The Wakefield study resonated widely throughout the scientific world and the media but the hypothesis of a possible link between the MMR vaccine and autism has been evaluated and rejected by numerous studies conducted in Europe and in the USA.
The hypothesis that the MMR (Measles-Mumps-Rubella) vaccine may be linked to autism was raised in the late 1990s, when the English gastroenterologist Wakefield and colleagues published an article in the Lancet entitled "Ileal lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children"1. In the article, the authors argued that the MMR vaccine could cause intestinal inflammation with increased permeability of the intestinal barrier, the circulation of toxic substances to the brain and the consequent development of autism. The study described twelve children who complained of gastrointestinal disorders and manifestations of autism after having been vaccinated with MMR.
Two other studies published by Wakefield et al. - one before and one after 1998 - suggested the existence of a relationship between autism and vaccination2-3.
Scientific elements refuting a causal relationship between MMR vaccine and autism
The Wakefield study resonated widely throughout the scientific world and the media but the hypothesis of a possible link between the MMR vaccine and autism has been evaluated and rejected by numerous studies conducted in Europe and in the USA4-28.
The Institute of Medicine of the National Academies (IOM) was tasked with assessing a list of adverse events associated with eight different vaccines (including MMR) and evaluating the scientific evidence of a possible link between vaccine and adverse event. The review of existing clinical and epidemiological studies led to the conclusion that the available evidence rejects the hypothesis of a causal relationship between the MMR vaccine and autism29. In the United States, the Center for Disease Control and Prevention and the American Academy of Pediatrics have reached the same conclusions30-31. The World Health Organization commissioned a review of the literature on the subject concluding a lack of association between the risk of autism and the MMR vaccine32.
Furthermore, the assumed mechanisms to explain how the MMR vaccine can determine the onset of an autistic syndrome are merely theoretical and not supported by scientific evidence21-33. The trivalent vaccine has not been shown to cause chronic intestinal inflammation or loss of intestinal barrier function, nor is there any evidence of a possible role played by the immune system in autism.
Conversely, in 2011 an American study showed that rubella vaccination (usually administered as part of the MMR) prevented hundreds and perhaps thousands of cases of autism spectrum disorders associated with congenital rubella syndrome in the period 2001-201034.
While the scientific community was studying the link between the MMR vaccine and autism, Wakefield's 1998 study, in which this link was first hypothesised, was put under investigation.
In 2004, the journalist Brian Deer published an inquiry in the Sunday Times that revealed how Wakefield's study was distorted by economic interests35. The English doctor had, in fact, failed to reveal that at the same time he was conducting another study, commissioned by lawyers who wanted to file a lawsuit against the MMR vaccine.
In addition to the epidemiological shortcomings of this study (lack of a control group, endoscopic and neuropsychological tests not ‘blinded’, appearance of gastrointestinal symptoms after and not before the appearance of autism for 7 of the 12 children). The investigations carried out by Deer in later years they showed that Wakefield had altered and falsified the patients’ medical history to support research results36:
- three of the nine cases reported in the study as suffering from regressive autism had never been diagnosed as autistic. Only one child had regressive autism;
- although the study reported that before the vaccination 12 children were "normal", five had documentation that attested to previous development problems;
- it was reported that some children had developed behavioural symptoms in the days following vaccination, while the clinical documentation stated that the onset of these symptoms had occurred several months after vaccination;
- in nine cases, the histopathological findings regarding the colon were modified from "no or minimal fluctuation in inflammatory cells" to "non-specific colitis";
- the parents of eight children blamed the MMR vaccine, but 11 families showed up in the hospital with this accusation. The exclusion of three patients who complained of symptoms which appeared months after vaccination helped to create a suspected time frame of 14 days;
- the subjects were recruited among groups of people opposed to MMR vaccination and the study was commissioned and funded with the aim of initiating a legal dispute.
The authors of the Wakefield study signed a statement withdrawing the conclusions of their work37: "We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient. [...] In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper".
Meanwhile, the British General Medical Council (GMC) investigated Wakefield for misconduct. This investigation showed that the autistic children under study had been subjected to unnecessary invasive medical procedures38, such as colonoscopies and lumbar punctures, and that Wakefield had acted without the necessary approval of the Ethics Committee.
On January 28, 2010, the GMC found him guilty of some thirty charges, including dishonesty and abuse of children with developmental problems, stating that Wakefield had "failed in his duties as a doctor", acting against the interests of his patients and had been "dishonest and irresponsible" in carrying out the research published.
None of the more than 25 studies conducted over the past 15 years has confirmed the existence of a causal relationship between the MMR vaccine and autism4-34. A very recent study published in The Journal of Paediatrics confirms the absence of a possible link between the vaccines administered in the first two years of childhood and the development of autism spectrum disorders39. The large size of the populations studied meant a level of statistical power sufficient to detect even rare associations was reached33. Faced with the proof of the falsification of the data used for the study, the Lancet formally withdrew the article40 and Wakefield was disbarred by the British Medical Council41.
The controversy initiated by Wakefield regarding the safety of the MMR vaccine resulted in a substantial fall in vaccination coverage in England and Europe with the appearance of thousands of new cases of measles, mumps and rubella and the onset of serious illnesses that could have been avoided with vaccination42-43. To this we must add the significant social and economic consequences that this unjustified alarmism has produced and continues to produce.
Serena Miotto (*), Antonio Ferro (**)
- Study in Science (February 2014)44: in murine models with autism there is an alteration in the activity of a neurotransmitter, GABA, which occurs towards the end of pregnancy. In healthy mice, at the time of delivery, there is a reversal of the function of GABA, which changes from excitatory to nerve transmission to inhibitory. This inversion is caused by a hormone released by the mother at birth, called oxytocin. In the unhealthy mouse, however, this change in the activity of GABA does not take place. Furthermore, using a substance that blocks the action of oxytocin in normal mice, the change of GABA to inhibitory action is prevented and autism develops in mice;
- Another article, published in March in the prestigious NEJM45, showed that in children with autism there is an abnormal development of the cerebral cortex in the womb. The cerebral cortex is fundamental for regulating several important cognitive functions such as memory, language, reasoning ability, and is formed by cells (neurons) organised in overlapping layers; in children with autism the architecture of the cortex is altered;
- An article published in JAMA supports the role played by genetic factors in the development of autism46.
These articles, like many others published in recent years, add further evidence to support the action of environmental or genetic factors before birth, during foetal development in the womb. As such, these studies confirm the non-existence of vaccinations as a possible cause in the development of the disease.
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