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Fetal Brains Suffer Badly From Effects of Alcohol

November 4, 2003
 By LINDA CARROLL 



 

Thirty years ago, scientists linked prenatal alcohol
exposure with a perplexing pattern of birth defects
including neurological problems, low birth weight, mental
retardation and a set of facial malformations. 

Up to that time, many doctors had assumed that alcohol was
so harmless that it was sometimes administered
intravenously to women who were thought to be at risk of
losing their pregnancies. 

But in recent decades, scientists have discovered that
alcohol can be remarkably toxic - more than any other
abused drug - to developing fetuses. New research with
imaging techniques is helping experts uncover which parts
of the developing brain are damaged by alcohol exposure. 

By pinpointing the damaged areas, they are beginning to
understand the origins of the problem behaviors and
learning disabilities linked to alcohol. 

Scientists are also homing in on a protein important to the
developing brain that is affected by alcohol. It is
possible, they say, that a medication can be created to
protect the brains of developing fetuses, even if pregnant
women cannot quit drinking. 

It is not surprising that it has taken researchers so long
to tease out the link between alcohol exposure and birth
defects. For one thing, the effects of alcohol exposure
seem to vary widely. 

Some fetuses seem to escape unscathed, even when their
mothers drink heavily, while others are severely damaged.
No one knows why. 

"It's not like thalidomide, where anyone who took it had an
affected child," said Dr. Sandra W. Jacobson, a professor
at Wayne State School of Medicine in Detroit, referring to
the morning-sickness drug linked to birth defects in the
late 1950's and early 1960's. "There's a range with
alcohol. You might get the full-blown syndrome in 4 out of
100 heavy drinkers." 

There are also many babies who are affected, but not
severely enough for the syndrome to be diagnosed. Some with
fetal alcohol effects may appear relatively normal but have
behavioral problems and learning deficits like those with
the syndrome. 

Further complicating matters is the question of how much
alcohol it takes to cause harm. In the past few years,
successive studies have shown an effect at increasingly
lower levels. One study, published last year, found a small
but significant effect on average in children born to women
who consumed just a drink and a half a week. 

"We were surprised by this," said the lead author, Dr.
Nancy Day, a professor of psychiatry at the Western
Psychiatric Institute and Clinic in Pittsburgh. The women
in the study were recruited from a prenatal clinic between
May 1983 and July 1985. 

"The children were in the normal range of growth," Dr. Day
said, "but if you compare them to children whose mothers
didn't drink at all, they weighed less, were shorter and
had smaller head circumferences." 

The effect of low levels of alcohol appears to be subtle,
said Dr. James R. West, head of the department of anatomy
and neurobiology at the Texas A&M medical school. 

"Perhaps instead of having an I.Q. of 120, you might end up
with 115," he said. "You might seem perfectly normal, but
not have the motor skills to make the high school football
team." 

Another factor making it difficult to tease out the impact
of alcohol is its widespread effects on the developing
brain and body. 

"Alcohol is a dirty drug," Dr. West added. "It affects a
number of different neurotransmitters, and all cells can
take it up." Compare this with cocaine, Dr. West said,
which is taken up by only one neurotransmitter. 

It is also difficult to identify the effects of alcohol
because a woman's drinking habits seem to make a big
difference. Experts say it matters when a pregnant woman
drinks, how often she drinks and what her pattern of
drinking is: whether she drinks small amounts daily or
periodically binges. 

Drinking in the first trimester can lead to facial
malformations, while in the second it can interrupt nerve
formation in the brain, Dr. West said. During the third, it
can kill existing neurons and interfere with nervous system
development, he added. 

Researchers have also determined that babies are more
likely to be affected if mothers drink in a binge pattern,
like five drinks one day rather than a single drink daily,
Dr. Jacobson of Wayne State said. 

Because alcohol affects so many sites in the brain,
researchers have come to believe that alcohol is far worse
for the developing fetus than any other abused drug. 

Dr. Jacobson's study included cocaine users who also used
varying quantities of alcohol. "We found more serious
cognitive impairment in relation to alcohol than cocaine or
other drugs, including marijuana and smoking," Dr. Jacobson
said. 

The damage done to fetuses often has been wrongly connected
to cocaine, many experts say. 

"The consensus, I think, at this point is that most of the
adverse effects that had been reported due to cocaine and
crack use were from alcohol use," said Dr. Kenneth R.
Warren, the director of the office of scientific affairs at
the National Institute on Alcohol Abuse and Alcoholism. "It
is the leading cause of birth defects due to an ingested
environmental substance in this country." 

In 1973, researchers coined the phrase fetal alcohol
syndrome to describe babies born with a certain pattern of
neurologic and physiologic defects related to alcohol
exposure in utero. 

Early on, it was clear that exposed children were wired
differently from normal ones and that they exhibited an
array of disabilities. 

Dr. Ann P. Streissguth, the director of the fetal alcohol
and drug unit at the University of Washington and a
professor at the medical school there, ticked off a list:
"These included attention problems, hyperactivity, learning
problems - particularly in arithmetic - language problems,
memory problems, fine and gross motor problems, poor
impulse control, poor judgment, intellectual deficits and
difficulty integrating past experience to plan and organize
future behavior." 

Researchers wondered whether specific areas of the brain
were being consistently harmed by alcohol exposure in
utero. Poor judgment, for example, might point to damage to
the frontal lobes. The lobes, as the control center of the
brain, are involved in planning, organizing and inhibiting
inappropriate responses, the researchers say. 

Thirty years ago, the only way researchers could learn
about the effects of alcohol on the brain was to study
children who died shortly after birth. 

"We knew from brain autopsies that in severe cases the
brains were terribly disorganized," said Dr. Edward P.
Riley, the director of the Center for Behavioral Teratology
at San Diego State University. Now, researchers use imaging
techniques like M.R.I.'s to look at the damage caused by
alcohol. Several recent studies using magnetic resonance
imaging have shown damage to the corpus callosum, a band of
nerve fibers that connects the left and right sides of the
brain. 

A report published in 2002 compared the brain scans of
adults and children who had severe or mild alcohol-related
disabilities with the scans of healthy counterparts. The
researchers found that the corpus callosa were abnormally
shaped in 80 percent of those who had been exposed to
alcohol in utero. 

Another study found that the corpus callosum was smaller
and shifted forward in children and young adults with the
syndrome. Using a technique known as diffusion tensor
imaging to look closer at the corpus callosum, researchers
at Emory University have seen abnormalities in the myelin,
the substance that insulates nerve cells. 

When the myelin is damaged, signals do not carry as crisply
through the cells, said Dr. Claire D. Coles, director of
the Fetal Alcohol Center at the Marcus Institute and a
professor of psychiatry and behavioral sciences at Emory. 

Another study published in 2002 found that frontal lobe
structures were smaller in teenagers and young adults who
had been exposed to alcohol prenatally. 

By pinpointing which sections of the brain are most likely
to be damaged by alcohol, scientists may find a way to
block its effects. 

Researchers recently recognized that some of alcohol's
effects were similar to those experienced by children born
with defects in genes that control L1 adhesion cells. Fetal
cells that are destined to grow into the brain and nervous
system bind to one another with the help of adhesion
molecules like L1, said Dr. Michael E. Charness, an
associate professor of neurology at Harvard. 

In laboratory experiments, Dr. Charness and his colleagues
showed that alcohol could interfere with L1's stickiness,
thus hampering crucial cell-to-cell attachments. In an
article published in The Proceedings of the National
Academy of Sciences in July, they showed that a protein,
NAP, could block alcohol's effect on L1. When NAP was given
to mice exposed to alcohol, the protein appeared to stave
off neurological effects. 

"The idea of giving drugs to pregnant women is
controversial," Dr. Charness said. "Drugs may have their
own risks." 

But, he said, there are areas of the world where fetal
alcohol syndrome is a huge problem. In parts of South
Africa, the incidence of the syndrome in first graders is
around 4.5 percent, he said. "The rate of drinking is
high," Dr. Charness added. "And the women won't stop
drinking despite interventions. It might be reasonable to
give them a drug that can prevent the more serious effects
of alcohol." 

http://www.nytimes.com/2003/11/04/health/04FETA.html?ex=1068952957&ei=1&en=1540ada24c52c2cc


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