THE NINE MONTHDANGER ZONE

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Science is constantly updating our understanding of the way our bodies function and how best we can live longer, healthier lives. Over the next three weeks we will be exploring the latest research into our well-being, starting with Hilary Bower on how our treatment in the womb can influence our susceptibility towards heart disease and strokes later in life. Next week, fertility and ways to extend it come under scrutiny; and our series concludes with the science of delaying death

A Foetus floating peacefully in its watery balloon, sucking its thumb, giving the odd kick, but for all the world, innocent, untouched, protected, biding its time until the shove into the real world. That's the standard image of life before birth.

Nine months of peace and quiet. Not.

While the genetic juggernaut has mesmerised many scientists, and the remainder have become submerged in scrutinising our bad habits for why we succumb in our thousands to ill-health or die prematurely from conditions such as heart disease, strokes and diabetes, a group of British scientists have been trying for 10 years to tell the world that a vital period of life has been ignored with major implications for preventing these conditions.

They believe that what happens not only in the first nine months of our own lives - but also in those womb-bound months of our mother, her mother and even her mother's mother - changes how our genes function and programmes our later susceptibility to major illnesses.

It all started when a five-year paper chase through the archives of Britain's records offices led Professor David Barker, director of the Medical Research Council's Environmental Epidemiology Unit at Southampton University, to a researcher's treasure trove.

The doubloons found were a series of turn-of-the century birth records in Hertfordshire, Sheffield and Preston which, for some unknown reason, were surprisingly large and detailed. They included not just the baby's weight but all manner of unusual measurements including head circumference, abdomen size, placenta weight and even the size of each mother's pelvis.

By tracing the lives of 16,000 people born between 1911 and 1930, the team have discovered that babies who weighed five and a half pounds or less were 50 per cent more likely to die of heart disease than the traditional seven-and-a-half pounder, and twice as likely as the bruisers who weighed nine and a half pounds or more. These light babies - who were not premature - were also three times more likely to develop non-insulin-dependent diabetes by adulthood, which is a major risk factor for heart disease.

But weight alone does not tell all about nutrition, says Professor Barker. "If you told me your weight, I wouldn't be able to recognise you on Southampton station, would I? The same goes for foetal experience. But if you know the head circumference of the baby and its length, its weight and size of the placenta, then you can make inferences about both the demand for nutrients and the extent to which that was met."

Working out these other links the team also found that babies who were thin or short at birth, whose bodies were out of proportion with their head size, or whose placenta was oversized, had vastly increased risks, 50 years or more later, of having high blood pressure, diabetes or high cholesterol - all of which are major contributors to heart attacks or strokes.

The findings have shaken the accepted wisdom, says Professor Barker, not because, in the genetic frenzy, most scientists do not accept that "nurture" influences the activities of our DNA at all, but because many have never considered that this influence could start long before the squall of birth.

So how does it work?

Cell division is the major activity of our early foetal life. Between fertilisation and adulthood, a total of 47 cycles of cell division take place, and 42 of these happen before birth. Each different tissue has critical periods of rapid growth during which having exactly the right supply of nutrients and oxygen is vital for their optimal development.

But, if either, or both, are in short supply, the foetus' evolutionary instinct is to protect the brain or the growth of the placenta and it shunts the lion's share of the reduced goodies in their direction by slowing the rate of growth elsewhere.

This go-slow can permanently change size or cell make-up of body parts, or alter the activity of certain genes - starting a time bomb ticking in a baby's body that cannot be changed after birth. Our cells no longer increase in number, but just grow in size.

Take, for example, babies born with a short body out of proportion to their head size. According to Professor Barker's hypothesis, their under- nutrition occurs in late pregnancy. To protect the brain, the foetus slows the growth of the liver which is at a critical point of development, permanently disrupting its ability to break down cholesterol and regulate blood-clotting factors such as fibrinogen - key players in the heart disease equation.

Animal studies also show that a lack of protein at this critical time affects two particular liver enzymes which don't normally become active until after birth. This means nutrition in the womb is actually changing the way genes express their proteins, says Professor Barker. Kidney growth may be slower too. This can reduce their ability later in life to cope with dietary salt, which pushes up blood pressure creating another major risk factor in heart disease.

Reduced rations late in pregnancy also seem to damage our reaction to growth hormone, which drives growth after birth. Instead of being used, it appears to stay in the blood stream, causing the heart to grow unhealthily bigger and triggering the plaque build-up that eventually leads to narrowed arteries.

The pattern is different for babies born thin and lacking in muscle, says Professor Barker. They have been under-nourished in mid gestation at the time when the placenta is greedily expanding to prepare itself for baby's final spurts of growth. To protect it, the foetus slows down muscle growth by making them resistant to insulin, a move which seems to impair glucose metabolism for life.

Using magnetic resonance imaging, scientists have discovered that these babies grow up to process glucose much more slowly in their muscles, regardless of what their grown size is, increasing the risk of developing non-insulin dependent diabetes - the type characterised by insulin resistance.

What about the small but perfectly proportioned baby then? Ironically, even this much sought-after attribute of adult life doesn't bestow a good start in health. Their Achilles' heel is high blood pressure. Small babies occur when under-nutrition early in pregnancy leads the foetus to rein in its big ideas and slow down the pace of growth from the beginning.

Why this causes raised blood pressure is a bit of a mystery but one possible explanation is that the placenta's defences against the mother's immune system chemicals are weakened, which somehow damages the elasticity of the blood vessel walls, increasing the pressure of the flow within. Another is that small foetuses may have to develop higher blood pressure just to keep the flow of nutrients moving across the placenta.

"Most people in Britain are going to die because their coronary circulation has done something unfortunate. Yet there's never been a study of the development of the coronary circulation in foetal life, even though we know that it is complete and unalterable and unique to each human being at birth," sighs Professor Barker. "We've focused so relentlessly on events at conception or on events at middle age that we have left a vital slab of life out.

"The average young woman in England doesn't look under-nourished but that doesn't mean that her foetus is well-nourished. The foetus and mother have a complex relationship and a mother simply does not give it everything she gets, neither is she capable of doing that because there is the great gatekeeper called the placenta standing in the way.

"We know for sure that the delivery of nutrition to the foetus is not just a matter of what the mother eats in pregnancy. The problem is intergenerational - the mother's own weight at birth and foetal growth is a crucial factor because the reproductive system is formed in utero. In animals, if you undernourish the pregnant female, her offspring's ability to deliver nutrients to its offspring is impaired. Now we know this happens in humans too."

From the Sheffield records, Professor Barker's team discovered that mothers pass on the results of their own and their mother's mother's poor nourishment in a vicious cycle that works like this: poor maternal nutrition disrupts the development of a girl baby's pelvis, impairing her ability to sustain such a large placenta when her time comes. This leaves her own foetus - which will have been encouraged to think big by its early gestation experience of late 20th century Western nutritional abundance - deprived of a big enough store of goodies in the last part of pregnancy to keep it in the style to which it has become accustomed.

Caught in the vicious cycle, the foetus goes into its brain sparing, body-growth-reducing routine and emerges with a propensity to high blood pressure, disrupted blood clotting and a high likelihood of having that other devastating cardiovascular condition of middle age, the stroke.

"This means there's a limit on what a woman can do to her baby in terms of good things and it may take some generations to improve things," says Professor Barker. But eating for two from the moment the pregnancy test turns pink is not the answer either, Professor Barker returns to the animal world to make his point.

"Farmers have known for 200 years that if you want a big lamb what you don't do is get a ewe, make her fat, mate her, put her in a field of green grass and ain't that great. It ain't great - what you do is get a ewe, make her fat, mate her, then you put her in poor pasture. That stimulates the growth of the placenta and when you move her back, about a third of the way through pregnancy, into better pasture, you've got a great big gate and food comes funnelling through that gate. Who would have thought you'd get a bigger lamb if you undernourish the ewe first?"

No chance of trying that on human females. But finding out exactly how what a mother eats acts upon her foetus is a crucial next step. The newest information to emanate from the Southampton team's number crunching shows for the first time a complex link between an excess of either animal protein or carbohydrate in early pregnancy, poor placental growth and high blood pressure in later life. But if you're waiting for a simple, categorical and reassuring sound-bite diet that says "eat this at this time, and that at another", it's some way off.

And it's not just physical health that may be programmed by life before birth. A mother's attitude towards her unborn babe may also mould its development.

In a study published last month in the British Journal of Psychiatry, Finnish researchers reported that schizophrenia was two and half times more common in the grown children of mothers who, during their pregnancy, said their baby was unwanted.

Other recent research suggests that mothers who identify early on with their foetus - by thinking of it as a person, naming it, talking to it and responding to its moves - produce babies who are more attentive and mentally active.

In biochemical terms, this is not so surprising. The amniotic cocktail is no benign sea but a potent and changing mix of chemicals integrally linked with the mother's chemical circulation.

Coping with daily life can cause just as many biochemical changes in the body as say, eating a good meal or breathing bad fumes. It has been suggested that feeling highly stressed could damage the brain development of the foetus because of the surge of corticosteroids it prompts.

But, is it possible to do good as well as harm, to give the baby a head start by, for example, taking it to pre-natal university, playing tapes of "stimulating" sounds through your stomach?

Certainly, it's now known that in the last three months before birth, the foetus actively processes sounds, clearly distinguishing between its mother's and others' voices - and responds with movements and changes in heart rate. There have also been studies that show newborns can even differentiate between languages - particularly if one is Thai. But Professor Peter Hepper, director of the Foetal Behaviour Research Centre at Queen's University, Belfast, who has been studying the mystery of foetal development ever since he discovered that newborns of soap opera-addicts recognised the theme tune of Neighbours, says that's because the foetus hears only rhythm and intonation, not because it understands the words or the emotions expressed. Professor Hepper says any gain by the newborn is much more likely to be due to the fact that their mothers are more actively involved in their pregnancy.

"It was always thought that brain development occurred under purely genetic control without other factors interfering unless it was something like thalidomide. Now we are beginning to see that a certain amount of sensation, sound and movement is vital to shape our nervous system and if that shaping goes wrong before birth, it may cause abnormalities in our nervous system in later life."

So, for instance, our eyes and other parts of the brain that process sight simply would not develop without visual stimulation - no matter what our genetic blueprint says.

Furthermore, research underway at Queen's suggests it may be foetal movements that trigger brain development rather than brain development that determines movement. Current wisdom is that the side of brain that develops first decides which side of the body develops first and therefore whether a person will be right or left handed, says Professor Hepper. But his work shows a preference for right-sided movement which may develop as early as 10 weeks, well before the brain is developed enough to influence movement.

"If this proves to be true, then there may be things we can do for conditions for which there is currently no cure, such as Down's syndrome. Perhaps if we could identify it early enough when the brain is forming, we might then be able to introduce something like movement techniques to attempt to stimulate brain growth during the critical time," explains Professor Hepper.

This intriguing but controversial hypothesis of foetal programming has not been universally embraced by other medical scientists. Indeed a group from Harvard University recently admitted they had given a study on birthweight and heart disease to a graduate student to pursue "just to get it out of the way" so that they could go back to thinking about diet in middle age. But the accumulated evidence - and Professor Barker's dogged persistence - has got to them, to the extent that they are planning one of the biggest trials of the hypothesis.

Critics point to the weight of research into the effects of 20th century adult lifestyle on cardiovascular risk and that babies exposed to an adverse environment in the womb are likely to be exposed to an adverse environment in later life.

But Professor Barker says that even if you take all lifestyle factors combined, they only have a limited ability to predict coronary heart disease. The commonest cause of death for a man falling into the lowest risk groups is still a heart attack, he says. What does happen is that adult life builds on what happened in the womb.

"People are going to throw flack at this hypothesis because it seems to threaten (a) the idea that by behaving properly in adult life, God will give you added years, which is a theory very close to the hearts of Western control freaks, and (b) because it seems to threaten the genetic trend.

"In fact it doesn't. What we're saying is the genes that enable you to survive in foetal life unfortunately don't always do good things to you in later life. Genes are yesterday, this is tomorrow's science." !

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