title: Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations.
abstract: BACKGROUND
  The prevalence of pervasive developmental disorders has increased in recent years. Links with the measles component of the measles-mumps-rubella vaccine and the cumulative exposure to thimerosal through other vaccines have been postulated.
  
  
  OBJECTIVE
  The purpose of this work was to estimate the pervasive developmental disorder prevalence in Montreal, Canada, in cohorts born from 1987 to 1998 and evaluate the relationship of trends in pervasive developmental disorder rates with: (1) changes in cumulative exposure to ethylmercury (thimerosal) occurring through modifications in the immunization schedule of young children and (2) trends in measles-mumps-rubella vaccination use rates and the introduction of a 2-measles-mumps-rubella dosing schedule during the study period.
  
  
  METHODS
  We surveyed 27749 children born from 1987 to 1998 attending 55 schools from the largest Anglophone school board. Children with pervasive developmental disorders were identified by a special needs team. The cumulative exposure by age 2 years to thimerosal was calculated for 1987-1998 birth cohorts. Ethylmercury exposure ranged from medium (100-125 microg) from 1987 to 1991 to high (200-225 microg) from 1992 to 1995 to nil from 1996 onwards when thimerosal was entirely discontinued. Measles-mumps-rubella coverage for each birth cohort was estimated through surveys of vaccination rates. The immunization schedule included a measles-mumps-rubella single dose at 12 months of age up to 1995, and a second measles-mumps-rubella dose at 18 months of age was added on after 1996.
  
  
  RESULTS
  We found 180 children (82.8% males) with a pervasive developmental disorder diagnosis who attended the surveyed schools, yielding a prevalence for pervasive developmental disorder of 64.9 per 10000. The prevalence for specific pervasive developmental disorder subtypes were, for autistic disorder: 21.6 of 10000; for pervasive developmental disorder not otherwise specified: 32.8 of 10000; and for Asperger syndrome: 10.1 of 10000. A statistically significant linear increase in pervasive developmental disorder prevalence was noted during the study period. The prevalence of pervasive developmental disorder in thimerosal-free birth cohorts was significantly higher than that in thimerosal-exposed cohorts (82.7 of 10000 vs 59.5 of 10000). Using logistic regression models of the prevalence data, we found no significant effect of thimerosal exposure used either as a continuous or a categorical variable. Thus, thimerosal exposure was unrelated to the increasing trend in pervasive developmental disorder prevalence. These results were robust when additional analyses were performed to address possible limitations because of the ecological nature of the data and to evaluate potential effects of misclassification on exposure or diagnosis. Measles-mumps-rubella vaccination coverage averaged 93% during the study interval with a statistically significant decreasing trend from 96.1% in the older birth cohorts (1988-89) to approximately 92.4% in younger birth cohorts (1996-1998). Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased. In addition, pervasive developmental disorder prevalence increased at the same rate before and after the introduction in 1996 of the second measles-mumps-rubella dose, suggesting no increased risk of pervasive developmental disorder associated with a 2-measles-mumps-rubella dosing schedule before age 2 years. Results held true when additional analyses were performed to test for the potential effects of misclassification on exposure or diagnostic status. Thus, no relationship was found between pervasive developmental disorder rates and 1- or 2-dose measles-mumps-rubella immunization schedule.
  
  
  CONCLUSIONS
  The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations.
authors.affiliation: Department of Psychiatry, McGill University, Montréal Children's Hospital, 4018 Ste-Catherine West, Montreal, Quebec, Canada H3Z 1P2. eric.fombonne@mcgill.ca
authors.forename: Eric
authors.initials: E
authors.lastname: Fombonne
authors.forename: Rita
authors.initials: R
authors.lastname: Zakarian
authors.forename: Andrew
authors.initials: A
authors.lastname: Bennett
authors.forename: Linyan
authors.initials: L
authors.lastname: Meng
authors.forename: Diane
authors.initials: D
authors.lastname: McLean-Heywood
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D020817:Asperger Syndrome / Q000453:epidemiology; D001321:Autistic Disorder / Q000453:epidemiology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology* / Q000209:etiology; D002675:Child, Preschool; D005034:Ethylmercuric Chloride; D005260:Female; D006801:Humans; D007114:Immunization / Q000009:adverse effects*; D007115:Immunization Schedule; D016015:Logistic Models; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine; D015995:Prevalence; D011792:Quebec / Q000453:epidemiology; D017678:Sex Distribution; D013849:Thimerosal
chemical_list: D022542:Measles-Mumps-Rubella Vaccine; D013849:Thimerosal; D005034:Ethylmercuric Chloride