is the answer from Children’s Medical Center in response to the TV program
May 2002 slamming Vaccines. It
seems we have these shows every Sweeps week during ratings. There is no mercury in Enfanrix DtaP, Prevnar, IPV (Polio),
MMR, HIB, Varicella (Chickenpox). There
is miniscule amount in the Tripedia DtaP <.0002% .
There is a small amount in the influenza vaccine.
media reports indicate dozens of lawsuits have been filed across the country
charging that vaccine mercury poisoning leads to neurodevelopmental
disorders in children, including autism. Additionally, recent publications
have raised the question concerning a relationship between MMR and autism.
8 investigative report beginning tonight (Monday, May 20) will examine this
issue, as well.
The following information indicates that autism is
not linked to these vaccines:
Three groups of studies support the fact that autism results from an event
or exposure that occurs during development of the central nervous system
early in utero: genetic studies of monozygotic and dizygotic twins,
in‑utero events and timing of onset of autism. Home video studies
demonstrate abnormalities of movement and behavior in children later
diagnosed with autism as early as 2‑3 months of age and 12 months of
age before exposure to MMR vaccine.
Studies of MMR
vaccine and autism ‑ The Immunization Safety Review Committee of the Institute of
Medicine reviewed all published and unpublished data and released a report
in April 2001 (www.nap.edu/catalo,g/10101.html). The committee
concluded that "a consistent body of epidemiological evidence shows no
association at the population level between MMR vaccine and autistic
spectrum disorders." A causal relationship and biological plausibility
were rejected since there have been no proven biological mechanisms that
would explain a casual relationship.
Large epidemiological studies have been performed in
the United Kingdom, Sweden and California; all failed to demonstrate any
association between MMR vaccine and autism.
Published data does not support the Wakefield
hypothesis that MMR vaccine causes intestinal inflammation, loss of
intestinal barrier function, entrance into the bloodstream of
encephalopathic proteins and consequent development of autism.
The Institute of Medicine, the American Academy of
Pediatrics (AA‑P) and the ACIP support the continued use of MMR
vaccine according to current recommendations. Recent decreases in the use of
the MMR vaccine in the United Kingdom and Germany have been associated with
measles outbreaks similar to those in the United States in 1989‑9 1.
Summarized information by Paul Offit, M.D., for the
AAP is available at www.cispimmunize.or0fam/mmr/a main.html. A set of
Frequently Asked Questions (FAQ) also is available for parents at www.cisl)immunize.ors~/fani/mnir/a
thimerosal‑containing vaccines and neurodevelopmental disorders ‑
Thimerosal contains ethyl mercury and has been used as a preservative in
multi‑dose vials since the 1930s to prevent bacterial contamination.
In response to the concern that the cumulative intake of mercury from
vaccines administered in the first six months of life could exceed the
guidelines for methyl mercury intake set by the EPA, (but still within the
safe limit according to the guidelines set by the FDA, ATSDR and the World
Health Organization) (MMWR 1999; 48:563), a thimerosal‑free hepatitis
B vaccine was licensed in August 1999. As of March 2001, all routinely recommended licensed pediatric vaccines
manufactured for the United States are thimerosal‑free.
The Immunization Safety Review Committee of the
Institute of Medicine reviewed all available data and published a report in
October 2001 (www.flap.edu/cataloiz/10208.htm]). The committee
concluded "the evidence is inadequate to accept or reject a causal
relationship between thimerosal exposures from childhood vaccines and the
neurodevelopmental disorders of autism, ADHD and speech or language
delay." Thimerosal‑free vaccines are recommended for routine
immunizations, but if the only choice is a thimerosal‑containing
vaccine, the committee recommends using it rather than not immunizing.
Specific evidence supporting the absence of a causal
No association between postnatal exposures to low doses of methyl
mercury and neurodevelop mental disorders has been found (Pediatrics 2001;
Signs and symptoms of mercury poisonings are not identical to autism,
ADHD or speech ‑language delays.
• There is only limited
toxicological information regarding ethyl Mercury.
• There are only two
epidemiological analyses of the association of neu rode velop mental
disorders with thimerosal‑containing
vaccines ‑ both are unpublished. When reviewed by the
IOM, no significant
associations were found in either study. One study, the CDC Vaccine
Safety Datalink (VSD)
project, included >130,000 children with 169 cases of autism.
results from ongoing studies of mercury metabolism at the NIAID of NIH
indicate the half‑life of ethyl mercury in infants who received
thimerosal‑containing vaccines is only 68 days and eliminated in
stool, compared with a half‑life of 45 days for methyl mercury. The
only vaccine in the United Kingdom containing thimerosal is DTP; however,
the autism case rate increased rapidly during the 1980s with no change in
thimerosal exposure, since all added vaccines were thimerosal free.
It is important
to assure parents that the current U.S. supply of routinely recommended
vaccines is thimerosal‑free and the AAP does not recommend testing
children who have received thimerosal‑containing vaccines for mercury.
The Influenza vaccine contains thimerosal, but this
vaccine is not used prior to 6 months of age and there is no longer any
cumulative effect from other vaccines.
If the U.S. Court of Federal Claims rules that
thimerosal is one of the components that comprise vaccines rather than a
contaminant, then allegations that thimerosal in the vaccine caused injury
or death must be filed with the Vaccine Injury Compensation Program (VICP)
before any civil litigation can be pursued for a VICP‑covered vaccine.
Helpful, frequently asked questions can be found at
For more information, contact Jane Siegel, M.D., at
214‑648‑3561 or e‑mail Jane.Siegel@UTSouthwestem.edu.
(ISSN 0031 4005). Copyright @ 2003 by the American Academy of Pediatrics.
has been expressed over the possibility that the mercury containing compound
thimerosal in vaccines may cause autism. Thimerosal is sodium ethylmercury
thiosalicylate, an organic compound of ethyl mercury, included in certain
vaccines to protect multiple dose ampules from bacterial and fungal
contamination. Mercury in sufficient dose is neurotoxic, and probably more
toxic in the immature brain. It is reasonable to ask whether thimerosal in
childhood vaccine increases risk of chronic childhood neurologic disability
and specifically of autism. The available data with which to address the
question are very limited and largely inferential. Most of the information
we have about mercury toxicity is related to exposure to methyl rather than
Bernard et al offered an hypothesis that autism is an expression of
mercury toxicity resulting from thimerosal in vaccines. They base this
hypothesis on their views that the clinical signs of mercury toxicity are
similar to the manifestations of autism, that the onset of autism is
temporally associated with immunization in some children, that the recent
increase in diagnosis of autism parallels exposure to thimerosal, and that
there are higher levels of mercury in persons with than without autism.
This review will examine these issues and others to ask whether, according
to evidence now available, thimerosal is a probable cause of autism. We will
not discuss which, if any, of the differing guidelines designed to limit
exposure to mercurials is appropriate for deciding whether thimerosal in
vaccines is in all regards safe for children. Our focus is on a narrower but
important question: whether current evidence indicates that mercury at any
known dose, form, duration, age, or route of exposure leads to autism.
ARE THE CLINICAL MANIFESTATIONS OF AUTISM SIMILAR TO THOSE OF RECOGNIZED MERCURY TOXICITY?
Bernard et all present a table listing 95 clinical findings they consider
to be shared by autism and mercury poisoning. Their table does not
distinguish typical and characteristic manifestations of either disorder
from the rare, unusual, and highly atypical.
In mercury poisoning, the characteristic motor findings are ataxia and
dysarthria (Table 1). These signs, along with tremor, muscle pains, and
weakness, are noted on relatively high‑dose exposure, acute or
chronic. In 3 Romanian children accidentally exposed to ethyl mercury in a
fungicide, these same symptoms were prominent. The outcome of fetal methyl
mercury poisoning in severe form also included spasticity. In contrast, in
autism, the only common motor manifestations are repetitive behaviors (stereotypies)
such as flapping, circling, or rocking. Persons with Asperger syndrome may
be clumsy, and hypotonia has been noted in some infants with autism; the
frequency of clumsiness and hypotonia in autism spectrum disorders is not
established. No other motor findings are common in autism, and indeed the
presence of ataxia or dysarthria in a child whose behavior has autistic
features should lead to careful medical evaluation for an alternative or
The most characteristic sensory finding of mercury poisoning is a highly
specific bilateral constriction of visual fields. With lesser exposure there
may be compromise of contrast sensitivity. In addition, there may be
paresthesias or, in infants, erythema and pain in hands and feet because of
peripheral neuropathy. In autism, decreased responsiveness to pain is
sometimes observed along with hypersensitivity to other sensory stimuli,
including hyperacusis. The "sensory defensiveness" of autism seems
to reflect altered sensory processing within the brain rather than
peripheral nerve involvement. 12‑14
1.Characteristic Findings in Autism and in Mercury Poisoning
aloof, insistence on sameness
psychosis; in mild cases, nonspecific depression, anxiety
Other signs that may appear in children with chronic mercury toxicity,
such as hypertension, skin eruption, and thrombocytopenia, 17 are seldom
seen in autism.
In relatively mild mercurism in persons without characteristic motor or
sensory changes, psychiatric symptomatology may be absent, and if present is
nonspecific, with findings such as depression, anxiety, and irritability.
There may be impairment of recent memory. Even for individuals with known
elevated postmortem levels of mercury in brain, it may be impossible to
conclude whether the nonspecific psychiatric findings they demonstrated in
life were the result of mercury toxicity.
When severe mercury poisoning occurs in prenatal life or early infancy,
head size tends to be small and microcephaly is common. Prenatal exposure to
other neurotoxins‑lead, alcohol, and polychlorinated biphenyls, for
example also predispose to decreased head size. In contrast, in autism
increasing evidence indicates that head size and, as measured by volumetric
magnetic resonance imaging, brain size tends to be larger than population
At sufficient dose mercury is indeed a neurotoxin, but the typical
clinical signs of mercurism are not similar to the typical clinical signs of
ONSET OF AUTISM SYMPTOMS AFTER
Evaluation of causation cannot depend on temporal association as reflected
by anecdotal observations of selected instances in which a relatively
uncommon outcome such as autism is noted after a common childhood exposure
such as immunization. Only rigorous methods that attempt to include all
instances of both exposure and outcome can provide evidence of association,
and association is necessary but not sufficient to establish causation.
Age of onset of symptoms can be highly misleading as an indicator that
some environmental event has caused or precipitated a disorder. Even single
gene disorders may have a period of apparently normal development (1.5 years
in Rett syndrome, 45 years in Huntington's chorea) before symptoms begin.
The onset of clinically recognizable signs and symptoms in Rett and
Huntington syndromes does not require an environmental "second
hit." In Rett syndrome, the mutation causes previously apparently
normal children to lose acquired developmental milestones after I years old
to 2 years old, with a phase during which they may present behaviors
consistent with autism. This disorder can also have its clinically apparent
onset soon after the completion of immunizations, but Rett syndrome is known
to be determined by a single genetic mutation that produces failure in the
normal program of brain development. If we did not understand its genetic
basis, we might suspect that Rett syndrome was attributable to environmental
factors including immunization. The situation for autism is still unknown,
but the onset of signs in the second year of life does not prove (nor
disprove) a role for environmental factors in etiology.
INCREASE IN DIAGNOSIS OF AUTISM IN
PARALLEL WITH INTRODUCTION OF MERCURYCONTAINING VACCINES
There has clearly been a broadening of the criteria for autism, better
case‑finding, increased awareness by clinicians and by families, and
an increase in referrals of children for services as it has become
recognized that early treatment improves life for the child and family.
Whether the sum of these is sufficient to account for the more frequent
diagnosis of autism is a matter of contention and is properly settled by
If, for the sake of discussion, we assume there was a true increase in the
occurrence of autism in the 1990s, is exposure to thimerosal the only or the
best hypothesis to explain the increase? There have been many changes in
life in industrialized countries during the last decades, including changes
in many environmental exposures and aspects of medical care that could be
considered for their biological plausibility as contributors to autism
occurrence or severity.
MERCURY LEVELS IN AUTISTIC PERSONS
Bernard et al state that "elevated mercury has been detected in
biological samples of autistic patients," but unfortunately do not
provide references. Aschner and Walker found no paper published in the peer
reviewed literature that reported an abnormal body burden of mercury, or an
excess of mercury in hair, urine, or blood. The one paper that sought a
relationship between autism and mercury levels in hair did not observe such
an association. We did not find evidence that chelation therapy has led to
improvement in children with autism.
A substantial literature describes the neurotoxicity of methyl mercury but
relatively little is known about the impact of ethyl mercury on the nervous
system, especially with repeated low dose exposure.
passage of methyl mercury across the bloodbrain barrier is facilitated by an
active transport mechanism, whereas the passage of ethyl mercury into the
brain does not have such a transport system and is further hindered by its
larger molecular size and faster decomposition. At equivalent doses, higher
levels of mercury have been found in the blood and less in brain following
administration of ethyl mercury than methyl mercury. These findings support
the observation that the risk of toxicity from ethyl mercury is overestimated
by comparison with the risk of intoxication from methyl mercury. Ethyl mercury
exposure has been reported to be more likely than methyl mercury to produce
lesions of the spinal cord, skeletal muscle, and myocardium.
The effects of mercurial compounds are influenced by dose and duration of
exposure and by maturational stage.
Studies in experimental animals exposed postnatally to ethyl mercury
indicate patchy damage in the cerebellar granule cell layer, while methyl
mercury produced a diffuse abnormality. Methyl mercury exposure has been
reported to disrupt neuronal migration primarily in the motor cortex and in
the cerebellar granule cell layer. In humans with massive exposure to
mercurials resulting in death, brains showed severe atrophy and gliosis of
calcarine cortex, as well as diffuse neuronal loss and gliosis of the
auditory, motor and sensory cortices, and extensive cerebellar atrophy.
The most extensive pathologic studies of the brain in mercury poisoning
followed methyl mercury exposure resulting from contaminated seafood in Japan
and from contaminated bread in Iraq. Microscopic findings in these brains
included decreased numbers of neurons and increased numbers of glial cells and
macrophages throughout the cortex, as well as loss of granule cells and
irregularity of the Purkinje cell layer in the cerebellum. In 2 Iraqi infants
exposed prenatally to methyl mercury there was a simplified gyral pattern,
short frontal lobe, and reduction in white matter volume, along with
derangement and lack of definition of the cortical layers and heterotopic
neurons in cerebrum and cerebellum.
Thus, in both prenatally and postnatally exposed brain, methyl mercury
resulted in neuronal cell loss and increased gliosis in the cerebral cortex,
in some adults marked atrophy of the calcarine cortex, and atrophy of the
cerebellum with consistent loss of granule cells and relative sparing of
Purkinje cells. The weight or volume of the mercury‑exposed brains has
not been presented, but the atrophy associated with neuronal loss and in the
infant cases the reduced white matter volume suggest that these brains were
likely to be reduced in size.
In ethyl mercury toxicity in children, nerve cell loss was widely present
but most marked in calcarine cortex, and there was diffuse proliferation of
glia, demyelination of ninth and tenth cranial nerve roots, and atrophy of the
cerebellar granule cell layer with relative sparing of Purkinje cells.
In contrast, examined at autopsy, brains of autistic persons are commonly
enlarged both by weight and volume. Larger head circumference and enlargement
seen on volumetric magnetic resonance imaging studies in autism have been
noted above. There have been no reports of significant cerebral cortical
neuronal loss or calcarine atrophy in autism. The most frequently reported
findings in the autistic forebrain have been unusually small, closely packed
neurons and increased cell packing density in portions of the limbic system,
consistent with curtailment of development of this circuitry.
Age related abnormalities have been observed in the deep cerebellar nuclei
and inferior olivary nucleus of the brainstern in autism. The most consistent
finding in the neuropathology of autism is reduction in Purkinje cells in the
cerebellum, primarily in the posterior inferior hemispheres. Involvement of
granule cells has rarely been reported. In contrast, mercury exposed brains
have shown significant and consistent damage to the cerebellar granule cell
layer with relative preservation of Purkinje cells.
Thus, there seem to be major differences in the neuroanatomic findings in
autism as compared with those in mercury toxicity.
IN HUMAN POPULATIONS EXPOSED TO
MERCURY, DID AUTISM INCREASE?
the first half of the 20th century, mercury was a constituent of medications
administered to treat worm infestations and teething pain. Use of these
compounds was associated with illness in young children, affecting chiefly
those 8 months old to 2 years old. These infants showed photophobia, anorexia,
skin eruption, and bright pink color of hands and feet, which peeled and were
painful. This condition, called "pink disease" or acrodynia, was
relatively common, and the cause of 103 deaths in England and Wales in 1947.
45 Survivors were not described to have behavioral disorders suggestive of
In the 1950s in Minamata and in the 1960s in Niigata, Japan, there were
epidemics of methyl mercury poisoning resulting from discharge of industrial
wastes into coastal waters, with consumption of contaminated fish by humans.
Heavy prenatal exposure resulted in low birth weight, microcephaly, profound
developmental delay, cerebral palsy, deafness, blindness, and seizures.
Affected adults experienced impairments of speech, constriction of visual
fields, ataxia, sensory disturbance, and tremor.
Was autism recognized with higher frequency in Japanese children in the
period of these toxic outbreaks or soon after it, especially in those born in
the regions affected by the tragic poisonings? Japanese reports in the English
language do not indicate that Japanese clinicians thought so. Comparable in
earlier periods, the rates of autism were higher as reported in Japan in the
1980s than in studies from other countries. This difference was attributed by
Japanese authors to broader diagnostic criteria and excellent ascertainment.
Definitions and methods of ascertainment were widely different in different
studies, so comparisons are difficult. A study in Fukushima‑ken
is described here in some detail because it provides an example of the
issues faced by studies of prevalence during this period and includes an
analysis by year of birth in an area not far distant from Niigata. In this
study, conducted in 1977, the authors attempted to evaluate all children with
autism 18 years old or less who were born in the province in 1960 through
1977. They ascertained cases by sending a letter and questionnaire to 2233
institutions to find children with "autistic behavior," not further
defined. Responses were received from 72.6% of the institutions, which covered
38% to 40% of children in the province. How responding institutions differed
from those not responding is not stated. The autism prevalence estimates
reported included children in the responding institutions in the numerator,
and all children in the area in the denominator. If the nonresponding
institutions had affected children in their care, and if there were changes
over the period of the study that might influence recruitment of affected
children at competing institutions, such changes could markedly influence the
result. Based on their final diagnosis, there were more children with
"autistic mental retardation" than with "early infantile
autism," but no information is provided on the basis for this
distinction, nor on birth year patterns for the former group.
The authors of the Fukushimaken study reported higher rates of autism in
children born between 1966 and 1974 than in births 1960 through 1965 or after
1975. The authors considered that the reason for the lower rates of autism in
children born before 1966 "was probably that autistic children had become
older, lost the unique feature[s] of young autistic children and had been
overlooked." This suggests that procedures for locating older subjects
and criteria for diagnosis were not appropriate for all of the wide age span
evaluated. For children born in the last years of the study, the low rates of
autism surely entail severe undercounts as these children were 3 years old or
less at the time of ascertainment. Although this study might have tested the
question as to whether autism was more frequent near to outbreaks of mercury
poisoning, methodologic problems potentially invalidate the time trend
analysis, and the short follow‑up for the most recent birth years means
that no conclusions can be drawn regarding children born 1974 or later.
Studies that followed victims of high dose acute or chronic mercury
poisoning resulting from contaminated foods in Iraq, Pakistan, Guatemala, and
Ghana have not reported manifestations suggestive of autism in survivors. In
contrast, many of these survivors had clinical signs such as persisting ataxia
and dysarthria that are seldom seen in autism.
An unpublished retrospective study was noted by the Institute of
Medicine's Immunization Safety Review Committee. As described in a Canadian
Communicable Disease Report, this study examined 10 years of data from a large
database derived from 7 health maintenance organizations that covered
‑2.5% of the United States population. A weak but statistically
significant (relative risk ratio <2.0) association was found between
measures of cumulative exposures to thimerosal and the presence of speech
delay and attention‑deficit/hyperactivity disorder, but not autism.
There were many limitations of this analysis and its ability to identify bias
and confounding. A second unpublished screening study did not confirm the
findings of the first. Although far from definitive, these studies represent
the only direct investigation to date of a possible association of thimerosal
exposure with autism. Neither study observed such an association.
Two studies have examined neurologic and psychologic function in young
children associated with lower dose but repeated dietary exposure to methyl
mercury. In the Faeroe Islands, exposure was via consumption of marine fishes
and mammals (whales). In the Faeroes, there may have been additional toxins
including polychlorinated biphenyls and perhaps others. The Faeroe study of
428 to 900 children at 7 years old observed an association of mercury levels
in cord blood or maternal hair with impaired performance in tests of
attention, memory for visuospatial information, the Boston Naming Test, fine
motor function, and verbal learning. In contrast, in the Sechylles study of
>700 children, exposure was to marine fish only, and boys with higher
levels of hair mercury performed better on some tests, including the Boston
Naming Test and 2 tests of visual motor coordination. The authors considered
their enhanced performance might be related to beneficial effects of
constituents other than mercury in fish. Myers et al have discussed sources of
difference in the results of these studies.
The Faeroe and Seychelles studies were probably large enough to detect a
substantial but not a minor increase in autism, if it was present. Neither
study was designed to investigate an association of mercury exposure with
autism, but autism in all but its milder forms produces fairly striking
behavioral aberration in young children. Were the endpoints examined
appropriate for identification of children with autism? The Faeroe study
included little behavioral assessment. Based on experience in lead toxicity
studies, the Seychelles study used the Child Behavior Checklist overall rating
at 66 months and 96 months. Testing at 66 months included Checklist subscales
related to withdrawal, anxiety, and problems in social function, attention,
and thought. The Child Behavior Checklist is not ideally sensitive for
recognition of autism, but would probably identify the majority of affected
children. Myers et al, reviewing nearly 50 years of research on mercury
exposure and 27 years experience in human neurotoxicity of methyl mercury,
concluded, "Our research has not identified any adverse associations
between [methyl mercury] exposure from fish consumption and clinical symptoms
Thimerosal is being eliminated from the vaccines used in routine infant
immunization programs in the United States and Canada. If thimerosal was an
important cause of autism, the incidence of autism might soon begin to
decline. One can hope but not expect that that will happen time will tell.
Mercury poisoning and autism both affect the central nervous system but
the specific sites of involvement in brain and the brain cell types affected
are different in the two disorders as evidenced clinically and by
neuropathology. Mercury also injures the peripheral nervous system and other
organs that are not affected in autism. Nonspecific symptoms such as anxiety,
depression, and irrational fears may occur both in mercury poisoning and in
children with autism, but overall the clinical picture of mercurismfrom any
known form, dose, duration, or age of exposure‑does not mimic that of
autism. No case history has been encountered in which the differential
diagnosis of these 2 disorders was a problem. Most important, no evidence yet
brought forward indicates that children exposed to vaccines containing
mercurials, or mercurials via any other route of exposure, have more autism
than children with less or no such exposure.
Continuing vigilance is necessary regarding the safety of vaccines, as is
open‑minded evaluation of new evidence. However, such evidence must be
of sufficient scientific rigor to provide a responsible basis for decisions
that influence the safety of children. When information is incomplete, as it
is at present for thimerosal‑autism questions, a balancing must be made
of risks posed by vaccine constituents and the benefits of disease prevention
achieved by keeping immunizations widely available. On the basis of current
evidence, we consider it improbable that thimerosal and autism are linked.
KARIN B. NIELSON, MD &
MARGARET L. BAUMAN, MD
. Copyright @ 2003 by the American Academy of Pediatrics.