proof the size of Texas is more accurate.

 

and yet you unquestioningly believe in the "war on terror"

 

Really? That's not what the literature says. But believe what you'd like.


Vaccines and Autism: Evidence Does Not
Support a Causal Association
F DeStefano1
A suggested association between certain childhood vac-
cines and autism has been one of the most contentious
vaccine safety controversies in recent years. Despite
compelling scientific evidence against a causal association,
many parents and parent advocacy groups continue to
suspect that vaccines, particularly measles–mumps–rubella
(MMR) vaccine and thimerosal-containing vaccines
(TCVs), can cause autism.
MMR AND AUTISM
Autism is a serious, life-long developmental disorder
characterized by marked impairments in social interactions;
communication skills; and repetitive, restrictive, or stereo-
typed behaviors, interests, and activities. Autism encompasses
the more severe end of autism spectrum disorders. Autism
may have a variety of causes, but in only a few cases has
a specific cause been identified. It has a strong genetic
component and associated neurological defects probably
occur early in embryonic development.1 Although a diag-
nosis of autism may not be made until later in life, when
communication delays and characteristic behaviors become
apparent, in most cases the underlying neuropathology of
autism is present at birth. In a minority of cases, a child can
appear to be developing completely normally but then regress
and develop autistic characteristics. It is for these cases of
regressive autism that, at least theoretically, a biologically
plausible link with vaccination could be made.
Concern about a possible link between vaccines and
autism was initially ignited by a publication in The Lancet in
February 1998.2 The report described 12 children with
inflammatory bowel conditions and regressive developmental
disorders, mostly autism. In 8 of the 12 cases, the children’s
parents or pediatricians believed that MMR vaccine
might have contributed to the onset of behavioral problems
because onset followed shortly after vaccination. The study’s
authors hypothesized that MMR vaccine may have been
responsible for the bowel dysfunction, which subsequently
resulted in neurodevelopmental disorders. Some of the same
investigators subsequently proposed a new syndrome con-
sisting of gastrointestinal disorders, primarily ileocolonic
lymphonodular hyperplasia and mild intestinal inflam-
mation, associated with behavioral regression. One of the
key pieces of evidence in support of the MMR and autism
hypothesis was the reported identification of measles virus
nucleic acid sequences in the blood cells and intestines of
some of the affected children.3,4 It was not determined,
however, if the genetic material was from wild or vaccine
strain virus. Other researchers have not been able to detect
measles virus genome sequences in leukocytes of autistic
children vaccinated with MMR.5 Independent investigators
have also been unable to find evidence of a unique syndrome
of gastrointestinal disorders and regression in autistic
children vaccinated with MMR,6 and no correlation has been
found with the onset of regression.7
One of the first population-based studies of the MMR and
autism hypothesis identified all 498 known cases of autism
spectrum disorders in a district of London who were born in
1979 or later and linked them to a regional vaccination
registry.8 The study found no sharp increase in autism after
the introduction of the MMR vaccine in 1988 and no
clustering of onset was identified within predefined intervals
after vaccination. The study did not find a temporal
relationship between vaccination and onset of regression.
Another study of UK data from 1959 to 1993 also failed to
find a step-up in the rates of autism following the 1998
introduction of MMR.9
Indirect evidence of a lack of association between MMR
vaccine and autism was also provided by early ecological
studies conducted in the United Kingdom10 and California.11
Each of these studies compared temporal trends in MMR
vaccination coverage with corresponding trends in autism
prevalence. Neither found a positive correlation. The
California data, in particular, received much attention
following the publication of a report documenting a large
increase in the number of people with autism enrolled in the
state’s Developmental Services System. Correlating changes in
the number of autism cases with changes in vaccination
coverage, however, is complicated by changes in diagnostic
criteria and possible increased awareness and recognition of
autism. Even if the service data are accepted as valid, the
study by Dales found that the increase in autism cases could
not be explained by MMR coverage, which was relatively
stable in California.11 Recent studies from Japan and Canada
have not found correlations between MMR use and autism
prevalence. Studies in Japan found that even though MMR
vaccination was completely discontinued in 1993, the
prevalence of autism diagnoses increased among cohorts of
children born between 1988 and 1996,12 and there was no
difference in the rates of regressive autism.13 Similarly, a
study conducted in Montreal found that the birth cohort
prevalence of pervasive developmental disorders, which
include autism, increased from 1987 to 1998, whereas during
the same time MMR vaccination coverage showed a
statistically significant decrease.14
Controlled epidemiologic studies have not found an
association between MMR vaccination and autism. A retro-
spective cohort study from Denmark is particularly persua-
sive.15 The study contained data on over half a million
Danish children, including nearly 100,000 who had not been
vaccinated with MMR. The relative risk associated with
MMR was 0.92 (95% confidence interval (CI): 0.68–1.24) for
autistic disorder and 0.83 (95% CI: 0.65–1.07) for other
autism spectrum disorders. A large, population-based case-
control study conducted by the Centers for Disease Control
and Prevention (CDC) also did not find evidence to support
an association between MMR and autism.16 The study
included 624 case children in metropolitan Atlanta and 1,824
matched controls. Vaccination data were abstracted from
immunization forms required for school entry. The overall
distribution of ages at MMR vaccination among children
with autism was similar to that of matched control children.
Another large case–control study of 1,294 cases of pervasive
developmental disorder and 4,469 controls from the UK
General Practice Research Database (GPRD) found a relative
risk of 0.86 (95% CI: 0.68–1.09) for MMR vaccine.17
The results of independent studies conducted after the
publication of the original report of a possible association
between MMR and autism provide compelling evidence
against the hypothesis. More recently, concerns have been
raised about possible biases in enrollment of participants in
the study by Wakefield et al.18 and 10 of the original 13
authors published a formal retraction of the conclusions of
the 1998 article.19 An Immunization Safety Review Commit-
tee of the Institute of Medicine (IOM) reviewed the
epidemiologic and other evidence on MMR vaccine and risk
for autism spectrum disorders and concluded that the
evidence favors rejection of a causal relationship.20
THIMEROSAL
Concerns that TCVs may cause autism stem from a Food and
Drug Administration (FDA) review of the mercury content of
vaccines. Thimerosal has been used as a preservative in
vaccines since the 1930s. It is 49.6% mercury by weight and is
metabolized into ethylmercury and thiosalicylate. In the late
1990s, prompted in part by increased awareness of the
risks of exposure even to low doses of organic mercury,
the FDA conducted a risk assessment of the use of thimerosal
in vaccines. Between 1989 and 1998, as more vaccines
(e.g., hepatitis B and hemophilus influenzae type b (Hib))
were added to the recommended infant immunization
schedule, exposure to ethylmercury from vaccines rose.
Estimates of maximum potential exposure suggested that
infants vaccinated according to the recommended schedule
could have received total doses of ethylmercury in excess of
the Environmental Protection Agency’s exposure limit for
methylmercury.21 Although the review found no evidence of
harm, the Public Health Service and the American Academy
of Pediatrics called for the removal of thimerosal from infant
vaccines as a precautionary measure and also because
vaccines represent a source of mercury exposure that can
be controlled.22
Concerns were quickly raised about the possibility that
exposure to thimerosal in vaccines may cause autism. The
evidence for a possible association was indirect and rested on
analogy with neurotoxic effects of mercury compounds,
ecological comparisons between vaccination and autism
trends, and extrapolation from laboratory and animal
studies. Studies of the neurodevelopmental effects of low
dose exposure to organic mercury compounds in humans
have mostly involved infants and children exposed in utero to
methylmercury, primarily through maternal fish consump-
tion. Subtle effects have been found on speech and verbal
abilities, dexterity, attention, and visuospatial abilities.23 The
findings, however, have been inconsistent24 and no studies
have found an association with autism. Moreover, the half-
life of ethylmercury, the form in thimerosal, is much shorter
than methylmercury,25,26 indicating that methylmercury is
not necessarily a suitable reference for risk assessment of
exposure to ethylmercury from thimerosal.26
A few studies have reported the effects of thimerosal
exposure on neuronal cells, biochemical pathways, or animal
behavior.26–28 A study in monkeys found persistent low levels
of inorganic mercury in the brains of monkeys exposed to
ethylmercury, but the meaning of this finding is not known.26
The laboratory data and animal models may provide
theoretical evidence of possible biological mechanisms, but
are of unproven relevance to effects in humans.
The increasing number of children with autism diagnoses
enrolled in school special education programs and develop-
mental disabilities services programs is cited as another
indication of a possible link to exposure to thimerosal in
vaccines. As noted previously, correlating changes in program
services data with changes in vaccination coverage can be
misleading because many other factors also changed over the
same time period. The only studies purporting to show an
association between TCVs and autism have been conducted
by the same pair of researchers,29 and all have been judged to
have serious flaws and to be uninterpretable by a review
committee of the IOM.20 Ecological studies from countries with population data on
autism diagnoses have not found an association with use of
TCVs. Although incidence and prevalence rates of autism in
Sweden and Denmark grew rapidly in the 1990s, the average
thimerosal exposures had begun to decrease in the late 1980s
and were virtually eliminated by the early 1990s.30 A recent
study in Montreal also found that the prevalence of pervasive
developmental disorders in birth cohorts not exposed to
thimerosal in vaccines was significantly higher than the
prevalence in thimerosal-exposed cohorts in which the
exposure levels were as high as those in the United States.14
The three controlled observational studies31–33 that have
been reported to date have not found an association between
TCVs and autism. An individual-level cohort study in
Denmark failed to find an increased risk of autism associated
with TCVs.31 A GPRD study of 103,043 British children
covering the years 1988–1999 included data on patient
consultations, referrals, and vaccine information.32 One
hundred and four cases of autism were identified, and no
increased risk was found in association with receipt of TCVs.
Because the only TCVs in Denmark and the United Kingdom
were diphtheric-tetanus-pertussis (DTP) or diphtheric-
tetanus (DT), the studies from those two countries do not
provide data on the higher levels of exposure to thimerosal
that occurred in the United States.
To date, the only published controlled study from the
United States was an analysis from the Vaccine Safety
Datalink (VSD)—a collaborative project between the CDC
and several health maintenance organizations (HMOs). For
the autism analyses, a retrospective cohort study was
conducted involving 110,833 children born in one of the
VSD HMOs between 1992 and 1998.33 Computerized
medical encounter and vaccination databases were reviewed
and 202 children with autism diagnoses were identified. The
relative risk of autism associated with increasing cumulative
exposure to thimerosal by 7 months of age was 1.00 (95% CI:
0.90–1.09) for each 12.5 mg increment of mercury exposure.
Although the VSD analysis did not find an association
between TCVs and autism, the CDC is conducting an
additional study that includes in-person evaluation of
potential cases and more in-depth information on vaccina-
tions and other exposures.
The IOM Immunization Safety Review Committee con-
cluded that the evidence is sufficient to reject a causal
association between TCVs and autism.20
CONCLUSION
The current scientific evidence does not support a causal
association between MMR vaccine or TCVs and autism.
CONFLICT OF INTEREST
The author declared no conflict of interest.
& 2007 American Society for Clinical Pharmacology and Therapeutics
1. Bauman, M. & Kemper, T. Neuroanatomic observations of the brain in
autism. In The Neurobiology of Autism (eds. Bauman, M., Kemper, T.)
119–145 (Johns Hopkins Univ. Press, Baltimore, 1997).
2. Wakefield, A.J. et al. Ileal-lymphoid-nodular hyperplasia, non-specific
colitis, and pervasive developmental disorder in children. Lancet 351,
637–641 (1998).
3. Kawashimi, H., Takayuki, M., Kashiwagi, Y., Takekuma, K., Akinori, H. &
Wakefield, A. Detection and sequencing of measles virus from
peripheral mononuclear cells from patients with inflammatory bowel
disease and autism. Dig. Dis. Sci. 45, 723–729 (2000).
4. Uhlmann, V. et al. Potential viral pathogenic mechanism for new
variant inflammatory bowel disease. Mol. Pathol. 55, 34–90 (2002).
5. D’Souza, Y., Fombonne, E. & Ward, B.J. No evidence of persisting
measles virus in peripheral blood mononuclear cells from children
with autism spectrum disorder. Pediatrics 118, 1664–1675
(2006).
6. Fombonne, E. & Chakrabarti, S. No evidence for a new variant of
measles–mumps–rubella induced autism. Pediatrics 108, E58 (2001).
7. Richler, J. et al. Is there a ‘regressive phenotype’ of autism spectrum
disorder associated with the measles–mumps–rubella vaccine? A
CPEA Study. J. Autism Dev. Disord. 36, 299–316 (2006).
8. Taylor, B. et al. Autism and measles, mumps, and rubella vaccine: no
epidemiological evidence for a causal association. Lancet 353,
2026–2029 (1999).
9. Chen, W., Landau, S., Sham, P. & Fombonne, E. No evidence for links
between autism MMR and measles virus. Psychol. Med. 34, 543–553
(2004).
10. Kaye, J.A., 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 322, 460–463 (2001).
11. Dales, L., Hammer, S.J. & Smith, N.J. Time trends in autism and in MMR
immunization coverage in California. JAMA 285, 1183–1185 (2001).
12. Honda, H., Shimizu, Y. & Rutter, M. No effect of MMR withdrawal on
the incidence of autism: a total population study. J. Child Psychol.
Psychiatry 46, 572–579 (2005).
13. Uchiyama, T., Kurosawa, M. & Inaba, Y. MMR-vaccine and regression in
autism spectrum disorders: negative results presented from Japan.
J. Autism Dev. Disord. 37, 210–217 (2007).
14. Fombonne, E., Zakarian, R., Bennett, A., Meng, L. & McLean-Heywood,
D. Pervasive developmental disorders in Montreal, Quebec, Canada:
prevalence and links with immunizations. Pediatrics 118, e139–e150
(2006).
15. Madsen, K.M. et al. A population-based study of measles, mumps, and
rubella vaccination and autism. N. Engl. J. Med. 347, 1477–1482
(2002).
16. DeStefano, F., Karapurkar, T., Thompson, W.W., Yeargin-Allsopp, M. &
Boyle, C. Age at first measles–mumps–rubella vaccination in children
with autism and school-matched controls: a population-based study
in metropolitan Atlanta. Pediatrics 113, 259–266 (2004).
17. Smeeth, L. et al. MMR vaccination and pervasive developmental
disorders: a case–control study. Lancet 364, 963–969 (2004).
18. Ferriman, A. MP raises new allegations against Andrew Wakefield.
BMJ 328, 726 (2004).
19. Murch, S. A statement by Dr Simon Murch. Allegations concerning
our 1998 study. Lancet 363, 821–822 (2004).
20. Immunization Safety Review Committee. Immunization Safety Review.
Vaccines and Autism Board of Health Promotion and Disease
Prevention, Institute of Medicine (National Academy Press,
Washington, DC, 2004).
21. Ball, L.K., Ball, R. & Pratt, R.D. An assessment of thimerosal use in
childhood vaccines. Pediatrics 107, 1147–1154 (2001).
22. Joint statement of the American Academy of Pediatrics (AAP) and the
United States Public Health Service (USPHS). Pediatrics 104, 568–569
(1999).
23. Grandjean, P. et al. Methylmercury exposure biomarkers as indicators
of neurotoxicity in children aged 7 years. Am. J. Epidemiol. 150,
301–305 (1999).
24. Davidson, P.W., Kost, J., Myers, G.J., ***, C., Clarkson, T.W. & Shamlaye,
C.F. Methylmercury and neurodevelopment: reanalysis of the
Seychelles Child Development Study outcomes at 66 months of age.
JAMA 285, 1291–1293 (2001).
25. Pichichero, M.E., Cernichiari, E., Lopreiato, J. & Treanor, J. Mercury
concentrations and metabolism in infants receiving vaccines
containing thiomersal: a descriptive study. Lancet 360, 1737–1741
(2002).
26. Burbacher, T.M., Shen, D.D., Liberato, N., Grant, K.S., Cernichiari, E. &
Clarkson, T. Comparison of blood and brain mercury levels in infant
758 VOLUME 82 NUMBER 6 | DECEMBER 2007 | www.nature.com/cpt
P R A C T I C E
monkeys exposed to methylmercury or vaccines containing
thimerosal. Environ. Health Perspect. 113, 1015–1021 (2005).
27. Hornig, M., Chian, D. & Lipkin, W.I. Neurotoxic effects of postnatal
thimerosal are mouse strain dependent. Mol. Psychiatry 9, 833–845
(2004).
28. Baskin, D.S., Ngo, H. & Didenko, V.V. Thimerosal induces DNA
breaks, caspase-3 activation, membrane damage, and cell death in
cultured human neurons and fibroblasts. Toxicol. Sci. 74, 361–368
(2003).
29. Geier, M.R. & Geier, D.A. Thimerosal in childhood vaccines,
neurodevelopmental disorders, and heart disease in the United
States. J. Am. Phys. Surg. 8, 6–11 (2003).
30. Stehr-Green, P., Tull, P., Stellfeld, M., Mortenson, P. & Simpson, D.
Autism and thimerosal-containing vaccines: lack of consistent
evidence for an association. Am. J. Prev. Med. 25, 101–106 (2003).
31. Hviid, A., Stellfeld, M., Wohlfahrt, J. & Melbye, M. Association between
thimerosal-containing vaccine and autism. JAMA 290, 1763–1766 (2003).
32. 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 114, 584–591 (2004).
33. Verstraeten, T. et al. Safety of thimerosal-containing vaccines: a two-
phased study of computerized health maintenance organization
databases. Pediatrics 112, 1039–1048 (2003).
CLINICAL PHARMACOLOGY & THERAPEUTICS | VOLUME 82 NUMBER 6 | DECEMBER 2007 759
P R A C T I C E

 

Another study, abbreviated:

Is there a "Regressive Phenotype" of Autism Spectral Disorder Associated with the Measles-Mumps-Rubella Vaccine? A CPEA Study

Richler et.al.

Journal of Autism and Developmental Disorders




This study addressed two questions: First, is there evidence for a ‘regressive phenotype’ of ASD? Second, is regression in ASD associated with the MMR vaccine?


...

The answer to the second question is more definitive: the present study provides no evidence that regression in ASD is associated with MMR vaccination.

 

Actually, the fact that people pick a fad diagnosis and jump on it, like ADD/ADHD, explains the spike in Autism. If a kid isn't the most popular kid in 3rd grade and friends with every single person in his/her class everyone screams "austism."