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Autism and Measles-Mumps-Rubella Vaccination Controversy Laid to Rest?

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Autism and Measles-Mumps-Rubella Vaccination Controversy Laid to Rest? CNS Drugs 2001; 15 (11): 831-837 CURRENT OPINION 1172-7047/01/0011-0831/$22.00/0 © Adis International Limited. All rights reserved. Autism and Measles-Mumps-Rubella Vaccination Controversy Laid to Rest? Frank DeStefano1 and Robert T. Chen2 1 National Center on Birth Defects and Developmental Disabilities, Atlanta, Georgia, USA 2 National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Abstract It has been suggested that vaccination, particularly with measles-mumps-ru- bella (MMR) vaccine, may be related to the development of autism. The main evidence for a possible association is that the prevalence of autism has been increasing at the same time that infant vaccination coverage has increased, and that in some cases there is an apparent temporal association in which autistic characteristics are first noted shortly after vaccination. Although the prevalence of autism and similar disorders appears to have increased recently, it is not clear if this is an actual increase or the result of increased recognition and changes in diagnostic criteria. The apparent onset of autism in close proximity to vaccination may be a coincidental temporal association. The clinical evidence in support of an association derives from a series of 12 patients with inflammatory bowel conditions and regressive developmental disorders, mostly autism. The possibil- ity that measles vaccine may cause autism through a persistent bowel infection has generated much interest, since it provides a possible biological mechanism. Epidemiological studies, however, have not found an association between MMR vaccination and autism. The epidemiological findings are consistent with current understanding of the pathogenesis of autism, which has a strong genetic compo- nent and in which the neurological defects probably occur early in embryonic development. It seems unlikely that a vaccination that is given after birth could cause autism. A minority of cases of autism may have onset after 1 year of age (regressive autism), but the single epidemiological study that included such cases did not find an association with MMR vaccination. Currently, the weight of the available epidemiological and related evidence does not support a causal associ- ation between MMR vaccine, or any other vaccine or vaccine constituent, and autism. It has been suggested that vaccination, particu- infant vaccination coverage has increased; and (ii) larly with measles-mumps-rubella (MMR) vac- in some cases of autism, there is an apparent tem- cine, may be related to the development of autism. poral association in which autistic characteristics The two main arguments that are used in support become apparent within a few weeks to a few of a possible association are: (i) the prevalence of months after vaccination. Neither argument, how- autism has been increasing at the same time that ever, is compelling. Although the prevalence of au- 832 DeStefano & Chen tism and similar disorders appears to have in- ral association with MMR vaccination was not ad- creased recently, it is not clear if this is an actual dressed. Fourthly, the most commonly identified increase or the result of increased recognition and bowel abnormality, ileocolonic lymphonodular hy- changes in diagnostic criteria. The apparent onset perplasia, may not necessarily represent a patho- in close proximity to vaccination may be a coinci- logical condition. Fifthly, the postulated link be- dental temporal association. Typically, autism is first tween bowel disease and autism was tenuous, as diagnosed or suspected during the second year of there was no confirmatory laboratory evidence (i.e. life, which is also when MMR vaccine is given. measles virus was not detected in the bowel) and In this report, we will review the evidence for a bowel disease did not precede onset of autism in possible causal association between MMR vaccine anyofthecases(aswouldberequiredforacausal and autism, as well as suggestions that other vac- association). cines or vaccine constituents may be related to Subsequent studies by Wakefield and collea- autism. We identified relevant articles through a gues[4,5] also were not supportive of the hypothesis. search of Medline and the reference lists of re- In particular, Wakefield’s group, as well as other viewed articles. The concerns about other vaccines have come to our attention primarily through con- researchers, reported that in patients with inflam- ferences or public meetings, the lay media, public matory bowel disease, the postulated mechanism inquiries and the internet. for autism after MMR vaccination, highly specific laboratory assays are in fact negative for measles virus.[4,6,7] Wakefield’s group also conducted an 1. The Autistic Enterocolitis Hypothesis epidemiological follow-up study of a 1970 British The hypothesis that MMR vaccine may cause birth cohort in which no overall association was autism was given prominence with the publication found between measles disease or measles vacci- of a report by Wakefield and colleagues[1] describ- nation and the subsequent occurrence of inflamma- ing 12 patients with inflammatory bowel condi- tory bowel disease (i.e. ulcerative colitis or Crohn’s tions and regressive developmental disorders, disease).[5] A case-control study conducted within mostly autism. In 8 of the 12 cases, the child’s par- the VaccineSafety Datalink project of the US Centers ents or paediatrician suspected that MMR vaccine for Disease Control and Prevention (CDC) found had contributed to the onset of behavioural prob- no association between MMR vaccine (or other [1] lems. Wakefield and colleagues hypothesised measles-containing vaccines) and inflammatory that MMR vaccine may have been responsible for bowel disease.[8] the bowel dysfunction (enterocolitis) which sub- Wakefield and collaborators have since pro- sequently resulted in neurodevelopmental disor- posed that they have identified a new syndrome ders. The report generated great interest because it consisting of milder gastrointestinal conditions, seemed to provide a biological mechanism by predominantly ileocolonic lymphonodular hyper- which MMR vaccine could cause autism. Others, however, including a special panel of the British plasia and mild intestinal inflammation, associated [9] Medical Research Council, found the evidence un- with behavioural regression. They have reported convincing for a number of reasons.[2,3] First, the identifying laboratory evidence of measles virus small number of cases referred to a gastroenterol- genome in the peripheral white blood cells and [10,11] ogy clinic may not have been representative of the bowel biopsy specimens of a few such patients. general population of children with autism and re- The relevance of these laboratory findings, how- ferral bias was possible. Secondly, no information ever, is not clear given that no association has been on the source population was provided and there established in epidemiological studies between was no unaffected comparison group. Thirdly, the MMR vaccine (or other measles-containing vac- possibility of a coincidental, but not causal, tempo- cines) and inflammatory bowel disease or autism. Adis International Limited. All rights reserved. CNS Drugs 2001; 15 (11) Autism and MMR Vaccination 833 2. Epidemiological Studies of of an association between MMR vaccine and autis- Measles-Mumps-Rubella Vaccine tic regression.[13] and Autism Three other published studies[14-16] also provide evidence against an association between MMR Since the initial publication of the Wakefield et vaccination and autism. A study in Sweden found [1] al. paper, epidemiological studies have failed to no increase in autism among children born after, find an association between MMR vaccination and compared with those born before, the introduction autism. The most thorough epidemiological study of MMR vaccination.[14] An analysis of a large data- to date was conducted by Taylor and colleagues.[12] base of British general medical practices found Those authors identified all 498 known patients that the incidence of autism increased seven-fold with autism spectrum disorders (ASDs) in the between 1988 and 1999, whereas the prevalence of North East Thames district of London who had MMR vaccination was over 95% throughout the been born in 1979 or later and linked them to an time period.[15] A similar analysis in California, US, independent regional vaccination registry. The also found increasing trends in the number of peo- ASDs included classical autism, atypical autism ple receiving developmental services for autism and Asperger’s syndrome, but the results were during a time when coverage with MMR vaccine similar when cases of classical autism were an- was fairly stable.[16] alysed separately. The authors first showed that the known number of ASD cases has been increasing since 1979 and there was no sharp increase after 3. Other Evidence Related to the introduction of MMR vaccine in 1988. Sec- Measles-Mumps-Rubella Vaccine and Autism ondly, they found that patients vaccinated before 18 months of age had similar ages at diagnosis as did patients who had been vaccinated after 18 The epidemiological findings are consistent with months or not vaccinated, indicating that vaccina- current understanding of the pathogenesis of au- tism, a syndrome defined by certain behavioural tion does not result in earlier expression of autistic and developmental characteristics that may have a characteristics. Thirdly, they showed that at age 2 variety of causes. In few cases,
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