A novel form of inflammatory bowel disease with pervasive developmental disorder: Evidence for and against the existence of the clinical phenotype and its association with exposure to MMR vaccine

Background: In 1998 Wakefield et al. published details of a form of inflammatory bowel disease with regressive developmental disorder. The report concluded that ‘… data do not demonstrate a causal link between the disorder and MMR exposure’. Nonetheless, the paper is frequently cited as the single body of evidence supporting any association between measles containing vaccine (MCV),  inflammatory bowel disease (IBD) and autism spectrum disorders (ASDs). Following publication, cases with similar presentation continued to be analysed and contributed to a working hypothesis about the putative association between autistic-like developmental regression, inflammatory bowel disease (IBD) and exposure to MCVs.
Whilst clinical evidence in support of the hypothesis has been reported, population-based studies have found no effect of MMR exposure on either onset or population frequency of the outcomes investigated.  Such studies are cited as providing evidence of ‘no association’ between MMR, IBD and autism spectrum disorder and as refuting the Wakefield hypothesis.

Objectives:

to examine the extent to which studies have been designed appropriately and with reference to the original Wakefield hypothesis and to examine the extent to which claims of its having been refuted or supported are valid

Methods:

A systematic review of published and publicly available reports pertinent to the hypothesis. Further discussion and evaluation is undertaken of those studies whose design allows examination of the hypothesis. Details are provided regarding design features that mitigated against inclusion of rejected studies

Results:

355 studies were identified. 297 were rejected and 58 underwent additional evaluation.  Five were identified as meeting criteria for further evaluation. 

Conclusions:

Few studies claiming to test the Wakefield hypothesis have successfully addressed it. No study meeting criteria was able to unequivocally demonstrate a causal role for the MMR vaccine in ASDs, four studies provided some support in favour of specific aspects.