| Is there any scientific evidence that proves a linkage between autism and vaccines?
To date, there is no conclusive evidence that any vaccine can cause autism.
What about the Wakefield study?
The study that initially suggested a link between the MMR vaccine and autism was
published in Lancet by Wakefield and colleagues in 1998 (Wakefield et al 1998).
Based on data from 12 patients who were diagnosed with bowel disease and autism, the
authors of this study speculated that, based on the parents� recall,
the measles/mumps/rubella (MMR) vaccine may have been a possible cause of the
neurological disease and bowel problems. The researchers
theorized that the bowel disease could have led to decreased absorption of essential
vitamins and nutrients, which in turn could have led to developmental disorders, like
autism. However, the study focused on anecdotal evidence; the authors performed no
scientific analyses to substantiate their theory. An editorial published in the same
issue of Lancet voiced concerns about the validity of the study (Chen and
DeStefano 1998). It is difficult to determine whether the 12 reported cases represent an
unusual or unique clinical syndrome without knowing the size of the patient population
from which the 12 were identified and the duration of time allotted for reporting cases.
Without evidence supporting or disputing a selective referral process, a referral bias
that sent only the 12 cases noted in the study to the authors practice cannot be ruled
out. The authors stated that additional cases have been identified; however, detailed
clinical characterization of the neurological diseases and documentation of timing of
vaccination, autism and bowel disease onset in all these children has not been provided.
The theory that autism might be caused by poor absorption of nutrients resulting from
a bowel inflammation is also not supported by clinical data. In at least four of the 12
cases reported in the Lancet study, behavioral problems appeared before the onset
of symptoms of inflammatory bowel disease; that is, the effect preceded the proposed
cause. The same authors published another study in which they performed highly specific
laboratory assays of patients with inflammatory bowel disease following MMR vaccination,
the cause for autism they posited in their initial study. These patients tested negative
for the measles virus, which would not support the theory the authors posed in their
original study (Chadwick et al 1998, Duclos and Ward 1998).
Subsequently, these authors and other collaborators have reported detection of
measles virus from blood cells and intestinal samples from children with autism and
inflammatory bowel disease (Kawashima et al 2000). The authors also report detection of
wild type and vaccine strains of measles virus RNA in patients with inflammatory bowel
diseases without the diagnosis of autism, thus making it impossible to associate measles
virus RNA with autistic disorders. Other scientists have published studies that measles
virus RNA (Afzal MA et al 2000) and protein (Iizuka M et al 2000) are not present in
intestinal specimens from patients with inflammatory bowel diseases.
Although gastrointestinal problems have been documented in a subgroup of persons with
autism, studies remain inconclusive. One recent study indicated that unrecognized
gastrointestinal disorders in non-verbal autistic patients may contribute to behavioral
problems (Horvath et al 1999). However, authors of the study were pointed in their
conclusion that additional research is required to determine any possible association
between the brain and gastrointestinal dysfunction in autistic children.
Is there any independent research that supports the safety of the MMR vaccine?
Other recent investigations show no causal relationship between MMR (or other
measles-containing vaccines) and either autism or inflammatory bowel disease.
In 1999, the Working Party on MMR Vaccine of the United Kingdom�s Committee on
Safety of Medicine evaluated several hundred reports, collected by lawyers of patients
with autism, Crohn�s disease, and similar disorders that were supposedly developed
after receiving the MMR or MR vaccine. The Party acknowledged that it was impossible to
prove or refute the suggested associations because of variable data quality, biased
selection of cases, and lack of a control group. However, after a systematic,
standardized review of parental and physician information, the Working Party concluded
that the information available did not support the suggested causal associations or give
cause for concern about the safety of MMR or MR vaccines.
Another study published in Lancet by Taylor and colleagues provides
population-based evidence that overcomes a number of limitations that the Working Party
and the Wakefield group experienced (Taylor et al 1999, DeStefano and Chen 1999). The
authors identified all 498 known cases of autism spectrum disorders (ASD) in children
living in certain districts of London who were born in 1979 or later and correlated the
cases to an independent vaccination registry. (ASD includes classical autism, Pervasive
Developmental Disorder, Not Otherwise Specified {PDD NOS} or atypical autism, and
Asperger�s syndrome.) The results of this study were as follows:
- The authors showed that the number of ASD cases has been increasing since 1979,
with no jump after the introduction of the MMR vaccine in 1988.
- The authors found that children who were vaccinated before 18 months of age were
diagnosed with autism at ages similar to children who were vaccinated after 18
months of age, indicating that the vaccination did not result in earlier expression
of ASD characteristics.
- The authors discovered that at age two, the MMR vaccination coverage among ASD
cases was nearly identical to vaccination coverage of children in the same birth
cohorts in the whole region, providing evidence of a lack of overall association
between the ASD and the vaccination.
- Taylor and colleagues established that the first diagnosis of autism or initial
signs of behavioral regression were not more likely to occur within time periods
following MMR vaccination than during other time periods. However, parental concern
clustered at six months post-vaccination.
- The results of the study were similar when cases of classical autism were analyzed
separately.
In 1997, the National Childhood Encephalopathy Study (NCES) examined any
possible link between measles vaccine and neurologic events (Miller et al 1997).
Researchers in England found no indication that the measles vaccine contributes to the
development of long-term neurological damage, including educational and behavioral
deficits.
Another study also showed no evidence of association between the MMR vaccine and
autism (Gillberg and Heijbel 1998). The study compared autism prevalence rates in
populations of children from two communities in Sweden (prior to 1982). The results
indicated no difference in autism prevalence between children born after the
introduction of the MMR vaccine in Sweden and those born before the vaccine was used.
Several other published epidemiological studies show no causal association between
MMR vaccination and autism or inflammatory bowel disease, including retrospective
studies that showed no association between the rates of autism and vaccine coverage in
young children (Dales, Hammer and Smith 2001; Kaye JA, del Mar Melero-Montes M, Jick H
2001), and prospective studies of vaccine associated adverse events (Peltola et al
1998). Other studies have reported no increased risk for inflammatory bowel disease in
children vaccinated with MMR (Davis RL et al 2001; Morris DL et al 2000). Additional
studies are underway (Smeeth et al 2001).
What is the Federal Government doing to protect the health of those people who
receive the MMR or other measles-containing vaccines?
To ensure the safety of vaccines, the Centers for Disease Control and Prevention
(CDC), the Food and Drug Administration (FDA), the National Institutes of Health (NIH),
and other Federal agencies routinely monitor and conduct research to examine any new
evidence that would suggest possible problems with the safety of vaccines.
The CDC has conducted research and found no epidemiological evidence for causal
association between autism and MMR vaccine (DeStefano F and Chen RT 2000). Currently,
the CDC is conducting a case-control study in metropolitan Atlanta, Georgia, to further
evaluate any possible association between the administration of MMR vaccine and autism.
This prevalence study uses the only current population-based sample of school-aged
children in the United States with autism. The results of this study are expected
sometime in 2001.
Similarly, the NIH is also conducting correlational studies of such an association. A
retrospective study of persons diagnosed with autism who regressed after apparently
normal development and matched comparison groups is underway. The National Institute of
Child Health and Human Development (NICHD) and the National Institute of Deafness and
Other Communication Disorders (NIDCD), two components of the NIH who fund the Network on
the Neurobiology and Genetics of Autism: Collaborative Programs of Excellence in Autism
(CPEA), are working together with the CDC in this endeavor. Additional funding and
participation from the CDC will allow more extensive medical evaluation, as well as
collection of vaccination serology and records information. The effort represents the
largest study to date comparing autistic patients who have regressed with groups of
autistic children who did not regress and children who developed normally.
In addition, the NICHD is working with other NIH Institutes, the CDC, the
Environmental Protection Agency, and other Federal agencies to conduct a large,
long-term study of the effects of the environment on children�s health. This study
will follow 100,000 children from before birth to age 20, to track growth and
development, as well as study genetic blueprints and environmental factors. Researchers
hope to establish or rule out links between a variety of environmental events and normal
and abnormal development, such as autism. This prospective study is currently under
design.
Another NIH Institute, the National Institute of Neurological Disorders and Stroke
(NINDS), is conducting a retrospective case-control study to identify any molecular
markers in neonatal blood of children with autism, with support from California
Department of Health Services and the Bioengineering and Physical Science (BEPS) Program
of the NIH.
Other recent NIH-sponsored research has also led to the refinement of screening and
diagnosis procedures for various autism disorders that will facilitate better estimates
of the incidence and prevalence of these disorders and provide earlier identification
and treatment. Overall, the thrust of the NIH research is to explore all the possible
causes of autism, including those that may be associated with regression after
apparently normal development.
Health care providers who administer vaccines are required to report any adverse
health events that occur in persons who have received vaccines to the Vaccine Adverse
Event Reporting System (VAERS), a database which is co-maintained by the CDC and the
FDA. More specific information on VAERS, adverse event reporting, and the reporting
process, is provided in the Vaccine Adverse Event Reporting section of
this information packet.
Because there are no proven data to suggest that the MMR vaccine increases the risk
of developing autism or another behavioral disorder, the CDC maintains its
recommendation that children with no known health contraindication receive two doses of
MMR vaccine. (&Recommendations of the Advisory Committee on Immunization
Practices {MMWR 1998} identifies specific contraindications.) The first dose is
recommended at age 12-to-15 months of age, while the second dose is recommended at
either four-to-six years of age or 11-to-12 years of age. Contraindications to the MMR
vaccine are outlined in the Recommendations of the Advisory Committee on Immunization
Practices (ACIP), MMWR 1998.
Is there a theoretical possibility of a connection between autism and the MMR or
any other vaccine?
Because millions of children have received the MMR and other vaccines without ill
health effects, it would have to be a rare occurrence for MMR or other vaccines to cause
autism.
In January 1990, an Institute of Medicine (IOM) committee examined possible health
effects associated with the diphtheria/tetanus/pertussis (DTP) vaccine. The Committee
concluded that there was no evidence to indicate a causal relationship between the DTP
vaccine, or the pertussis component of the vaccine, and autism. Furthermore, data
obtained from the CDC�s Monitoring System for Adverse Events Following Immunization
(MSAEFI) showed no reports of autism occurring within 28 days of DTP immunization from
1978 to 1990. Approximately 80.1 million DTP vaccines were administered during
this time period, with no documented link to a case of autism.
From January 1990 through February 1998, VAERS reported only a small number of autism
behavior disorder cases that occurred following an immunization. Because the number of
cases reported in this eight-year period was so small, autism researchers concluded that
they likely represent unrelated events that occurred around the time of vaccination.
Additional research is needed to determine whether individuals who may have a
susceptibility to a vaccine, or one or more components of a vaccine, or who may need
adjustments to the timing or number of vaccinations they receive can be identified. DTP,
oral polio vaccine, and MMR were the vaccines most often cited in the VAERS-reported
cases.
What are the known side effects of the MMR vaccine?
- Most people who receive the MMR vaccination have no reaction to it.
- About 5-15 percent of those receiving the MMR vaccination develop a fever after
5-12 days. Similarly, 5 percent may develop a rash after 5-12 days.
- Central nervous system conditions, including encephalitis and encephalopathy, have
been reported with a frequency of less-than 1 per 1,000,000 doses of vaccine
administered.
- As with the administration of any agent that can cause fever, the MMR vaccine may
cause simple febrile seizures in some children. These convulsions affect children
with no known risk factors for seizure. Children with a prior history of convulsions
may be at increased risk for febrile seizures following MMR vaccination.
For more information on autism and autism research, contact the National Institute of
Child Health and Human Development (NICHD) Clearinghouse at 1-800-370-2943, or visit
these NIH web sites:
http://www.nlm.nih.gov/medlineplus/autism.html
http://www.nichd.nih.gov/autism/
The CDC�s National Center on Birth Defects and Developmental Disabilities (NCBDDD)
also provides information about autism on their web site at: http://www.cdc.gov/ncbddd/dd/ddautism.htm.
For more information on vaccines and vaccine safety, contact the National
Immunization Program (NIP) at 800-232-2522 (English) or 1-800-232-0233 (Spanish), or
visit the NIP web site at http://www.cdc.gov/nip.
Resources
Afzal MA, Minor PD, Begley J, et al. Absence of measles-virus genome in inflammatory
bowel disease. Lancet 1998;351:646.
Afzal MA, Armitage E, Ghosh S, Williams LC, Minor PD. Further evidence of the absence
of measles virus genome sequence in full thickness intestinal specimens from patients
with Crohn�s disease. J Med Virol 2000; 62:377-82.
**American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition. Washington, DC: American Psychiatric Association,
1994.
Bailey, A., Hervas, A., Matthews, N., et al. International Molecular Genetic Study of
Autism Consortium. (1998). A full genome screen for autism with evidence for linkage to
a region on chromosome 7q. Human Molecular Genetics, 7:571-578.
*Bristol MM, Cohen DJ, Costello EJ, et al. State of the science in autism: Report to
the National Institutes of Health. J Autism Developmental Disorders 1996;26:121-54.
Chadwick N, Bruce IJ, Schepelmann S, Pounder RE, Wakefield AJ. Measles virus DNA is
not detected in inflammatory bowel disease using hybrid capture and reverse
transcriptase followed by polymerase chain reaction. J Med Virol 1998;55:305-311.
Chen RT, DeStefano F. Vaccine adverse events: causal or coincidental? Lancet
1998; 351:611 -612.
Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage
in California. JAMA 2001; 285:1183-5.
Davis RL, Kramarz P, Bohlke K, Benson P, Thompson RS, Mullooly J, Black S, Shinefield
H, Lewis E, Ward J, Marcy SM, Eriksen E, DeStefano F, Chen R. Arch Pediatr Adolesc Med
2001; 155:354-359.
DeStefano F, Chen RT. Negative association between MMR and autism. Lancet
1999;353:1987-8.
DeStefano F, Chen RT. Autism and measles, mumps and rubella vaccine: No
epidemiological evidence for a causal association. J Pediatr 2000 136:125-6.
Duclos P, Ward BJ. Measles vaccines: a review of adverse events. Drug Safety
1998;19:435-454.
Ekbom A, Wakefield AJ, Zack M, Adami HO. Perinatal measles infection and subsequent
Crohn's disease. Lancet 1994;344:508-10.
**Fombonne E, Epidemiological Findings on Autism and Related Developmental Disorders.
Workshop on Educational Interventions for Children with Autism. The National Academies
(NAS), Washington, DC, Dec. 13-14, 1999.
Gillberg C, Coleman M. Autism and medical disorders: A review of the literature.
Developmental Medicine and Child Neurology 1996;38:191-202.
Gillberg C, Heijbel H. MMR and autism. Autism 1998;2:423-4.
Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal
abnormalities in children with autistic disorders. J Pediatr 1999 Nov;135(5):559-63.
IOM, Adverse Effects of Pertussis and Rubella Vaccines, Institute of Medicine, 1991.
IOM, Adverse Events Associated with Childhood Vaccines, Evidence Bearing on
Causality, 1994.
Iizuka M, Chiba M, Yukawa M, Nakagomi T, Fukushima T, Watanabe S, Nakagomi O.
Immunohistochemical analysis of the distribution of measles related antigen in the
intestinal mucosa in inflammatory bowel disease. Gut 2000; 46:163-9.
Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A. Detection and
sequencing of measles virus from peripheral mononuclear cells from patients with
inflammatory bowel disease and autism. Dig Dis Sci 2000; 45:723-9.
Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles and rubella vaccine and the
incidence of autism recorded by general practitioners: a time trend analysis. BMJ 2001;
322:460-3.
Medicines Commission Agency/Committee on Safety of Medicines. The safety of MMR
vaccine. Curr Probl Curr Pharmacovigilance 1999;25:9-10.
Metcalf J. Is measles infection associated with Crohn's disease? Brit Med J
1998;316:561.
Miller D, Wadsworth J, Diamond J, Ross E. Measles vaccination and neurological
events. Lancet 1997;349:730-31.
MMWR, Measles prevention: recommendations of the immunization practices advisory
committee, MMWR 1989;Vol.38 / No.S-9.
& MMWR, Measles, mumps, and rubella-vaccine use and strategies for
elimination of measles, rubella and congenital rubella syndrome and control mumps:
recommendations of the advisory committee on immunization practices. MMWR. 1998. Vol.
47. No. RR-8.
Morris DL, Montgomer SM, Thompson NP, Ebrahim S, Pounder Re, Wakefield AJ. Measles
vaccination and inflammatory bowel disease: a national British cohort study. Am J
Gastroenterol 2000; 95:3507-12.
Peltola H, Patja A, Leinikki P, Valle M, Davidkin I, Paunio M. No evidence for
measles, mumps and rubella vaccine-associated inflammatory bowel disease or autism in a
14-year prospective study. Lancet 1998; 351:1327-8.
Piven J, The Biological Basis of Autism, Current Opinion in Neurobiology, 1997, 7:
708-12.
Rodier PM, Hyman SL. Early environmental factors in autism. MRDD Research Reviews
1998;4:121-128.
Smeeth L, Hall AJ, Fombonne E, Rodriques LC, Huang X, Smith PG. A case-control study
of autism and mumps-measles-rubella vaccination using the general practice research
database: design and methodology. BMC Public Health 2001; 1:2.
Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella
vaccine: no epidemiological evidence for a causal association. Lancet
1999;353:2026-9.
Wakefield AJ, Murch S, Anthony A, et al. Ileal lymphoid nodular hyperplasia,
non-specific colitis, and regressive developmental disorder in children. Lancet
1998;351:637-41.
MEDLINEplus Health Information: http://www.nlm.nih.gov/medlineplus/autism.html
NIH, National Institute of Child Health and Human Development: http://www.nichd.nih.gov/
CDC, National Immunization Program: http://www.cdc.gov/nip
Last updated: August 2001
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