Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association
B Taylor 1 , E Miller, C P Farrington, M C Petropoulos, I Favot-Mayaud, J Li, P A Waight
| AAP: Researchers looked for any change in number or age of children diagnosed with autism associated with the MMR vaccine being introduced in the United Kingdom in 1988. The study identified 498 cases of autism (261 “core” autism; 166 “atypical” autism; 71 “Asperger syndrome”) in children born in the UK since 1979. There was a steady increase in autism cases by year of birth with no sudden change after the MMR vaccine was introduced. 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 causal association between onset of autism within 1 or 2 years after vaccination with MMR. Developmental regression was not clustered in the months after vaccination. |
Abstract
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.
WHAT CRITICS SAID:
■ Older children, born in 1984-1986, also received the vaccine as part of the United Kingdom’sCatch-up campaign.
■ The authors erroneously concluded that the rise in autism started several years before MMR was introduced and therefore had nothing to do with this vaccine. In fact a substantial number (n=36) of their cohort had formed part of the Catch-up campaign, and the step-up in autism occurred at precisely the time the first children received MMR vaccine in North London.
■ In their defense, the authors claimed that review of the records in the older recipients of MMR had identified parental concerns before MMR vaccination. They used this argument as justification for interpretation of a graph which simply presented number of children with autism versus year of birth, and owed nothing to apparent expressions of parental concern.
■ The authors tested the hypothesis of temporal clustering of age at diagnosis of autism in defined time periods post MMR vaccination, an analysis which, because of the considerable delay in diagnosis, is likely to bias towards a negative finding.
■ Despite this, they still found significant clustering of diagnoses by 6 months post MMR.
■ The authors tested a hypothesis and found a positive association.
WHAT THE COCHRANE REPORT SAID:
■ The absence of unvaccinated controls limits the inductive statements that can be made from this study.
■ The authors were “uncertain as to the power and generalisability of the findings from the single case-only design study.”
■ “This study demonstrates the difficulties of drawing inferences in the absence of a non-exposed population or a clearly defined causal hypothesis.”
■ This study failed to report complete vaccine identification information, “including lot numbers, adjuvants, preservatives, strains, product and manufacturer.”
■ This study failed to report any vaccine strains at all.
WHAT THE IOM SAID
There was an association between bowel problems and developmental regression – with almost twice the rate of bowel symptoms found in the regressive population. Thirty-one of the 118 children [26 percent] with regression and 49 of the 351 children [14 percent] without regressive autism reported bowel symptoms. “Single and multivariable logistic regression models, however, showed no association with these factors and MMR vaccine.”
SUMMARY:
Taylor et al. is another study that set out to address the issue of vaccine exposure in the correct set of (regressive onset) children and found an association between exposure and age of onset (within 6 months of exposure) and between regressive onset autism and bowel disease – both factors of crucial importance to the Wakefield hypothesis. The fact that the authors report the findings, but fail to discuss their potential importance, devalues the paper substantially. In addition, the design was not one from which observations on causality could be made and should be considered a descriptive study. Nonetheless the study provides clear evidence to support further evaluation of the precise factors outlined by the Wakefield hypothesis as being key to the potential MMR-autism association.