Although it is not clear what is or are the causes of
Autism, and we understand that correlation is not causation, we believe that it
is important to publish research that may be useful and have easily implemented
recommendations in treating, or even better, preventing a condition. On this line
of thought there are interesting studies linking Autism with a deficiency of
iron on the mother and/or the baby, and on the interruption of blood flow from
the mother to the newborn baby due to early umbilical cord clamping.
This will be a long article, and you can go to the
concussions if you are not in a reading mood, yet I hope you stick with me as I
develop the argument and recommendation.
The brain is approximately 2.5% of the body mass on an
average individual, yet it receives around 15% of the cardiac output and is
responsible for around 25% of the body’s total oxygen consumption (or to get
technical a little over 700 mL/min of blood flow for a 1,350 gram brain, with
the arteriovenous O2 difference relatively high to achieve higher
oxygenation vs. cardiac output).
We know how important it is the constant delivery of
oxygen to the brain to prevent tissue damage. Oxygen is not consumed equally
throughout the brain, and the grey matter consumes most of it, as much as 94%,
while the white matter consumes the rest, or as little as 6%.
How is early clamping of the umbilical cord, oxygen
deficiency in the newborn, and iron deficiency related to autism?
Since clamping timing and iron deficiencies would fall
under environmental (non-genetic) factors, first let’s establish whether there
are any statistically significant non-genetic factors that could account for
Autism, because if Autism is mostly a genetic disorder with little
environmental components, then we would be wasting our time searching in that
direction.
A good place to start would be the prevalence of autism
in identical twins vs. fraternal twins? On a 2007 report in “Stanford News”, according
to Joachim Hallmayer MD Autism was strongly genetic, and this was the generally
accepted idea…until very recently.
On a 2011 large size study of both fraternal and
identical twins conducted at Stanford by Dr. Hallmayer (who was the first
author of the paper, which appeared in the July 4 2011 issue of Archives of General Psychiatry),
the conclusions were surprising. What set this study apart is that the subjects
on the study came from a diverse population, which means that the results are
more reliable and apply more broadly than prior studies which studied small,
homogeneous groups. The conclusion of the study revealed that genetic factors
accounted for only 38% as compared to the generally accepted 90%, and this
would make a huge difference in terms of the study of the possible
environmental factors (62%), and how they interact with the genetic factors;
genetic factors that may make the subject more or less sensitive to those very
environmental factors. The study's senior author is Neil Risch, PhD, professor
of biostatistics at UC-San Francisco and director of the UCSF Institute for Human Genetics.
So, if the findings of that study are generally in the right
direction, we cannot ignore that there is a still a higher prevalence of Autism
in identical vs. fraternal twins. Actually this would be consistent with the
results of the study since according to it genetics still play a significant
role. It is important to understand that fraternal twins have different
placenta while identical twins share the same placenta, and this makes a
difference in the blood supply available for the babies, making clamping timing
even more critical for the identical twins.
Ok, so there seems to be significant but unknown environmental
(non-genetic) component(s) involved in Autism, so, let’s continue.
What does the current standard of care say about
umbilical cord clamping timing?
According to the World Health Organization report Care of
the Umbilical Cord, “the umbilical cord can be clamped immediately after birth
or later. Late clamping, after cord pulsations have ceased, is the usual
procedure in traditional births [the
way Mother Nature intended, my note], and early clamping is
common in institutions. The timing of cord clamping may have effects on
both mother and infant.” And also “There have been concerns that the increase
in the newborn's blood volume and red blood cell volume that is associated with
delayed cord clamping could result in overload of the heart and respiratory difficulties.
These effects have not, however, been demonstrated. In fact, there is probably
a self-regulatory mechanism in the infant which limits the extent of placental
transfusion.”
So, there seems to be no permanent negative effects when
clamping late (when cord pulsations cease), but are there possible negative
effects if the umbilical cord is clamped early? Can this contribute to the
later onset of Autism, especially if there are genetic factors that make some
newborns more sensitive to oxygen deprivation than others? Let’s continue.
It has been well established that the Amish have a very
low incidence of Autism in their population. The incidence seems to vary from
Amish group to Amish group, and if we go to the results of the studies the
presence of Autism varies from 1 in 271 children (International Meeting for
Autism Research: Prevalence Rates of Autism Spectrum Disorders Among the Old
Order Amish, May 2010), to 1 in 10,000 in the groups treated by Dr. Max
Wiznitzer, a pediatric neurologist from Rainbow Babies in Children's Hospital
in Cleveland and the neurologist for Amish groups in northern east Ohio (CNN
Larry King Live aired April 3, 2012).
Two things have been said regarding the Amish, there is anecdotal data suggesting that they do not vaccinate their babies, and the fact that they
do not clamp the umbilical cord until the placental delivery.
Regarding the vaccination argument linking it to Autism, well it has been
generally debunked (among other studies see “Increasing Exposure to
Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated
with Risk of Autism” Journal of Pediatrics March 6 2013), or at least the
vaccination argument seems to be a toothless tiger.
On the subject of the Amish, in the same Larry King
interview Dr. Wiznitzer said regarding
the relation of vaccination among the Amish and Autism: “Years ago, I thought
about this idea among the Amish population here in northeast Ohio, to whom I am
actually the neurologist. And I went to the public health nurses and said, tell
me about their vaccination rates. And I was told that there is a very high rate
of vaccination amongst the Amish population. Out of ten thousand of individuals
in our population, we have one child with autism. I see all these children.”
Furthermore, Thimerosal, the mercury-based preservative
in some vaccines and a popular target for anti-vaccinationists, was removed
from Swedish vaccines prior to the Somali immigration in the 1990′s. It
was also removed from childhood vaccines in the US by 2002, yet the incidence
of Autism among immigrant Somalis in Sweden is even higher than in the general
population. Lack of Vitamin D has also been suspect as a contributing factor
because of Sweden’s long winters, but there is another cluster in sunny
Australia, yet, the vitamin D argument as a contributing factor will be analyzed
in a future article.
However, it is a fact that the general rule amongst the
Amish is to clamp after placental delivery. At no point we are saying that
oxygen deprivation caused by early umbilical cord clamping is the only cause of
Autism, but that it can be a contributing factor, and maybe an important one.
Also, in the case of the Amish, because they are a close knit group that lives
separate from the general population, there may be less genetic predisposition
to Autism. This brings us back to those Somalian immigrants.
According to Somali parents of Autistic children, they
don’t recall children with Autistic symptoms among their family and friends in
Somalia, but there are no real studies to ascertain the true rate of Autism in
Somalia, and at this point we are relaying on anecdotal evidence that may be tainted
by cultural biases that may not even recognize the existence of Autism. By a
way of comment, as stated above, the Care of the Umbilical Cord study from the
World Health Organization stated “Late clamping after cord pulsations have
ceased is the usual procedure in traditional births, and early clamping is
common in institutions.”, and I suspect that late clamping is the more common
custom in Somalia as it is in many nations with a less institutionalized
medicine, but as of today I have no official source to quote on this…yet it
seems to be a logical conclusion.
By now we have established that it would not be
unreasonable to conclude that early umbilical cord clamping may contribute to
create the conditions conducive to Autism via oxygen deprivation and by
preventing the full transfer of blood from the placenta to the newborn baby. We
can also conclude that by clamping early, all kind of nutrients, key minerals
and other chemical components are left together with that blood in the
placenta, depriving the baby of a lot more than just oxygen. If these key
components are replenished easily through diet or other means such as
supplements, then we are only left with the oxygen deprivation, but if the baby
cannot produce or/and absorb that (or those) component in enough quantities for
an extended period of time, then we would likely have consequences.
A case in point is iron. A baby from age 0 to 6 months
has problems absorbing iron, and the baby will depend a lot on the iron
produced during the last trimester of gestation. According to the 2002 Human
Vitamin and Mineral Requirements report from the FAO (Food and Agriculture
Organization of the United Nations), the newborn term infant has an iron
content of 250 to 300mg which after birth is redistributed from degradable red
blood cells to iron stores. This, together with the iron provided by breast
milk should last the baby the 4 to 6 months it takes to get to the point that he
can start to properly absorb iron and he starts to change his diet.
The
baby can absorb approximately 50% of the iron he gets form the mother’s milk,
compared to only 7% absorption from formula, and a 4% absorption from infant
cereals (Dallman 1986). In general I read that iron absorption is less than 12%
when it comes from sources other than breast milk, including less than 10% from
cow milk.
Regarding the table above, notice that there
is no “Recommended Intake” for a baby 0 to 6 months old, there is just an
“Adequate Intake” which is basically the approximate expected intake from
breast feeding. If we do a little math and multiply .27 mg/d times 180 days (6
months) we get a total intake of iron of 48.6 mg, add that to an average of 275
mg at birth that will eventually go into stores (250mg+300mg/2), and you get
1.8 mg available for use for those 6 months. According to a MedlinePlus article
titled Iron Deficiency Anemia – Children, “Babies are born with iron stored in
their bodies. Because they grow rapidly, infants and children need to absorb an
average of 1 mg of iron per day. Since children only absorb about 10% of the
iron they eat, most children need to receive 8-10 mg of iron per day. Breastfed
babies need less, because iron is absorbed 3 times better when it is in breast
milk.”, so 1.8 mg seems like an OK value since most of it comes from stores
which are already absorbed inside the body.
Nevertheless, a reduction in
the amount of iron stores in the newborn due to early clamping may become critical
when you have 1.8 mg/d available for use if you want it to last 180 days, and
that is only attained comfortably if
the baby is full term, if the
mother does not have an iron deficiency to start with, and if the clamping is done after cord pulsations have ceased so
the maximum possible amount of iron is transferred from the placenta to the
baby. Again, the amount of daily iron that Mother Nature selected under the
right conditions must be the right number for healthy development of the baby
under natural selection, so a decrease in stores due to premature birth, iron
deficiency in the mother, or early clamping of the umbilical cord must affect
this balance, and some processes probably will get delayed or not completed
because during the baby development each step depends on the successful
execution of previous steps.
But what is the evidence
that there could be iron deficiency in otherwise healthy babies?
In a June 2004 report published by the National
Institutes of Health via PubMed called “Evaluation of erythropoiesis by serum
transferrin receptor and ferritin in infants aged 0-6 months” a group from the
Ankara University School of Medicine shed some light on the matter. The aim of
that study was to evaluate the production of red blood cells in 198 healthy
babies aged 0-6 months. Anemia and unusually small red blood cells (Microcytosis)
were present in 9% and 13% of the sample, respectively. The rate of unusually
small red cells was as high as 45% in 6-month-old babies. This research showed
a high frequency of iron deficiency detected in otherwise healthy babies.
I don’t know the clamping
practices in Turkey, but as it is a European Union member I suspect that as a
general rule it resembles the practices of institutionalized medicine in the
rest of the west. If their practice is to clamp the umbilical cord late then
the incidence of iron deficiency for early clamping babies should be even worse.
What is the transcendence of lack of iron and how does it
relate to Autism?
Dr. David Blake, a researcher in the Department of
Neurology at the Medical College of Georgia on a comment on Dr. Mike
Merzenich’s blog wrote, and I quote ” What is the significance of iron
deficiency anemia? Well, the two biggest brain-related pathways involved are
production of “myelin basic protein”, and “dopamine”. The former is a basic
building block that every developing brain needs, and there are a number of
well-described issues in brain myelination in autism, and in antibody responses
specifically to myelin basic protein. The dopamine pathway you may recognize
from its role in treating ADD. The ADD child gets a dopamine “booster”, and it
normalizes their behavior. A side effect of the dopamine metabolic abnormality
with iron deficiency anemia is urinary noradrenaline – this is also found in
autistics. Another interesting finding is that iron supplementation helps
autistics” (could iron deficiency and early clamping play a role also on ADD cases as suggested here? We will get into it on a future article)
Iron Deficiency in infancy, a common disorder, “is
associated with cognitive, motor and behavioral deficits that may be related to
impaired myelination…Because premature births deprive infants of the primary period
of fetal iron deposition the risks are still higher in these
infants…Additionally supportive of an effect on myelination is the recognition
of the crucial role of iron in myelination”, this according to “Neurology of
the Newborn, Volume 899” page 101.
Furhtermore, a 2009 study from Department of
Neurosurgery, Pennsylvania State University College of Medicine titled Oligodendrocytes
and myelination: the role of iron states: “The importance of iron in myelin
production has been demonstrated by studies showing that decreased availability
of iron in the diet is associated with hypomyelination. The timing of iron
delivery to oligodendrocytes during development
is also important because hypomyelination and the associated neurological
sequelae persist long after the systemic iron deficiency has been corrected”.
Oligodendrocytes are the myelinating cells of
the central nervous system (CNS). They are the end product of a cell lineage
which has to undergo a complex and precisely timed program of proliferation,
migration, differentiation, and myelination to finally produce the insulating
sheath of axons. Due to this complex differentiation program, and due to their
unique metabolism/physiology, oligodendrocytes count among the most vulnerable
cells of the CNS
Conclusions:
Early clamping of the umbilical cord, a common practice
in institutionalized medicine, may be the precursor of negative outcomes in the
development of the baby because it could cause oxygen deprivation
during birth, and because the early clamping does not allow all the necessary
blood to move from the placenta to the baby, limiting the amount of iron stores
needed during the first 6 months of life.
Oxygen deprivation and iron deficiency can affect the
normal development of the brain, and could be a contributory factor to the development
of Autism as well as other cognitive, behavioral and motor deficits. Because
clamping after the cord pulsations have ceased is an easy procedure to
implement, has very limited if any downsides, and the potential upsides could
be very important, we recommend pregnant women to ask their doctors to clamp the
umbilical cord only after cord pulsations have ceased.
Physiorenovo, in conjunction with a hospital in South
America, may start in the near future a study to formalize with more data the conclusions
of this article.
