Vaccines do not cause autism

  • edited by Serena Miotto (*), Antonio Ferro (**)
  • (*) Department of Molecular Medicine, Institute of Hygiene, University of Padua, Italy
    (**) Department of Prevention, ULSS 17 - Este, Padua, Italy
    • published on 09/03/2020
    • updated on 09/03/2020

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

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.

Conclusions

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.

Sources / Bibliography
  1. Wakefield AJ et al. Ileal lymphoid-nodular hyperplasia, non specific colitis and pervasive developmental disorder in children. Lancet, 1998 351 (9103):637-41
  2. Evidence of Persistent Measles Virus Infection in Crohn’s Disease. Wakefield AJ et al. J Med Virol 1993; 39(4):345-53 *Subjects: Electron microscopy specimens from Crohn’s disease and control patients
  3. Potential Viral Pathogenic Mechanism for a New Variant Inflammatory Bowel Disease. Uhlmann V et al. Mol Pathol 2002; 55(2):84-90 *Subjects: 91 patients with a confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis and 70 controls
  4. Immunocytochemical Evidence of Listeria, Escherichia coli, and Streptococcus Antigens in Crohn’s Disease. Liu Y et al. Gastroenterology 1995; 108(5):1396-1404 *Subjects: Intestines and mesenteric lymph node specimens from 21 persons from families with a high frequency of Crohn’s disease
  5. Exposure to Measles in Utero and Crohn’s Disease: Danish Register Study. Nielsen LL et al. BMJ 1998; 316(7126):196-7 *Subjects: 472 women with measles
  6. No Evidence for Measles, Mumps, and Rubella Vaccine-Associated Inflammatory Bowel Disease or Autism in a 14-year Prospective Study. Peltola H et al. Lancet 1998; 351:1327-8 *Subjects: 3,000,000 doses of MMR vaccine
  7. Absence of Detectable Measles Virus Genome Sequence in Inflammatory Bowel Disease Tissues and Peripheral Blood Lymphocytes. Afzal MA et al. J Med Virol 1998; 55(3):243-9 *Subjects: 93 colonoscopic biopsies and 31 peripheral blood lymphocyte preparations
  8. Autism and Measles, Mumps, and Rubella Vaccine: No Epidemiological Evidence for a Causal Association. Taylor B et al. Lancet 1999;353 (9169):2026-9 *Subjects: 498 children with autism
  9. Further Evidence of the Absence of Measles Virus Genome Sequence in Full Thickness Intestinal Specimens from Patients with Crohn’s Disease. Afzal MA, et al. J Med Virol 2000; 62(3):377-82 *Subjects: Specimens from patients with Crohn’s disease
  10. Mumps, Measles, and Rubella Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time Trend Analysis. Kaye JA et al. BMJ 2001; 322:460-63 *Subjects: 305 children with autism
  11. Time Trends in Autism and in MMR Immunization Coverage in California. Dales L et al. JAMA 2001; 285(9):1183-5 *Subjects: Children born in 1980-94 who were enrolled in California kindergartens (survey samples of 600–1,900 children each year)
  12. Measles-Mumps-Rubella and Other Measles-Containing Vaccines Do Not Increase the Risk for Inflammatory Bowel Disease: A Case-Control Study from the Vaccine Safety Datalink Project. Davis RL et al. Arch Pediatr Adolesc Med 2001;155(3):354-9 *Subjects: 155 persons with IBD with up to 5 controls each
  13. No Evidence for a New Variant of Measles-Mumps-Rubella-Induced Autism. Fombonne E et al. Pediatrics 2001;108(4):E58 *Subjects: 262 autistic children (pre- and post-MMR samples)
  14. Measles, Mumps, and Rubella Vaccination and Bowel Problems or Developmental Regression in Children with Autism: Population Study. Taylor B et al. BMJ 2002; 324(7334):393-6 *Subjects: 278 children with core autism and 195 with atypical autism
  15. Relation of Childhood Gastrointestinal Disorders to Autism: Nested Case Control Study Using Data from the UK General Practice Research Database. Black C et al. BMJ 2002; 325:419-21 *Subjects: 96 children diagnosed with autism and 449 controls
  16. A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism. Madsen KM et al. N Engl J Med 2002; 347(19):1477-82 *Subjects: All 537,303 children born 1/91–12/98 in Denmark
  17. Neurologic Disorders after Measles-Mumps-Rubella Vaccination. Makela A et al. Pediatrics 2002; 110:957-63 *Subjects: 535,544 children vaccinated between November 1982 and June 1986 in Finland
  18. Prevalence of Autism and Parentally Reported Triggers in a North East London Population. Lingam R et al. Arch Dis Child 2003; 88(8):666-70 *Subjects: 567 children with autistic spectrum disorder
  19. 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 et al. Pediatrics 2004; 113(2): 259-66 *Subjects: 624 children with autism and 1,824 controls
  20. MMR Vaccination and Pervasive Developmental Disorders: A Case- Control Study. Smeeth L et al. Lancet 2004; 364(9438):963-9 *Subjects: 1294 cases and 4469 controls
  21. Immunization Safety Review: Vaccines and Autism. Institute of Medicine. The National Academies Press: 2004 *Literature review
  22. Relationship between MMR Vaccine and Autism. Klein KC, Diehl EB. Ann Pharmacother. 2004; 38(7-8):1297-300 *Literature review of 10 studies
  23. Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links with Immunizations. Fombonne E et al. Pediatrics. 2006;118(1):e139-50 *Subjects: 27,749 children born from 1987 to 1998 attending 55 schools
  24. Immunizations and Autism: A Review of the Literature. Doja A, Roberts W. Can J Neurol Sci. 2006; 33(4):341-6 *Literature review
  25. No Evidence of Persisting Measles Virus in Peripheral Blood Mononuclear Cells from Children with Autism Spectrum Disorder. D’Souza Y et al. Pediatrics 2006; 118(4):1664-75 *Subjects: 54 children with autism spectrum disorder and 34 developmentally normal children
  26. MMR-Vaccine and Regression in Autism Spectrum Disorders: Negative Results Presented from Japan. Uchiyama T et al. J Autism Dev Disord 2007; 37(2):210-7 *Subjects: 904 children with autism spectrum disorder (Note: MMR was used in Japan only between 1989 and 1993)
  27. Measles Vaccination and Antibody Response in Autism Spectrum Disorders. Baird G et al. Arch Dis Child 2008; 93(10):832-7. Subjects: 98 vaccinated children aged 10-12 years in the UK with autism spectrum disorder (ASD); two control groups of similar age: 52 children with special educational needs but no ASD and 90 children in the typically developing group
  28. Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study. Hornig M et al. PLoS ONE 2008; 3(9): e3140 doi:10.1371/journal.pone.0003140 *Subjects: 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls)
  29. Adverse Effects of Vaccines: Evidence and Causality: Institute of Medicine. The National Academies Press: 2011 *Literature review
  30. American Academy of Pediatrics. Facts for Parents about Autism and Vaccine Safety. Published March 1 2008. Ultimo accesso 12 aprile 2012
  31. Halsey N, Hyman S, and The Conference Writing Panel. Measles-mumps-rubella vaccine and autistic spectrum disorders. Pediatrics 2001;107(5): e84-107
  32. GACVS meeting of 16-17 December 2002, published in the WHO Weekly Epidemiological Record on 24 January 2003
  33. Gerber SJ, Offit PA. Vaccines and autism: a tale of shifting hypotheses. Clin Infect Dis, 2009; 48(4):456-461
  34. Berger BE, Navar-Boggan AM, Omer SB. Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination – United States , 2001-2010. BMC Public health 2011, 11:340
  35. Goodle F, Smith J, Marcovitch H. Wakefield’s article linking MMR vaccine and autism was fraudulent. BMJ 2011;342:64-66
  36. Deer B. How the case against the MMR vaccine was fixed. BMJ 2011;342:c5347
  37. Murch SH, Anthony A, Casson DH, Malik M, et al. Retraction of an interpretation. Lancet, 2004; 363(9411):750
  38. Ferriman A. "MP raises new allegations against Andrew Wakefield". BMJ, 2004; 328 (7442): 726
  39. Destefano F, Price CS, Weintraub ES. Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of Autism. J Pediatr. 2013 Mar 29
  40. Editors of the Lancet. Retraction: Ileal lymphoid-nodular hyperplasia, non specific colitis and pervasive developmental disorder in children. Lancet, 2010;375:445
  41. General Medical Council, Fitness to Practise Panel Hearing, 24 May 2010, Andrew Wakefield, Determination of Serious Professional Misconduct" (PDF). General Medical Council.
  42. Asaria P, MacMahon E, Measles in the United Kingdom: can we eradicate it by 2010? BMJ. 2006 October 28; 333(7574): 890–895
  43. European Centre for Disease Prevention and Control (ECDC) – Surveillance and Communication Unit (2008). "Measles once again endemic in the United Kingdom". Eurosurveillance 13 (27): 18919
  44. Science, n. 343, 2014 – Oxytocin-mediated Gaba inhibition during delivery attenuates autism pathogenesis in rodent offspring
  45. Stoner R, et al "Patches of disorganization in the neocortex of children with autism" N Eng J Med 2014; 370: 1209-1219
  46. Jama, 2014, n. 17 - The familial risk of autism