| [The introductory message,
related questions and answers and study abstract
is provided by David Pisani and Ellen Powell EPowell@modimes.org
of the March of Dimes. This study was funded in
part by the M.I.N.D. Institute. Thanks again to
Today some exciting research findings on autism
and mental retardation are being released by the
California Birth Defects Monitoring Program (CBDMP)
and the National Institutes of Health. Because of
your interest in this issue, we want to share them
with you right away.
A successful pilot study conducted by Department
of Health Services/ California Birth Defects Monitoring
Program (CBDMP) and the National Institutes of
Health (NIH), with collaborators at the Department
of Developmental Services and The M.I.N.D. Institute,
provides an important clue for researchers looking
for causes of and cures for these conditions.
The abstract of this study is provided below.
In brief, the study looked for biomarkers at birth
in children with autism, mental retardation or
cerebral palsy by analyzing newborn blood samples.
The results are compelling: strikingly higher
levels of four substances crucial in nervous system
development in 95% of children with autism and
mental retardation. Children with cerebral palsy
had different biomarkers indicating prenatal exposure
to common and treatable medical conditions may
underlie many cases.
If the findings hold, there are dramatic implications.
If we can identify babies at risk for these conditions
at birth, we may be able to jump start intervention.
Equally important, the possibility of biomarkers
at birth gives scientists a new and highly promising
research direction in the search for causes.
The next step in this research is to obtain funding
so that CBDMP can confirm and expand upon these
findings with a larger group. As this pilot project
demonstrates, the Program is uniquely qualified
to lead this effort. CBDMP has proven competency
in data collection and state-of-the-art research.
DHS archives newborn blood specimens and has an
established relationship with the only laboratory
in the country currently capable of performing
this procedure. DDS Regional Centers are single
points of entry into services-- 85-90% of affected
children can be found and diagnostic information
obtained. The CBDMP's demonstrated research capability,
ability to find cases, and access to newborn blood
specimens is unique in the nation.
The March of Dimes supports additional State
funding for the California Birth Defects Monitoring
Program to investigate causes of autism, cerebral
palsy and mental retardation. Investing in this
* may uncover the causes of these serious disabilities
and contribute to improved interventions;
* will contribute to answering critical public
health questions; and
* positions the State to receive millions in Federal
David Pisani and Ellen Powell EPowell@modimes.org
March of Dimes
"Neuropeptides and neurotrophins in neonatal
blood of children with autism, mental retardation,
or cerebral palsy"
Key Findings and Implications
In the first study to find biomarkers for children
with autism and mental retardation at birth, we
Strikingly higher levels of four substances crucial
in nervous system development in children with
The same high levels in children with mental retardation,
suggesting a similar biologic process;
Elevated levels of the four substances in 95%
of children with autism and/or mental retardation;
Children with cerebral palsy had biomarkers similar
to healthy children.
This successful pilot study provides new hope
for parents and an important clue for researchers
looking for causes of and cures for these disabilities.
The implications are phenomenal:
If we can identify babies at risk for these conditions
at birth, we may be able to jump start intervention.
It is important to confirm these results. However,
this is a very promising new lead that may help
solve the puzzle more quickly.
Autism and mental retardation are among the most
serious and common lifelong disabilities, and
some reports suggest autism is on the rise.
Questions and Answers
What did the study find?
A: The study found that children with autism or
mental retardation, when compared to children
without these conditions, had higher levels in
the blood at the time of birth of four specific
proteins that are crucial to nervous system development.
How was the study conducted?
A: We conducted laboratory tests on blood samples
from newborn children who were later diagnosed
with autism, mental retardation or cerebral palsy
and children who were free of these conditions.
In each group there were approximately 60 children.
All of the children were born between 1983 - 1985
to mothers living in one of four San Francisco
Bay area counties. Those years and counties were
chosen for study because of existing data from
that period and for that location on children
with cerebral palsy and "control" children.
Building on existing data enabled researchers
to conduct this research more quickly.
Where did the data come from?
A: The diagnostic data on children with autism
or mental retardation was provided by the California
Department of Developmental Services (DDS) and
the Regional Centers. Blood samples were obtained
through the Newborn Screening Program of the DHS
Genetic Disease Branch. The study was approved
by the California Committee for Protection of
Human Subjects, which has responsibility for assuring
the confidentiality of all data.
Aren't these data confidential?
A: Yes. Confidentiality of these data was maintained
throughout the study. We have extensive procedures
in place to protect the privacy of every child
in our studies.
Why was autism the focus of the study?
A: Recent reports suggest that not only is autism
common among children, but the condition may be
increasing. Typically, autism, mental retardation
and cerebral palsy cannot be reliably diagnosed
until a few years after birth. If these conditions
can be identified earlier, intervention that may
help children with these conditions can begin
What is autism?
A: Autism is a severe disorder of communication
and social interaction resulting in lifelong disability.
Who conducted the study?
A: The study was conducted by the California Birth
Defects Monitoring Program (CBDMP) of the California
Department of Health Services, and the National
Institutes of Health (NIH), in collaboration with
the California Department of Developmental Services.
Funding was provided by CBDMP and NIH, with partial
support from The M.I.N.D. (Medical Investigation
of Neurodevelopmental Disorders) Institute at
the University of California, Davis.
Do the study findings mean we now have a way to
positively identify children with autism or mental
retardation at birth?
A: No. However, based on this exciting new finding,
we can target our research with the hope of developing
a screening tool in the future. First, our findings
must be confirmed.
Why were these proteins selected for measurement?
A: We selected proteins that are known to have
a role in regulating growth and development of
the brain during gestation and proteins that are
known to contribute to long term memory, learning
and responses to sensory stimuli. These aspects
of behavior are particularly important in autism.
We found two neuropeptides and two neurotrophins,
whose levels were dramatically higher in children
with autism or mental retardation than in the
"control" children or children with
Given that the diagnosis of autism is sometimes
difficult, how can you be sure that the children
in your study were correctly diagnosed? Are there
similar concerns for cerebral palsy and mental
A: We are very confident. We know that the diagnosis
of each of these conditions is quite complicated
so we went to great lengths to confirm the diagnoses
on all children in the study.
Do these findings confirm that autism and mental
retardation are conditions that develop during
gestation and are not due to environmental factors
A: Our findings showed abnormal levels of certain
proteins present at birth in children with autism
or mental retardation. These findings suggest
a potential biological indicator at birth, but
they do not address the more complex question
of WHEN these conditions occur. We know that the
brain develops from gestation through early childhood.
Is there any evidence that might suggest a link
between autism and infant immunizations?
A: Although there has been much speculation about
such a link, this study could not address that
Do these findings suggest that genes may play
a role in causing autism or mental retardation?
A: There is considerable evidence already to indicate
that there is a genetic component to autism and
mental retardation. This research provides some
clues for identifying which genes may be important
in the development of these conditions.
Could these findings lead to prevention strategies
that might be implemented after birth?
A: First, these findings must be replicated in
further studies. If our findings are correct,
we'll be able to identify children at risk for
these conditions much earlier than currently,
and practitioners can try various interventions
to see what works.
Parents of children with autism have suspected
that diet may play a role in their child's condition.
Does this study provide any information on that
A: No. Issues involving diet were not part of
Do the results suggest a similarity between autism
and mental retardation that we have not recognized
A: Yes. For the proteins we studied, children
with autism and children with mental retardation
without autism had the same result. As other proteins
are studied, differences may become apparent.
Will these findings lead to a screening mechanism
for all babies at birth?
A: It is much too early to know. First, we must
be sure that these findings are true. Then scientists
must develop the technology to screen large numbers
of babies-if screening is appropriate. Finally,
policymakers must determine whether widespread
screening or some other mechanism would be beneficial.
Could the results also suggest that these proteins
could be measured even before birth by drawing
a sample of the unborn baby's blood?
A: Again, it's much too early to know. Our results
are based on one point in time-the newborn period.
We do not know how levels of these proteins are
different at different points in time. Future
research must address this question.
How confident are you of your results?
A: As is true for all research, the scientific
process depends on getting the same results several
times. With this new and startling finding, we
are anxious to continue this work. We have enough
confidence in this study to launch a bigger study,
once funds become available.
How do you explain why levels of these proteins
in the blood of children with cerebral palsy were
different from the levels found in children with
autism or mental retardation?
A: This result is consistent with current knowledge
that cerebral palsy represents a different kind
of problem in the brain than autism or mental
retardation. We suspect that cerebral palsy has
different origins than autism or mental retardation.
This study supports that hypothesis.
Does this study suggest that if we could lower
these high levels of proteins in children with
autism or mental retardation that their condition
A: No. The study does not answer that question.
We don't know whether the high levels of these
proteins could cause autism and mental retardation,
or whether the high levels are a sign of something
else going wrong.
What is the next step?
A: First, in accordance with standard scientific
protocol, we want to confirm these results by
looking at blood samples from more children. Then
we want to develop a database of children with
these conditions so that we can look at other
ways in which they are alike and different in
order to find additional clues about causes. We
also want to expand our communications efforts
so that we can keep the public informed about
this research as we go forward. Additional funding
will be necessary to accomplish these goals.
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This abstract was presented at the annual meeting
of the American Academy of Neurology, San Diego,
May 3, 2000. The manuscript detailing these findings
will be published in late summer.
NEUROPEPTIDES AND NEUROTROPHINS IN NEONATAL BLOOD
OF CHILDREN WITH AUTISM, MENTAL RETARDATION, OR
Karin B. Nelson, M.D., J.K. Grether, Ph.D., James
M. Dambrosia, Ph.D., Lisa A. Croen, Ph.D., Ben
F. Dickens, Ph.D., Robin L. Hansen, M.D., Terry
M. Phillips, Ph.D.
Category: Autism, Mental Retardation, and Cerebral
Objective: To investigate whether concentrations
of certain neuropeptides and neurotrophins in
neonatal blood of children with autism, mental
retardation (MR), or cerebral palsy (CP) differed
from those in control children.
Background: The etiology of these developmental
disabilities is incompletely understood and there
is no known biomarker for these disorders.
Methods: Case status was identified from records
of California state service agencies. Immunoassays
were performed masked to outcome by recycling
immunoaffinity chromatography on archived neonatal
blood drawn for routine metabolic screening, measuring
vasoactive intestinal peptide (VIP), calcitonin-related
gene peptide (CGRP), brain derived neurotrophic
factor (BDNF), neurotrophin 4 (NT4), substance
P (SP), and antibodies to myelin basic protein
(MBP), glial fibrillary acidic protein (GFAP)
and neuron-axon filament protein (NAFP). Concentrations
of analytes that best distinguished autism and
MR from controls were chosen by recursive partitioning
Results: Concentrations of SP and antibodies
to MBP were not different in the 4 outcome groups.
Antibodies to GFAP and NAFP were significantly
lower in children with autism and children with
MR compared to control children, but there was
considerable overlap in the distributions. Mean
concentrations of VIP, CGR, BDNF, or NT4 were
not different in children with autism who did
or did not also have MR, nor among children with
CP who were or were not also mentally retarded.
Children with concentrations of 2 or more analytes
exceeding these values:
VIP >31.5 pg/ml, CGRP >32.8, BDNF >24.9,
or NT4 >48.8
N (n) %
Autism 64 (62) 96.9 %
MR only 66 (61) 92.4 %
CP 65 (6) 9.2 %
Controls 54 (0) 0 %
Conclusions: Most children with autism or MR had
concentrations of 2 or more of the measured neuropeptides
or neurotrophins in peripheral blood in the earliest
days of life that exceeded the levels indicated,
while few children with CP and no control child
did. These substances did not distinguish children
with autism from those with MR.
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More on the Blood Protein Study
[This from Susan Owens email@example.com on some
erroneous conclusions some are making from the
recently reported blood protein study. The study
appears to suggest that autism is a pre-natal
Please don't be alarmed that the study results
announced today may point to a condition that
was present at birth. A child's in utero immune
history may predispose him to later have an inappropriate
response to vaccine: there may have been immunological
things happening in mother that could have had
an impact on her child's readiness for the world
of germs and vaccines.
The study funded by the MIND Institute was reported
to say that two autoantibodies were sought in
the blood spots, and they did NOT find elevations
of those two autoantibodies in children who later
developed autism. Quite the opposite: despite
elevations of these autoantibodies being quite
common in older children with autism, these babies
at birth had levels that were lower than those
found in controls. I wish we knew if the total
IgG antibodies from the blood spots were lower
than usual, but maybe these scientists can look
at that as they proceed.
As Teresa pointed out to us earlier, immediately
after birth, a baby has either been free of infection
in utero, or else has picked up an infection that
crossed the placenta, or else became infected
in the birth process. Immunoglobulins are a late-stage
response to infection, and they take too long
to be produced for there to be a chance that immunoglobulins
found in a blood spot at birth would reflect a
post-utero exposure to germ.
For that reason, the antibodies that are found
in a baby at birth will be made up of either maternal
IgG that crossed the placenta, or it will represent
an infection that occurred in utero, or it will
represent an anti-idiotypic antibody response
to mother's IgG.
Anti-idiotypic antibodies are antibodies that
form against other antibodies. Through anti-idiotypic
processes, some fetal antibodies will form against
the variable region of IgG antibodies that come
into the fetal circulation from mother, and the
shape of the fetus's new antibody's variable regions
can be identical to the shape of the original
antigen. By forming a cascade of these anti-idiotypes,
the immune system will eventually down-regulate
an immune response after an infection has abated,
and in a fetus, this process gives him a safe
environment to try out his immunological wings.
This process is very normal.
So, in utero, the baby can form antibodies against
the anti-idiotypes that he has just formed, and
some of them will look like the antibodies formed
from an original response to infection, but will
be far lower in quantity than in a real infection.
In this way the immune system is primed before
birth to the antigens to which the mother has
been exposed. It is really amazingly clever.
So what is of particular interest in the study
results today is that those with autism may have
had a lower exposure to maternal IgG than controls.
Why would that happen? It ends up that what is
happening in mother's immune system will determine
how well her antibodies cross the placenta, and
if her beta-2-microglobulin is elevated, as you
would expect in a mother who had some sort of
autoimmune disease, then her antibodies would
have difficulty crossing the placenta. This sounds
like nature is being wise, actually, for why would
you want to start development with your mother's
immunoglobulins attacking your own cells?
I'm sending two relevant studies separately.
If you've forgotten the theory I presented last
summer about beta-2-microglobulin, please feel
free to check the archives.
Years ago when I was pregnant with Grace and
knew my own autoimmune history, I was very concerned
that my ob/gyn did not have tools to understand
how he could protect my child from any repercussions
from my immune history. There was very little
science to base a strategy upon and we made some
mistakes, I think. I have Grace's present immune
problems to remind me that until the proper research
is done to identify these relationships and popularize
the notion that they require careful medical management,
we may expect these problems will continue to
increase and to effect even more families.
The words of the FDA today showing a new heart
regarding vaccine policy should give us hope that
attitudes really are changing. Perhaps we who
wait for necessary funds for research will soon
be able to roll up our sleeves and get to work.