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Institute for Vaccine Safety

Johns Hopkins Bloomberg School of Public Health

615 N. Wolfe Street

Room W5041

Baltimore, MD 21205

www.vaccinesafety.edu

 

Vaccines Do Not Cause Autism

Institute for Vaccine Safety, February 8, 2017

The Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), concluded that the body of evidence favors rejection of a causal relationship between autism and MMR vaccine and thimerosal-containing vaccines [1,2]. MMR vaccine prevents rubella disease, thus preventing congenital rubella syndrome and its associated cases of autism.

Why this is an issue: Andrew Wakefield, a gastroenterologist at the Royal Free Hospital in England, published a case series in the medical journal The Lancet in 1998. In this article he described 12 children with pervasive developmental disorder associated with gastrointestinal symptoms, 8 of whom had behavioral issues temporally associated with MMR vaccination via retrospective accounts by their parents or physicians [3]. Despite study authors acknowledging that this did not prove an association between the vaccine and autism, the lead author went far beyond the paper’s conclusions in a press release and ongoing interactions with the media [4,5]. Public concern on the topic grew quickly. In 2010, Dr. Wakefield’s license to practice medicine in the UK was revoked by the British General Medical Council and his study was retracted by The Lancet as evidence of serious professional misconduct mounted. Among other infractions, Wakefield was found to have ordered unnecessary invasive procedures on children without approval of the hospital ethics committee and received undeclared financial considerations from the Legal Aid Board, a group pursuing multiparty legal action for allegedly vaccine-damaged children [6-11]. In addition, he had applied for patents for vaccines to rival MMR vaccine. It was also revealed that, for most of the children in the original study, their symptoms either started well before or long after MMR vaccination. Despite the refutation of Wakefield’s findings, concern among many parents still exists.

Vaccines of interest: While the initial vaccine targeted by Dr. Wakefield was MMR, over time and as epidemiological evidence accumulated that the MMR vaccine was not associated with autism spectrum disorder (ASD), the target shifted from MMR vaccine to the preservative thimerosal as well as simultaneous vaccination with multiple vaccines.

Epidemiological evidence: There have been 13 methodologically sound, controlled epidemiological studies exploring an association between ASD and receipt of MMR vaccine [12-17], thimerosal in vaccines [18-22], and simultaneous vaccination with multiple vaccines [23,24], in addition to the relevant systematic reviews [2,25-28] and one meta-analysis [29]. These studies include more than 1.8 million children. Notwithstanding 11 studies from another pair of authors [30-40], all of which had substantial methodological flaws [2,26,27,41], the epidemiological evidence consistently shows no association between MMR vaccine, thimerosal in vaccines, or simultaneous vaccination and ASD.

Proposed biological mechanism: The overlapping times of childhood vaccine administration and usual onset of ASD symptoms have led to speculations about a possible causal pathway; however, the proposed links have been unsubstantiated [42]. Several different theories were proposed to attribute the cause of ASD to vaccines. Wakefield suggested that a dysregulated immune response to measles antigen in the MMR vaccine led to persistent intestinal infection, allowing “toxins” to enter the blood stream and enter the central nervous system leading to developmental regression in children. He claimed support for this because of his alleged detection of measles virus RNA in bowel specimens of several children with ASD [3]. However, his referenced study was found to be fraudulent, and no evidence of persistent infection has been shown in studies that used appropriate methods [43-45]. Another proposed trigger for ASD was thimerosal, an ethyl-mercury containing preservative that used to be present in some vaccines, although not in the MMR vaccine. This theory was based on observed similarities in some features of ASD and mercury poisoning [46]; however, the degree of these similarities and the plausibility of this suspected association was refuted by neurologists [47]. The IOM found no valid mechanistic evidence connecting MMR or thimerosal-containing vaccines and ASD [1,2].

References

1. IOM (Institute of Medicine). 2012. Adverse effects of vaccines: Evidence and causality. Washington, DC: The National Academies Press.
2. IOM (Institute of Medicine). 2004. Immunization Safety Review:Vaccines and Autism. Washington, DC: The National Academies Press.
3. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998;351(9103):637-41.
4. Horton R. A statement by the editors of The Lancet. Lancet 2004;363(9411):820-1.
5. Murch SH, Anthony A, Casson DH, et al. Retraction of an interpretation. Lancet 2004;363(9411):750.
6. Eggertson L. Lancet retracts 12-year-old article linking autism to MMR vaccines. CMAJ 2010;182(4):E199-200.
7. Retraction--Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 2010;375(9713):445.
8. Deer B. Wakefield's "autistic enterocolitis" under the microscope. BMJ 2010;340:c1127.
9. Deer B. How the case against the MMR vaccine was fixed. BMJ 2011;342:c5347.
10. Deer B. Secrets of the MMR scare . How the vaccine crisis was meant to make money. BMJ 2011;342:c5258.
11. Deer B. Secrets of the MMR scare. The Lancet's two days to bury bad news. BMJ 2011;342:c7001.
12. Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999;353(9169):2026-9.
13. Taylor B, Miller E, Lingam R, et al. Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. BMJ 2002;324(7334):393-6.
14. Farrington CP, Miller E, Taylor B. MMR and autism: further evidence against a causal association. Vaccine 2001;19(27):3632-5.
15. Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med 2002;347(19):1477-82.
16. Smeeth L, Cook C, Fombonne E, et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet 2004;364(9438):963-9.
17. Mäkelä A, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 2002;110(5):957-63.
18. Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism. JAMA 2003;290(13):1763-6.
19. Verstraeten T, Davis RL, DeStefano F, et al; Vaccine Safety Datalink Team. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics 2003;112(5):1039-48.
20. Andrews N, Miller E, Grant A, et al. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association. Pediatrics 2004;114(3):584-91.
21. Croen LA, Matevia M, Yoshida CK, Grether JK. Maternal Rh D status, anti-D immune globulin exposure during pregnancy, and risk of autism spectrum disorders. Am J Obstet Gynecol 2008;199(3):234.e1-6.
22. Price CS, et al. Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism. Pediatrics 2010;126(4):656-64.
23. Uno Y, Uchiyama T, Kurosawa M, A, et al. The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: the first case-control study in Asia. Vaccine 2012;30(28):4292-8.
24. 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;163(2):561-7.
25. IOM. 2001. Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. Washington, DC: National Academy Press.
26. Parker SK, Schwartz B, Todd J, Pickering LK. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics 2004;114(3):793-804.
27. Schultz ST. Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature. Acta Neurobiol Exp (Wars) 2010;70(2):187-95.
28. Maglione MA, Das L, Raaen L, et al. Safety of vaccines used for routine immunization of U.S. children: a systematic review. Pediatrics 2014; 134(2):325-37.
29. Taylor LE, Swerdfeger AL, Eslick GD. Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine 2014;32(29):3623-9.
30. Geier MR, Geier DA. Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication. Exp Biol Med (Maywood) 2003;228(6):660-4.
31. Geier DA, Geier MR. An assessment of the impact of thimerosal on childhood neurodevelopmental disorders. Pediatr Rehabil 2003;6(2):97-102.
32. Geier D, Geier MR. Neurodevelopmental disorders following thimerosal-containing childhood immunizations: a follow-up analysis. Int J Toxicol 2004;23(6):369-76.
33. Geier DA, Geier MR. An evaluation of serious neurological disorders following immunization: a comparison of whole-cell pertussis and acellular pertussis vaccines. Brain Dev 2004;26(5):296-300.
34. Geier DA, Geier MR. A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism. Med Sci Monit 2004;10(3):PI33-9.
35. Geier DA, Geier MR. A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis. Med Sci Monit 2005;11(4):CR160-70.
36. Geier DA, Geier MR. An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. J Toxicol Environ Health A 2006;69(15):1481-95.
37. Geier DA, Geier MR. A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States. Neuro Endocrinol Lett 2006;27(4):401-13.
38. Geier DA, Geier MR. An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines. Med Sci Monit 2006;12(6):CR231-9.
39. Young HA, Geier DA, Geier MR. Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink. J Neurol Sci 2008;271(1-2):110-8.
40. Kern JK, Haley BE, Geier DA, et al. Thimerosal exposure and the role of sulfation chemistry and thiol availability in autism. Int J Environ Res Public Health 2013;10(8):3771-800.
41. Deer B. Autism research: What makes an expert? BMJ 2007;334(7595):666-7.
42. Halsey NA, Hyman SL; Conference Writing Panel.. Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12-13, 2000. Pediatrics 2001;107(5):E84.
43. Hornig M, Briese T, Buie T, et al. Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLoS One 2008;3(9):e3140.
44. Libbey JE, Coon HH, Kirkman NJ, et al. Are there altered antibody responses to measles, mumps, or rubella viruses in autism? J Neurovirol 2007;13(3):252-9.
45. D'Souza Y, Fombonne E, Ward BJ. No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder. Pediatrics 2006;118(4):1664-75.
46. Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury poisoning. Med Hypotheses 2001;56(4):462-71.
47. Nelson KB, Bauman ML. Thimerosal and autism? Pediatrics 2003;111(3):674-9.