Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis

British Medical Journal, Feb 24, 2001 by James A. Kaye, Maria del Mar Melero-Montes, Hershel Jick

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Among the vaccinated children, the median age at first MMR vaccination was 14 months, and 95% of those vaccinated received their first MMR vaccination by age 20 months. Among 110 cases of autism in boys aged 2 to 5 years born in 1988-93 for whom MMR vaccination could be assessed, the distribution of age at first MMR vaccination was nearly identical to that of the population as a whole, and 109 (99%) were vaccinated, a prevalence nearly identical to that in the general population.

Discussion

Previous publications have reported that the overall incidence of clinically diagnosed autism began to rise in the late 1980s, and that the incidence occurs predominantly in boys.[2 3 6] This study shows that the incidence has continued to increase during the past decade. Our analysis of the risk of diagnosed autism for boys aged 2 to 5 years showed a progressive increase for each successive birth cohort from 1988 to 1993, during which time the prevalence of MMR vaccination was over 95%. It should be noted that the MMR vaccine is given first at about 15 months of age and that autism is not typically diagnosed until age 2 years or later.

If the MMR vaccine were a major cause of the increasing incidence of autism then the risk of autism in successive birth cohorts would be expected to stop rising within a few years of the vaccine being in full use. This was not the case in our study as the cumulative incidence for boys ages 2 to 5 years rose almost fourfold in the 1993 birth cohort (with follow up to 1999) compared with the 1988 birth cohort, whereas the prevalence of MMR vaccination was over 95%. Thus no time correlation exists between the prevalence of MMR vaccination and the incidence of autism in each birth cohort from 1988 to 1993.

We recognise that the diagnosis of autism in our study was not confirmed from original records but consider that differential misclassification of the diagnosis in vaccinated and unvaccinated children is unlikely to vary over the period of the study.

Time trend analysis for the evaluation of the relation of an exposure to an illness is a relatively crude method. This is particularly true where the exposure and the illness are both rising during the period of study as such a correlation may be coincidental and due to changes in other factors that are correlated over time with the outcome illness. Nevertheless, when the incidence of an illness is rising rapidly in each birth year cohort at the same time that an exposure is steady and almost universal, the exposure cannot be the explanation for the rapid increase in incidence that was observed.

The increase in recorded diagnoses of autism that we observed in the UK general practice research database could be due to increased awareness of the condition among parents and general practitioners, changing diagnostic criteria, or environmental factors not yet identified. A strength of our study is that we were able to use population based data in the general practice research database to estimate the birth cohort specific incidence of autism recorded by general practitioners as well as the prevalence of MMR vaccination. A limitation is that we have not yet obtained and evaluated full clinical record information from general practitioners to describe more fully the characteristics of children diagnosed as having autism and to explore other possible explanations for the marked increase in the incidence of this illness during the past decade. Nevertheless, these results provide evidence against a causal relation between MMR vaccination and the risk of autism.