Incidence of autism spectrum disorders: Changes over time and their meaning *

Aim: Several reviews have noted a huge increase in the rate of diagnosed autism spectrum disorders. The main aims of this paper are: 1) to use published empirical findings to consider whether the rise reflects a true increase in incidence, as distinct from the consequences of better ascertainment and a broadening of the diagnostic concept; and 2) to consider how epidemiological data may be used to test hypotheses about possible causal influences, using MMR and thimerosal as examples. Methods: Search of the literature for studies with a large epidemiological base population, systematic standardized screening, a focus on an age group for which diagnostic assessments are reliable and valid, and diagnosis by trained professionals using high‐quality research assessments. Also, search of a broader literature to consider the evidence from all epidemiological studies with respect to the hypothesized causal effect of MMR and thimerosal on autism spectrum disorders. Results: The true incidence of autism spectrum disorders is likely to be within the range of 30–60 cases per 10 000, a huge increase over the original estimate 40 years ago of 4 per 10 000. The increase is largely a consequence of improved ascertainment and a considerable broadening of the diagnostic concept. However, a true risk due to some, as yet to be identified, environmental risk factor cannot be ruled out. There is no support for the hypothesis for a role of either MMR or thimerosal in causation, but the evidence on the latter is more limited.

[1]  Geraldine Dawson,et al.  Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation , 2002, Development and Psychopathology.

[2]  Bernard Rimland,et al.  Association between thimerosal-containing vaccine and autism. , 2003, JAMA.

[3]  N. Fejerman Disintegrative Psychosis of Childhood: Teenage Follow‐up , 1986, Developmental medicine and child neurology.

[4]  N. Andrews,et al.  Prevalence of autism and parentally reported triggers in a north east London population , 2003, Archives of disease in childhood.

[5]  A. Caspi,et al.  The natural history of change in intellectual performance: who changes? How much? Is it meaningful? , 1993, Journal of child psychology and psychiatry, and allied disciplines.

[6]  Immunization Safety Review : Vaccines and Autism , 2004 .

[7]  E. Saemundsen,et al.  Prevalence of Autism in Iceland , 2001, Journal of autism and developmental disorders.

[8]  L. Dales,et al.  Time trends in autism and in MMR immunization coverage in California. , 2001, Journal of the American Medical Association (JAMA).

[9]  P. Howlin,et al.  THE RECOGNITION OF AUTISM IN CHILDREN WITH DOWN SYNDROME‐IMPLICATIONS FOR INTERVENTION AND SOME SPECULATIONS ABOUT PATHOLOGY , 1995, Developmental medicine and child neurology.

[10]  M. McCormick,et al.  Immunization Safety Review: Thimerosal-Containing Vaccines and Neurodevelopmental Disorders , 2001 .

[11]  H. Asperger,et al.  Die „Autistischen Psychopathen” im Kindesalter , 1944, Archiv für Psychiatrie und Nervenkrankheiten.

[12]  E. Fombonne,et al.  No evidence for a new variant of measles-mumps-rubella-induced autism. , 2001, Pediatrics.

[13]  L. Rosenbloom,et al.  Disintegrative Psychosis in Childhood , 1978, Developmental medicine and child neurology.

[14]  L. Wing,et al.  Asperger's syndrome: a clinical account , 1981, Psychological Medicine.

[15]  E. Fombonne,et al.  The epidemiology of autism: a review , 1999, Psychological Medicine.

[16]  Patricia Howlin,et al.  Diagnosis in Autism , 1997 .

[17]  Mogens Vestergaard,et al.  A population-based study of measles, mumps, and rubella vaccination and autism. , 2002, The New England journal of medicine.

[18]  D. Geier,et al.  Response to Comments by J.R. Mann , 2003 .

[19]  M. Rutter Genetic Influences and Autism , 2005 .

[20]  A. Wendroff The toxicology of mercury. , 2004, The New England journal of medicine.

[21]  Robert L Davis,et al.  Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. , 2003, Pediatrics.

[22]  D. Kocijan-Hercigonja [Infantile autism]. , 1989, Vojnosanitetski pregled.

[23]  L. Croen,et al.  Response: A Response to Blaxill, Baskin, and Spitzer on Croen et al. (2002), “The Changing Prevalence of Autism in California” , 2003 .

[24]  C. Klicpera,et al.  A retrospective analysis of the clinical case records of 'autistic psychopaths' diagnosed by Hans Asperger and his team at the University Children's Hospital, Vienna. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[25]  Diane Simpson,et al.  Autism and thimerosal-containing vaccines: lack of consistent evidence for an association. , 2003, American journal of preventive medicine.

[26]  E. Fombonne,et al.  No evidence for links between autism, MMR and measles virus , 2004, Psychological Medicine.

[27]  L. Kanner Autistic disturbances of affective contact. , 1968, Acta paedopsychiatrica.

[28]  S. Selvin,et al.  The Changing Prevalence of Autism in California , 2002, Journal of autism and developmental disorders.

[29]  Leon Eisenberg,et al.  Autism and Asperger syndrome , 1992, The Lancet.

[30]  R. Tuchman,et al.  Regression in pervasive developmental disorders: seizures and epileptiform electroencephalogram correlates. , 1997, Pediatrics.

[31]  B Hagberg,et al.  Brief Report: Autism and Asperger Syndrome in Seven-Year-Old Children: A Total Population Study , 1999, Journal of autism and developmental disorders.

[32]  David A Geier,et al.  Neurodevelopmental Disorders after Thimerosal-Containing Vaccines: A Brief Communication , 2003, Experimental biology and medicine.

[33]  H. Naruse The biology of the autistic syndromes Gillberg C, Coleman M. 2nd Edition. Clinics in Developmental Medicine No. 126. London: MacKeith Press, 1992: 317 pp , 1993, Brain and Development.

[34]  A. Bailey,et al.  Autism: The Phenotype in Relatives , 1998, Journal of autism and developmental disorders.

[35]  W. Spitzer,et al.  Commentary: Blaxill, Baskin, and Spitzer on Croen et al. (2002), The Changing Prevalence of Autism in California , 2003, Journal of autism and developmental disorders.

[36]  E. Fombonne,et al.  Pervasive developmental disorders in preschool children. , 2001, JAMA.

[37]  G. Bock,et al.  Autism: Neural Basis and Treatment Possibilities , 2003 .

[38]  Jun Li,et al.  Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association , 1999, The Lancet.

[39]  L. Wing,et al.  Severe impairments of social interaction and associated abnormalities in children: Epidemiology and classification , 1979, Journal of autism and developmental disorders.

[40]  J. Roger The MMR question , 2000, The Lancet.

[41]  A Pickles,et al.  A broader phenotype of autism: the clinical spectrum in twins. , 1996, Journal of child psychology and psychiatry, and allied disciplines.

[42]  M. Lauritsen,et al.  Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. , 2003, Pediatrics.

[43]  K. Ness,et al.  Analysis of prevalence trends of autism spectrum disorder in Minnesota. , 2003, Archives of pediatrics & adolescent medicine.

[44]  C. Gillberg,et al.  AUTISM AND MEDICAL DISORDERS: A REVIEW OF THE LITERATURE , 1996, Developmental medicine and child neurology.

[45]  C. N. Hendry Childhood disintegrative disorder: should it be considered a distinct diagnosis? , 2000 .

[46]  Jean Aicardi,et al.  A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: Report of 35 cases , 1983, Annals of neurology.

[47]  H Jick,et al.  Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis , 2001, BMJ : British Medical Journal.

[48]  G. Roberts MMR vaccination and autism , 1999, The Lancet.

[49]  A. Bailey,et al.  Autism and known medical conditions: myth and substance. , 1994, Journal of child psychology and psychiatry, and allied disciplines.

[50]  C P Farrington,et al.  MMR and autism: further evidence against a causal association. , 2001, Vaccine.

[51]  C. Gillberg,et al.  Is Autism More Common Now than Ten Years Ago? , 1991, British Journal of Psychiatry.

[52]  D. V. Krevelen Early infantile autism and autistic psychopathy , 1971 .

[53]  D. V. van Krevelen Early infantile autism and autistic psychopathy. , 1971, Journal of autism and childhood schizophrenia.

[54]  C. Gillberg,et al.  Rett syndrome in Sweden , 1987, Journal of autism and developmental disorders.

[55]  K. Papanikolaou,et al.  Brief Report: Autism in Individuals with Down Syndrome , 2005, Journal of autism and developmental disorders.

[56]  H. Jick,et al.  Epidemiology and Possible Causes of Autism , 2003, Pharmacotherapy.

[57]  S. Malhotra,et al.  Childhood disintegrative disorder , 2002, European Child & Adolescent Psychiatry.

[58]  C. Gillberg,et al.  Autism and Autistic-like Conditions in Swedish Rural and Urban Areas: a Population Study , 1986, British Journal of Psychiatry.

[59]  W. Fraser,et al.  The changing prevalence of autistic disorder in a Welsh health district , 1997, Developmental medicine and child neurology.

[60]  M. Wiznitzer,et al.  AIDS and the Nervous System , 1988, Neurology.

[61]  J. Miles,et al.  Prevalence of autism in Missouri: changing trends and the effect of a comprehensive state autism project. , 2000, Missouri medicine.

[62]  E. Fombonne,et al.  Prevalence of pervasive developmental disorders in the British nationwide survey of child mental health , 2003, International review of psychiatry.

[63]  C. Gillberg,et al.  Autism in 3-6-Year-Old Children in a Suburb of Goteborg, Sweden , 1997 .

[64]  Hideo Honda,et al.  No effect of MMR withdrawal on the incidence of autism: a total population study. , 2005, Journal of child psychology and psychiatry, and allied disciplines.

[65]  K Reesten M Eldgaard,et al.  A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism , 2002 .

[66]  E. Fombonne Epidemiological Surveys of Autism and Other Pervasive Developmental Disorders: An Update , 2003, Journal of autism and developmental disorders.

[67]  Victor Lotter,et al.  Epidemiology of autistic conditions in young children , 1966, Social psychiatry.

[68]  P. Standen,et al.  Prevalence of autism in early 1970s may have been underestimated , 2001, BMJ : British Medical Journal.

[69]  S Bernard,et al.  Autism: a novel form of mercury poisoning. , 2001, Medical hypotheses.

[70]  Y. Ohashi,et al.  Cumulative Incidence and Prevalence of Childhood Autism in Children in Japan , 1996, British Journal of Psychiatry.

[71]  A. Couteur,et al.  Development and current functioning in adolescents with Asperger syndrome: a comparative study. , 2001, Journal of child psychology and psychiatry, and allied disciplines.

[72]  G. Baird,et al.  A screening instrument for autism at 18 months of age: a 6-year follow-up study. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[73]  Corri Black,et al.  Changes in risk of autism in the U.K. for birth cohorts 1990-1998. , 2003, Epidemiology.

[74]  T. Hashimoto,et al.  DEVELOPMENTAL BRAIN CHANGES INVESTIGATED WITH PROTON MAGNETIC RESONANCE SPECTROSCOPY , 1995, Developmental medicine and child neurology.

[75]  A. Sandler Changes in the incidence of childhood autism and other autism spectrum disorders in preschool children from two areas of the West Midlands , 2001 .

[76]  H. Zoghbi,et al.  Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 , 1999, Nature Genetics.

[77]  Robert T. Chen,et al.  A retrospective cohort study of the association of varicella vaccine failure with asthma, steroid use, age at vaccination, and measles-mumps-rubella vaccination. , 2003, Pediatrics.

[78]  C. Gillberg Infantile autism and other childhood psychoses in a Swedish urban region. Epidemiological aspects. , 1984, Journal of child psychology and psychiatry, and allied disciplines.

[79]  A. Sabrá,et al.  Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children , 1998, The Lancet.

[80]  J. Powell,et al.  Changes in the incidence of childhood autism and other autistic spectrum disorders in preschool children from two areas of the West Midlands, UK , 2000, Developmental medicine and child neurology.