Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
March 06, 2010
"What causes autism? Exploring the environmental contribution"
That's the title of Philip J. Landrigan's recently published review
(1). That such a essay (see also 2) would be presented in Current Opinion in Pediatricsis a
step in the right direction even as major flaws in Dr. Landrigan's
review merit attention.
Background: Current Opinion in Pediatricsis
among the journals that promote vaccinations (eg, 3-6) and that endorse
recommendations of the CDC's Advisory Committee on Immunization
Practices (ACIP; eg, 4,6,7). Caution is warranted.
For instance, the ACIP recently recommended flu shots for the elderly
(8) despite a major Cochrane Database review which found that existing
data do not imply that influenza vaccinations for the elderly have been
found efficacious (9). Similarly, Current
Opinion in Pediatricsand the CDC's ACIP
endorse Gardasil vaccinations (5, 12), despite well-documented reports
of adverse effects (eg, 9-13).
That Current Opinion in
Pediatricsrepresents individuals and
corporations who profit from vaccinations may have shaped Dr.
Landrigan's review in at least two ways. Firstly, his review offers
prenatal timing as virtually the only possible time for disruption of
neurodevelopment in ways inducing autism or one of the other
autism-spectrum disorders (ASDs). Secondly, his review offers as
quasi-sacred truth that "There is no credible evidence that vaccines
cause autism" - despite a growing body of evidence that vaccinations
induce or are associated with autism in some children. Furthermore,
whereas Dr. Landrigan calls attention to "thousands of synthetic
chemicals", his essay omits peer-reviewed citations (a) documenting
autism associations with mercury, arsenic, trichloroethylene,
pesticides, etc, and (b) documenting thimerosal's relevance to autism.
Timing: Human neurodevelopment is
not limited to in utero timing and continues postnatally. Exposures to
pollutants not adequately detoxified would augment neurodevelopmental
risk pre- as well as post-natally. Postnatal exposures - including
vaccinations - may be etiologically significant in some children and
ought not be precluded a priori.
"In humans, synaptogenesis is reported to begin as early as gestation
month 2 and continues into postnatal life, with a peak in the first
year of life (14, citing 15) and continuing into the human's second
year (16). Indeed, late-onset autism has been described (eg, 17).
Autism having only in-utero timing, as set forth in Landrigan's review,
stands in contrast with late-onset autism, a phenomenon which is at
least consistent not only with the timing of autism-symptoms onset
(>6 months old)
described by Ozonoff et al (18-19) and but also with parent reports of
regression into autism (eg, 20).
Surprisingly but consistent with his preferred rationale, Dr.
Landrigan's review doesn't mention Hannah Poling's regression, her
late-onset development of autistic traits subsequent to a
multiple-vaccinations incident (eg, 21-22). Clearly, factors
etiologically significant in the development of autism can occur
postnatally and perceived as regressions. In regard to the timing of
autism's causal events, Dr. Landrigan's review is misleading.
Vaccinations and
autism: A growing body of data
indicate that autism and other ASDs are associated with vaccinations,
whether the injected biologics contained thimerosal or live-viruses.
Nonetheless, the Landrigan review states, "There is no credible
evidence that vaccines cause autism." (1)
His strident rhetoric reflects a dilemma: If scientists find
associations between vaccinations and one or more ASDs, those findings
are a priori other than credible because they violate principles of
orthodox vaccinology. Similarly, if researchers document mechanisms by
which thimerosal-containing or live-virus vaccines cause pathologies,
then those studies are to be ignored when mainstream researchers omit
inculpatory evidence of neurologic and other sequelae while presenting
egregiously erroneous statements (as did Landrigan, see quote above in
this paragraph).
Although research teams affiliated with vaccine manufacturers or with
vaccine-sections of the CDC use study designs that lead to the
minimizing or elimination of vaccination-associated adverse-effects
findings (eg, 23-25), other researchers report different findings. For
instance, thimerosal is associated with autism, other ASDs, and with
increased need for special education services (eg, 26-29). Mechanisms
of by which thimerosal induces pathologies are described (eg, 30-36).
Similarly for the MMR, some researchers have dared report signals of
adverse events related to autism and seizures; and mechanisms of
MMR-induced damage are described, including "viral interference" when
co-infections occur or multiple live-viruses are injected
simultaneously (eg, 37-41; additional cites in 42-43).
Autism-pollutant
studies Landrigan omitted:
Although Dr. Landrigan mentions "synthetic chemicals", his study
omitted autism-pollutant associations already delineated in
peer-reviewed articles. Among these associations are mercury from
coal-fired power plants, pesticides, trichloroethylene, arsenic,
cadmium, vinyl chloride, etc (eg, 44-47).
Clinical significance: Near the
end of his paper, Dr. Landrigan calls for "Toxicological...,
Neurobiological, and Prospective epidemiological studies" and mentions
the National Children's Study (1). Whereas these are important foci,
the Landrigan essay omits already published studies with clinical
relevance to pollutants, nutrient status, and detoxification pathways
in autistic patients (eg, 48-55). Research into clinicial profiles (see
also 56) and pollutant-related treaments has begun and needs be
expanded.
Conclusion: Philip J. Landrigan,
M.D., is a respected researcher with decades of experience. Why he
chose to omit important studies regarding pollutants and autism and
their clinical significance is not known. Why he chose a fictional
denial of vaccinations' relevance to autism and other ASDs is more
understandable in view of modernity's enforcement of an orthodoxy of
vaccinationism. However, although his review seems a welcome addition
to autism literature, his essay's omissions sustain misunderstandings
regarding the subgroups of infants and toddlers adversely affected by
vaccinations and prolongs delay in clinicians' and theoreticians'
appreciation for the detoxification of pollutants, whether breathed,
injected, or in other ways ingested.
References:
1. What causes
autism? Exploring the environmental
contribution
Landrigan PJ.
Curr Opin Pediatr. 2010 Jan 16. [Epub ahead of print]
PURPOSE OF REVIEW: Autism is a biologically based disorder of brain
development. Genetic factors - mutations, deletions, and copy number
variants - are clearly implicated in causation of autism. However, they
account for only a small fraction of cases, and do not easily explain
key clinical and epidemiological features. This suggests that early
environmental exposures also contribute. This review explores this
hypothesis. RECENT FINDINGS: Indirect evidence for an environmental
contribution to autism comes from studies demonstrating the sensitivity
of the developing brain to external exposures such as lead, ethyl
alcohol and methyl mercury. But the most powerful proof-of-concept
evidence derives from studies specifically linking autism to exposures
in early pregnancy - thalidomide, misoprostol, and valproic acid;
maternal rubella infection; and the organophosphate insecticide,
chlorpyrifos. There is no credible evidence that vaccines cause autism.
SUMMARY: Expanded research is needed into environmental causation of
autism. Children today are surrounded by thousands of synthetic
chemicals. Two hundred of them are neurotoxic in adult humans, and 1000
more in laboratory models. Yet fewer than 20% of high-volume chemicals
have been tested for neurodevelopmental toxicity. I propose a targeted
discovery strategy focused on suspect chemicals, which combines
expanded toxicological screening, neurobiological research and
prospective epidemiological studies
2. Gene-environment
interaction and children's health and
development
Wright RO, Christiani D.
Curr Opin Pediatr. 2010 Jan 19. [Epub ahead of print]
$ http://tinyurl.com/ybf3ofo
PURPOSE OF REVIEW: A systematic approach to studying gene-environment
interaction can have immediate impact on our understanding of how
environmental factors induce developmental disease and toxicity and
will provide biological insight for potential treatment and prevention
measures. RECENT FINDINGS: Because DNA sequence is static, genetic
studies typically are not conducted prospectively. This limits the
ability to incorporate environmental data into an analysis, as such
data is usually collected cross-sectionally. Prospective environmental
data collection could account for the role of critical windows of
susceptibility that likely correspond to the expression of specific
genes and gene pathways. The use of large-scale genomic platforms to
discover genetic variants that modify environmental exposure in
conjunction with a-priori planned replication studies would reduce the
number of false positive results. SUMMARY: Using a genome-wide
approach, combined with prospective longitudinal measures of
environmental exposure at critical developmental windows, is the
optimal design for gene-environment interaction research. This approach
would discover susceptibility variants, and then validate the findings
in an independent sample of children. Designs that combine the
strengths and methodologies of each field will yield data that can
account for both genetic variability and the role of critical
developmental windows in the etiology of childhood disease and
development.
3. Immunization
updates and challenges
Keeton VF, Chen AK.
Curr Opin Pediatr. 2010 Jan 30. [Epub ahead of print]
PURPOSE OF REVIEW: Childhood vaccination recommendations in the United
States have increased throughout the years. Many providers, patients,
and families are overwhelmed and have concerns regarding the safety and
efficacy of vaccines. Various barriers and challenges exist for
healthcare providers to successfully implement the vaccination
recommendations. This review will discuss the 2009 and newly released
2010 immunization recommendations, as well as challenges and strategies
to improve vaccination in children and adolescents. RECENT FINDINGS:
Seasonal influenza immunization continues to be promoted for all
children, and recommendations for vaccination against novel influenza A
have emerged as well. Concerns surrounding vaccine safety and necessity
may cause increasing rates of vaccine refusal among some parents, but
clear messages from providers and unbiased information about benefits
and risks of immunization may counteract these doubts. Barriers to
immunizing adolescents continue as access to healthcare in this age
group changes. SUMMARY: Pediatric providers currently face numerous
challenges in improving rates of immunization among children and
adolescents. Promoting coverage through the influenza vaccines,
counseling parents with clear information about the risks and benefits
of vaccines, and taking advantage of nonpreventive visits for
immunization are some strategies suggested to address these
challenges.
4. Update on
universal annual influenza immunization recommendations for
children
Bekker A, Chou C, Bernstein HH.
Curr Opin Pediatr. 2009 Feb;21(1):122-6.
PURPOSE OF REVIEW: To provide an update of current recommendations and
research findings on universal annual influenza immunization of
children. RECENT FINDINGS: The Advisory Committee on Immunization
Practices of the Centers for Disease Control and Prevention and the
American Academy of Pediatrics now recommend annual influenza
vaccination for all children 6 months through 18 years. New research
has examined the effect of 'herd immunity' associated with immunizing
all school-aged children, the suboptimal antigenic match between the
trivalent vaccine strains and circulating virus strains of last
2007-2008 influenza season, the efficacy of live attenuated influenza
vaccine versus trivalent inactivated influenza vaccine, and the
tolerance for influenza vaccine in infants less than 6 months of age.
With a goal of improving the overall rates of influenza immunization
and an eye toward the anticipated increase in volume with expansion of
the universal recommendations in children, Advisory Committee on
Immunization Practices and American Academy of Pediatrics emphasize the
value of extending the timeframe for immunization beyond December and
into April, establishing school-based immunization programs and other
alternative vaccination sites outside medical homes, and conducting
large, population-based studies that examine the overall impact of
universal childhood influenza immunization. SUMMARY: Annual influenza
vaccination recommendations have been expanded, and research continues
on vaccine efficacy, administration, and cost associated with
vaccinating all school-aged children.
5. Human
papillomavirus vaccine: a paradigm shift for
pediatricians
Jenson HB.
Curr Opin Pediatr. 2009 Feb;21(1):112-21.
PURPOSE OF REVIEW: Recommendations for human papillomavirus (HPV)
vaccination during adolescence primarily for a disease, cancer, that
occurs only during adulthood is a paradigm shift for pediatricians.
Additional postlicensure data and guidelines about HPV biology and
epidemiology, disease association, adverse effects, vaccination during
pregnancy, and cost-benefit analyses are now available to inform
pediatricians and guide HPV vaccination recommendations. RECENT
FINDINGS: The prespecified, end-of-study combined analysis of HPV
vaccine efficacy studies for prevention of cervical cancer, and now
also for prevention of vulvar and vaginal cancers, confirmed 98-100%
vaccine efficacy. Postlicensure surveillance identified a new
association of vaccine administration with syncope, and provides
assurance of the safety of inadvertent vaccination during pregnancy.
Several cost-effectiveness analyses consistently demonstrated that HPV
vaccination of 12-year-old girls and catch-up vaccination through 18
years of age, and possibly to 26 years of age, is cost-effective,
although the thresholds of affordability vary by study. The downward
trend in age of initial HPV infection and the need to educate parents
and patients about HPV disease and vaccination underscore the essential
role of pediatricians in managing HPV illness. SUMMARY: It is critical
for pediatricians to thoroughly understand HPV biology and disease and
champion HPV vaccination to prevent cervical, vulvar, and vaginal
cancers, even though these benefits accrue during adulthood and will
likely require 2-4 decades to realize the financial and public health
benefits. Several new developments are expected in the near future,
including licensure for use in boys and men and the approval of a
second, bivalent HPV vaccine.
6. Update on
universal childhood immunizations
Hamlin J, Senthilnathan S, Bernstein HH.
Curr Opin Pediatr. 2008 Aug;20(4):483-9.
PURPOSE OF REVIEW: To provide an update of research findings and
recommendations regarding immunizations. RECENT FINDINGS: New research
has examined the efficacy of the 2007-2008 influenza vaccine, the
transmission and incidence of human papillomavirus, the increased
prevalence of pneumococcal serotypes not included in the 7-valent
pneumococcal conjugate vaccine, the emergence of a drug-resistant
strain of Streptococcus pneumoniae, febrile seizure rates following
measles-mumps-rubella-varicella vaccination, and the 2006 mumps
outbreak in the American Midwest. The Food and Drug Administration has
approved the expansion of live attenuated influenza virus vaccine and
quadrivalent meningococcal conjugate vaccine for use in children no
younger than 2 years of age. The Advisory Committee on Immunization
Practices now recommends immunization with quadrivalent meningococcal
conjugate vaccine for all previously unvaccinated 11-18-year-old
children and has revised its recommendations for Streptococcus
pneumoniae catch-up vaccinations. The Advisory Committee on
Immunization Practices no longer expresses a preference for the use of
the combination measles-mumps-rubella-varicella vaccine over separate
measles-mumps-rubella and varicella administration. Because of a
notable recall of Haemophilus influenzae type B vaccines by Merck &
Co Inc, Whitehouse Station, New Jersey, USA, the Advisory Committee on
Immunization Practices recommends that pediatric providers conserve
available Haemophilus influenzae type B vaccines by delaying the
administration of the booster dose of the vaccine in healthy children.
SUMMARY: New vaccine recommendations continue to be made, and research
continues on infectious diseases, vaccine safety, and vaccine
efficacy.
7. The Advisory
Committee on Immunization Practices (ACIP)
http://www.cdc.gov/vaccines/recs/acip/default.htm
8. CDC advisory panel
says virtually everyone should get a seasonal flu
shot
February 24, 2010 | 4:53 pm
http://latimesblogs.latimes.com/booster_shots/2010/02/cdc-advisory-panel-says-virtually-everyone-should-get-a-seasonal-flu-shot.html
The Centers for Disease Control and Prevention's Advisory Committee on
Immunization Practices recommended Wednesday that all Americans over
the age of 6 months -- with the exception of those who are allergic to
eggs -- should receive a seasonal flu shot every year, beginning this
fall. The advice must be accepted by the CDC director and the
Department of Health and Human Services before it becomes official, but
that ratification is usually pro forma. The CDC has been slowly
broadening the recommendations for flu shots over the last few years to
the point where about 85% of the population is now covered. The primary
exception now is adults ages 19 to 49 who do not have underlying
medical conditions. But the committee noted that many such adults do
not realize they are at risk because of diabetes, hypertension or other
hidden problems and do not seek the shots.
9. Vaccines for
preventing influenza in the elderly
Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S,
Thomas RE.
Vaccines Field, The Cochrane Collaboration, Via Adige 28a, Anguillara
Sabazia, Roma, Italy, 00061.
Cochrane Database Syst Rev. 2010 Feb 17;2:CD004876.
$ http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004876/frame.html
BACKGROUND: Vaccines have been the main global weapon to minimise the
impact of influenza in the elderly for the last four decades and are
recommended worldwide for individuals aged 65 years or older. The
primary goal of influenza vaccination in the elderly is to reduce the
risk of complications among persons who are most vulnerable.
OBJECTIVES: To assess the effectiveness of vaccines in preventing
influenza, influenza-like illness (ILI), hospital admissions,
complications and mortality in the elderly. To identify and appraise
comparative studies evaluating the effects of influenza vaccines in the
elderly. To document types and frequency of adverse effects associated
with influenza vaccines in the elderly. SEARCH STRATEGY: We searched
the Cochrane Central Register of Controlled Trials (CENTRAL), which
contains the Cochrane Acute Respiratory Infections (ARI) Group's
Specialised Register (The Cochrane Library 2009, issue 4); MEDLINE
(January 1966 to October Week 1 2009); EMBASE (1974 to October 2009)
and Web of Science (1974 to October 2009). SELECTION CRITERIA:
Randomised controlled trials (RCTs), quasi-RCTs, cohort and
case-control studies assessing efficacy against influenza
(laboratory-confirmed cases) or effectiveness against influenza-like
illness (ILI) or safety. Any influenza vaccine given independently, in
any dose, preparation or time schedule, compared with placebo or with
no intervention was considered. DATA COLLECTION AND ANALYSIS: We
grouped reports first according to the setting of the study (community
or long-term care facilities) and then by level of viral circulation
and vaccine matching. We further stratified by co-administration of
pneumococcal polysaccharide vaccine (PPV) and by different types of
influenza vaccines. We analysed the following outcomes: influenza,
influenza-like illness, hospital admissions, complications and deaths.
MAIN RESULTS: We included 75 studies. Overall we identified 100 data
sets. We identified one RCT assessing efficacy and effectiveness.
Although this seemed to show an effect against influenza symptoms it
was underpowered to detect any effect on complications (1348
participants). The remainder of our evidence base included non-RCTs.
Due to the general low quality of non-RCTs and the likely presence of
biases, which make interpretation of these data difficult and any firm
conclusions potentially misleading, we were unable to reach clear
conclusions about the effects of the vaccines in the elderly. AUTHORS'
CONCLUSIONS: The available evidence is of poor quality and provides no
guidance regarding the safety, efficacy or effectiveness of influenza
vaccines for people aged 65 years or older. To resolve the uncertainty,
an adequately powered publicly-funded randomised, placebo-controlled
trial run over several seasons should be undertaken.
10. A 16-Year-Old
Girl With Bilateral Visual Loss and Left Hemiparesis Following an
Immunization Against Human Papilloma Virus
Francis J. DiMario, Jr, MD et al.
Journal of Child Neurology,
Vol. 25, No. 3, 321-327 (2010)
$ http://jcn.sagepub.com/cgi/content/abstract/25/3/321
We report the course of a 16-year-old girl who presented with near
complete visual loss associated with chiasmal neuritis and a biopsy
proven tumefactive demyelinating lesion on magnetic resonance imaging
(MRI) in association with a recent immunization against human papilloma
virus.
11. New Worries About
Gardasil Safety
CBS Evening News Exclusive: Vaccine-Safety Group Study Shows Higher
Instance Of Medical Side-Effects Than Another Vaccine
By Sharyl Attkisson
http://www.cbsnews.com/stories/2009/02/06/eveningnews/main4781658.shtml
12. Reports of Health
Concerns Following HPV Vaccination
CDC {accessed March 5, 2010}
http://www.cdc.gov/vaccinesafety/Vaccines/HPV/gardasil.html
13. Judicial Watch
Investigates Side-Effects of HPV Vaccine
http://www.judicialwatch.org/gardasil
14. A model of the
development of the brain as a construct of the thyroid
system
Howdeshell KL.
Environ Health Perspect. 2002 Jun;110 Suppl 3:337-48.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241181/pdf/ehp110s-000337.pdf
15. Neurobiological
bases of behavioral development in the first
year
Herschkowitz N, Kagan J, Zilles K.
Neuropediatrics. 1997 Dec;28(6):296-306.
16. Neurobiological
bases of behavioral development in the second
year
Herschkowitz N, Kagan J, Zilles K.
Neuropediatrics. 1999 Oct;30(5):221-30.
17. Acquired
reversible autistic syndrome in acute encephalopathic illness in
children
DeLong GR, Bean SC, Brown FR 3rd.
Arch Neurol. 1981 Mar;38(3):191-4.
http://archneur.ama-assn.org/cgi/reprint/38/3/191
18. The onset of
autism: patterns of symptom emergence in the first years of
life
Ozonoff S, Heung K, Byrd R, Hansen R, Hertz-Picciotto I.
Autism Res. 2008 Dec;1(6):320-8.
19. A Prospective
Study of the Emergence of Early Behavioral Signs of
Autism
Sally Ozonoff et al.
J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(3):258 –268.
available here
20. Ileal-lymphoid-nodular hyperplasia,
non-specific colitis, and pervasive developmental disorder in
children
Wakefield AJ et al.
Lancet. 1998 Feb 28;351(9103):637-41.
available
here
21. Developmental
regression and mitochondrial dysfunction in a child with
autism
Poling JS, Frye RE, Shoffner J, Zimmerman AW.
Department of Neurology and Neurosurgery, Johns Hopkins Hospital
J Child Neurol. 2006 Feb;21(2):170-2.
{free online}
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2536523&blobtype=pdf
22. Hannah Poling, her medical
issues, and her post-vaccinal regression into autism have been widely
discussed. Her father and mother have participated in some of these
discussions. Noteworthy is the fact that the U.S. Department of Health
& Human Services conceded a suit regarding Hannah's
vaccination-induce autism. Here are three examples regarding the
significance of the HHS concession regarding Hannah Poling,
mitochondria disorders, vaccinations, and autism:
22a. Vaccine Injury
Case Offers a Clue to the Causes of Autism
Could a group of disorders involving the "power plants of the cell"
explain why some vaccinated children develop autism but the vast
majority don't?
By Nikhil Swaminathan, April 22, 2008
http://www.scientificamerican.com/article.cfm?id=vaccine-injury-case-offer
22b. Father: Child's
case shifts autism debate
By Jon S. Poling
Atlanta Journal-Constitution, 04/11/08
http://www.ajc.com/services/content/opinion/stories/2008/04/11/polinged0411.html
22c. Hanna Poling v.
Secretary of HHS: Landmark First Concession of Vaccine-Induced Autism
by U.S. Dept. of Health & Human Services
http://www.drhusbands.com/articles/March%2008%20Newsltr%20Article.pdf
23. Generation Zero
{FOIA-based analysis of CDC's 1999 thimerosal findings}
Blaxill M, Safeminds 2004
http://www.safeminds.org/research/library/GenerationZeroPowerPoint.pdf
24. A survey of
vaccination studies fraught with conflicts of
interest
http://www.fourteenstudies.org/
25. Critiques of
Danish studies regarding thimerosal and MMR
http://www.whale.to/a/danish.html
26. Neurodevelopmental Disorders after Thimerosal-Containing
Vaccines: A Brief Communication
Geier MR, Geier DA.
Exp Biol Med 228:660–664, 2003
http://tinyurl.com/y9ndrh3
27. Thimerosal
exposure in infants and neurodevelopmental disorders: an assessment of
computerized medical records in the Vaccine Safety
Datalink.
Young HA, Geier DA, Geier MR.
J Neurol Sci. 2008 Aug 15;271(1-2):110-8. Epub 2008 May 15.
[These findings confirm the 1999 CDC findings of Verstraeten et al; see
cite 23]
The study evaluated possible associations between neurodevelopmental
disorders (NDs) and exposure to mercury (Hg) from Thimerosal-containing
vaccines (TCVs) by examining the automated Vaccine Safety Datalink
(VSD). A total of 278,624 subjects were identified in birth cohorts
from 1990-1996 that had received their first oral polio vaccination by
3 months of age in the VSD. The birth cohort prevalence rate of
medically diagnosed International Classification of Disease, 9th
revision (ICD-9) specific NDs and control outcomes were calculated.
Exposures to Hg from TCVs were calculated by birth cohort for specific
exposure windows from birth-7 months and birth-13 months of age.
Poisson regression analysis was used to model the association between
the prevalence of outcomes and Hg doses from TCVs. Consistent
significantly increased rate ratios were observed for autism, autism
spectrum disorders, tics, attention deficit disorder, and emotional
disturbances with Hg exposure from TCVs. By contrast, none of the
control outcomes had significantly increased rate ratios with Hg
exposure from TCVs. Routine childhood vaccination should be continued
to help reduce the morbidity and mortality associated with infectious
diseases, but efforts should be undertaken to remove Hg from vaccines.
Additional studies should be conducted to further evaluate the
relationship between Hg exposure and NDs.
28. Hepatitis B
triple series vaccine and developmental disability in US children aged
1-9 years
Gallagher C, Goodman M. Toxicol Environ Chem 2008 90(5):997-1008.
{free online}
http://fourteenstudies.org/pdf/hep_b.pdf
29. Hepatitis B
vaccination of male neonates and autism
[conference abstract as published]
CM Gallagher, MS Goodman, Graduate Program in Public
Health, Stony Brook University Medical Center, Stony Brook, NY
Annals of Epidemiology, p659
Vol. 19, No. 9 Abstracts (ACE) September 2009: 651–680.
PURPOSE: Universal newborn immunization with hepatitis B vaccine was
recommended in 1991; however, safety findings are mixed. The Vaccine
Safety Datalink Workgroup reported no association between hepatitis B
vaccination at birth and febrile episodes or neurological adverse
events. Other studies found positive associations between hepatitis B
vaccination and ear infection, pharyngitis, and chronic arthritis; as
well as receipt of early intervention/special education services (EIS);
in probability samples of
U.S. children. Children with autistic spectrum disorder (ASD) comprise
a growing caseload for EIS. We evaluated the association between
hepatitis B vaccination of male neonates and parental report of ASD.
METHODS: This cross-sectional study used U.S. probability samples
obtained from National Health Interview Survey 1997–2002 datasets.
Logistic regression modeling was used to estimate the effect of
neonatal hepatitis B vaccination on ASDrisk amongboys age 3–17 years
with shot records, adjusted for race, maternal education, and
two-parent household.
RESULTS:Boyswho received the hepatitis B vaccine during the first month
of life had 2.94 greater odds for ASD (nZ31 of 7,486; OR Z 2.94; p Z
0.03; 95% CI Z 1.10, 7.90) compared to later- or unvaccinated boys.
Non-Hispanicwhite boys were 61% less likely to have ASD(ORZ0.39;
pZ0.04; 95% CIZ0.16, 0.94) relative to non-white boys.
CONCLUSION: Findings suggest that U.S. male neonates vaccinated with
hepatitis B vaccine had a 3-fold greater risk of ASD; risk was greatest
for non-white boys.
30. Activation of
methionine synthase by insulin-like growth factor-1 and dopamine: a
target for neurodevelopmental toxins and
thimerosal
Waly M et al.
Mol Psychiatry. 2004 Apr;9(4):358-70.
http://www.nature.com/mp/journal/v9/n4/abs/4001476a.html
31. Thimerosal
induces DNA breaks, caspase-3 activation, membrane damage, and cell
death in cultured human neurons and
fibroblasts
Baskin DS, Ngo H, Didenko VV.
Toxicol Sci. 2003 Aug;74(2):361-8. Epub 2003 May 28.
http://toxsci.oxfordjournals.org/cgi/content/full/74/2/361
32. Cellular and
mitochondrial glutathione redox imbalance in lymphoblastoid cells
derived from children with autism
James SJ et al. FASEB J. 2009 Aug;23(8):2374-83.
33. Homozygous gene
deletions of the glutathione S-transferases M1 and T1 are associated
with thimerosal sensitization
Westphal GA et al. Int Arch Occup Environ Health. 2000
Aug;73(6):384-8.
34. Biochemical and
molecular basis of thimerosal-induced apoptosis in T cells: a major
role of mitochondrial pathway
Makani S et al. Genes Immun. 2002 Aug;3(5):270-8.
{free online}
http://www.nature.com/gene/journal/v3/n5/abs/6363854a.html
35. Thimerosal
neurotoxicity is associated with glutathione depletion: protection with
glutathione precursors
James SJ et al. Neurotoxicology. 2005 Jan;26(1):1-8.
36. Inhibition of the
human erythrocytic glutathione-S-transferase T1 (GST T1) by
thimerosal
Muller M et al. Int J Hyg Environ Health. 2001 Jul;203(5-6):479-81.
37. Pediatric MMR
Vaccination Safety
Mark R. Geier, MD, PhD; David A Geier
International Pediatrics 2003;18(2):203-208.
The Vaccine Adverse Events Reporting System (VAERS) database was
analyzed for the incidence rate of permanent brain damage, cerebellar
ataxia, autism and mental retardation reported following MMR vaccine
and diphtheria, tetanus and whole-cell pertussis (DTwcP)
containing-vaccines from 1994 through 2000 in the US. Statistically significant increases in
the incidence of serious neurologic disorders following pediatric MMR
vaccine in comparison to DTwcP vaccine were found. The potentially globally destructive effects of natural
measles, mumps and rubella infections means that continued vaccination
is necessary, but improvements in MMR vaccines are needed to improve
its safety.
38. A comparative
evaluation of the effects of MMR immunization and mercury doses from
thimerosal-containing childhood vaccines on the population prevalence
of autism.
Geier DA, Geier MR.
Med Sci Monit. 2004 Mar;10(3):PI33-9. Epub 2004 Mar 1.
CONCLUSIONS: The results of this study agree with a number of
previously published studies. These studies have shown that
there is biological
plausibility and epidemiological evidence showing a direct relationship
betweenincreasing doses of mercury from
thimerosal-containing vaccines and neurodevelopmental disorders, and
measles-containing vaccines
and serious neurological disorders. It is
recommended that thimerosal be removed from all vaccines, and
additional research be undertaken to produce a MMR vaccine with an
improved safety profile.
39. Serological
association of measles virus and human herpesvirus-6 with brain
autoantibodies in autism
Singh VK, Lin SX, Yang VC.
Clin Immunol Immunopathol. 1998 Oct;89(1):105-8.
40. Acute
Encephalopathy Followed by Permanent Brain Injury or Death Associated
With Further Attenuated Measles Vaccines: A Review of Claims Submitted
to the National Vaccine Injury Compensation
Program
Received Jul 30, 1997; accepted Sep 23, 1997.
Robert E. Weibel*, Vito Caserta*, David E. Benor Dagger, and Geoffrey
Evans*
>From the * Division of Vaccine Injury Compensation, National
Vaccine Injury Compensation Program, Health Resources and Services
Administration, Public Health Service, Rockville, Maryland; and the
Dagger Office of the General Counsel, United States Department of
Health and Human Services, Rockville, Maryland.
PEDIATRICS Vol. 101 No. 3 March 1998, pp. 383-387
http://pediatrics.aappublications.org/cgi/content/abstract/101/3/383
{some highlights added in abstract}
Objective. To determine if there is evidence for a causal relationship
between acute encephalopathy followed by permanent brain injury or
death associated with the administration of further attenuated measles
vaccines(Attenuvax or Lirugen, Hoechst
Marion Roussel, Kansas City, MO), mumps vaccine(Mumpsvax, Merck and
Co, Inc, West Point, PA), or rubella vaccines(Meruvax or
Meruvax II, Merck and Co, Inc, West Point, PA), combined measles and rubella
vaccine(M-R-Vax or M-R-Vax II, Merck and
Co, Inc, West Point, PA), or combined measles, mumps, and rubella
vaccine(M-M-R or M-M-R II, Merck and Co,
Inc, West Point, PA), the lead author reviewed claims submitted to the
National Vaccine Injury Compensation Program...
Conclusions. This
clustering suggests that a causal relationship between measles vaccine
and encephalopathy may exist as a rare complication of measles
immunization.
41. [An excellent and thorough review]
Measles, mumps,
rubella vaccine: through a glass, darkly.
Wakefield AJ, Montgomery SM.
Adverse Drug React Toxicol Rev. 2000 Dec;19(4):265-83; reviewer
comments 284-92.
42. Lancet editor
reverses himself: MMR and adverse events
Teresa Binstock, 2010
http://www.ravenintellections.com/gre/wakefield-mmr-lancet-horton-reversal.htm
43.
Vaccinations and
autism: cause or coincidence?
Teresa Binstock, 2010
http://ravenintellections.com/gre/vax-autism-link-not-coincidence.htm
44. Environmental
mercury release, special education rates, and autism disorder: an
ecological study of Texas
Palmer RF et al. Health Place. 2006 Jun;12(2):203-9.
{free online}
http://www.generationrescue.org/pdf/seed.pdf
45. Proximity to
point sources of environmental mercury release as a predictor of autism
prevalence
Palmer RF et al. Health Place. 2009 Mar;15(1):18-24.
{free online}
http://images.huffingtonpost.com/2009-01-29-Palmer2008.pdf
46. Paraoxonase gene
variants are associated with autism in North America, but not in Italy:
possible regional specificity in gene-environment
interactions
D'Amelio M et al.
Mol Psychiatry. 2005 Nov;10(11):1006-16.
47.Autism spectrum disorders in relation
to distribution of hazardous air pollutants in the san francisco bay
area
Windham GC, Zhang L, Gunier R, Croen LA, Grether JK.
Environ Health Perspect. 2006 Sep;114(9):1438-44.
{free online}
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1570060&blobtype=pdf
OBJECTIVE: To explore possible associations between autism spectrum
disorders (ASD) and environmental exposures, we linked the California
autism surveillance system to estimated hazardous air pollutant (HAP)
concentrations compiled by the U.S. Environmental Protection Agency.
METHODS: Subjects included 284 children with ASD and 657 controls, born
in 1994 in the San Francisco Bay area. We assigned exposure level by
census tract of birth residence for 19 chemicals we identified as
potential neurotoxicants, developmental toxicants, and/or endocrine
disruptors from the 1996 HAPs database. Because concentrations of many
of these were highly correlated, we combined the chemicals into
mechanistic and structural groups, calculating summary index scores. We
calculated ASD risk in the upper quartiles of these group scores or
individual chemical concentrations compared with below the median,
adjusting for demographic factors. RESULTS: The adjusted odds ratios
(AORs) were elevated by 50% in the top quartile of chlorinated solvents
and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not
for aromatic solvents. Adjusting for these three groups simultaneously
led to decreased risks for the solvents and increased risk for metals
(AORs for metals: fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third
quartile = 1.95 ; 95% CI, 1.2-3.1) . The individual compounds that
contributed most to these associations included mercury, cadmium,
nickel, trichloroethylene, and vinyl chloride. CONCLUSIONS: Our results
suggest a potential association between autism and estimated metal
concentrations, and possibly solvents, in ambient air around the birth
residence, requiring confirmation and more refined exposure assessment
in future studies.
48. Metabolic
biomarkers of increased oxidative stress and impaired methylation
capacity in children with autism.
James SJ et al. Am J Clin Nutr. 2004 Dec;80(6):1611-7
http://www.ajcn.org/cgi/content/full/80/6/1611
BACKGROUND: Autism is a complex neurodevelopmental disorder that
usually presents in early childhood and that is thought to be
influenced by genetic and environmental factors. Although abnormal
metabolism of methionine and homocysteine has been associated with
other neurologic diseases, these pathways have not been evaluated in
persons with autism. OBJECTIVE: The purpose of this study was to
evaluate plasma concentrations of metabolites in the methionine
transmethylation and transsulfuration pathways in children diagnosed
with autism. DESIGN: Plasma concentrations of methionine,
S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine,
homocysteine, cystathionine, cysteine, and oxidized and reduced
glutathione were measured in 20 children with autism and in 33 control
children. On the basis of the abnormal metabolic profile, a targeted
nutritional intervention trial with folinic acid, betaine, and
methylcobalamin was initiated in a subset of the autistic children.
RESULTS: Relative to the control children, the children with autism
had significantly lower baseline plasma concentrations of methionine,
SAM, homocysteine, cystathionine, cysteine, and total glutathione and
significantly higher concentrations of SAH, adenosine, and oxidized
glutathione. This metabolic profile is consistent with impaired
capacity for methylation (significantly lower ratio of SAM to SAH) and
increased oxidative stress (significantly lower redox ratio of
reduced glutathione to oxidized glutathione) in children with autism.
The intervention trial was effective in normalizing the metabolic
imbalance in the autistic children. CONCLUSIONS: An increased
vulnerability to oxidative stress and a decreased capacity for
methylation may contribute to the development and clinical
manifestation of autism.
49. Metabolic
endophenotype and related genotypes are associated with oxidative
stress in children with autism.
James SJ et al.
Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141B(8):947-56.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610366/pdf/nihms68264.pdf
Autism is a behaviorally defined neurodevelopmental disorder usually
diagnosed in early childhood that is characterized by impairment in
reciprocal communication and speech, repetitive behaviors, and social
withdrawal. Although both genetic and environmental factors are thought
to be involved, none have been reproducibly identified. The metabolic
phenotype of an individual reflects the influence of endogenous and
exogenous factors on genotype. As such, it provides a window through
which the interactive impact of genes and environment may be viewed and
relevant susceptibility factors identified. Although abnormal
methionine metabolism has been associated with other neurologic
disorders, these pathways and related polymorphisms have not been
evaluated in autistic children. Plasma levels of metabolites in
methionine transmethylation and transsulfuration pathways were measured
in 80 autistic and 73 control children. In addition, common polymorphic
variants known to modulate these metabolic pathways were evaluated in
360 autistic children and 205 controls. The metabolic results indicated
that plasma methionine and the ratio of S-adenosylmethionine (SAM) to
S-adenosylhomocysteine (SAH), an indicator of methylation capacity,
were significantly decreased in the autistic children relative to
age-matched controls. In addition, plasma levels of cysteine,
glutathione, and the ratio of reduced to oxidized glutathione, an
indication of antioxidant capacity and redox homeostasis, were
significantly decreased. Differences in allele frequency and/or
significant gene-gene interactions were found for relevant genes
encoding the reduced folate carrier (RFC 80G > A), transcobalamin II
(TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A),
methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A >
C), and glutathione-S-transferase (GST M1). We propose that an
increased vulnerability to oxidative stress (endogenous or
environmental) may contribute to the development and clinical
manifestations of autism.
50. Efficacy of
methylcobalamin and folinic acid treatment on glutathione redox status
in children with autism
James SJ et al.
Am J Clin Nutr. 2009 Jan;89(1):425-30. Epub 2008 Dec 3.
http://www.ajcn.org/cgi/content/full/89/1/425
BACKGROUND: Metabolic abnormalities and targeted treatment trials have
been reported for several neurobehavioral disorders but are relatively
understudied in autism. OBJECTIVE: The objective of this study was to
determine whether or not treatment with the metabolic precursors,
methylcobalamin and folinic acid, would improve plasma concentrations
of transmethylation/transsulfuration metabolites and glutathione redox
status in autistic children. DESIGN: In an open-label trial, 40
autistic children were treated with 75 microg/kg methylcobalamin (2
times/wk) and 400 microg folinic acid (2 times/d) for 3 mo. Metabolites
in the transmethylation/transsulfuration pathway were measured before
and after treatment and compared with values measured in age-matched
control children. RESULTS: The results indicated that pretreatment
metabolite concentrations in autistic children were significantly
different from values in the control children. The 3-mo intervention
resulted in significant increases in cysteine, cysteinylglycine, and
glutathione concentrations (P < 0.001). The oxidized disulfide form
of glutathione was decreased and the glutathione redox ratio increased
after treatment (P < 0.008). Although mean metabolite concentrations
were improved significantly after intervention, they remained below
those in unaffected control children. CONCLUSION: The significant
improvements observed in transmethylation metabolites and glutathione
redox status after treatment suggest that targeted nutritional
intervention with methylcobalamin and folinic acid may be of clinical
benefit in some children who have autism. This trial was registered at
(clinicaltrials.gov) as NCT00692315.
51. The severity of
autism is associated with toxic metal body burden and red blood cell
glutathione levels
Adams JB et al.
J Toxicol. 2009;2009:532640. Epub 2009 Aug 26.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809421/pdf/JT2009-532640.pdf
52. Safety and
efficacy of oral DMSA therapy for children with autism spectrum
disorders: part A--medical results
Adams JB et al.
BMC Clin Pharmacol. 2009 Oct 23;9:16.
http://www.biomedcentral.com/1472-6904/9/16
53. Safety and
efficacy of oral DMSA therapy for children with autism spectrum
disorders: part B - behavioral results
Adams JB et al.
BMC Clin Pharmacol. 2009 Oct 23;9:17.
http://www.biomedcentral.com/1472-6904/9/17
54. Porphyrinuria in
childhood autistic disorder: implications for environmental
toxicity
Nataf R, Skorupka C, Amet L, Lam A, Springbett A, Lathe R.
Toxicol Appl Pharmacol. 2006 Jul 15;214(2):99-108.
55. An investigation
of porphyrinuria in Australian children with
autism
Austin DW, Shandley K.
J Toxicol Environ Health A. 2008;71(20):1349-51.
56. Evidence of
Mitochondrial Dysfunction in Autism and Implications for
Treatment
Daniel A. Rossignol, J. Jeffrey Bradstreet
American Journal of Biochemistry and Biotechnology 4 (2): 208-217,
2008
{free online}
http://www.scipub.org/fulltext/ajbb/ajbb42208-217.pdf
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