1.1 Aim
This paper will investigate into a sample of studies examining the causal relationship between MMR-vaccination and autism in an attempt to determine whether there is a link.
An attempt will be made to answer the following question:
Is the Aetiology of Autism linked to the Administration of MMR-Vaccination? Or Are Parents Fears Unfounded?
2.0 Method
Studies were acquired for recruitment to this investigation by means of electronic journal search engines. The following search engines were used:
- Science Direct
- Ingenta Journal
- British Medical Journal (search across multiple journals option)
- PsychInfo
- New England Journal of Medicine
- The Lancet
- Medline central
Several searches were conducted using the following search terms within the ‘title’, ‘abstract’, ‘keywords’ fields:
- “Autism”
- “Autism AND MMR”
- “Aetiology of Autism”
The searches were conducted to include all relevant scientific information between the dates of 1942 to 2003.
A selection criterion was then applied to the results of the journal search in an attempt to recruit papers with reliable and comparable results. This criterion included:
- Retrospective or prospective studies on individuals up to the age of 15 years, published between 1969-2003
- Cohort, time-series or ecological studies
- Samples above 50
- Controlled studies
- Single-sex or dual sex studies
- Peer-reviewed published research within a medical journal
The criteria were developed before the searches were conducted to eliminate experimenter bias and reduce the risk of rejecting a paper blindly.
3.0 Results
3.1 Search Results
The initial searches conducted revealed in total 113 hits. Of these only 8 articles were relevant studies, of which four studies were recruited:
3.1.1 Table to Show Studies Recruited for Investigation
Also included for comparison was the original study linked to the hypotheses that Wakefield proposed in 1998 – Wakefield et al, 1998 n=12. According to the criterion used to recruit papers to this investigation, Wakefield’s study would have been rejected.
3.2 Results of Each Study
3.2.1 Fombonne et al, 2001
Hypothesis proposed: “There is a link between MMR-vaccine and a form of Autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunisation”.
Thus not only is there a link between MMR and autism but that there is a new phenotype of the disorder that is induced by administration.
Methods Used: Three samples were used:
- 96 children immunised with MMR who had a pervasive developmental disorder (known as post-MMR sample)
- 98 autistic children (pre-MMR)
- 68 autistic children (post-MMR)
Data regarding age of parental concern, developmental regression, bowel symptoms and immunisation dates were analysed.
Main Results:
- Rate of developmental regression reported in the post-MMR group was not different from the pre-MMR group
- Subset of autistic children with regression had no other developmental or clinical characteristics which could be used to argue a specific aetiologically different phenotype
Conclusions:
- No evidence was found to support a distinct syndrome of MMR-induced autism or of ‘autistic enterocolitis’
- Failure to find support an association between MMR and autism at population level
- Current findings do not argue for changes with current immunisation programs and recommendations
-
Masden et al, 2002
Hypotheses: “It has been suggested that the measles, mumps and rubella vaccine causes autism”
Methods Used: Retrospective cohort study of all children born in Denmark between Jan 1991 and Dec 1998 = 537,303 children of which 82% received the MMR-vaccine
Immunisation status, autistic diagnoses and other confounding information was then analysed.
Main Results:
- Relative risk of autistic disorder for MMR-group was 0.92% compared with unvaccinated group
- Relative risk of another autistic-spectrum disorder was 0.83%
- For either disorder no significant difference between non-vaccinated group and vaccinated group
Conclusion:
- This study provides strong evidence against the hypothesis that MMR-vaccination causes autism
-
Taylor et al, 2002
Hypotheses: “To investigate whether measles, mumps and rubella vaccination is associated with bowel problems and developmental regression in children with autism, looking for evidence of a ‘new-variant’ form of autism”
Methods Used: Population study of 278 core autistic children and 195 atypical autistic children from five health districts in London. Information regarding immunisation status, age of reported regression of child’s development and bowel symptoms were analysed.
Main Results:
- Proportion of children with developmental regression (25% overall) or bowel symptoms (17% overall) did not change significantly during the 20 years from 1979, a period which included the introduction of MMR-vaccination in Oct 1998
- No significant difference was found in rates of bowel symptoms or regression in children who received MMR after such concern as compared to those who had not received it
- A possible association between non-specific bowel problems and regression in children with autism was seen but this was not related to MMR-vaccination
Conclusions
- Failure to support an MMR-associated ‘new-variant’ form of autism with developmental regression and bowel problems
- This study adds further evidence against involvement of MMR-vaccine in the initiation of autism
-
Dales et al, 2001
Hypotheses: “To determine if a correlation exists in secular trends of MMR-immunisation coverage among young children and autism occurrence”
Methods Used: Retrospective analyses of MMR-immunisation coverage rates and autism diagnoses. Main outcome measures were MMR coverage rates as of ages 17 months and 24 months and numbers of Department of Developmental Services system enrolees diagnosed with autism, grouped by birth
Main Results:
- No correlation observed between secular trend of early childhood MMR-rates in California and the secular trend in numbers of children with autism
- A marked sustained increase in autism case numbers of children with autism but changes in MMR coverage over the same time period were much smaller and of shorter duration
Conclusion:
- These data do not suggest an association between MMR-immunisation among young children and an increase in autism occurrence
3.2.5 Wakefield et al, 1998
Hypotheses: No specific questions found, “We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder”
Methods Used: 12 children between 3-10 years referred to paediatric gastroenterology unit with history of normal development followed by a loss of acquired skills. Children underwent gastroenterological, neurological and developmental assessment.
Main Results:
- Onset of behavioural symptoms was associated, by the parents, with MMR-vaccination in 8 of 12 children
- Behavioural disorders included 9 with autism, 1 with disintegrative psychosis and 2 with possible postviral or vaccinal encephalitis
Conclusion:
- Gastrointestinal disease and developmental regression in a group of previously normal children is associated with possible environmental triggers
- In most cases onset of symptoms was after MMR-immunisation
4.0 Discussion
Any conclusion drawn by this investigation should only be taken as a possible truth since only the conclusions drawn by each study examined have been taken into consideration. No independent statistical testing has been applied to the results making the significance difficult to estimate.
In addition to this, the sample of papers reviewed is subject to a restricted constraint. Despite the search criteria of papers up to 2003 was included, the search was limited financially since only ‘free-to-view’ papers were recruited. Most search engines do not release papers on ‘free-to-view’ 6 months to a year after publication.
In conjunction with this issue, it cannot be certain that the sample included all investigations conducted in this area since a lot of material may be unpublished or rejected from journals for political reasons (see below). Such material can only be accessed from unsupervised websites where it is difficult to ascertain the validity of results owing to the lack of academic peer-review.
One limitation of all the studies recruited is their source of financial support. Although this was not investigated formally, most studies appeared to have financial backing from the Government. Such support immediately introduced researcher bias since the experimenter may be under pressure to produce favourable results in line with the guidelines set out by the Government.
Another limitation is the design of the studies recruited. Most of them employ a retrospective design looking back at data already collated. This poses problems with standardisation of information, falsification of data and corrupted or missing files. A lot of information may be lost or damaged without the knowledge of the researcher. In essence, to eliminate this problem a better design may involve a prospective experiment of a large sample involving a clear control group (unvaccinated children) and an experimental group (vaccinated children) with follow-ups up to 3 years after vaccination.
The flaws briefly discussed above are a few of many. There are other limitations of both this study and the studies recruited for examination.
- Conclusions
This review suggests that there is no link between the aetiology of autism and the administration of MMR-vaccine. With the exception of Wakefield’s report, all the studies recruited for review fail to find support for such a theory.
Wakefield’s work has been heavily criticised on methodological grounds in terms of sampling and also design study. In November 2003, Murch (one of Wakefield’s original team) approached the press claiming no link between MMR and autism after a review of research conducted into this area as a consequence to his original research.
However, an answer has to be found regarding the aetiology of autism, if MMR-vaccine is not a causative factor then what is? And can it be prevented? With increasing numbers of Autistics, there is a mounting pressure to determine cures or preventative measures. It is clear that a substantial amount of continuing research in this area is required.
6.0 References
6.1 Journal Articles
Boseley S (2001) Fear of Measles Epidemic as Jab Rate Drops. London, UK: The Guardian; 5 January 2001
Dales L, Hammer S J, Smith N J (2001) Time Trends in Autism and in MMR Immunization Coverage in California. JAMA 322:460-3p
Fombonne E, Chakrabarti S (2001) No Evidence for New Variant of Measles-Mumps-Rubella-Induced Autism. Pediatrics 108:4:1-8p
Kanner L (1943) Autistic Disturbances of Affective Contact. Nervous Child 2:217-50p
Kaye J A, Melero-Montes M d M, Jick H (2001) Mumps, Measles and Rubella Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time Trend Analysis. British Medical Journal 322:460-3p
Offit P A, Coffin S E (2003) Communicating Science to the Public: MMR Vaccine and Autism. Vaccine 22:1-6p
Scalon T (2002) MMR Vaccine Uptake May Be Lower Than Reported Because of Manipulation of Target Groups. British Medical Journal 324:724p
Volkmar F R, Pauls D (2003) Autism. The Lancet 362:1133-41p
Wakefield A J, Murch S H, Anthony A, Linnell J, Casson D M, Malik M, Berelowitz M, Dhillon A P, Thomson M A, Harvey P, Valentine A, Davies S E, Walker-Smith J A (1998) Ileal-Lymphoid-Nodular Hyperplasia, Non-Specific Colitis, and Pervasive Developmental Disorder in Children. The Lancet 351:637-41p
6.2 Electronic Resources
British Medical Journal: dates accessed 09/11/2003, 10/11/2003,12/11/2003
Ingenta Journals: date accessed 12/11/2003
Medline Central: dates accessed 09/11/2003, 10/11/2003, 11/11/2003
National Autistic Society: date accessed 09/11/2003
New England Journal of Medicine: date accessed 09/11/2003
PsychInfo Journals: date accessed 12/11/2003
Science Direct: dates accessed 09/11/2003, 12/11/2003
The Lancet: dates accessed 09/11/2003, 10/11/2003, 11/11/2003
Appendices
1.0 Taken from Volkmar & Pauls (2003)
