MMR & Autism

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Madsen KM et al. "Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism". The New England Journal of Medicine. 2002. 347(19):1477-1482.
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Clinical Question

In children born between 1991 and 1998, does vaccination against measles, mumps, and rubella increase the incidence of autism?

Bottom Line

  • The risk of autism in vaccinated and unvaccinated children is similar.
  • There is no association between time of diagnosis of autism and interval since vaccination.
  • Autistic disorder and other autism-spectrum disorders are not associated with MMR vaccination.

Major Points

Previous studies evaluating the potential link between MMR vaccination and autism lacked adequate statistical power. This study out of Denmark includes all children born in the country between 1991 and 1998, and provides strong evidence against the MMR-autism association. MMR vaccine was identical to the one used in the US. The diagnosis of autism in the study population was based on the ICD-10.

Design

  • Retrospective follow-up study of all children born in Denmark from 1991 to 1998
    • N=537,303
  • Cohort followed from age 1 year through diagnosis of autism, diagnosis of a related condition, emigration, death, or December 31, 1999- whichever occurred first.
  • Vaccination status determined from data reported to the National Board of Health
    • Vaccinated: 440,655
    • Unvaccinated: 96,648
  • Diagnoses of autism obtained from Danish Psychiatric Central Register
    • Number of cases: 316
    • Records of 40 children with autism (13%) were validated by a consultant in child psychiatry
  • Analysis: Incidence-rate ratios in vaccinated versus unvaccinated children

Population

Inclusion Criteria

  • All children born in Denmark from 1991 to 1998
  • Based on data from the Danish Civil Registration System

Exclusion Criteria

  • Data from children with the following inherited conditions known to be associated with autism were excluded:
    • Tuberous sclerosis
    • Angelman’s syndrome
    • Fragile X
    • Congenital rubella

Baseline Characteristics

  • No statistically significant difference in gender distribution, birth weight, gestational age, socioeconomic status, or mother’s level education between vaccinated and unvaccinated children.
  • Mean age at diagnosis for autistic disorder: 4y 3m
  • Mean age at diagnosis for other autism spectrum disorders: 5y 3m
  • Mean age at MMR vaccination: 17 months

Intervention

Outcomes

Comparisons are MMR vaccination vs non-vaccination

Primary Outcomes

Adjusted relative risk of autistic disorder
0.92 (95% CI 0.68-1.24)
Adjusted relative risk of autism-spectrum disorders
0.83 (95% CI 0.65-1.07)

Secondary Outcomes

Association between development of autistic disorder and age at vaccination
p = 0.23
Association between development of autistic disorder and interval since vaccination
p = 0.42
Association between development of autistic disorder calendar period at the time of vaccination
p = 0.06

Funding

Grants from:

  • The Danish National Research Foundation
  • The National Vaccine Program Office and National Immunization Program
  • Centers for Disease Control and Prevention
  • National Alliance for Autism Research

Further Reading

Stratton K, Gable A, Shetty P, McCormick M, eds. Immunization safety review: measles-mumps-rubella vaccine and autism. Washington, D.C.: Na- tional Academy Press, 2001.

Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage in California. JAMA 2001;285:1183-5.

Singh VK, Lin SX, Newell E, Nelson C. Abnormal measles-mumps- rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci 2002;9:359-64.