Articles 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, 7–9 but these findings failed to reassure the public. 10–12 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). 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 patients registered with contributing general practices. The practices are broadly representative of all practices in England and Wales in terms of geographical distribution, practice size, and the age and sex of registered patients. 18 The GPRD aims to include complete prescribing and diagnostic information for every registered patient. Data are anonymised. The quality of the information in the database has been found to be high in independent validation studies. 17 Two studies have assessed the completeness of recording of diagnoses made in medical facilities outside the practice, and found recording rates in excess of 90%. 19,20 There is excellent agreement between prescribing data from the GPRD and national data from the Prescription Pricing Authority. 21 For patients who were not registered with a practice in the GPRD from birth, information on previous vaccinations and diagnoses should be entered into their electronic record when they transfer into the practice. The number Lancet 2004; 364: 963–69 Department of Epidemiology and Population Health (Liam Smeeth MRCGP); Department of Infectious and Tropical Diseases (C Cook MSc, Prof L C Rodrigues PhD, Prof P G Smith DSc, Prof A J Hall FRCP); London School of Hygiene and Tropical Medicine, London, UK; Department of Psychiatry, McGill University, Montreal Children’s Hospital, Canada (Prof E Fombonne FRCPsych); and Institute of Psychiatry, Kings College, London, UK (L Heavey PhD) Correspondence to: Dr Liam Smeeth, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK autism@lshtm.ac.uk www.thelancet.com Vol 364 September 11, 2004 963 MMR vaccination and pervasive developmental disorders: a case-control study Liam Smeeth, Claire Cook, Eric Fombonne, Lisa Heavey, Laura C Rodrigues, Peter G Smith, Andrew J Hall 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.