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

British Medical Journal 2001;322:460-463  24feb01

James A Kaye, epidemiologist,  Maria del Mar Melero-Montes, epidemiologist,  Hershel Jick, associate professor of medicine. 

Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, 11 Muzzey Street, Lexington, MA 02421, USA

Correspondence to: J A Kaye jkaye@narsil.com

Objective: To estimate changes in the risk of autism and assess the relation of autism to the mumps, measles, and rubella (MMR) vaccine.
Design: Time trend analysis of data from the UK general practice research database (GPRD).
Setting: General practices in the United Kingdom.
Subjects: Children aged 12 years or younger diagnosed with autism 1988-99, with further analysis of boys aged 2 to 5 years born 1988-93.
Main outcome measures: Annual and age specific incidence for first recorded diagnoses of autism (that is, when the diagnosis of autism was first recorded) in the children aged 12 years or younger; annual, birth cohort specific risk of autism diagnosed in the 2 to 5 year old boys; coverage (prevalence) of MMR vaccination in the same birth cohorts.
Results: The incidence of newly diagnosed autism increased sevenfold, from 0.3 per 10 000 person years in 1988 to 2.1 per 10 000 person years in 1999. The peak incidence was among 3 and 4 year olds, and 83% (254/305) of cases were boys. In an annual birth cohort analysis of 114 boys born in 1988-93, the risk of autism in 2 to 5 year old boys increased nearly fourfold over time, from 8 (95% confidence interval 4 to 14) per 10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993. For the same annual birth cohorts the prevalence of MMR vaccination was over 95%.
Conclusions: Because the incidence of autism among 2 to 5 year olds increased markedly among boys born in each year separately from 1988 to 1993 while MMR vaccine coverage was over 95% for successive annual birth cohorts, the data provide evidence that no correlation exists between the prevalence of MMR vaccination and the rapid increase in the risk of autism over time. The explanation for the marked increase in risk of the diagnosis of autism in the past decade remains uncertain.