Conclusion
Childhood vaccines do not cause autism. Maternal vaccines have not been shown to cause autism.
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 also 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 Wakefield’s license to practice medicine in the UK was revoked by the British General Medical Council and his study was retracted by The Lancet as evidence of serious professional misconduct mounted.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 complete refutation of Wakefield’s fraudulent findings by the scientific community, concern still exists among some parents.
Vaccines of Interest
While the initial vaccine targeted by Dr. Wakefield was MMR, the target has shifted over time, especially as epidemiological evidence accumulated that the MMR vaccine was not associated with autism spectrum disorder (ASD). Other targets have included the preservative thimerosal as well as simultaneous vaccination with multiple vaccines. See the Can Vaccine Ingredients Cause Adverse Events? and the Can Simultaneous Vaccination Cause Adverse Events? summaries for more details.
Epidemiological Evidence
There have been 16 methodologically sound, controlled epidemiological studies exploring an association between ASD and receipt of MMR vaccine (12-20), thimerosal in vaccines (19, 21-25), and simultaneous vaccination with multiple vaccines (26, 27), in addition to the relevant systematic reviews (2, 28-31) and one meta-analysis (32). Together, these studies included more than 1.8 million children. Notwithstanding 11 studies from another pair of authors (33-43), all of which had substantial methodological flaws (2, 29, 30, 44), the epidemiological evidence consistently shows no association between MMR vaccine, thimerosal in vaccines, or simultaneous vaccination and ASD.
One study suggested a possible increased risk of ASD among children whose mothers received an influenza vaccination during their first trimester of pregnancy, although this association was not statistically significant after a post hoc analysis adjusting for multiple comparisons, and there was no association between ASD and influenza vaccination received during any trimester (45). Another study showed that receiving Tdap vaccine during pregnancy is not associated with increased risk of ASD in the child (46).
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 (47). 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 (48, 49, 50). 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 (51); however, the degree of these similarities and the plausibility of this suspected association was refuted by neurologists (52). The IOM found no valid mechanistic evidence connecting MMR or thimerosal-containing vaccines and ASD (1, 2).
References
1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, editors. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
2. Institute of Medicine Immunization Safety Review C. The National Academies Collection: Reports funded by National Institutes of Health. Immunization Safety Review: Vaccines and Autism. Washington (DC): National Academies Press (US); 2004.
3. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, 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, Malik M, Berelowitz M, Dhillon AP, 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, Petropoulos MC, Favot-Mayaud I, Li J, 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, Andrews N, Simmons A, Stowe J. 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, Schendel D, Wohlfahrt J, Thorsen P, et al. A population-based study of measles, mumps, and rubella vaccination and autism. The New England journal of medicine. 2002;347(19):1477-82.
16. Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet. 2004;364(9438):963-9.
17. Makela A, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics. 2002;110(5):957-63.
18. Jain A, Marshall J, Buikema A, Bancroft T, Kelly JP, Newschaffer CJ. Autism occurrence by MMR vaccine status among US children with older siblings with and without autism. Jama. 2015;313(15):1534-40.
19. Uno Y, Uchiyama T, Kurosawa M, Aleksic B, Ozaki N. Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder. Vaccine. 2015;33(21):2511-6.
20. Hviid A, Hansen JV, Frisch M, Melbye M. Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort StudyMeasles, Mumps, Rubella Vaccination and Autism. 2019.
21. Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism. Jama. 2003;290(13):1763-6.
22. Verstraeten T, Davis RL, DeStefano F, Lieu TA, Rhodes PH, Black SB, et al. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics. 2003;112(5):1039-48.
23. Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. 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.
24. 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.
25. Price CS, Thompson WW, Goodson B, Weintraub ES, Croen LA, Hinrichsen VL, et al. Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism. Pediatrics. 2010;126(4):656-64.
26. Uno Y, Uchiyama T, Kurosawa M, Aleksic B, Ozaki N. 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.
27. DeStefano F, Price CS, Weintraub ES. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism. The Journal of pediatrics. 2013;163(2):561-7.
28. Institute of Medicine Immunization Safety Review C. In: Stratton K, Gable A, Shetty P, McCormick M, editors. Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. Washington (DC): National Academies Press (US); 2001.
29. 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.
30. Schultz ST. Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature. Acta neurobiologiae experimentalis. 2010;70(2):187-95.
31. Maglione MA, Das L, Raaen L, Smith A, Chari R, Newberry S, et al. Safety of vaccines used for routine immunization of U.S. children: a systematic review. Pediatrics. 2014;134(2):325-37.
32. 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.
33. Geier MR, Geier DA. Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication. Experimental biology and medicine (Maywood, NJ). 2003;228(6):660-4.
34. Geier DA, Geier MR. An assessment of the impact of thimerosal on childhood neurodevelopmental disorders. Pediatric rehabilitation. 2003;6(2):97-102.
35. Geier D, Geier MR. Neurodevelopmental disorders following thimerosal-containing childhood immunizations: a follow-up analysis. International journal of toxicology. 2004;23(6):369-76.
36. Geier DA, Geier MR. An evaluation of serious neurological disorders following immunization: a comparison of whole-cell pertussis and acellular pertussis vaccines. Brain & development. 2004;26(5):296-300.
37. 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. Medical science monitor : international medical journal of experimental and clinical research. 2004;10(3):Pi33-9.
38. Geier DA, Geier MR. A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis. Medical science monitor : international medical journal of experimental and clinical research. 2005;11(4):Cr160-70.
39. 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. Journal of toxicology and environmental health Part A. 2006;69(15):1481-95.
40. Geier DA, Geier MR. A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States. Neuro endocrinology letters. 2006;27(4):401-13.
41. Geier DA, Geier MR. An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines. Medical science monitor : international medical journal of experimental and clinical research. 2006;12(6):Cr231-9.
42. 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.
43. Kern JK, Haley BE, Geier DA, Sykes LK, King PG, Geier MR. Thimerosal exposure and the role of sulfation chemistry and thiol availability in autism. International journal of environmental research and public health. 2013;10(8):3771-800.
44. Deer B. Autism research: What makes an expert? Bmj. 2007;334(7595):666-7.
45. Zerbo O, Qian Y, Yoshida C, Fireman BH, Klein NP, Croen LA. Association Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum Disorder. JAMA pediatrics. 2017;171(1):e163609.
46. Becerra-Culqui TA, Getahun D, Chiu V, Sy LS, Tseng HF. Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination and Autism Spectrum Disorder. Pediatrics. 2018.
47. Halsey NA, Hyman SL. 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.
48. Hornig M, Briese T, Buie T, Bauman ML, Lauwers G, Siemetzki U, et al. Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PloS one. 2008;3(9):e3140.
49. Libbey JE, Coon HH, Kirkman NJ, Sweeten TL, Miller JN, Lainhart JE, et al. Are there altered antibody responses to measles, mumps, or rubella viruses in autism? Journal of neurovirology. 2007;13(3):252-9.
50. 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.
51. Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury poisoning. Medical hypotheses. 2001;56(4):462-71.
52. Nelson KB, Bauman ML. Thimerosal and autism? Pediatrics. 2003;111(3):674-9.
