Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association

BACKGROUND We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism. METHODS Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method. FINDINGS We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden "step-up" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder. INTERPRETATION Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.

[1]  L. Wing,et al.  Autistic spectrum disorders , 1996, BMJ.

[2]  C P Farrington,et al.  Relative incidence estimation from case series for vaccine safety evaluation. , 1995, Biometrics.

[3]  W. Mayr,et al.  Blood groups Lewis(b) and ABH expression in gastric mucosa: lack of inter-relation with Helicobacter pylori colonisation and occurrence of gastric MALT lymphoma. , 1997, Gut.

[4]  J. Stephenson,et al.  Evidence of persistent measles virus infection in Crohn's disease , 1993, Journal of medical virology.

[5]  A. Beale Autism, inflammatory bowel disease, and MMR vaccine , 1998, The Lancet.

[6]  R. Pounder,et al.  Is measles vaccination a risk factor for inflammatory bowel disease? , 1995, The Lancet.

[7]  G. Elliott,et al.  How Children with Autism are Diagnosed: Difficulties in Identification of Children with Multiple Developmental Delays , 1988, Journal of developmental and behavioral pediatrics : JDBP.

[8]  Robert T. Chen,et al.  Vaccine adverse events: causal or coincidental? , 1998, The Lancet.

[9]  A. Sabrá,et al.  Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children , 1998, The Lancet.

[10]  E. Fombonne,et al.  Autism and associated medical disorders in a French epidemiological survey. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[11]  C P Farrington,et al.  Case series analysis of adverse reactions to vaccines: a comparative evaluation. , 1996, American journal of epidemiology.

[12]  R. Pounder,et al.  Measles vaccination: A risk factor for inflammatory bowel disease? , 1995 .

[13]  Andrew J Wakefield MMR vaccination and autism , 1999, The Lancet.

[14]  E. Miller,et al.  Impact of anti-vaccine movements on pertussis control: the untold story , 1998, The Lancet.

[15]  C. Gillberg,et al.  MMR and Autism , 1998 .

[16]  E. Ross,et al.  MMR vaccination and autism 1998 , 1998, BMJ.

[17]  R. Pounder,et al.  Measles virus RNA is not detected in inflammatory bowel disease using hybrid capture and reverse transcription followed by the polymerase chain reaction , 1998, Journal of medical virology.

[18]  R. Pounder,et al.  Perinatal and childhood risk factors for inflammatory bowel disease: a case-control study. , 1995, European journal of gastroenterology & hepatology.

[19]  M Rush,et al.  A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines , 1995, The Lancet.