Research shows no MMR–autism link

Friday September 5 2008

“Fresh research rules out MMR-autism link”, is the headline in The Daily Telegraph . The newspaper goes on to describe a new study that replicates one conducted in 1998 by Dr Andrew Wakefield. This earlier study is described by the Daily Mail as being the one that “caused a furore” by suggesting a link between autism and the MMR vaccine.

The new study replicates the methods of the original study even using, along with another two laboratories, the same laboratory that Wakefield and his colleagues used to analyse their samples. The researchers conclude that their study provides strong evidence against any association of autism with persistent measles in the bowel or with MMR vaccination. The belief by patients that MMR might cause autism has ultimately been responsible for the surge in measles cases in the UK and the US as parents choose not to vaccinate their children, leaving them unprotected against this potentially dangerous disease.

Where did the story come from?

Dr Mady Hornig and colleagues from Columbia University, Harvard Medical School and other medical and academic institutions across the US carried out this study. The research was funded by the Centre for Disease Control (CDC) and by the National Institutes of Health. It was published in the peer-reviewed medical journal: PLoS One .

What kind of scientific study was this?

Researchers in this case-control study were investigating whether there was evidence of measles virus RNA (RNA is a type of genetic material) in the bowels of children with autism who also have gastrointestinal disturbances.

The researchers say that the first set of studies that suggested a link between the MMR vaccine and autism reported intestinal abnormalities in children with autism and other developmental disturbances. Later, the presence of measles virus RNA in bowel tissue in children with these disorders was reported. They say that although many different types of study have disproved any link between MMR and autism, none has repeated the methods of the original study that sparked the controversy in 1998.

The original 1998 study looked for the presence of measles virus RNA in bowel samples from children who had received MMR vaccination and who had autism and gastrointestinal disturbances. It did not compare those results with children who did not have autism.

In this latest study, the researchers were specifically interested in seeing whether children with autism and gastrointestinal disturbances were more likely to have evidence of measles virus in bowel samples than children with gastrointestinal disturbances who did not have autism.

Families of children aged between three and 10 years old who were due to have an ileocolonoscopy with biopsy (i.e. a bowel examination with a sample of tissue being taken for analysis) as a routine part of their care were invited to participate. All of these children had significant gastrointestinal disturbances. In order to be eligible for the study, children also had to have had at least one prior immunisation containing the measles virus vaccine strain (but those that had had it within six months of their planned biopsy were excluded). The study compared children who also had autism (diagnosed by a child neurologist, psychiatrist or developmental paediatrician using rigorous assessments) with a control group of children who did not have autism. The children in the two groups were matched in terms of their age.

The researchers initially enrolled 47 children into the study but, after dropouts, were left with 25 children with both autism and gastrointestinal problems (cases) and 13 children with gastrointestinal problems only (controls). They collected detailed information from parents (confirmed by medical records) including the timing of vaccinations, types of vaccinations, dates of onset of gastrointestinal problems and dates of onset of autism.

The researchers then compared biopsy results (taken from two sections of the bowel – the terminal ileum and caecum – four random samples from each) between the two groups, specifically examining for evidence of the measles virus in bowel samples, by looking for RNA (a type of genetic material) belonging to the measles virus. If, during the examination, evidence of inflammatory lesions was seen, additional specimens were taken. Those performing the investigations were “blinded” as to whether the child had autism or not. In the laboratory, the RNA was extracted from the samples, purified and examined for the presence of measles virus RNA.

The researchers also looked at the timing of the onset of bowel problems and autism and the timing of vaccination. If MMR “causes” autism or bowel problems, it would be expected that vaccination would precede symptoms. The researchers wanted to see whether this was the case.

What were the results of the study?

Overall, children received their MMR vaccination at similar ages – 16 months. Evidence of measles virus RNA in bowel samples was found in only two children – one in the case group (i.e. one child who had autism) and the second in the control group (a child who didn’t have autism).

The researchers found no difference between cases and controls in the number of children who had MMR before the onset of gastrointestinal problems. They also found no evidence that the MMR vaccine preceded development of either gastrointestinal problems or autism, that is, their results do not support the theory that MMR immunisation is linked to gastrointestinal problems, which are, in turn, linked to autism.

What interpretations did the researchers draw from these results?

The researchers conclude that their study “eliminates the remaining support for the hypothesis that autism spectrum disorder with gastrointestinal complaints is related to MMR exposure”.

What does the NHS Knowledge Service make of this study?

This study uses similar methods to the original studies that raised concern about the safety of the MMR vaccine, particularly those conducted by Dr Andrew Wakefield and colleagues. It looked for evidences of measles virus in bowel samples from children with autism and gastrointestinal problems and then went on to explore the timing between exposure (i.e. getting the vaccine) and outcome (developing gastrointestinal problems or autism). Despite a growing amount of good evidence to the contrary, concerns that MMR causes autism still linger on. These unfounded fears are having a negative effect on children in the US and the UK where cases of measles are on the rise. This study adds to a now persuasive body of evidence disproving the idea that MMR is linked with gastrointestinal problems which are, in turn, related to autism. There are several points to highlight:

  • Given that this study replicates that of Wakefield’s – even using the same laboratory he used to analyse his samples (alongside two others for verification), some of the methodological concerns with his study hold for this one:
  • The design cannot by itself “prove” causation. However, unlike Wakefield’s original study, there is a control group (children without autism), which makes this study much stronger than the Wakefield study. Where Wakefield’s original study was a cross-sectional study in 12 children, this is a case-control study with 25 cases (children with gastrointestinal problems and autism) and 13 controls (gastrointestinal problems only). 
  • This is still a small study and the findings may still be due to chance, but it is more than double the size of the original one.
  • In Wakefield’s study, the investigators were not blinded (i.e. they knew what samples they were examining and that all children had autism); in this study researchers analysing the bowel samples didn’t know which were the control samples and which were the case samples.

The bottom line is that several studies have confirmed that the risk of intestinal abnormalities, autism or both, is not increased by MMR vaccination. This is another that that adds to the evidence that MMR vaccine is safe. Parents who continue to have concerns should speak to their doctors, but should also keep in mind that measles is a serious disease and complications arising from it can lead to death.

Sir Muir Gray adds...

This issue is now closed.

Analysis by Bazian
Edited by NHS Choices