Research Paper On Autism And Vaccines Study

Two studies have been cited by those claiming that the MMR vaccine causes autism. Both studies are critically flawed.

First study

In 1998, Andrew Wakefield and colleagues published a paper in the journal Lancet. Wakefield's hypothesis was that the measles, mumps and rubella (MMR) vaccine caused a series of events that include intestinal inflammation, entrance into the bloodstream of proteins harmful to the brain, and consequent development of autism. In support of his hypothesis, Dr. Wakefield described 12 children with developmental delay — eight had autism. All of these children had intestinal complaints and developed autism within one month of receiving MMR.

The Wakefield paper published in 1998 was flawed for two reasons:

  1. About 90 percent of children in England received MMR at the time this paper was written. Because MMR is administered at a time when many children are diagnosed with autism, it would be expected that most children with autism would have received an MMR vaccine, and that many would have received the vaccine recently. The observation that some children with autism recently received MMR is, therefore, expected. However, determination of whether MMR causes autism is best made by studying the incidence of autism in both vaccinated and unvaccinated children. This wasn't done.
  2. Although the authors claim that autism is a consequence of intestinal inflammation, intestinal symptoms were observed after, not before, symptoms of autism in all eight cases.

This study was subsequently retracted; in scientific terms, this means that the paper is not part of the scientific record because it was found to be based on scientific misconduct. In this case, the studies were deemed fraudulent and data misrepresented.

Second study

In 2002, Wakefield and coworkers published a second paper examining the relationship between measles virus and autism. The authors tested intestinal biopsy samples for the presence of measles virus from children with and without autism. Seventy-five of 91 children with autism were found to have measles virus in intestinal biopsy tissue as compared with only 5 of 70 patients who didn't have autism. On its surface, this was a concerning result. However, the second Wakefield paper was also critically flawed for the following reasons:

  1. Measles vaccine virus is live and attenuated. After inoculation, the vaccine virus probably replicates (or reproduces itself) about 15 to 20 times. Measles vaccine virus is likely to be taken up by specific cells responsible for virus uptake and presentation to the immune system (termed antigen-presenting cells or APCs). Because all APCs are mobile, and can travel throughout the body (including the intestine), it is plausible that a child immunized with MMR would have measles virus detected in intestinal tissues using a very sensitive assay. To determine if MMR is associated with autism, one must determine if the finding is specific for children with autism. Therefore, children with or without autism must be identical in two ways. First, children with or without autism must be matched for immunization status (i.e., receipt of the MMR vaccine). Second, children must be matched for the length of time between receipt of MMR vaccine and collection of biopsy specimens. Although this information was clearly available to the investigators and critical to their hypothesis, it was specifically omitted from the paper.
  2. Because natural measles virus is still circulating in England, it would have been important to determine whether the measles virus detected in these samples was natural measles virus or vaccine virus. Although methods are available to distinguish these two types of virus, the authors chose not to use them.
  3. The method used to detect measles virus in these studies was very sensitive. Laboratories that work with natural measles virus (such as the lab where these studies were performed) are at high risk of getting results that are incorrectly positive. No mention is made in the paper as to how this problem was avoided.
  4. As is true for all laboratory studies, the person who is performing the test should not know whether the sample is obtained from a case with autism or without autism (blinding). No statements were made in the methods section to assure that blinding occurred.

Several studies have been performed that disprove the notion that MMR causes autism.

Brent Taylor and co-workers

In 1999, Brent Taylor and co-workers examined the relationship between receipt of MMR and development of autism in an excellent, well-controlled study. Taylor examined the records of 498 children with autism or autism-like disorder.

Cases were identified by registers from the North Thames region of England before and after the MMR vaccine was introduced into the United Kingdom in 1988. Taylor then examined the incidence and age at diagnosis of autism in vaccinated and unvaccinated children. He found that:

  1. The percentage of children vaccinated was the same in children with autism as in other children in the North Thames region.
  2. No difference in the age of diagnosis of autism was found in vaccinated and unvaccinated children.
  3. The onset of symptoms of autism did not occur within two, four, or six months of receiving the MMR vaccine.

Madsen and colleagues

One of the best studies was performed by Madsen and colleagues in Denmark between 1991 and 1998 and reported in the New England Journal of Medicine. The study included 537,303 children representing 2,129,864 person-years of study. Approximately 82 percent of children had received the MMR vaccine. The group of children was selected from the Danish Civil Registration System, vaccination status was obtained from the Danish National Board of Health, and children with autism were identified from the Danish Central Register. The risk of autism in the group of vaccinated children was the same as that in unvaccinated children. Furthermore, there was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autism.

Subsequent studies and meta-analysis have corroborated the findings that the MMR vaccine does not cause autism.

Watch as Dr. Offit talks about vaccines and autism in this short video, part of the Talking about Vaccines with Dr. Paul Offit video series.

Genetics

One of the best ways to determine whether a particular disease or syndrome is genetic is to examine the incidence in identical and fraternal twins. Using a strict definition of autism, approximately 60 percent of identical and 0 percent of fraternal twins have autism. Using a broader definition of autism (i.e. autistic spectrum disorder), approximately 92 percent of identical and 10 percent of fraternal twins have autism. Therefore, autism clearly has a genetic basis.

"Home-movie" studies

Clues to the causes of autism can be found in studies examining when the symptoms of autism are first evident. Perhaps the best data examining when symptoms of autism are first evident are the "home-movie studies. These studies took advantage of the fact that many parents take movies of their children during their first birthday (before they have received the MMR vaccine).

Home movies from children who were eventually diagnosed with autism and those who were not diagnosed with autism were coded and shown to developmental specialists. Investigators were, with a very high degree of accuracy, able to separate autistic from non-autistic children at 1 year of age. These studies found that subtle symptoms of autism were present earlier than some parents had suspected, and that receipt of the MMR vaccine did not precede the first symptoms of autism. Other investigators extended the home-movie studies of 1-year-old children to include videotapes of children taken at 2 to 3 months of age.

Timing of first symptoms

Using a sophisticated movement analysis, videos from children eventually diagnosed with autism or not diagnosed with autism were coded and evaluated for their capacity to predict autism. Children who were eventually diagnosed with autism were predicted from movies taken in early infancy. This study supported the hypothesis that very subtle symptoms of autism are present in early infancy and argues strongly against vaccines as a cause of autism.

Structural abnormalities of the nervous system

Toxic or viral insults to the fetus that cause autism, as well as certain central nervous system disorders associated with autism, support the notion that autism is likely to occur in the womb. For example, children exposed to thalidomide during the first or early second trimester were found to have an increased incidence of autism. Thalidomide was a medication that used to be prescribed to pregnant women to treat nausea. However, autism occurred in children with ear, but not arm or leg, abnormalities. Because ears develop before 24 days gestation, and arms and legs develop after 24 days gestation, the risk period for autism following receipt of thalidomide must have been before 24 days gestation. In support of this finding, Rodier and colleagues found evidence for structural abnormalities of the nervous system in children with autism. These abnormalities could only have occurred during development of the nervous system in the womb.

Natural rubella infection

Similarly, children with congenital rubella syndrome are at increased risk for development of autism. Risk is associated with exposure to rubella before birth but not after birth.

The following studies all support the fact that autism occurs during development of the nervous system early in the womb:

  • The genetics of autism
  • The timing of the first symptoms of autism (home-movie studies)
  • The relationship between autism and the receipt of the MMR vaccine
  • Structural abnormalities of the nervous system of children with autism
  • Thalidomide and natural rubella infection

Unfortunately, for current and future parents of children with autism, the controversy surrounding vaccines has caused attention and resources to focus away from a number of promising leads.

The Autism Science Foundation is a non-profit organization that follows the developments related to autism; in particular, making sure that the studies are scientifically sound. Their website provides up-to-date information about what is known about the causes of autism.

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Taylor B, Miller E, Lingam, et al. Measles, Mumps, and Rubella Vaccination and Bowel Problems or Developmental Regression in Children with Autism: A Population Study. BMJ. 2002; 324:393-396.

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Beyond the Autism/Vaccine Hypothesis: What Parents Need to Know about Autism Research

A decade ago most researchers agreed that we needed to study vaccines in relation to autism. We had to reconcile the fact that the number of vaccines children were receiving was increasing, and at the same time, the number of children who were being diagnosed with autism also was on the rise. Fortunately this was a question that could be studied – and answered – by science. We looked at children who received vaccines and those who didn’t, or who received them on a different, slower schedule. There was no difference in their neurological outcomes. Multiple studies have been completed which investigated the measles, mumps and rubella vaccination in relation to autism. Researchers have also studied thimerosal, a mercury-based preservative, to see if it had any relation to autism. The results of studies are very clear; the data show no relationship between vaccines and autism. Read the studies themselves below and browse our recommended reading list.

Making the CASE for Vaccines

Click here to read and download our guide to talking about vaccines.

Read the Science

Literature Reviews: Autism and Vaccines

Autism Occurrence by MMR Vaccine Status Among US Children With Older Siblings With and Without Autism
http://jama.jamanetwork.com/article.aspx?articleid=2275444
The Journal of the American Medical Association
April 2015

Safety of Vaccines Used for Routine Immunization of U.S. Children: A Systematic Review
http://www.ncbi.nlm.nih.gov/pubmed/25086160
Pediatrics
August 2014

Vaccines are Not Associated with Autism: An Evidence-Based Meta-Analysis of Case-Control and Cohort Studies
http://www.ncbi.nlm.nih.gov/pubmed/24814559
Vaccine
June 2014

On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes
http://pediatrics.aappublications.org/cgi/content/abstract/125/6/1134
Pediatrics
Smith, M and Woods, C
June 2010

Vaccines and Autism: A Tale of Shifting Hypotheses
http://www.journals.uchicago.edu/doi/full/10.1086/596476
Clinical Infectious Diseases
Offit, Paul and Gerber, Jeffrey S.
February 2009

Immunization Safety Review: Vaccines and Autism
http://www.iom.edu/reports/2004/immunization-safety-review-vaccines-and-autism.aspx
Institute of Medicine
May 2004

Adverse Effects of Pertussis and Rubella Vaccines: A Report of the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines
http://www.nap.edu/catalog/1815/adverse-effects-of-pertussis-and-rubella-vaccines
Institute of Medicine
1991

Too Many Too Soon?

Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?
http://pediatrics.aappublications.org/cgi/content/full/109/1/124
Pediatrics
Offit, Paul A., Quarles, Jessica, et al.
2002

Immunization Safety Review: Multiple Immunizations and Immune Dysfunction
http://www.iom.edu/reports/2002/immunization-safety-review-multiple-immunizations-and-immune-dysfunction.aspx
Institute of Medicine
February 2002

Cellular Immune Responses in Neonates

http://www.ncbi.nlm.nih.gov/pubmed/10763708

International Reviews of Immunology

Fadel S, Sarazotti M.

2000

Neonatal and Early Life Vaccinology
http://www.ncbi.nlm.nih.gov/pubmed/11348697
Vaccine
Siegrist CA.
2001

The Problem with Dr. Bob’s Alternative Vaccine Schedule
http://pediatrics.aappublications.org/content/123/1/e164.abstract
Pediatrics
Offit, Paul A. and Moser, Charlotte A.
January 2009

Thimerosal and Autism Studies

Neuropsychological performance 10 years after immunization in infancy with thimerosal-containing vaccines.
http://pediatrics.aappublications.org/cgi/content/abstract/123/2/475?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=neuropsychological+performance&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
Pediatrics
Tozzi AE, Bisiacchi P, Tarantino V, De Mei B, D’Elia L, Chariotti F, Salmaso S.
January 2009

Continuing Increases in Autism Reported to California’s Developmental Services System
http://archpsyc.ama-assn.org/cgi/content/full/65/1/19
Archives of General Psychiatry
Robert Schechter, MD, MSc and Judith K. Grether, PhD
January 2008

Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
http://content.nejm.org/cgi/content/full/357/13/1281
New England Journal of Medicine
Thompson WW, Price C, Goodson B, et al.
September 2007

Lack of Association Between Rh Status, Rh Immune Globulin in Pregnancy and Autism
http://www3.interscience.wiley.com/cgi-bin/abstract/114264055/ABSTRACT
American Journal of Medical Genetics
Judith H. Miles and T. Nicole Takahashi
May 2007

Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16079072&query_hl=1
Environmental Health Perspectives
Thomas M. Burbacher, PhD
April 2005

Thimerosal Exposure in Infants and Developmental Disorders: A Prospective Cohort Study in the United Kingdom Does Not Support a Causal Association
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15342824&query_hl=5
Pediatrics
John Heron and Nick Andrews, PhD and Jean Golding, DSc
September 2004

Neurotoxic Effects of Postnatal Thimerosal Are Mouse Strain Dependent
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15184908&query_hl=10
Molecular Psychiatry
M Hornig, M
June 2004

Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Database
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14595043&query_hl=59
Pediatrics
Thomas Verstraeten, MD
November 2003

Association Between Thimerosal-Containing Vaccine and Autism
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14519711&query_hl=16
Journal of the American Medical Association
Anders Hviid, MSc
October 2003

Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population-Based Data
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15496004&query_hl=19
Pediatrics
Kreesten M. Madsen, MD
September 2003

“Autism and Thimerosal-Containing Vaccines: Lack of Consistent Evidence for an Association”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12880876&query_hl=21
American Journal of Preventive Medicine
Paul Stehr-Green, DrPh, MPH
August 2003

Thimerosal and Autism?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12612255&query_hl=22
Pediatrics
Karen Nelson, MD
March 2003

Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: A descriptive study
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12480426&query_hl=30
The Lancet
Michael Pichichero, MD
November 2002

Measles-Mumps-Rubella (MMR) Vaccine and Autism Studies

Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior
http://ehp.niehs.nih.gov/wp-content/uploads/advpub/2015/2/ehp.1408257.acco.pdf
Environmental Health Perspectives
February 2015

Early Exposure to the Combined Measles-Mumps-Rubella Vaccine and Thimerosal-Containing Vaccines and Risk of Autism Spectrum Disorder
http://www.ncbi.nlm.nih.gov/pubmed/25562790
Vaccine
January 3, 2015

Remembering How to Fight Measles
http://www.nytimes.com/2014/03/28/opinion/remembering-how-to-fight-measles.html?emc=eta1&_r=0
New York Times
Paul A. Offit, MD
March 2014

How to Think About the Risk of Autism
http://www.nytimes.com/2014/03/30/opinion/sunday/how-to-think-about-the-risk-of-autism.html
New York Times
Sam Wang, Ph.D.
March 2014

Lack of Association Between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study
http://www.plosone.org/article/info%3Adoi/10.1371/journal.pone.0003140
PLoS One
Hornig M, Briese T, Buie T, Bauman ML, Lauwers G, et al.
September 2008

Measles Vaccination and Antibody Response in Autism Spectrum Disorders
http://adc.bmj.com/cgi/content/abstract/adc.2007.122937v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=baird&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
Archives of Disease in Childhood
Gillian Baird, F.R.C.Paed.
February 2008

Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links With Immunizations
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16818529&query_hl=2&itool=pubmed_docsum
Pediatrics
Eric Fombonne, MD
July 2006

MMR Vaccination and Pervasive Developmental Disorders: A Case-Control Study
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15364187&query_hl=38
The Lancet
Liam Smeeth, MRCGP
September 11, 2004

Association of Autistic Spectrum Disorder and the Measles, Mumps, and Rubella Vaccine
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12860782&query_hl=40
Archives of Pediatrics & Adolescent Medicine
Kumanan Wilson, MD, MSc, FRCP
July 2003

Neurologic Disorders After Measles-Mumps-Rubella Vaccination
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12415036&query_hl=64
Pediatrics
Annamari Makela, MD
November 2002

No Evidence for a New Variant of Measles-Mumps-Rubella-Induced Autism
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11581466&query_hl=66
Pediatrics
Eric Fombonne, FRCPsych
October 2001

Autism and Vaccines in the Media

A Journalist’s Guide to Covering Outbreaks of Vaccine-Preventable Disease
http://tangledbankstudios.org/sites/default/files/Documents/journalist-guide-disease-outbreaks-pub.pdf
From the producers of the PBS-NOVA special “Vaccines—Calling the Shots.”

On January 21st, 2011, Dr. Paul Offit was on The Colbert Report speaking about his new book, “Deadly Choices: How The Anti-Vaccine Movement Threatens Us All.” Click Here to Watch the Interview.

On September 9, 2014, ASF President Alison Singer was on The Leonard Lopate Show to talk about the risks of not vaccinating. Click here to listen to the program.

What’s Next?

If we ask the same questions we’ll get the same answers. We’ve asked the autism vaccine question over two dozen times and each time we get the same response: no relationship. We need to move on. We need to invest in studying genetics, the brain structures of children with autism, and environmental factors that may be playing a role.

Downloadable Materials

Below are three fact-sheets prepared by physicians at the Children’s Hospital of Philadelphia. They are excellent resources to distribute at events.

Below are two tables prepared by the initiative Every Child By Two. These tables summarize the major procedures and conclusions of the most recent studies regarding autism and Thimerosal, as well as autism and the MMR vaccine.

 

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