August 1999
LONDON - A recent U.K. study found no causal association between the measles, mumps and rubella (MMR) vaccine and autism.
"If such an association occurs, it is so rare we could not detect any effect in this large sample of children with autism," said Brent Taylor, PhD, professor in the department of community child health, Royal Free Campus, Royal Free and University College Medical School, University College London.
To determine if there is an association between the MMR vaccine and autism, Taylor and his colleagues conducted a population-based study in the North East Thames region. The MMR vaccines were supplied by SmithKline Beecham, Pasteur Mérieux Connaught and Merck Sharp and Dome over the study period.
"We used a variety of epidemiological techniques, including case-series analysis methods to test for clustering of onsets within defined postvaccination periods," he explained.
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In mid-1998, computerized special needs/disability registers at child development centers and records in special schools were examined to identify children who were born after 1979 with autistic disorders in eight health districts. Three experienced pediatric registrars extracted information from clinical records on children with these disorders who were younger than 16 years. Information extracted included the age at which the autistic disorder was diagnosed, the recorded age at which the parents first became concerned about the child's developmental state and the age at which the regression became obvious, if that was a feature.
"By use of the criteria of the International Classification of Diseases,10th revision, the diagnosis of autism was checked against information in the available records on the child's present condition and his or her condition between the ages of 18 months and 3 years," Taylor said.
Inter-rater reliability was tested on 20 case records, with more than a 95% concordance rate. Immunization data, including exact dates, were recorded independently of the clinical record and were obtained from the Regional Interactive Child Health Computing System.
Three statistical analyses were performed. Using Poisson regression, trends in the time series of cases were analyzed. Additionally, the age at diagnosis was compared in vaccinated and unvaccinated children with autism diagnosed after 18 months of age.
"Children were classified into three categories: those who had received MMR vaccine before the age of 18 months; those never vaccinated with MMR; and, those who had received MMR vaccine at age 18 months or later," he added.
The third statistical analysis concerned possible temporal associations between vaccinations and the age at diagnosis of autism, the recorded age at parental concern and the age of onset of regression. These were analyzed by the case-series method.
In the study, 498 children with autism were identified: 261 had typical autism, 166 had atypical autism and 71 had Asperger's syndrome. The diagnosis could be confirmed with criteria from the International Classification of Diseases, 10th revision, in 214 cases of typical autism, 52 cases of atypical autism and 27 cases of Asperger's syndrome. This syndrome is defined by overdevelopment of one mental faculty or skill in an otherwise autistic person.
A neurodevelopmental pediatrician examined 441 children, a speech therapist examined 411 and a child psychiatrist or a clinical or educational psychologist assessed 422. Additionally, 192 were assessed at a center specializing in autism.
"Age at parental concern showed big peaks at 18 months and 24 months for core and atypical autism. With one exception, the earliest age at diagnosis was 18 months in the core and atypical autism groups and 30 months in the Asperger's syndrome group. Regression was recorded for 29% of core autism cases compared with 18% of atypical cases and 6% of those with Asperger's syndrome," Taylor explained.
"A total of 389 children with core autism, atypical autism or Asperger's syndrome were born after 1987; 336 of these had received MMR vaccine by the end of the second year of life and a further 17 received the vaccine after this age. The modal age at which MMR vaccine was given was 13 months," he added.
MMR vaccine coverage in the 389 study cases was similar to that in the same birth cohorts in the North East Thames region as a whole. Trends in the incidence of autism by birth cohort since 1987 were not temporally associated with changes in vaccine coverage.
"Of the 356 cases of core or atypical autism with age at diagnosis of 18 months or greater, 233 received MMR vaccine before this age, 64 never received MMR vaccine and 59 received MMR vaccine at 18 months or later. There were no differences in age at diagnosis between those vaccinated before or after 18 months of age and those never vaccinated and no interaction between these vaccine categories and year of birth. The case-series analyses showed no evidence of temporal clustering between MMR or other measles-containing vaccines and diagnosis of autism," he said.
"The general message from our work is that doctors and others concerned with immunization can reassure parents of children with autism that the MMR vaccine did not cause their child's condition, and also those parents with children due for MMR vaccination, that their child will not develop autism (or inflammatory bowel disease) as a result," Taylor concluded.
For more information:
- Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999;353:2026-2029.
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