You are here

MMR Vaccination and Autism Revisited in 2016

Daily News Navigator

by F Edward Yazbak MD

 

Many parents have suspected that their previously normal children regressed and were later diagnosed with autism following Measles, Mumps and Rubella (MMR) vaccination.

The Vaccine Injury Compensation Program (VICP) a joint effort of HHS, the Department of Justice and the US Court of Federal Claims (CFC) has been operational since October 1988 in order to compensate vaccine injured individuals.

The first MMR related autism case was filed with VICP in 2001.

When the number of cases exploded in a short time, the Chief Special Master of the Vaccine Court created the Omnibus Autism Proceeding to adjudicate the expected flood of cases (5,600 by January 2011.)   http://pediatrics.aappublications.org/content/127/Supplement_1/S74

A PubMed search revealed the listing of multiple publications on MMR vaccination and autism after 1998. Those reports, many by European authors, were mostly published in British medical journals.

Experts from The Centers for Disease Control and Prevention (CDC) have always denied any causal relationship between the triple live virus vaccine and autistic regression, fearing that any mention of such relationship might lead to lower vaccination rates and the return of measles to the United States, after it had been eradicated.  

F. DeStefano MD, MPH authored or co-authored most of the CDC publications on the subject. In 2001, the year the first MMR –Autism case was filed with VICP, Dr. DeStefano and R T Chen MD published "Autism and measles-mumps-rubella vaccination: controversy laid to rest?”, casually stating that “the weight of the available epidemiological and related evidence does not support a causal association between MMR vaccine, or any other vaccine or vaccine constituent, and autism.”

In 2002,  Dr. DeStefano and W.W. Thompson PhD of the National Center on Birth Defects and Developmental Disabilities published an Editorial: “MMR vaccination and autism: is there a link?” in Volume I Issue 2 of Expert Opinion on Drug Safetyhttp://www.tandfonline.com/doi/pdf/10.1517/14740338.1.2.115 

The detailed and well researched publication is certainly worth reading. It listed 32 references but mostly stressed the importance of a particular 1999 publication by Taylor et al (Reference 14) that Drs. DeStefano and Thompson described in the reference table, as “The most scientifically rigorous epidemiological study of a possible association between MMR vaccine and autism. No association was found.” http://www.ncbi.nlm.nih.gov/pubmed/10376617

Under “3- Epidemiological studies of MMR and autism”, DeStefano and Thompson referred again to the Taylor et al Study as “The most scientifically rigorous study to date” and under “5- Causality assessment”, the CDC authors lauded Taylor’s research as “the only population based epidemiological study that has been able to calculate relative risks and no association was found between MMR vaccine and development of autism.”

I certainly respect the right of Drs. DeStefano and Thompson to be impressed by the June 1999 Lancet publication by TaylorFarrington, PetropoulosFavot-MayaudLi and Waight titled “Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association.”

I also respectfully disagree with their opinion, first and foremost because Dr. Taylor persistently and adamantly refused to release the raw data of his study for review by independent U.S. researchers in spite of repeated requests by U.S. Representative for Indiana's 5th Congressional District Daniel Burton, ARI Founder/Director Bernard Rimland PhD and AAPS Executive Director Jane M. Orient MD.

At an AAP conference I attended in Oak Brook IL in June 2000, Neal A Halsey MD of Johns Hopkins Bloomberg School of Public Health, who was moderating a session, asked Dr. Taylor to release his raw data for review and again, Dr. Taylor refused. Minutes later, NVIC Founder and Director Barbara Loe Fisher asked Taylor to at least share his raw data confidentially with anyone at the Institute of Medicine and again he flatly refused. (The report of that particular conference is listed as Reference 26 in the DeStefano and Thompson publication.)

Dr. Brent Taylor was Professor of Community Child Health at the Royal Free and University College Medical School, University College London Royal Free Campus, London, the very same institution where Dr. Andrew Wakefield, whom he immensely and visibly disliked, had practiced for years and had conceived and carried out his original truly remarkable research. 

Taylor’s lead co-author was Dr. Elizabeth Miller of the Immunisation Division, Public Health Laboratory Service, Communicable Disease Surveillance Centre, London, also a fervently outspoken critic of Wakefield and a frequent correspondent with her CDC counterparts on first name basis. Lastly the study was funded by the UK Medicines Control Agency.

Under methods, Taylor et al mentioned that “Clustering of onsets within defined post vaccination periods was investigated by the case-series method.”

The choice of this method to investigate “Autism” was at least questionable if not suspicious when statistician C. Paddy Farrington, a co-author, had stated that the case-series method “is typically used to evaluate the association between a transient exposure and an acute event…”  http://smm.sagepub.com/content/18/1/7.abstract

It takes a lot of Chutzpah to consider “transient” the exposure to THREE live virus vaccines that are supposed to protect an infant against three illnesses for a lifetime. It takes even more Chutzpah to call autism an “acute event” when it often destroys a child’s whole life and ... the parents’ lives too. Taylor and friends did not search for autism cases. Indeed they tried very hard to miss them.

In a letter to the Editor of Lancet, J H Roger stated in part:

Sir

Rather than clarify the measles, MMR, and autism confusion with your editorial,1 you perpetuated the myth that good scientific evidence rejects a link between MMR vaccination and autism.

You quote Taylor and colleague2 as publishing “epidemiological evidence contradicting this alleged association”. On March 28, 2000, I presented a talk to the Royal Statistical Society, in which I showed how the currently published data, including that from this study, are consistent with an appreciable number of autism cases being triggered by MMR vaccination. In short, Taylor and colleagues used the wrong study design to detect an association between immunisation and a disease with chronic onset, such as autism. Rather than use a conventional case-control approach, the study used a case-series design. The case-series approach is appropriate for investigating acute adverse events such as febrile convulsion but is not suitable for long-term effects of vaccination.3

Three possible proxy events for onset of autism were chosen: diagnosis, parents' first concern, and regression. Regression was recorded in less than a third of cases and typically occurred 6 months after first concern, diagnosis on the other hand, typically occurred 2 years after first parental concern. The gastrointestinal model for autism described by Wakefield and others,4 would suggest a variable delay for perhaps several months between immunisation and first symptoms of autism. It is arguable whether we might expect first parental concern to predate these first symptoms. It is not surprising then that the study found no clustering of diagnosis within 1 year or 2 years of immunisaton, when diagnosis would typically be delayed by more than 2 years. Time of first parental concern and time of regression have highly grouped values at age 12 months, 18 months, and 24 months. This grouping reflects the slow progressive nature of onset of autism and the parent's difficulty in identifying a specific time of onset. That any true association could be spotted when looking at quite short intervals after immunisation, typically 6 months, is unlikely. First parental concern is significantly increased in the 6 months after immunisation (p=0·03). What we can conclude from this study is that either MMR triggering autism is a rare event or, as the model would suggest, it leads to a chronic onset of autistic symptoms.

Like you, I wish to see a full scientific description of O'Leary and colleagues' study as soon as possible. But, we must realise that the current epidemiological evidence does not refute MMR immunisation possibly triggering the onset of autism. In everyone's interest, we must keep an open mind.” [End of quote] http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)73169-X/fulltext

*****

Drs. DeStefano and Thompson listed several other statistical studies and discussed the gastro-intestinal (GI) symptoms and other findings reported by Dr. Wakefield.

I have in the past reviewed most of those publications and systematically refuted their rather stale arguments.

Of note is the fact that even the authors of a CDC-financed Danish study criticized many of the reports and publications that DeStefano and Thompson listed as strongly endorsing and supporting CDC claims. 

The “Big Study from Denmark” by Madsen et al was published in November 2002. It was considered by many, including the CDC, as the most robust evidence against any connection between autism and MMR vaccination. 

 The authors of that Danish study stated and documented by references that:

·        There were case reports of children in whom signs of both developmental regression and gastrointestinal symptoms developed shortly after MMR vaccination

·        The widespread use of the MMR vaccine had reportedly coincided with an increase in the incidence of autism in California

·        Measles virus had been found in the terminal ileum in children with developmental disorders and gastrointestinal symptoms but not in developmentally normal children with gastrointestinal symptoms

Discussing previous studies on the subject, Madsen et al stated that "Studies designed to evaluate the suggested link between MMR vaccination and autism do not support an association, but the evidence is weak and based on case-series, cross-sectional, and ecologic studies. No studies have had sufficient statistical power to detect an association, and none had a population-based cohort design." Ref. 10-16

Madsen’s reference 10 was the study by Taylor et al that Drs. DeStefano and Thompson mentioned superlatively in their publication. References 11 to 16 were also listed by the CDC authors as strongly supporting the position that MMR vaccination was in no way associated with autistic disorders.

*****

Possibly dissatisfied by the impact of their 2002 message, Drs. DeStefano and Thompson went on researching the issue of MMR vaccination and autism in more detail.

In February 2004, they published (with others):

Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan atlanta. DeStefano F, Bhasin K, Thompson WW, Yeargin-Allsopp M, Boyle C. Pediatrics. 2004 Feb;113(2):259-66. PMID: 14754936

Also in February 2004, DeStefano and Thompson published a “Perspective” titled “MMR vaccine and autism: an update of the scientific evidence” Expert Rev Vaccines. 2004 Feb;3(1):19-22. PMID: 14761240.  http://www.ncbi.nlm.nih.gov/pubmed/14761240

They stated: An hypothesis published in 1998 suggested that measles-mumps-rubella vaccine may cause autism as a result of persistent measles virus infection of the gastrointestinal tract. Results of early studies were not supportive and in 2001 a review by the Institute of Medicine concluded that the evidence favors the rejection of a causal relationship at the population level between measles-mumps-rubella vaccine and autistic spectrum disorder. Studies published since the Institute of Medicine report have continued not to find an increased risk of autistic spectrum disorder associated with measles-mumps-rubella. The vaccine also has not been found to be associated with a unique syndrome of developmental regression and gastrointestinal disorders. The evidence now is convincing that the measles-mumps-rubella vaccine does not cause autism or any particular subtypes of autistic spectrum disorder.

The authors could not have stated more emphatically that MMR vaccination does not cause autism basing their optimism on multiple reports and publications. But they were also fair enough to mention that the 2001 Institute of Medicine Report “… could not exclude the possibility that the MMR vaccine could contribute to ASD in a small number of children because the epidemiological evidence lacks the precision to assess rare occurrences of a response to the MMR vaccine leading to ASD and the proposed biological models linking MMR vaccine to ASD, although far from established, are nevertheless not disproved.”

DeStefano and Thompson lauded the findings and importance of the above-mentioned Metropolitan Atlanta Study that will not be further discussed. 

They mostly poured much of their praise on the well known very large Danish study that was published in the New England Journal of Medicine in November 2002 and that was fondly called “The Large Autism Study from Denmark”. They stated: Of recently published epidemiological studies, a retrospective cohort study from Denmark provides particularly persuasive evidence against a causal association between the MMR vaccine and autism [7]. To date, this is the only cohort study to address the hypothesized association. A major strength of this study was the availability of a large sample of children who had not received the MMR vaccine. The study involved an analysis of data on over half a million Danish children, including nearly 100,000 who had not received the MMR vaccine. Through linkages of various national registries and medical databases, the study found that the relative risk associated with MMR was 0.92 (95% confidence interval [CI], 0.68–1.24) for autistic disorder and 0.83 (CI, 0.65–1.07) for other ASDs. The narrow CIs reflect the large size of the study and indicate that it is highly unlikely that MMR increases the risk of autism.

The 2002 Danish Study by Kreesten Meldgaard Madsen, M.D., Anders Hviid, M.Sc., Mogens Vestergaard, M.D., Diana Schendel, Ph.D., Jan Wohlfahrt, M.Sc., Poul Thorsen, M.D., Jørn Olsen, M.D., and Mads Melbye, M.D. was titled “Kreesten Meldgaard Madsen, M.D., Anders Hviid, M.Sc., Mogens Vestergaard, M.D., Diana Schendel, Ph.D., Jan Wohlfahrt, M.Sc., Poul Thorsen, M.D., Jørn Olsen, M.D., and Mads Melbye, M.D. was titled “A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism. (N Engl J Med 2002; 347:1477-1482) http://www.nejm.org/doi/full/10.1056/NEJMoa021134

We had the pleasure to review the Madsen study and to publish our findings in the Fall of 2004. http://www.jpands.org/vol9no3/goldman.pdf

We found:

-That prevalence of autism among children aged 5-9 years increased from a mean of 8.38/100,000 in the pre-licensure era (1980- 1986) to 71.43/100,000 in 2000

- That said prevalence leveled off during 2001-2002.

- That the relative risk (RR) was therefore 8.5 (95% CI, 5.7 to 12.7).

- That after adjusting for greater diagnostic awareness, the RR was 4.7 (95% CI, 3.1 to 7.2).

- That among individuals less than 15 years old, the adjusted RR was 4.1 (95% CI, 3.5 to 4.9).

- That longitudinal trends in prevalence data suggested a temporal association between the introduction of MMR vaccine in Denmark and the rise in autism and that this clearly contradicted an earlier report.

We concluded:

- That trends in prevalence data in Denmark suggested a temporal association between the introduction of MMR vaccination and the rise in autism.

- That because thimerosal was not used in any pediatric vaccine in Denmark since 1992 and the greatest increase in autism prevalence followed that year, it is likely that one or more of the viral components or their combination in the MMR vaccine contributed to the reported increase.

- That US autism rates surpassed those of Denmark. Notably, in the U.S. the MMR vaccine was administered at the age of 12 months, often with two thimerosal containing products, the Hemophilus influenzae B and hepatitis B vaccines, while it was usually administered alone age of 15 months in Denmark.

- That additionally, by the age of 6 months, infants in the United States had been exposed to 12 vaccines and up to 187.5 micrograms of  thimerosal compared to 6 vaccines and NO thimerosal in Denmark.

In summary, we showed that when properly examined and reviewed, the Madsen findings did not justify his conclusions and did not support all the denial expressed by Drs. DeStefano and Thompson.

In October 2007, Dr. DeStefano published “Vaccines and Autism: Evidence Does Not Support a Causal Association” in Clinical Pharmacology & Therapeutics.”

This time, Dr. DeStefano also discussed the Thimerosal issue stating A suggested association between certain childhood vaccines and autism has been one of the most contentious vaccine safety controversies in recent years. Despite compelling scientific evidence against a causal association, many parents and parent advocacy groups continue to suspect that vaccines, particularly measles–mumps–rubella (MMR) vaccine and thimerosal-containing vaccines (TCVs), can cause autism.”

 http://www.ncbi.nlm.nih.gov/pubmed/17928818

With all due respect to the authors, they presented little “compelling scientific evidence” to convince me or to convince the well-informed parents who have witnessed their normally developing toddlers stop progressing and then slowly lose language, intelligence and social skills.

The fact that Drs. DeStefano and Thompson did not follow up with any updates in over 8 years suggests a lack of reliable new scientific evidence supporting their rigid assertions.

*****

It is very disturbing to note how rarely autism is mentioned nowadays.

The only time we hear anything about the biggest epidemic of modern days that we face is when someone reports some new alarming prevalence rate. Lately a few uncomplicated Zika virus disease cases seemed to have attracted more attention than the thousands of very disabled children with autism.

According to the latest CDC survey, about 1 in 68 children and 1 boy in 42 have now been identified with an autism spectrum disorder. http://www.cdc.gov/ncbddd/autism/data.html

If that is not a DISASTER, I do not know what is.