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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.
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
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.
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.
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