Even small amount of alcohol can damage fetus

http://www.newscientist.com/article/mg19125581.500;jsessionid=PCKFPFODHIGE

Sobering news for pregnant women

29 June 2006
NewScientist.com news service
Phyllida Brown

AT FIRST, Susie's teachers thought she was a bright child. Her
adoptive mother knew different. Give Susie a set of instructions and
only a few seconds later she would have forgotten them. She was
talkative, with a large vocabulary, but could not seem to form lasting
friendships. Then, one day, Susie's adoptive mother heard a lecture
that described fetal alcohol syndrome - a condition which affects some
children born to heavy drinkers. "Bells went off in my head," she
says. "The lecturer described eight traits, and my daughter had seven
of them."

Children like Susie could well be just the tip of the iceberg. Fetal
alcohol syndrome was once thought to affect only the children of heavy
drinkers, such as Susie's biological mother, but a mounting body of
research suggests that even a small amount of alcohol can damage a
developing fetus - a single binge during pregnancy or a moderate seven
small glasses of wine per week.

The new research has already prompted some governments to tighten up
their advice on drinking during pregnancy. Others, however, say there
is no convincing evidence that modest alcohol intake is dangerous for
the fetus. With advice varying wildly from one country to another, the
message for pregnant women has never been so confusing.

Last year the US Surgeon General revised official advice warning
pregnant women to limit their alcohol intake. Now they are told
"simply not to drink" alcohol - not only in pregnancy, but as soon as
they plan to try for a baby. France also advises abstinence, as does
Canada. The UK's Department of Health says that pregnant women should
avoid more than "one to two units, once or twice a week", but is
finalising a review of the latest evidence, which it will publish
within weeks. In Australia, women are advised to "consider"
abstinence, but if choosing to drink should limit their intake to less
than seven standard Australian drinks a week, with no more than two
standard drinks on any one day (see Diagram).

Whichever guidelines women choose to follow, some level of drinking
during pregnancy is common in many countries. The last time pregnant
women in the UK were asked, in 2002, 61 per cent admitted to drinking
some alcohol. Even in the US, where abstinence is expected, and where
pregnant women in some states have been arrested for drinking, 13 per
cent still admit to doing it.

Children with fetal alcohol syndrome (FAS) are generally smaller than
average and have a range of developmental and behavioural problems
such as an inability to relate to others and a tendency to be
impulsive. They also have distinctive facial features such as a thin
upper lip, an extra fold of skin in the inner corners of the eyes and
a flattening of the groove between the nose and upper lip.

In recent years researchers investigating the effects of alcohol in
pregnancy have begun to widen their definition of antenatal alcohol
damage beyond the diagnosis of FAS. They now talk of fetal alcohol
spectrum disorders, or FASD, an umbrella term that covers a range of
physical, mental and behavioural effects which can occur without the
facial features of FAS. Like children with FAS, those with FASD may
have problems with arithmetic, paying attention, working memory and
the planning of tasks. They may be impulsive, find it difficult to
judge social situations correctly and relate badly to others, or be
labelled as aggressive or defiant. In adulthood they may find it
difficult to lead independent lives, be diagnosed with mental
illnesses, or get into trouble with the law. Some have damage to the
heart, ears or eyes.

While some children with FASD have been exposed to as much alcohol
before birth as those with FAS, others may be damaged by lower levels,
says Helen Barr, a statistician at the University of Washington,
Seattle. Barr has spent 30 years tracking children exposed to alcohol
before birth and comparing them with non-exposed children. The less
alcohol, in general, says Barr, the milder the effects, such as more
subtle attention problems or memory difficulties. Other factors that
can affect the type of damage include the fetus's stage of development
when exposed to alcohol and the mother's genetic make-up.

Although FASD is not yet an official medical diagnosis, some
researchers estimate that it could be very common indeed. While FAS is
thought to account for 1 in 500 live births, Ann Streissguth and her
colleagues at the University of Washington believe that as many as 1
in every 100 babies born in the US are affected by FASD. Others put
the figure at about 1 in 300. Whichever figure is more accurate, it
would still make the condition far more common than, say, Downs
syndrome, which affects 1 in 800 babies born in the US.

Streissguth was among the first to study the long-term effects of
moderate drinking in pregnancy. In 1993 she reported that a group of
7-year-olds whose mothers had drunk 7 to 14 standard drinks per week
in pregnancy tended to have specific problems with arithmetic and
attention. Compared with children of similar IQ whose mothers had
abstained during pregnancy, they struggled to remember strings of
digits or the details of stories read to them, and were unable to
discriminate between two rhythmic sound patterns.

When Streissguth's team followed the alcohol-exposed children through
adolescence and into their early twenties they found them
significantly more likely than other individuals of similar IQ and
social background to be labelled as aggressive by their teachers.
According to their parents, these children were unable to consider the
effects of their actions on others, and unable to take hints or
understand social cues. As young adults, they were more likely to
drink heavily and use drugs than their peers.

These findings were borne out by similar studies later in the 1990s by
Sandra Jacobson and Joseph Jacobson, both psychologists at Wayne State
University in Detroit, Michigan. To try and work out what dose of
alcohol might be harmful, the Jacobsons ran a study of children born
to 480 women in Detroit. In it, they compared the children born to
women who, at their first antenatal appointment, said they drank seven
or more standard US drinks a week with the babies of women who drank
less than seven, and with those whose mothers abstained altogether.
The psychologists then tested the children's mental function in
infancy and again at 7 years old. In the children whose mothers had
seven drinks or more, the pair found significant deficits in their
children's mental function in infancy, and again at age 7, mainly in
arithmetic, working memory and attention (Alcoholism: Clinical and
Experimental Research, vol 28, p 1732). Where the mother drank less
than that they found no effect.
Spread it out

Seven drinks a week may be more than many pregnant women manage, but
according to the Jacobsons, what's important is when you are drinking
them, whether you have eaten, and how quickly your body metabolises
alcohol. In their study, only one woman of the 480 drank daily; most
of the others restricted their drinking to a couple of weekend
evenings. If a woman is drinking seven standard drinks on average
across the week, but having them all on two nights, she must be
reaching four drinks on one night. That constitutes a binge. "Women
don't realise that if they save up their alcohol 'allowance' to the
end of the week, they are concentrating their drinking in a way that
is potentially harmful," she says. This means that even women who have
fewer than seven glasses per week could potentially be putting their
babies at risk if they drink them all on one night.

There is also some evidence that fewer than seven drinks a week could
have measurable effects on an unborn baby. Peter Hepper at Queen's
University, Belfast, UK, examined the movements of fetuses scanned on
ultrasound in response to a noise stimulus. Having asked women about
their drinking habits, they compared the responses of fetuses exposed
to low levels of alcohol - between 1 and 6 British units per week,
each containing 10 millilitres of alcohol - and those exposed to none.
When tested between 20 and 35 weeks, the fetuses exposed to alcohol
tended to show a "startle response" usually found only in the earlier
stages of pregnancy, when the nervous system is less developed. Five
months after birth, the same babies showed different responses to
visual stimuli from the babies whose mothers had abstained. Hepper
interprets these findings as evidence that a low dose of alcohol has
some as yet unexplained effect on the developing nervous system.
Whether or not these differences will translate into behaviour
problems in later life is as yet unknown.

When Ed Riley and colleagues at San Diego State University in
California looked at children's brains using magnetic resonance
imaging, they found obvious changes in the brain structure of children
whose mothers drank very heavily, but also some changes in children
born to moderate drinkers. For example, there were abnormalities in
the corpus callosum, the tract of fibres connecting the right and left
hemispheres of the brain. The greater the abnormality, the worse the
children performed on a verbal learning task.

Despite these recent studies, the link between alcohol and fetal
development is far from clear. Not all babies born to alcoholic women
have FAS, yet other babies appear to be damaged by their mothers
indulging in just a single binge. And if 61 per cent of British women
drink while pregnant, how come there are not hundreds of thousands of
British children with FASD? Wouldn't we notice if 1 in 100 children
being born were affected?

Hepper argues that few teachers would raise an eyebrow if they had two
or three children in a class of 30 with marked behaviour difficulties,
and several more with milder, manageable problems. He therefore thinks
it is plausible to suggest that 1 in 100 children could have
alcohol-related problems of some sort.

Hepper's research is widely quoted by anti-drinking campaigners such
as FAS Aware, an international organisation which advertises in the
women's bathrooms of bars to encourage pregnant women not to drink.
The posters warn that "drinking in pregnancy could leave you with a
hangover for life" and that "everything you drink goes to your baby's
head".

Critics of these tactics point out that trying to scare women into
abstinence is not helpful. There are reports in North America of women
rushing off for an abortion because they had one drink before they
knew they were pregnant or being racked with guilt about past drinking
if they have a child with a mild disability.

Researchers like the Jacobsons acknowledge that it is hard to be
certain about how alcohol affects a developing fetus on the basis of
epidemiological studies, especially when they measure the notoriously
messy subject of human behaviour. Any effect on the developing brain
would vary depending on exactly when the fetus was exposed, and since
some behavioural effects may not become apparent until several years
after birth, it is difficult to pin down specific disabilities to
specific antenatal exposure to alcohol.

To try and get around the epidemiological problem, John Olney, a
neuroscientist at Washington University in St Louis, Missouri, has
examined the impact of alcohol on developing rodent brains as a model
for what happens in humans. Six years ago Olney and others showed that
alcohol causes neurons in the developing rat brain to undergo
programmed cell death, or apoptosis (Science, vol 287, p 1056).

Olney found that alcohol does the most serious damage if exposure
happens during synaptogenesis, a critical time in development when
neurons are rapidly forming connections. In rats, this happens just
after birth, but in humans it begins in the second half of pregnancy
and continues for two or more years. In the Science study, the team
found that exposure to alcohol for baby rats during this developmental
stage, at levels equivalent to a binge lasting several hours, could
trigger the suicide of millions of neurons, damaging the structure of
the animals' forebrains. The alcohol seems to interfere with the
action of receptors for two chemical signals or neurotransmitters,
glutamate and GABA (gamma amino butyric acid), that must function
normally for connections to form.
Lost neurons

The changes to brain development in rodents, Olney believes, could
explain some of the behavioural problems seen in children with FASD,
including attention deficit, learning and memory problems. For
example, in the rat study, large numbers of neurons were lost in the
brain regions that comprise the extended hippocampal circuit, which is
disrupted in other disorders of learning and memory (Addiction
Biology, vol 9, p 137). Loss of cells in the thalamus, which is
thought to play a role in "filtering" irrelevant stimuli, may partly
explain why FASD children are easily distracted.

The timing of alcohol exposure during pregnancy dictates what type of
damage will occur, Olney says: if it is early on, when facial
structures are forming, the facial characteristics of FAS may be
obvious. Later, when synapses are forming, mental function may be
affected. This runs counter to the popular view that the fetus is only
vulnerable in the first trimester; in fact, different stages may be
vulnerable in different ways.

Olney has recently tried to find out exactly how much alcohol is
enough to trigger apoptosis. This year he reported that, in infant
mice whose brains are at the equivalent stage of development to a
third-trimester fetus, some 20,000 neurons are deleted when they are
exposed to only mildly raised blood alcohol levels, for periods as
short as 45 minutes. In humans, he says, this is equivalent to
deleting 20 million neurons with a 45-minute exposure to blood alcohol
levels of just 50 milligrams per 100 millilitres of blood - which is
well below the legal limit for driving, and easily achieved in "normal
social" drinking (Neurobiology of Disease, DOI:
10.1016/j.nbd.2005.12.015). At blood alcohol levels below this, the
team found no apoptosis.

Olney is quick to stress that, alarming as 20 million neurons sounds,
it is "a very small amount of brain damage" in the context of the
human brain, which is estimated to have trillions of neurons. He has
no evidence that such small-scale damage would translate into any
detectable effects on a child's cognitive abilities. "But if a mother
is advised that one or two glasses of wine with dinner is OK, and if
she then has two glasses with dinner three times a week, this is
exposing the fetus to a little bit of damage three times a week," he
says.

The bottom line is that, as yet, it's impossible to translate these
findings into blanket advice for women about how many drinks they can
or can't have when pregnant. A drink before food will raise blood
alcohol concentrations faster than a drink with a meal; two drinks
downed quickly will raise it more sharply than two drinks spread over
3 hours. Because of this uncertainty, some researchers - and some
authorities - would rather take no chances. "The best possible advice
I can give mothers is to totally abstain from alcohol the moment they
know they are pregnant," Olney says.