Vaccines and Autism

As a pediatrician and a father of a son with autism, I am in a unique position to be able to discuss the vaccines and autism topic from both personal and professional levels. This is a very interesting and sometimes volatile topic with people, especially for parents of children with autism or other developmental diagnoses. Many parents ask for guidance regarding vaccines and developmental concerns regardless of whether their child is developing normally or not. Many of my patients (with knowledge that I have a son with autism) ask what I personally do with my own three children regarding vaccines. “Simple! I tell them…. I follow the vaccine schedule as put forth by the Centers for Disease Control and I do not split up nor alter the schedule, even for my own children”. If they ask me how I came to that decision, I let them know of all the science behind my decision (which is summarized below) and that my “Simple” comment above is really rather an in depth scientific decision. A few quick bullet points for families to know:

• There is no link between vaccines and autism…proven now in over 40 international research studies (see below).
• There is no link between vaccines and autism…proven now in over 40 international research studies (see below).
• There is no link between thimerosol (the mercury containing preservative) and autism (over 15 studies to prove that) (see below).
• There are no scientific studies to date (domestic or international) that show any causal link between vaccines and autism.
• Thimerosol was removed from all vaccines in 2001 (except for the seasonal flu shot) and the incidence of autism has risen in the same proportion for the 5 years pre and post removal.
• The seasonal flu shot for ages 3 years and above is the only vaccine with a trace of thimerosol in it. Many providers and families opt for the preservative free version.
• Contrary to popular belief, we still see many of the diseases we vaccinate against. For example, I saw 9 cases of pertussis in 2009 alone (culture proven). While pertussis is usually benign for older children and adults, it can be fatal to an infant (and yes I have seen that too).
• The inciting article — 1998 article in Lancet Medical Journal from the Andrew Wakefield study (of 12 children) where he insinuated a link between mmr and autism, has finally been retracted and stricken from the archives of the journal (this has never been done in the history of lancet) due to conflicts of interest, monetary gain for Dr. Wakefield and misinterpretation of data (see history below).
• Generally, if a patient has an illness with fevers I hold the vaccines and have them come back when the child is healthy in a week or two. If the patient has a cold for a week or two but no fever, there is no reason to delay vaccines at the visit.

SCIENTIFIC DATA

Here is the information of what I relay to parents of my patients regarding vaccines and autism. I try to keep it objective and pertinent to the current medical literature research. I most definitely keep out any discussion of anecdotal stories and media hype and stick to the proven (and disproven); otherwise I am just speculating. Being an individual of science, I have been fascinated by the timeline history of how this topic has evolved and equally interested in how the media outlet has perpetuated many myths. Here is a snapshot (summarized nicely by compiling data from the Centers from Disease Control, Lancet, the National Institute of Health and Wikipedia) of the timeline as we know it in the medical literature, starting with the inciting event, the 1998 paper in Lancet Medical Journal published by Andrew Wakefield, et al:

1998 LANCET PAPER

In February 1998, a group led by Andrew Wakefield published a controversial paper in the respected British medical journal The Lancet. The paper reported on twelve children with developmental disorders referred to the Royal Free Hospital in London. The parents or physicians of eight of these children had linked the start of behavioral symptoms to MMR vaccination. The paper described a collection of bowel symptoms, endoscopy findings and biopsy findings that were said to be evidence of a possible novel syndrome that Wakefield would later call autistic enterocolitis, and recommended further study into the possible link between the condition and the MMR vaccine. The paper suggested that the connection between autism and the gastrointestinal pathologies was real, but said it did not prove an association between the MMR vaccine and autism.[3] At a press conference before the paper’s publication, Wakefield said that he thought it prudent to use single vaccines instead of the MMR triple vaccine until this could be ruled out as an environmental trigger, given that parents of eight of the twelve children studied were said to have blamed the MMR vaccine, saying that symptoms of autism had set in within days of vaccination at approximately 14 months. He declared, “I can’t support the continued use of these three vaccines given in combination until this issue has been resolved.”[21] In a video news release issued by the hospital to broadcasters in advance of the press conference, he called for MMR to be &ldauo;suspended in favor of the single vaccines.”[22] In a BBC interview Wakefield’s mentor Roy Pounder, who was not a coauthor, admitted the study was controversial, and added: “In hindsight it may be a better solution to give the vaccinations separately, although administratively it is a wonderful idea. When the vaccinations were given individually there was no problem.”[23] These suggestions were not supported by Wakefield’s coauthors nor by any scientific evidence.[24]

The initial press coverage of the story was mixed. The Guardian and the Independent put it on their front pages, while the Daily Mail placed the story in the middle of the paper, and the Sun didn’t cover it. A total of 122 articles mentioned the subject in 1998.[25]

CONTROVERSY FOLLOWING PUBLICATION OF REPORT

The controversy gained momentum in 2001 and 2002; in the latter year, 1257 stories were published about it.[25] The paper, press conference and video sparked a major health scare in the United Kingdom. As a result of the scare, full confidence in MMR fell from 59% to 41% after publication of the Wakefield research. In 2001, 26% of family doctors felt the government had failed to prove there was no link between MMR and autism and bowel disease.[26] After it became clearer that Wakefield’s claims were not supported by scientific evidence, confidence in the MMR vaccine increased. A 2003 survey of 366 family doctors in the UK reported that 77% of them would advise giving the MMR vaccine to a child with a close family history of autism, and that 3% of them thought that autism could sometimes be caused by the MMR vaccine.[27] A similar survey in 2004 found that these percentages changed to 82% and at most 2%, respectively, and that confidence in MMR had been increasing over the previous two years.[28]

Administration of the combined vaccine instead of separate vaccines decreases the risk of children catching the disease while waiting for full immunization coverage.[31] The combined vaccine’s two injections results in less pain and distress to the child than the six injections required by separate vaccines, and the extra clinic visits required by separate vaccinations increases the likelihood of some being delayed or missed altogether;[31][32] vaccination uptake significantly increased in the UK when MMR was introduced in 1988.[31] Health professionals have heavily criticized media coverage of the controversy for triggering a decline in vaccination rates.[33] There is no scientific basis for preferring separate vaccines, or for using any particular interval between separate vaccines.[34]

John Walker-Smith, a coauthor of Wakefield’s report and a supporter of the MMR vaccine, wrote in 2002 that epidemiology has shown that MMR is safe in most children, but observed that epidemiology is a blunt tool and studies can miss at-risk groups that have a real link between MMR and autism.[35] However, if a rare subtype of autism were reliably identified by clinical or pathological characteristics, epidemiological research could address the question whether MMR causes that autism subtype.[36] There is no scientific evidence that MMR causes damage to the infant immune system, and there is much evidence to the contrary.[34]

In 2001, Berelowitz, one of the co-authors of the paper, said “I am certainly not aware of any convincing evidence for the hypothesis of a link between MMR and autism”.[37]

Over the last 10 years, The World Health Organization, The Canadian Paediatric Society,[38] the Centers for Disease Control and Prevention,[11] the Institute of Medicine of the National Academy of Sciences,[12] and the UK National Health Service[13] have all concluded that there is no evidence of a link between the MMR (or any) vaccine and autism.

CONFLICT OF INTEREST ALLEGATIONS REGARDING THE ANDREW WAKEFIELD PAPER

In February 2004, investigative reporter Brian Deer wrote in The Sunday Times of London that Wakefield had received £55,000 funding from Legal Aid Board solicitors seeking evidence to use against vaccine manufacturers, that several of the parents quoted as saying that MMR had damaged their children were also litigants, and that Wakefield did not inform colleagues or medical authorities of the conflict of interest.[4] Although Wakefield maintained that the legal aid funding was for a separate, unpublished study,[39] the editors of The Lancet judged that the funding source should have been disclosed to them.[40] Richard Horton, the editor-in-chief, wrote, “It seems obvious now that had we appreciated the full context in which the work reported in the 1998 Lancet paper by Wakefield and colleagues was done, publication would not have taken place in the way that it did.”[41] Several of Dr. Wakefield’s co-researchers also strongly criticized the lack of disclosure.[4]

Deer continued his reporting in a BBC television documentary, MMR: What They Didn’t Tell You, broadcast on November 18, 2004. This documentary alleges that Wakefield had applied for patents on a vaccine that was a rival of the MMR vaccine, and that he knew of test results from his own laboratory at the Royal Free Hospital that contradicted his claims.[6] Wakefield’s patent application was also noted in the 2008 book Autism’s False Prophets by Paul Offit.

In 2006, Deer reported in The Sunday Times that Wakefield had been paid more than £400,000 by British trial lawyers attempting to prove that the vaccine was dangerous, with the undisclosed payments beginning two years before the Lancet paper’s publication.[42] This funding came from the UK legal aid fund, a fund intended to provide legal services to the poor.[21]

RETRACTION OF AN INTERPRETATION

The Lancet and many other medical journals require papers to include the authors’ conclusions about their research, known as the “interpretation”. The summary of the 1998 Lancet paper ended as follows:
Interpretation We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.[3]
In March 2004, immediately following the news of the conflict of interest allegations, ten of Wakefield’s twelve coauthors retracted this interpretation.[5]

MANIPULATION OF DATA

On February 8, 2009, Brian Deer reported in The Sunday Times that Wakefield had manipulated patient data and misreported results in his 1998 paper, creating the appearance of a link with autism.[7] Wakefield denied these allegations,[43] but Deer expanded on laboratory aspects of his findings in an April 2010 report in the BMJ, recounting how normal clinical histopathology results generated by the Royal Free Hospital were later changed in the medical school to abnormal results, published in The Lancet.[44] In July 2009, the Press Complaints Commission stated that it was staying an investigation initiated by Wakefield’s complaint regarding the Times article, pending the conclusion of the GMC investigation.[45]

GENERAL MEDICAL COUNCIL INVESTIGATION

The General Medical Council (GMC), which is responsible for licensing doctors and supervising medical ethics in the UK, investigated the affair.[46] The GMC examined, among other ethical points, whether Wakefield and his colleagues obtained the required approvals for the tests they performed on the children; the data-manipulation charges reported in the Times were not at question in the hearings.[47] Two of Wakefield’s colleagues, Professor John Walker-Smith and Professor Simon Murch, also faced charges of serious professional misconduct over their roles in the affair. The General Medical Council alleged that the trio acted unethically and dishonestly in preparing the research into the MMR vaccine. They denied the allegations.[48] The case proceeded in front of a GMC fitness to practice panel of three medical and two lay members.[49] In 2010, Wakefield was found by the GMC to have acted “dishonestly and irresponsibly” and to have acted with “callous disregard” for the children involved in his study, conducting unnecessary and invasive tests.[50][51] The trial involved procedures with medical risks but was not approved by an Independent Ethics Committee and Wakefield was shown to have conflicts of interest in the conduct of the study. These are basic requirements for medical research ethics laid out in the Declaration of Helsinki, the broadly recognized standard for research bioethics.[52]

FULL RETRACTION

In response to the GMC investigation and findings, the editors of The Lancet announced on February 2, 2010 that they “fully retract this paper from the published record.”[10]

BANNED FROM PRACTICING MEDICINE

Britain”s General Medical Council (which licenses and oversees doctors in the United Kingdom) found Andrew Wakefield guilty of serious misconduct and stripped him of his medical license and is no longer recognized as a doctor to practice medicine. He has resided in Austin Texas since 2004 where he worked in an autism research center. He quit this endeavor in 2010.

RECENT STUDIES

The number of reported cases of autism increased dramatically in the 1990s and early 2000s. This increase is largely attributable to changes in diagnostic practices; it is not known how much, if any, growth came from real changes in autism’s prevalence, and no causal connection to the MMR vaccine has been demonstrated.[53] The following studies were published after the 1998 Wakefield et al. paper.

• A 1998 population study of Swedish children found no difference in the prevalence of autistic children born before and after the 1982 introduction of the MMR vaccine in Sweden.[54]
• A 2002 retrospective cohort study of all 537,303 children born in Denmark from January 1991 through December 1998 found no statistically significant difference in risk of autism among the 440,655 who were vaccinated with MMR. This study provided strong evidence against the hypothesis that MMR vaccination causes autism.[55]
• In February 2004, a population-based case-controlled study of 624 cases and 1,824 matched controls, conducted by the Centers for Disease Control, found no evidence to support an association between MMR and autism.[56]
• In September 2004, a case-controlled study of 1,294 cases of pervasive developmental disorder (an autism spectrum disorder) and 4,469 controls from the UK General Practice Research Database found a relative risk of 0.86 for MMR vaccine, which suggests that MMR is not associated with an increased risk of pervasive developmental disorders such as autism; on the contrary, the 0.86 represents a decreased risk, though this decrease was not statistically significant.[57]
• In October 2004, a meta review, financed by the European Union, was published in the October 2004 edition of Vaccine[58] that assessed the evidence given in 120 other studies and considered unintended effects of the MMR vaccine. The authors concluded that
  • the vaccine is associated with some positive and negative side effects,
  • it was “unlikely” that there was a connection between MMR and autism, and
  • “The design and reporting of safety outcomes in MMR vaccine studies … are largely inadequate”.
• In January 2005, a study of all younger residents of Olmsted County, Minnesota reported an eightfold increase in the age-adjusted incidence of research-identified autism over a period beginning in the early eighties and ending in the late nineties, but found no evidence of a link with MMR. The study’s authors said that the timing of the increase suggested that it may have been due to improved awareness of the disorder, a growth in services, and changing definitions.[59]
• Japan provided a natural experiment on the subject: combined MMR vaccine was introduced in 1989, but the program was terminated in 1993 and only single vaccines used thereafter. In March 2005 a study of over 30,000 children (278 cases) born in one district of Yokohama concluded “The incidence of all autistic spectrum disorders (ASD), and of autism, continued to rise after MMR vaccine was discontinued. The incidence of autism was higher in children born after 1992 who were not vaccinated with MMR than in children born before 1992 who were vaccinated. The incidence of autism associated with regression was the same during the use of MMR and after it was discontinued.” The authors concluded: “The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.”[63]
• In October 2005, the Cochrane Library published a review of 31 scientific studies, which found no credible evidence of an involvement of MMR with either autism or Crohn’s disease. The review also stated “Measles, mumps and rubella are three very dangerous infectious diseases which cause a heavy disease, disability and death burden in the developing world … The impact of mass immunization on the elimination of the diseases has been demonstrated worldwide.”
• In July 2006, a study of 27,749 Canadian children ruled out an association between pervasive developmental disorder and MMR vaccinations.[64]
• A review published in September 2006 found no scientific evidence that the MMR vaccine plays any part in the causes or triggering of autism, even in a subgroup of children with the condition.[65]
• A 2006 study found no evidence of measles virus genome sequences persisting in the blood of autistic children vaccinated with MMR.[66]
• A 2006 multi-site study of 351 children with ASD found no evidence that onset of autistic symptoms or of regression was related to MMR vaccination.[67]
• A 2007 study found that there was no change in the rates of regressive autism after MMR was withdrawn from Japan.[68]
• A 2007 case study used the figure in Wakefield’s 1999 letter to The Lancet alleging a temporal association between MMR vaccination and autism[69] to illustrate how a graph can misrepresent its data, and gave advice to authors and publishers to avoid similar misrepresentations in the future.[70]
• A 2007 review of independent studies performed after the publication of Wakefield et al.’s original report found that these studies provide compelling evidence against the hypothesis that MMR is associated with autism.[71]
• A review of the work conducted in 2004 for UK court proceedings but not revealed until 2007 found that the polymerase chain reaction analysis essential to the Wakefield et al. results was fatally flawed due to contamination, and that it could not have possibly detected the measles that it was supposed to have detected.[72]
• A 2008 study examined the blood of children aged about 10 years that had been given the MMR vaccine, and found no difference in levels of measles virus or antibodies between children diagnosed with autism and those who had not.[73]
• A 2008 study found a significant increase in selective nonreceipt of MMR vaccine in the U.S. that was temporally associated with the publication of the Wakefield report, and which decreased to baseline levels by the time significant media coverage began two years later; this suggests that parents learned about the controversy from sources other than the media.[74]
• A 2008 study found that children with autism had no more peptides in their urine than typical children, casting doubt on the proposed mechanism for the hypothesized diagnosis of autistic enterocolitis.[75]
• A 2008 letter reported that younger siblings of Canadian children with autism are significantly less likely to receive MMR and other immunizations, suggesting that their parents are delaying or avoiding these children’s vaccinations.[77]
• A 2008 study of children with gastrointestinal disturbances found no difference between those with ASD and those without, with respect to the presence of measles virus RNA in the bowel; it also found that gastrointestinal symptoms and the onset of autism were unrelated in time to the administration of MMR vaccine.[78]
• A 2009 review of studies on links between vaccines and autism discusses the MMR vaccine controversy as one of three main hypotheses which epidemiological and biological studies fail to support.[79]

LITIGATION

During the 1980s and 1990s, a number of lawsuits were brought in the United States against manufacturers of vaccines, alleging the vaccines had caused a variety of physical and mental disorders in children. While these lawsuits were unsuccessful they did lead to a large jump in the costs of the MMR vaccine, and pharmaceutical companies sought legislative protections. In 1993, Merck KGaA became the only company willing to sell MMR vaccines in the United States and the United Kingdom. A pressure group called JABS (Justice, Awareness, Basic Support) was established to represent families with children who, their parents said, were “vaccine-damaged.” This litigation is now discontinued.[80] £15 million in public legal aid funding was spent on the litigation, of which £9.7 million went to solicitors and barristers, and £4.3 million to expert witnesses.[72]

The Omnibus Autism Proceeding is currently in progress before the Office of Special Masters of the U.S Court of Federal Claims, commonly called the vaccine court. The Petitioners’ Steering Committee have advanced theories that MMR vaccines can cause autism, possibly in combination with thiomersal-containing vaccines.[81] In 2007 three individual test cases were presented to test the theory about the combination. Test cases were also scheduled on whether MMR vaccines alone cause autism, but the special masters hearing the cases have said that these may not be needed.[82] On February 12, 2009, the vaccine court ruled against the plaintiffs in all three cases, stating that the evidence presented did not validate their claims that vaccinations caused autism in these specific patients, or in general.

WEBSITES FOR SCIENTIFIC DATA ON AUTISM AND VACCINES

• www.cdc.gov (Centers for Disease Control)
• www.nih.gov (National Institute of Health)
• www.nationalacademies.org (National Academies)
• www.who.int/en (World Health Organization)
• www.nhs.uk (United Kingdom National Health Service)
• www.mayoclinic.com (The Mayo Clinic)

I know this document is lengthy but I feel it is necessary to outline the science behind the statement “how we know vaccines do not cause autism”. I hope you enjoyed reading the information and that it stimulates discussion on the safety of vaccines for you and your family.

Jeffrey P. Yannette, MD, FAAP
Board Certified by the American Board of Pediatrics
Fellow of the American Academy of Pediatrics
Advisory Board Member to KcATC
Father of a son with Autism