With the help of old maternity notes, scientists have discovered that adult health is directly related to childhood nutrition, says David Derbyshire.
Ethel Burnside was not the sort of woman you would mess with. An imposing figure with dark hair harshly scraped back against a long thin face, she had a forceful, obstinate personality and she usually she got what she wanted.
And what she wanted, as she toured Edwardian Hertfordshire on her bicycle visiting new mothers and babies, was to tackle Britain’s appalling rates of infant mortality. At the turn of the century, one in 10 babies died in the first year of life. Many that survived to reach adulthood were sick and infirm. As the county’s first health visitor, Burnside created an army of trained midwives to attend births and advise mothers.
A stickler for organisation, she insisted that they record every detail of the babies in their care — when teeth appeared, whether they were bottle fed, whether they used dummies and when they were weaned. And crucially she persuaded her bosses to buy portable spring measuring scales to record their weight at birth and one year later. Burnside’s drive continued through the first world war, earning her an OBE in 1918.
But her greatest legacy came decades after her death, aged 75, in 1953. Those detailed records, forgotten in the archives of Hertfordshire County Hall for decades, have started to change the way we think about disease. Using Burnside’s notes, researchers have shown that the seeds of adult disease are sown in the womb and first two years of life. They have revealed that a baby’s nutrition during the first 1,000 days after conception influence whether they will enjoy a happy old age or one afflicted with heart disease, diabetes, stroke and lung problems.
The figure at the heart of the search for these foetal origins of disease is Professor David Barker of Southampton University. In the 1980s, he noticed a similarity between a map of heart disease in England and a map showing infant mortality in 1910. Regions with the least healthy Edwardian babies – the north-west, south Wales, the West Midlands and the north-east – were hotspots for heart disease 60 years later. Intrigued, he and colleagues searched for records to shed light on the puzzle and struck gold in Hertford, where Burnside’s 1911 to 1940 data was in storage.
Working with a team from the Medical Research Council, Barker tracked down 15,000 of the babies born before 1930 and compared their birth details with their adult medical histories. The findings were astonishing.
Men who had a low birth weight as babies, or a low weight aged one – and so who were suffering from poor nutrition – were at much higher risk of developing coronary heart disease as adults. In women, low birth weight was also linked to strokes, although there was no link with weight at first birthday. Over the following years more links between early nutrition and health emerged. Babies with low birth weight tended to have higher blood pressure as adults, less elastic arteries, altered stress responses and were more likely to have chronic bronchitis. And the structure of their hearts was different.
The findings led to the Barker Hypothesis. It argues there are key windows of development between conception and a child’s second birthday. If nutrition is not good enough at any of those stages, imperfections will be built into the growing person. Given the right genetic and environmental factors, these design flaws will make someone more prone to illness later in life. Many of these crucial moments are in the womb. But a child’s brain, immune system and skeleton continue to develop until around their second birthday — the 1,000 days that matter.
Professor Caroline Fall at Southampton University, who took part in the early Hertfordshire studies, said: “We know that when a foetus is undernourished it starts to prioritise what parts it is able to grow with the little nutrition it has and it dumps the things it doesn’t need like muscles. One way it does that is by diverting more blood to the brain, and sacrificing blood to the lower body. In the process you get changed development of the key abdominal organs such as the liver, kidneys and pancreas, which maintain our blood sugar, blood pressure and keep cholesterol under control.”
Malnourished foetuses may also develop damaged hormone systems, which increase the risk of disease. Nourishment in the womb doesn’t just come from a mother’s diet at the time. Many of the nutrients needed by a baby are taken from reserves that have been building up in a woman’s body years before conception. And it’s not just severely underweight babies at risk. Any drop in birth weight is linked to an increased risk of heart disease later in life — even for babies within the normal weight range. Big babies aren’t immune either. Those over 9.5lb are more at risk of diabetes and obesity later in life.
The idea that conditions in the womb influence our health is nothing new. After all, links between smoking and small, sickly babies have been documented for decades. But the idea that infants are primed for ill-health decades later by malnutrition was radical. Since those initial discoveries of the 1980s, more evidence for the foetal origins of disease came from the Avon Longitudinal Study of Parents and Children — an ongoing investigation into the health of 14,000 mothers and their children in the Bristol area. The most comprehensive cohort study of its kind, it has shown that the children of women who put on too much weight in pregnancy tend to be fatter, have higher blood pressure and lower levels of “good” cholesterol. It has also linked anxiety in pregnancy with asthma in babies, and shown that babies born in late summer tend to be taller, probably because their mothers got more vitamin D from the sun. It has shown that eating oily fish in pregnancy may boost the visual development of children and that higher levels of male sex hormones in a mother during pregnancy can influence whether her daughter is a tomboy.
As some researchers were confirming the foetal origins of disease, others went further back. Using the Avon study, they found that the lifestyles of fathers before they reach adolescence can affect their children’s life chances. The sins of the fathers really can be passed down to future generations.
Professor Marcus Pembrey, a clinical geneticist at the Institute of Child Health in London, working with the Avon team, found men who smoked while boys had sons who were fatter by the age of nine, even when other lifestyle factors, such as family income, were taken into account. More startling evidence that the environment of one generation influences the next has come from Sweden. Professor Lars Byrgen, a preventative health specialist at Umea University, investigated records in a remote parish of Overkalix in the north of the country. The parish was so isolated that in the 19th century people starved if the harvest was bad. In other years, there was so much that people could gorge for months.
Byrgen found that boys who went through lean years in the runup to puberty had grandsons who lived longer. A plentiful food supply in mid-childhood, in contrast, was associated with a fourfold increased risk of diabetes on their grandchild’s death certificate.
These Swedish and British findings – which have been supported by animal studies – are profound. According to strict Darwinian theory, only natural selection can rewrite our genes – not the day-to-day experiences of famine and feast, smoking or sunshine. Yet there are now documented environmental effects in one generation that appear to be passed down to future generations. What could explain such a muddle of nature and nurture?
For Pembrey, the answer is likely to lie in a recently developed branch of science – epigenetics. In the 10 years since scientists presented the first draft of the Human Genome Project – the mammoth task in which scientists recorded the 3bn chemical letters that make up a human being’s DNA – it has become increasingly clear that it doesn’t just matter what genes you inherit from your parents, but how they are controlled and expressed.
This is the world of epigenetics. It is the study of the layer of chemical switches and signals that activate, silence and crank up our genes. It is where nature bumps into nurture.
Pembrey suspects that heritable changes in gene expression were passed down from the Swedish grandfathers to their grandsons on the Y sex chromosome carried by sperm. ”We now have enough evidence to say trans-generational responses exist in humans,” he said. ”The idea that you start at conception with a clean sheet and that the cause of small birth weight or a different size placenta is purely the exposure from conception onwards is almost certainly wrong. The eggs and sperm are already arriving with a gene expression pattern determined by ancestral exposures.“
The mechanism for how signals are passed across generations is still unclear. Some epigenetic changes are caused by a process called DNA methylation. A methyl is a small molecule that attaches itself to DNA. In the right place it can switch off a gene, or affect its behaviour. Others are caused by modifications of histones, the proteins that help package DNA into our chromosomes. Epigenetic changes can also involve micro RNA, strands of genetic material that play a crucial role in silencing genes.
Whatever the mechanisms, Pembrey argues that it makes evolutionary sense for our bodies to send signals about environment across the generations. If a baby is being conceived in a world of famine, then its chances of survival will obviously be increased if its body can be “prepared” before birth.
So if signals are being transmitted through generations, and if our babies are being affected by maternal diet and lifestyles in the womb, what implications does that have for medicine?
Well, for a start it raises the possibility that the obesity epidemic sweeping the western world may be influenced by the childhood diet of baby boomers and war babies – and not just by modern day overeating and lack of exercise. It also suggests the lifestyles of the current generation can influence the health of babies born 50 years later. That means preventative medicine isn’t just about improving a patient’s own life chances, but the future health of their children and grandchildren.
Professor Cyrus Cooper, director of the Lifecourse Epidemiology Unit at the University of Southampton, estimates that prenatal and early childhood environment contribute to 30% to 40% of the risk factors for cardiovascular disease, and around 20% to 25% of osteoporosis and obesity. His team is developing a public health programme to change the eating habits of teenage girls to prevent future heart and bone disease.
“A mother from a deprived socio-economic background often has a diet that is not optimal for the foetus growing in her,” he said. “There is then a tendency for this to lead to poor infant feeding practice and a child at higher risk of obesity by age four years. We are studying how we might alter the food choice of young girls before and during pregnancy, as well as methods to correct deficiencies of nutrients such as vitamin D.”
Another implication is for personalised medicine – the idea that treatments should be tailored to meet a patient’s own genetic makeup.
The work on foetal and ancestral origins of ill health suggests doctors may need to look at their epigenetic make up as well as their genes.
Earlier this year, researchers at University College London, funded by the British Heart Foundation, showed that a drug, thymosin beta 4, can “prime” a heart to repair itself in the event of a heart attack. The catch with the drug is that it has to be used before a cardiac arrest. But if doctors know from patient profiling – including epigenetic profiling – that someone was at high risk of heart attack, they could be given a tablet by their GP to prime their heart just in case.
It’s not just about preventative health. In the US, four epigenetic drugs for cancer have been approved by FDA. “We already know that modification of the epigenome may help in the treatment of cancer and there is huge scope for understanding whether such modification will help treat other disorders,” said Cooper. “Those drug targets could well be in obesity, osteoporosis and osteoarthritis, all of which are strongly linked to body composition.”
At the UCL Institute of Cancer, Professor Stephan Beck is mapping the epigenetic markers in different types of cells – including those with and without cancer – to see which ones contribute to disease. “I’m pretty sure we will get to the point where we can identify major epigenetic difference in these diseases and where we can reset them,” he said. “If you look at cancer, the aim should be to change cancer into a chronic disease. If you could get a cancer jab every day that keeps it under control – like you do for insulin jabs in diabetes – your quality of life would be hugely improved.”
Source: The Guardian – http://goo.gl/fZTSe
