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While the genes we inherit provide us with the basic blueprint for life, and death, most human disease is the result of the interaction of genetic susceptibility and environmental factors. While most research has looked at environmental effects after birth, studies at Southampton University and elsewhere are increasingly showing that the 266 or so days from conception to birth is the time when much of what will happen during the decades ahead is determined.
As well as longevity, the likelihood of developing heart disease, cancer, asthma, high blood pressure, osteoporosis, obesity, depression and schizophrenia can all be influenced by what happens during those nine months. And there’s more: fertility, family size, soccer ability, navigational skills, personality and even the likely lifetime number of sexual partners may all have some links to events in utero.
At the heart of the research is the “foetal origins of disease” hypothesis, which suggests that diseases may originate through foetal adaptations to under-nutrition, over-nutrition or unbalanced nutrition, or to other environmental changes. The debate now is not so much about the validity of the theory, as to how strong its effects are, and how they can be changed.
“The fundamental controversy now revolves around not whether but to what degree environmentally induced factors in early life are major determinants of disease risk,” says Mark Hanson, the British Heart Foundation Professor of Cardiovascular Science at Southampton University and co-author of a new report on the theory being published in the science journal Biology of the Neonate. “The implications of this are profound. If early-life factors are important, it leads to a fundamental shift in the management of care prior to conception, during pregnancy, and following birth.”
The mechanisms by which this foetal adaptation occurs are still being investigated but one suggestion is that the foetus has a genetically determined range of responses and that the one it selects is determined by the environment in the womb.
The theory, first put forward by researchers at Southampton University, is that the foetus responds to an adverse environment by re-setting its growth plans to prepare for a life in a deprived environment. But if that environment turns out not to be deprived it is not best equipped to survive. Fearing that life outside the womb is going to be as deprived as it is inside, the foetus may, for example, create a level of insulin resistance that allows survival in times of famine through efficient storage of fat in rare times of plenty. But in a postnatal world of constant plenty, that set-up would lead to a greater risk of obesity, diabetes and heart disease. Research shows that babies conceived during the Dutch famine (1944-1945) were more prone to heart disease and obesity.
Professor Peter Gluckman, a respected paeditritian at the University of Auckland says: “If the foetus has predicted its future environment correctly, then the developmental path chosen will lead to health in adult life. However, if the foetal prediction is wrong, then as an adult it will not have settings appropriate to its environment and disease risk is enhanced. In other words, the risk of disease is determined by the degree of match between the prenatal anticipated environment and the actual postnatal environment faced as an adult.”
This anticipatory effect could have an effect on disease risk and longevity. A new study at the Max Planck Institute for Demographic Research based on 1,487 elderly Germans found that people born in June, whose first trimester would have been in the winter, were 23 per cent less likely to reach 105 than those born in December. In the womb, perhaps they had been preparing for starvation.
The elements of the environment that can affect the developing baby in this way include the mother’s diet, hormonal changes, changes in the placenta, maternal exposure to disease and the general weight, fitness and lifestyle of the mother. “We think it is a combination of maternal diet and maternal body composition and, potentially, lifestyle, which might include stress and levels of exercise, as well as smoking of course,” says Professor Hanson.
()There is some evidence, for example, that a shortage of food in the womb may shorten lifespan, which could explain the difference in longevity between the rich and the poor. There’s work too that suggests that loss of bone density later in life is greater in those people who did not grow well in the womb.
The research suggests that a change in diet, a switch in lifestyle, a change in hormone levels or a brief infection in the first nine months of life can have an impact on health decades later. It opens up the possibility of being able to manipulate the womb environment to improve health years later. Some research, for example, suggests that the risk of schizophrenia could be reduced by giving mums supplements of fatty acids, which have an effect on brain cells.
The research will also help to identify people at risk of disease. “To me the good news is that it is not just genetic,” says Professor Hanson. “We may be able to pick up markers in early life which will tell us how genes involved in disease will be turned on or off later in life. There is therefore the potential to spot the child who will, for example, have to watch his diet. We are at the forefront of a new medical initiative here. It is all very exciting.”
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