Autism, inflammatory bowel disease, and MMR vaccine

Abstract

We are concerned about the potential loss of confidence in the mumps, measles, and rubella (MMR) vaccine after publication of Andrew Wakefield and colleagues’ report (Feb 28, p 637),1Wakefield AJ Murch SH Anthony A et al.Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children.Lancet. 1998; 351: 637-641Summary Full Text Full Text PDF PubMed Scopus (1763) Google Scholar in which these workers postulate adverse effects of measles-containing vaccines. As a result, we fear there may be a reduction in vaccine uptake in the UK and elsewhere. The main thrust of the report is to add to the record 12 possible cases of bowel disease associated with developmental regression (including autism), which is a useful contribution to research. However, an association was also alluded to between these two factors and environmental triggers such as receipt of MMR vaccine. Wakefield and co-workers state “We did not prove an association between measles, mumps, and rubella vaccines and the syndrome described”. However, there are enough references in the text to lead the reader to the assumption that there is sufficient evidence provided by the study, and by other scientific publications, to suggest that there is a likely (although as yet unproven) link. The study suggests a temporal relation between the so-called autism-bowel syndrome and administration of MMR in eight of the 12 cases. However, the interval between receipt of vaccine and onset of symptoms is provided in only five cases (1–14 days), and the age at which the vaccine was given was provided in only three (15 months, 16 months, and 4·5 years). Parents identified MMR to be the immediate precursor of developmental delay in eight of the 12 children, but developmental delay is likely to be detected by a gradual awareness over a period of time, not on a particular day. Although autism is rarely diagnosed before 18 months, the insidious onset of symptoms often predates the diagnosis by many months. As described by Wakefield, parents had trouble making a temporal link between the onset of autism and the onset of gastrointestinal symptoms for similar reasons. We therefore question the conclusion that there was a temporal association of the autism-bowel syndrome and MMR. To prove a causal relation is much harder—it requires a selection of patients and matched controls, and a sample size that is capable of detecting a statistically significant difference between the two groups. The investigators may need to be blinded for such aspects as clinical assessments and laboratory tests. How does Wakefield's study match up? There was no patient selection other than 12 patients referred to him. There were no controls. There was no blinding of investigators. The accompanying commentary by Robert Chen and Frank DeStefano2Chen RT DeStephano F Vaccine adverse events; causal or coincidental?.Lancet. 1998; 351: 611-612Summary Full Text Full Text PDF PubMed Scopus (121) Google Scholar elegantly explains the difference between temporal and causal association. We concur with them that Wakefield's study fails at every level to make a causal association. Is it possible that we are confronted by a genuine causal association which has shown up by chance in these eight cases? Is it possible that these cases have brought to light a previously unnoticed association? Wakefield claims that the association between autism and MMR has been documented in the past—an important point to clarify. However, the two references they cite from Fundenburg and Gupta (refs 16 and 17 in their report) need further scrutiny. The first deals mainly with the association of autism and transfer factor (DLyE) and also mentions “live rubella immunization at 15 months has precipitated fever convulsions followed by autistic symptoms; so has live hepatitis B vaccine in 2 infants at 2 years”. These anecdotal associations do not advance the argument for causality. We could not obtain the Gupta reference through usual library channels. Wakefield and colleagues’ findings confront us with a new hypothesis—that measles-containing vaccine may trigger developmental regression. It is known that such speculation may seriously damage important public health programmes, causing a decline in vaccine uptake and a rise in the target disease.3Gangarosa EJ Galazka AM Wolfe CR et al.Impact of anti-vaccine movements on pertussis control: the untold story.Lancet. 1998; 351: 356-361Summary Full Text Full Text PDF PubMed Scopus (498) Google Scholar We can now expect such damage to occur in many countries. We question the merit of publishing this particular study. Publication of this study is especially tragic because WHO and all consulted national public health authorities agree that it does not alter in any way the continued recommendation to use measles-containing vaccines throughout the world. Current measles containing vaccines are highly safe and effective. Autism, inflammatory bowel disease, and MMR vaccineAuthors’ reply Full-Text PDF Autism, inflammatory bowel disease, and MMR vaccineAuthor's reply Full-Text PDF