Question

• The parents of a young child are afraid to have their child immunized due to concerns about the possible role of the MMR vaccine in causing autism. Does the MMR vaccine cause autism?

Clinical Bottom Lines

1. It is unlikely that the MMR vaccine causes autism.
   
2. It is impossible to rule out that there may be some unknown subgroup that is predisposed to autism when exposed to MMR; however such a group must be very small or the effect must be very minor.

Summary of Key Evidence

1. This retrospective cohort study looked at records of all children born in Denmark from 1991 to 1998 (537,303 kids), of whom 82% received the MMR vaccine.
2. Those children who were diagnosed with autism by ICD-10 criteria (316 with autism, 422 with autistic spectrum) were reported to a central government registry, which was used in this study. Some of these charts were randomly reviewed in a blinded manner by a child psychiatrist as part of the study in order to ensure validity.
3. Outcomes were presence or absence of diagnosis of autism or autistic spectrum disorder.
4. The following subjects were excluded: 45 kids who had a congenital disorder that has autistic behavior as a component of their disorder, and 5028 who either died or emigrated.
5. Method of analysis: Data was broken down into person-years, with children assigned to non-vaccinated group until the time that they were vaccinated, if it occurred. Analysis also looked at temporal relationship of vaccine administration to see if a dose-effect response was seen. Logistic regression analysis was used.
6. Results: for autistic disorder, RR 0.92 with 95% CI 0.68 to 1.24. For autistic spectrum disorders, RR 0.83 with 95% CI 0.65 to 1.07. These findings support the null hypothesis (no association between autism and MMR vaccine).
7. Applicability: Vaccine strains identical to those used in USA, age of administration similar to USA, and diagnostic criteria similar to those used in the USA.
8. Validity and limitations: There may exist subgroups with predispositions that have not yet been identified. However, given the results and the large size of this study, such groups would have to either be small in size or the predisposition be minor in effect. Even if we feel that this study was good, we still cannot exclude that MMR vaccine may cause or contribute to autism in some children. However, we can say that if such an effect is present, it must be small. Such an effect could be outweighed by risk of diseases prevented by the vaccine.

Additional Comments

• It has been noted that the incidence of autism is increasing, and autism tends to appear at 15 months or so, which is the standard timing of MMR vaccination.
  
• Alleged biological mechanism is that MMR vaccine may cause an autoimmune reaction that leads to development of autism, but the details of this alleged mechanism are unknown.
  
• Other studies have been performed to examine this issue, but they have been of the case-control type or other less-satisfying types of studies.
  
• The large size and thorough nature of this study was made possible by the careful record keeping and the socialized nature of the Danish health care system.
  
• Despite the impressive size and findings of this cohort study, there are still many who believe that MMR vaccine is responsible for the rise in the incidence of autism.

Citation

1. Madsen, et al. A population-based study of measles, mumps, and rubella vaccination and autism." N Engl J Med 2002; 347:1477-82.

CAT Author: Kenneth P. Fowler, MD

CAT Appraisers: Katherine Layton, MD

Date appraised: April 14, 2003