Elsevier

The Lancet

Volume 364, Issue 9438, 11–17 September 2004, Pages 963-969
The Lancet

Articles
MMR vaccination and pervasive developmental disorders: a case-control study

https://doi.org/10.1016/S0140-6736(04)17020-7Get rights and content

Summary

Background

Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders.

Methods

We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice.

Findings

1294 cases and 4469 controls were included. 1010 cases (78·1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82·1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0·86 (95% CI 0·68–1·09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism.

Interpretation

Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders.

Introduction

In 1998, it was suggested that measles-mumps-rubella (MMR) vaccination might cause autism, on the basis of a study of 12 children with pervasive developmental disorder referred to a paediatric gastroenterology unit, with no comparison group.1 In a subsequent larger case series, the condition postulated to be associated with MMR vaccination was referred to as autistic enterocolitis.2 These studies, and the findings of gut epithelial damage in children with autism,3 led the researchers to suggest that MMR vaccination could act as a trigger for a particular phenotype of autism.4 Fragments of measles virus genome were reported in the intestinal tissue of children with autism and associated gut disease more frequently than in a comparison group of children, some of whom had gut disease but all of whom were developmentally normal.5 The origin of the fragments of measles virus genome in these children has not been established. Furthermore, whether the presence of the fragments was specific to this subgroup of children, or whether they were due to intestinal disease rather than a cause of it, is unknown.6

Subsequent epidemiological studies did not confirm an association between MMR vaccination and autism,7, 8, 9 but these findings failed to reassure the public.10, 11, 12 The coverage of MMR vaccine by the age of 2 years in England fell from 92% in 1995–96 to 82% in 2002–03,13 and was followed by measles outbreaks.14, 15 In the light of continuing concern, we did a large case-control study to assess the risk of autism and other pervasive developmental disorders (PDDs) associated with MMR vaccination, by use of the UK General Practice Research Database (GPRD).

Section snippets

Methods

The study methods have been described in detail elsewhere.16 In brief, we did a case-control study to investigate whether MMR vaccination was associated with an increased risk of autism or other PDDs. Data were abstracted from the GPRD, a database that includes patients' records of vaccination and diagnoses of autism or other PDDs. The GPRD was set up in 1987, under the name of VAMP (Value Added Medical Products) Research Bank.17 The database consists of the electronic clinical records of

Results

The numbers of cases and controls initially identified, reasons for exclusion, and numbers included in the analyses are shown in figure 1. When there were no entries in the GPRD record for 12 months before the diagnosis or index date, or no clinical data recorded at all (apart from the PDD diagnosis for cases), cases and controls were excluded because of concerns about the completeness of the clinical data recorded. All cases were registered with a practice contributing to the GPRD on their

Discussion

We found that MMR vaccination was not associated with an increased risk of subsequently being diagnosed with a PDD. The findings were similar when analysis was restricted to children classified as having autism, or to children who had MMR vaccination before age 3 years.

An unexpected finding was that the odds ratio associated with MMR vaccination varied according to the age at which a person joined the GPRD. In particular, the odds ratio associated with MMR vaccination was higher among children

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