with studies of comparable publication dates and diagnostic criteria. Studies were first identified through a literature review (PubMed, Google Scholar) and previous reviews [pic](29, 92, 94). Studies reported prevalence rates for autistic disorder. All studies which reported only incidence rates for ASD were excluded in the primary systematic review, and will be discussed separately. All studies were peer-reviewed journal articles that were conducted in Japanese, American, United Kingdom, or Swedish populations and were published in English. Studies initially screened a large geographically defined population of children to identify autistic individuals. They identified cases of autistic disorder by additional diagnostic testing of selected children. Diagnostic criteria used to assess autistic disorder were specifically
stated, and all studies included children younger than 18 (92). If a complete English version of the article could not be located or if the diagnostic criteria used in the study were unclear, the study was excluded. For articles that reported prevalence of autistic disorder at multiple time points, the most recent prevalence estimate was included (37). A summary of the inclusion criteria can be seen in Figure 1. In this systematic literature review, studies with comparable publication dates and diagnostic criteria are analyzed together to control for the effect of these variables on reported prevalence rates. Summaries of the included studies can be seen in Table 1 [pic](8, 15, 16, 18, 19, 21-23, 32, 34, 37-39, 42, 49, 55, 58, 61, 64, 67, 78, 79, 81-83, 85, 93).
Although the autistic disorder prevalence rates analyzed in this systematic literature review do not necessarily imply rising numbers of autism cases, they can be used to study whether the societal burden of autistic disorder is increasing. Two methods, incidence and prevalence rates, are primarily used in epidemiological studies to assess disease occurrence in a community. Incidence measures the rate of new cases of a disease in a population per a unit of time (70). The population considered consists only of individuals at risk for the disease at a given time period. While incidence rates are the best measure to determine disease etiology, autistic disorder incidence rates are difficult to obtain because it is difficult to diagnose the precise onset of the disease (94). Prevalence identifies all disease cases present in the population at a given time and depends on both disease incidence and duration (70). Since prevalence depends on both incidence and duration, increasing prevalence rates may not imply increasing disease cases. Because autistic disorder is a chronic disease with lifetime duration, prevalence estimates for autistic disorder are larger than incidence estimates. Prevalence rates are useful, however, because they measure the burden of a disease in a population and can be used to determine if additional services are needed to treat a disease. Prevalence rates of autistic disorder are analyzed in this systematic literature review because incidence rates were not available for multiple time points in Japan, the United States, the United Kingdom, and Sweden.
Prevalence Patterns
Prevalence rates for autistic disorder generally increase over time in Japan, the United States, the United Kingdom, and Sweden. Reported prevalence rates and corresponding 95% confidence intervals were used to create a forest plot for all studies included in the systematic literature review (Figure 2). Studies from all countries exhibit a general trend of increasing autism prevalence from 1966 to the present, suggesting that these studies are a good case study for analyzing how diagnostic criteria, study design, and prevalence of associated diseases influence rates of autistic disorder prevalence.
Japanese prevalence rates for autistic disorder were generally higher than those in the United States at all time periods. Japanese study Hoshino et al. reports an autistic disorder prevalence that us outside the 95% confidence interval for comparable American study Treffert et al. (39, 85)(Fig. 2). Japanese studies published in the late 1980’s or early 1990’s report autistic disorder prevalence estimates above the 95% confidence interval of corresponding American studies [pic](21, 58, 61, 67, 79, 81)(Fig. 2). Recent Japanese studies report autistic disorder prevalence 1.2 times those found in corresponding American studies [pic](18, 23, 37, 38)(Fig. 2). These observations suggest that between Japan and the United States, there are geographical differences in autistic disorder prevalence.
When comparing studies from Japan, Sweden, and the United Kingdom, relative levels of autism prevalence in each country vary over time. Although early Japanese study Hoshino et al. reports levels of autism prevalence below the 95% confidence interval of one corresponding study from the United Kingdom, Lotter et al., this study’s prevalence levels are within the confidence intervals of three other comparable studies from Sweden and the United Kingdom [pic](19, 32, 39, 55, 93)(Fig. 2). Although there were no comparable studies conducted in the United Kingdom during the late 1980’s and early 1990’s, Japanese studies in that period reported prevalence estimates that were outside the 95% confidence interval for all Swedish studies in that period [pic](32, 58, 61, 78, 79, 81)(Fig. 2). Studies from all countries in the late 1990’s and 2000’s report a wide variety of prevalence rates [pic](8, 15, 16, 18, 22, 23, 37, 38, 42, 49, 64, 82, 83, 89)(Fig. 2). Although the Swedish reported prevalence rates tend to be higher in this period, the extreme variation among reported prevalence rates prevents a clear pattern from emerging. The variation in relative autism prevalence patterns in these countries suggests that no intrinsic aspect of the location of these studies is strong enough to create a clear pattern of autism prevalence over time.
Although early studies in the United Kingdom and Sweden report higher levels of autism prevalence than the United States, later studies report comparable levels of autistic disorder in the three countries. Studies from the 1960’s until the 1980’s in the United States report autism prevalence levels out of the 95% confidence interval of studies from Sweden and the United Kingdom conducted at similar times [pic](19, 21, 32, 55, 67, 78, 85, 93). Studies in the late 1990’s and 2000’s in all three countries report comparable levels of autism prevalence with overlapping confidence intervals [pic](8, 15, 16, 18, 22, 23, 42, 49, 64, 82, 83, 89). These findings suggest that it is also unlikely that an intrinsic difference in these countries is likely to explain the patterns of autism prevalence.
Diagnostic Criteria
Changing diagnostic criteria are likely to contribute to the rising autistic disorder prevalence in rates of time in Japan, the United States, the United Kingdom and Sweden. In studies from all countries, reported prevalence of autistic disorder prevalence increases as diagnostic criteria evolves from the older Kanner criteria to the newer DSM-IV and ICD-10 criteria (Fig. 1). Studies from all countries using the comparable Kanner and Rutter criteria report the lowest levels of autism prevalence in each country[pic](19, 32, 39, 55, 85, 93). Studies using DSM-III or DSMIII-R criteria alone report higher levels of autism compared to studies from the same country using the Kanner criteria. Likewise, studies using the comparable DSM-IV or ICD-10 criteria report higher levels of autistic disorder that studies from the same country using DSM-III or DSM-III-R criteria. The affect of diagnostic criteria on autistic disorder prevalence is confirmed because studies from the same country using the same diagnostic criteria report similar rates. Studies from the United Kingdom Lotter et al. and Wing et al. both use the Kanner criteria and report 4.1 and 4.8 autistic individuals per 10,000 respectively (55, 93). Likewise, Swedish studies using the Rutter criteria report values of 3.0 per 10,000 and 2.0 per 10,000, with each value within the confidence interval of the other study [pic](19, 32). Similar patterns were seen in American and Japanese studies included in the review using the DSM-III [pic](21, 58, 61, 67, 79, 81). Although studies from the same country using DSM-IV and ICD-10 diagnostic criteria show more variability in prevalence rates, the general correspondence between prevalence rates and diagnostic criteria suggests that diagnostic criteria plays a role in increasing autistic disorder prevalence over time. Researchers have found that Kanner criteria diagnose 33 – 45 % of the individuals that DSM-IV/ICD-10 criteria do when the criteria are applied to the same population [pic](8, 42, 46, 86). In the United States, Japan, and Sweden, studies using the Kanner or Rutter criteria reported values much less than 33 to 45% of the prevalence values reported in studies from the same country. While this was true for most studies in the United Kingdom, the high variation in reported prevalence values for studies using the DSM-IV or ICD-10 criteria made it impossible to validate such findings in all cases. While the studies included in the literature review follow the prevalence patterns expected based on analyses of the Kanner, DSM-IV, and ICD-10 criteria, this was not the case of DSM-III-R criteria. Although reviews have found a study has found that the DSM-III-R criteria is more inclusive than the DSM-III and ICD-10 criteria, studies from Japan, the United Kingdom, and Sweden using DSM-III-R criteria report lower prevalence levels than those studies using ICD-10 criteria [pic](34, 61, 89). Ultimately, while there is strong evidence that diagnostic criteria contributes to the pattern of increasing autistic disorder prevalence over time in these countries, diagnostic criteria alone cannot explain all of the changes in prevalence in autistic disorder over time.
Changing diagnostic criteria is not likely to contribute to observed geographical differences in autism prevalence. Changing diagnostic criteria’s influence on geographic prevalence patterns can be examined by comparing studies using similar diagnostic criteria published at similar times. Japanese studies using Kanner/Rutter criteria reported prevalence levels on average 3.3 times those of American studies, 0.52 times those of studies in the United Kingdom, and 0.93 times those of Swedish studies [pic](19, 32, 39, 55, 85, 93). Although there are several American, Japanese, and Swedish studies published in the 1980’s using the DSM-III criteria, such Japanese studies report prevalence rates that are on average 11.3 high than those in American studies and 3 times higher than those in Swedish studies [pic](21, 58, 67, 79, 81). Japanese studies reporting ICD-10/DSM-IV criteria reported prevalence levels on average 1.2 times those of American studies, 1.5 times those of studies in the United Kingdom, and 0.68 times those of Swedish studies [pic](8, 16, 18, 22, 37, 38, 49, 83). Because there are significant differences in prevalence even when comparing American and Japanese studies with similar diagnostic criteria, changes in such criteria are not likely to contribute to observed patterns in global prevalence. Since studies in the United Kingdom and Sweden have very similar values to those from Japanese studies regardless of diagnostic criteria, such criteria is not likely to influence geographic patterns of prevalence between these countries.
Study Design
Smaller samples sizes of screened populations are likely to contribute significantly to autistic disorder prevalence patterns in Japan, the United States, the United Kingdom, and Sweden. Why would this be? In the United States, although Bertrand et al. and Croen et al. were conducted at similar time intervals and both used DSM-IV diagnostic criteria, the larger study with 4,950,333 individuals found a prevalence of 40.5 autistic individuals per 10,000 and the smaller study with 8,896 individuals found a prevalence of only 11.0 per 10,000 (18, 23). Similarly, in the United Kingdom, studies Lingam et al. and Trebruegge et al., conducted at similar times with ICD-10 criteria, report respective prevalences of 23.7 per 10,000 and 14.9 per 10,000 with population sizes of 186,206 and 2,536 respectively (49, 83). Although it appears that U.K. Taylor et al. and the 2006 Baird et al. studies have unusually high prevalence levels of 30.8 per 10,000 and 38.9 per 10,000 respective, their small population sizes of 16,235 and 56946 individuals seems like a convincing explanation for this pattern (16, 82). Comparable study 2000 Baird et al., with a population of 490,000 individuals, reports a prevalence of only 8.7 per 10,000 (15). In Sweden, comparable studies Arvidsson et al. and Kadesjo et al. exhibit a similar pattern of reported prevalence correlating with population size (8, 42). Together, this evidence suggests that population size can have a significant impact on reported prevalence. The studies from all countries included in this analysis tend to have smaller study populations in more recent studies; this suggests that this sample size effect may influence the increasing reported prevalence of autism over time. The average study size tends to be larger in the United States than in Japan, Sweden, and the UK, implying that study population size may contribute to differing geographical levels of autism prevalence. The fact that the Japanese levels of autism prevalence generally tend to be higher than those in the United States suggests that other factors must contribute to this prevalence pattern.
Although different screening methods do not seem to explain temporal autistic disorder prevalence patterns, they may explain global differences in autism prevalence. A previous meta-analysis has reported that the type of case-finding method employed in a study is associated with reported autistic disorder prevalence levels (94). Treffert et al., Bertrand et al., Croen et al., Matsuishi et al., Ohtaki et al., Wing et al., Taylor et al., Powell et al., Lingam et al., Tebruegge et al., and Baird et al. (2006) used records to find cases of autism [pic](16, 18, 23, 49, 58, 61, 64, 82, 83, 85, 93). Burd et al., Rivto et al., Hoshino et al., Webb et al., Bohman et al., Gillberg et al. (1984), Steffenberg et al., Gillberg et al. (1991), and Kadesjo et al. sent letters to get referrals for autistic patients [pic](19, 21, 32, 34, 39, 42, 67, 78, 89). Tanoue et al., Sugiyama et al., Honda et al. (1996), Honda et al. (2005), Chakrabarti et al., and Arvidsson et al. used routine clinical checks to identify autistic individuals [pic](8, 22, 37, 38, 79, 81). Lotter et al. and Baird et al. (2000) used questionnaires to identify those with autistic disorder (15, 55). No clear temporal pattern exists between screening methods and increases in autism prevalence over time, suggesting that screening methods are an inadequate explanation for temporal patterns in autism prevalence. Differences in screening methods may explain global patterns of autism prevalence however. Japanese studies were both more likely to use clinical checks for autism and to have higher autism prevalence while studies from the United States, the United Kingdom, and Sweden tended to report use a mixture of letter and record based measures. A recent article has found that levels of all PDDs has increased in Japan due to an integrated screening network that includes clinical checks, further supporting that screening method can significantly impact prevalence levels (45). Overall, this evidence suggests that the screening methods unique to Japanese studies may help explain their higher levels of autistic disorder prevalence.
The age of children screened is not likely to explain temporal or geographical differences in autistic disorder prevalence observed in Japan, the United States, the United Kingdom, or Sweden. A previous meta-analysis found strong associations between the screened children’s age and autistic disorder prevalence, and suggested that this could be due to ease in identifying autism in older children (92). In this analysis, American and Swedish studies tended to include a broader range of children studied whereas studies from Japan and the U.K. included more children of a specific age. While 4 out of 5 U.S. studies and 5 out of 6 Swedish studies used an age range of greater than two years, only 3 out of 7 Japanese studies and 6 out of 10 U.K. studies did so [pic](8, 19, 21, 23, 32, 34, 39, 49, 55, 58, 61, 64, 67, 78, 85, 89, 93). For studies in all countries, no pattern appears to exist between screened children age and rising autistic disorder prevalence rates over time. To determine if screened children age influenced geographical prevalence patterns, autistic disorder prevalence rates for specific age ranges were determined from information provided by the temporally and diagnostically comparable studies Rivto et al. and Matsuishi et al. (58, 67). Rivto et al. observed 2.17 autistic disorder cases per 10,000 children ages 3 to 7 and 3.57 cases per 10,000 children ages 8 to 12 (67). Matsuishi et al. reported 16.4 cases per 10,000 children ages 4 to 7 and 14.9 cases per 10,000 children ages 8 to 12 (58). This example suggests that screened children age is not likely to influence geographic autistic disorder prevalence patterns because Matsuishi et al. still reports much higher rates of autism prevalence for when screened child age is accounted.
Urbanization of area screened is not likely to explain the observed temporal and geographic prevalence patterns between countries. A previous meta-analysis found that urban areas were more likely than mixed urban/rural areas to have high prevalence of autism. Urban areas may have higher reported levels of autism prevalence because they have more complete diagnostic records, more specialized clinicians to diagnose autism, and higher response rates (92). All included American studies used a mixed population, with the exception of Bertrand et al., which used a rural population [pic](18, 21, 23, 67, 85). Similarly, all included Swedish studies used a mixed population, with the exception of Kadesjo et al. which used an urban population [pic](8, 19, 32, 34, 42, 78). Japanese studies Matsuishi et al., Sugiyama et al., and Honda et al. (1996 and 2005) used urban populations [pic](37, 38, 58, 79). While Tanoue et al. used a rural population, Hoshino et al. and Ohtaki et al. used a mixed urban/rural population (29, 46, 63). Half of the studies conducted in the U.K. use urban populations (10, 11, 42, 64, 74), The other half of U.K. studies used mixed urban/rural populations (17, 36, 49, 66, 71). No apparent correlation exists between urbanization level and rising autistic disorder prevalence over time in any of the four countries. Although one may argue that the higher number of studies conducted in urban populations may contribute to the higher levels of autism in Japan, the large number of studies conducted in urban populations in the U.K. suggests that urbanization level is not a likely cause for this geographic difference in autism prevalence. A comparison between Matsuishi et al., Sugiyama et al., and Tanoue et., three Japanese studies using identical diagnostic criteria, confirms this assessment. Although the first two studies used urban populations and Tanoue et al. used a rural population, the reported autistic disorder prevalence for each study was within the 95% confidence interval of the other two studies (45, 62, 63). These observations suggest that urbanization level of area screened does not strongly impact temporal or geographic prevalence patterns of autistic disorder.
The prospective or retrospective study design does not seem to explain the temporal or geographic autistic disorder prevalence patterns between Japan, the United States, the United Kingdom, and Sweden. While some have found that retrospective studies report lower prevalence estimates than prospective studies, retrospective studies generally have higher amounts of confounding and bias because they examine the history of exposure to certain factors in individuals with a condition instead of following populations over time to identify cases (94). All included Japanese and Swedish studies were prospective (3, 14, 25-30, 45, 46, 61-63, 73). All American studies excluding Treffert et al. and Croen et al. were prospective (13, 16, 18, 52, 67). Half of the studies conducted in the U.K. were prospective [pic](15, 22, 55, 89, 93). As the pattern of retrospective or prospective study nature does not correlate with temporal or geographical patterns of autistic disorder prevalence, it is unlikely that this is a significant factor influencing reported prevalence levels.
Prevalence of Associated Diseases
Diagnostic substitution and misdiagnosis of associated diseases may contribute to the differences in autistic disorder prevalence in Japan, the United States, the United Kingdom, and Sweden. Autism is associated with many other conditions including Rett’s syndrome, tuberous sclerosis complex (TSC), Down syndrome, and other neurological disorders (28). Before autism was well known, individuals with both autism and an associated condition would only be diagnosed with the associated condition, making the reported prevalence of autistic disorder artificially low. The increasing recognition of autistic disorder makes it likely that the individuals with both conditions will be diagnosed with both autism and the associated condition, increasing the prevalence. Similarly, individuals with only the associated disorder may be incorrectly diagnosed as autistic. Both diagnostic substitution and misdiagnosis of associated diseases increase the levels of autistic disorder and decrease the prevalence of associated disorders (76). Analysis of prevalence of Rett’s syndrome, TSC, and Down syndrome in Japan, the United States, the United Kingdom, and Sweden will suggest whether such diagnostic substitution and misdiagnosis of autistic disorder-like diseases is likely. British, American, and Swedish studies reported higher levels of Rett’s syndrome than Japanese studies. A 1999 nationwide British survey reported 3.8 cases per 10,000 girls ages 5 to 15 while a 1993 U.S. study reported 0.44 cases per 10,000 girls ages 2 to 18 (31, 48). A 1985 Swedish study reported 0.66 cases per 10,000 girls (36). A 1995 Japanese study reported lower levels of 0.22 cases per 10,000 girls aged 6 to 14 (84). Although the higher prevalence of Rett syndrome in the U.S., U.K., and Sweden could be due to larger rages of screened children or differences in study design, Rett syndrome misdiagnosis in Japan could contribute to their higher reported autistic disorder rates. Similarly, American, U.K., and Swedish studies reported higher levels of TSC prevalence. While a 1985 American study reported 1.06 cases per 10,000 and a 1984 U.K. study reported 0.65 cases per 10,000, a 1994 Swedish study reported 0.78 per 10,000 individuals ages 0 to 20 [pic](5, 40, 90). A 1981 Japanese study reported only 0.323 TSC cases per 10,000 (60). Such lower Japanese prevalence suggest that misdiagnosis of TSC in Japan may contribute to higher levels of autistic disorder prevalence. Unlike Rett syndrome and TSC, Down syndrome prevalence was higher in Japan than in the United States and U.K. A Japanese study reported 15.2 Down syndrome cases per 10,000 live births in Tottori, Japan from 1980 to 1999 (80). An American study observed only 9.2 cases per 10,000 live births from 1983 to 1990 and U.K. study observed 10.8 per 10,000 live births form 1989 to 2008 (1, 59). During this time period, only Swedish studies reporting incidence were available and were this not comparable (41). These studies suggest that misclassification of Down syndrome patients with autistic disorder is not likely to contribute to the observed geographic patterns in autistic disorder prevalence. The observed differences in prevalence of Rett’s syndrome, TSC, and Down syndrome between the four observed countries could be caused by genetic differences between countries instead of differences in autistic disorder misdiagnosis. Ultimately, these studies suggest that it is possible that autistic disorder misdiagnosis and diagnostic substitution could contribute to geographic autistic disorder prevalence patterns.
Comparisons with Studies Reporting ASD Prevalence
Many recently published studies analyze the prevalence of ASD instead of the prevalence of autistic disorder alone. To evaluate whether the methods for assessing autism such as diagnostic criteria and study design influence the reported ASD prevalence, studies from Japan, the United States, the United Kingdom, and Sweden reporting ASD prevalence will be analyzed in a systematic manner. After briefly describing the geographic and temporal trends of ASD prevalence in these countries, diagnostic procedure, screened population size, screening methods, screened child age, urbanization of area screened, and prospective/retrospective study nature will be analyzed as potential causes for the observed trends. As in the previous analysis, studies with comparable publication dates and diagnostic criteria are analyzed together. Like the studies in the autistic disorder systematic review, studies were identified thorough a literature review (PubMed, Google Scholar) and previous reviews [pic](29, 92, 94). Criteria for inclusion are summarized in Figure 3. While some recent studies reported levels of ASD, they were excluded as they did not use additional diagnostic testing of selected children (35, 47). Summaries of the included studies can be seen in Table 2 [pic](2-4, 8, 15, 16, 18, 19, 21, 22, 30, 32-34, 37, 42, 49, 64, 73, 78, 83, 93, 97).
Recently reported ASD prevalence rates in Japan, the United States, the United Kingdom, and Sweden are generally extremely high and do not appear to differ significantly geographically. Reported ASD prevalence rates and 95% confidence intervals were used to create a forest plot from all studies included in the systematic literature review (Figure 4). Because there were not studies available from all countries and time points, it was not possible to determine definitive temporal patterns for ASD prevalence. Within the United States, the United Kingdom, and Sweden, the countries with enough available data, studies from the United States and the United Kingdom reported higher values of ASD prevalence outside of the 95% confidence intervals of previous studies in some cases [pic](2-4, 15, 22, 64, 73, 83, 97). This pattern is by no means perfect, and there are several studies that prove exceptions to the rule [pic](8, 16, 18, 30, 34, 42, 49). When comparing studies from the late 1990’s and 2000’s from all countries, no clear geographical prevalence pattern appears to emerge. Although the U.K. has more studies from this time region with lower values, all countries report ASD prevalence values within the 95% confidence level of studies from other countries [pic](2-4, 8, 15, 16, 18, 22, 30, 33, 34, 37, 42, 49, 64, 73, 83, 97). Despite the absence of clear temporal and geographical prevalence patterns from this group of studies, it is still useful to analyze how diagnostic criteria and aspects of study design could influence their reported prevalence rates as their rates tend to be significantly higher that those reported rates for autistic disorder.
The similarities in diagnostic criteria in the included studies suggests that diagnostic criteria does not influence the overall geographic patterns of ASD prevalence; however, examples from studies using alternate criteria suggests that diagnostic criteria can significantly influence the reported prevalence of individuals studies. The low number of studies reporting ASD prevalence from before the late 1990’s makes it impossible to make definite conclusions about the role of diagnostic criteria in influencing temporal ASD prevalence patterns. These early studies using Kanner, Rutter, DSM-III, and DSM-III-R criteria do report ASD prevalence values outside of the 95% confidence internal from studies using more recent criteria in the same country [pic](19, 21, 32, 34, 78, 93). This trend suggests that diagnostic criteria may influence the temporal pattern of ASD prevalence as it influences the temporal pattern of autistic disorder prevalence. In Japan and the United Kingdom from 2000 onward, all studies use ICD-10 criteria alone or combined with DSM-IV criteria [pic](15, 16, 22, 30, 37, 49, 64, 73, 83). While studies from the United States use a mixture of DSM-IV and DSM-IV-TR criteria, Swedish studies use ICD-10, DSM-IV, and Gillberg’s criteria, based off of ICD-10 criteria and that used in Gillberg et al., 1991 [pic](2-4, 18, 33, 97). While the ICD-10, DSM-IV, and DSM-IV-TR criteria have been proven to be comparable, the Gillberg criteria has not (87). The study that uses this criteria also has the highest reported ASD prevalence, suggesting that this diagnostic criteria may be broader than others and contribute to higher ASD prevalence levels (42). The presence of studies with similar diagnostic criteria and ASD prevalence levels within 95% confidence intervals such as Japanese Honda et al. and British Tebruegge et al. suggests that similar diagnostic criteria may lead to similar levels of ASD prevalence (37, 83). Ultimately, the wide range of reported values in the United States and United Kingdom from studies using the same diagnostic criteria suggests that this is not the primary driving factor leading to these differences in ASD prevalence. While previous meta-analyses have found associations between diagnostic criteria used and ASD prevalence, this analysis suggests that diagnostic criteria contributes to individual differences between studies instead of overall geographic prevalence patterns (92).
Both sample size and age of child screened seem to contribute to patterns of ASD prevalence in Japan, the United States, the United Kingdom, and Sweden. Studies from the United States, United Kingdom, and Sweden suggest that as with autistic disorder prevalence, smaller samples size appears to contribute to higher prevalence values. In the United States, Bertrand et al. has a small sample size of 8,896 and reports a much lower prevalence value than comparable U.S. study Yeargin-Allsopp et al. with a larger population size of 289,456 (18, 97). Similarly in the United Kingdom, Tebruegge et al., the study with the smallest sample size of 2,536 has the largest reported ASD prevalence (83). In Sweden, Kadesjo et al. has an extremely small sample size of 826 and the highest reported ASD prevalence of all Swedish studies (42). While U.K. studies Chakrabarti et al. and Baird et al. also have small sample sizes and large prevalence, Fombonne et al. has a similarly small sample size yet small prevalence [pic](15, 22, 30). These exceptions suggest that sample size is likely one of many factors influencing ASD prevalence. A previous meta-analysis by Williams et al. found associations between reported ASD prevalence and the age of the children screened, suggesting that this could be another contributing factor (92). In the United States, the studies screen children in a one to two year age range have the largest reported ASD prevalence [pic](2-4). Similarly, in the U.K., three of the four studies using children in a one or two year age range report the highest levels of ASD prevalence [pic](15, 22, 83). In Sweden, Kadesjo et al. also uses a small age range of two years and reports high levels of autism prevalence (42). The presence of studies with high prevalence and large age ranges or vice versa suggests that additional factors also contribute to ASD prevalence levels [pic](16, 33, 73). Ultimately, both sample size and age of child screened seem to impact reported ASD prevalence.
Screening method, level of urbanization, and prospective or retrospective study nature do not appear to contribute to patterns of ASD prevalence in Japan, the United States, the United Kingdom, and Sweden. Out of the included studies, 11 screened for ASD patients using records [pic](2-4, 16, 18, 33, 49, 64, 83, 93, 97), 7 sent letters to get referrals [pic](19, 21, 32, 34, 42, 73, 78), 3 used routine checks [pic](8, 22, 37), and 2 used questionnaires [pic](15, 30, 92). Within countries, there appeared to be no association between the type of screening method used and the reported ASD prevalence level. Similarly, differences in screening methods between countries did not seem to contribute to geographic differences in ASD prevalence. Although a previous meta-analysis has found an association between urban or rural study area and ASD prevalence, no such pattern emerges in this analysis (92). The majority of the studies were conducted in a mixed urban/rural environment [pic](2-4, 8, 19, 21, 22, 30, 32, 34, 49, 64, 73, 78, 83). The rest of the studies were conducted in urban environments [pic](15, 16, 18, 33, 37, 42, 93, 97). Within and between countries, neither studies conducted in mixed or urban environments exhibited consistently higher ASD reported prevalence rates. Similarly, the prospective or retrospective study nature did not seem to significantly influence the reported ASD prevalence rates. While the majority of studies were prospective [pic](2, 3, 8, 15, 18, 19, 21, 22, 30, 33, 34, 37, 42, 78, 93), a significant number were retrospective [pic](16, 49, 64, 73, 83, 97). Retrospective and prospective study nature did not seem to be associated with higher reported ASD prevalence between or within countries. Ultimately, these analyses suggest that ASD prevalence may not be significantly impacted by screening method, level of urbanization, and prospective or retrospective study nature.
Conclusions
This systematic literature review assessed whether diagnostic criteria, study design, and prevalence of autism-like diseases contribute to the temporal and geographic patterns of autistic disorder and ASD prevalence in Japan, the United States, the United Kingdom, and Sweden. The following can be concluded:
1. Autistic disorder prevalence rose in all countries over time; however, Japan reported higher prevalence values than the United States at all time intervals and relative prevalence levels between the United States, the United Kingdom, and Sweden varied over time. While there was not enough data to determine the temporal pattern of ASD prevalence, there appeared to be no substantial geographical variation in ASD prevalence between Japan, the United States, the United Kingdom, and Sweden.
2. The factors most likely to influence autistic disorder prevalence rates were diagnostic criteria, sample size, and screening methods used. While diagnostic criteria was likely to contribute strongly to the temporal prevalence patterns, sample size and screening methods seemed to influence the geographical prevalence patterns. It would be helpful to summarize the size of variations associated with these factors compared with overall variations in prevalence.
3. The factors most likely to influence ASD prevalence rates were sample size why? Is this a known statistical problem among epidemiologists? There is work on the placebo effect that indicates that smaller samples are more likely to report a large effect, suggesting that statistical fluctuation in small samples leads researchers to overreport large results. That kind of thing. and the age of the children screened. Although there was not enough data to rule out the influences of the other analyzed factors, these factors appeared to contribute most to individual study variations in ASD prevalence.
4. It is possible that misdiagnosis of autism-associated diseases such as Rett’s syndrome and TSC contribute to the changing autistic disorder and ASD prevalence rates.
This is a remarkably thorough review of the literature on prevalence of autism. It’s impressive.
What seems missing is just a little more synthesis of what the major trends are, which hypotheses are ruled out, which are still possible, that kind of thing. For instance, the fact that increases have occurred in many countries over the same period argues against the spread of autism-related alleles in a population. One can imagine environmental causes, but the twin studies seem to throw a major wrench into that hypothesis.
Further Research on the Role of Ethnicity in Autism
The remaining portion of this thesis seeks to further analyze whether the hypothesis that ethnicity is correlated with differences in autism prevalence. Preliminary research presented in this chapter suggests that autistic disorder prevalence varies globally and temporally due to changes in diagnostic criteria, sample size, and screening methods. While there was not sufficient data to determine whether a temporal increase in ASD prevalence occurred, no clear global prevalence pattern emerged. While this systematic review ultimately suggests that it is possible that ethnicity correlates with differences in autism prevalence due to the observed global patterns, this review does not assess this relationship in depth. Further chapters will seek to assess the genetic and neurological underpinnings of autism to determine if the current theories of the etiology of autism suggest if it is possible that ethnicity could be associated with autism prevalence. A case study of Somali immigrants in Minnesota will allow an in depth analysis of the role that ethnicity plays in autism prevalence. By analyzing the global patterns of autism prevalence as well as the genetic, cultural, and environmental causes of autism, a conclusion on the relationship between autism and ethnicity can be drawn.
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-----------------------
[1] Portions of this chapter taken from the spring junior paper prepared by this author.
-----------------------
Figure 2. Forest plots of the prevalence of autistic disorder and corresponding 95% confidence intervals from included studies conducted in the United States, Japan, Sweden, and the United States. X axis represents Prevalence per 10,000 in a Log Scale.
Figure 1: Inclusion Criteria – Autistic Disorder
1. Reported prevalence rates for autistic disorder.
2. Conducted in populations in Japan, the United States, the United Kingdom, or Sweden.
3. Peer reviewed journal article.
4. Published in English; Complete English version accessible.
5. Initial screening of a large geographically defined population of children.
6. Subsequent identification of cases of autistic disorder using clearly defined diagnostic criteria on selected children.
7. Included children under the age of 18.
[pic]
Figure 3: Inclusion Criteria – Autistic Spectrum Disorders
1. Reported prevalence rates for autistic spectrum disorders
2. Conducted in populations in Japan, the United States, the United Kingdom, or Sweden.
3. Peer reviewed journal article or government publication.
4. Published in English; Complete English version accessible.
5. Initial screening of a large geographically defined population of children.
6. Subsequent identification of cases of autistic disorder using clearly defined diagnostic criteria on selected children.
7. Included children under the age of 18.
Figure 4. Forest plots of the prevalence of autistic spectrum disorder (ASD) and corresponding 95% confidence intervals from included studies conducted in the United States, Japan, Sweden, and the United States. X axis represents Prevalence per 10,000 in a Log Scale.
[pic]
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