From Womb to Tomb

Can events that happened before we were born dictate our life span and our susceptibility to adult disease? Many people squirm at the idea of predestination, the notion that our fates are somehow beyond our control. Now an emerging but still hotly debated theory suggests that our destinies--or at least our susceptibilities to various diseases--might, to a significant extent, be decided before we are born. Earlier this month, an international group of scientists assembled in Brighton, U.K., for the Second World Congress on Fetal Origins of Adult Disease. There they examined the idea that early events, either in utero or during infancy, can determine our health in adulthood and even our life span itself. If the seeds of future health are sown in the womb, the public health implications could be enormous: Society might need to bolster its investment in prenatal care to stave off diseases normally associated with growing old. Physicians have long known that conditions in the womb can have lasting consequences: Developing embryos that don't receive enough folic acid, for example, have an increased risk of neural tube defects. But the "fetal origins hypothesis"--sometimes called the "Barker hypothesis," after the controversial medical scientist David Barker of the University of Southampton, U.K.--goes beyond birth defects, suggesting that malnutrition during pregnancy can severely compromise the long-term health and longevity of a woman's offspring. In the late 1980s, Barker published data showing that babies born with low birth weights in Hertfordshire, U.K., had a higher incidence of heart disease as adults. After other studies revealed similar findings, Barker proposed that fetuses deprived of essential nutrients in utero might be programmed to suffer from later-life chronic conditions such as hypertension, coronary heart disease, and diabetes. Barker contends that a fetus responds to malnutrition during development by reducing the number of cells in its organs, for example, or by altering the structure of the organs themselves--adaptations that could make the body more susceptible to chronic diseases and, ultimately, shorten life span. Taken to an extreme, the fetal origins hypothesis has some alarming implications. As Nobel laureate Robert Fogel, an economist at the University of Chicago, has written, the theory provides a kind of "double blow" to the elderly: First, it suggests that the chronic conditions from which they suffer could perhaps have been prevented earlier in life. Second, such a notion could prompt society to divert monies and resources earmarked for the very old to the very young and unborn. Peter Nathanielsz, a New York University medical scientist and Barker acolyte, has even suggested that in the future, health insurers might first demand that those seeking coverage divulge their birth weights and then adjust rates accordingly. Today many scientists believe that the fetal origins hypothesis holds at least a kernel of truth, and some strongly believe in it. Few, however, are willing to make public health recommendations on that basis--at least not yet. Although numerous epidemiological studies show correlations between early-life conditions and the risk of a slew of later-life diseases, no one yet knows how strong the supposed Barker effect is or the extent to which leading a healthy life can overcome it. Even researchers who remain skeptical of Barker's work have found some data that support the notion that prenatal and early postnatal conditions affect adult health. Research by epidemiologists Gabriele Doblhammer and James W. Vaupel of the Max Planck Institute for Demographic Research in Rostock, Germany, shows that in the early part of the 20th century, babies born in Austria and Denmark during autumn had a greater life expectancy at age 50 than did those born in spring. The most likely explanation for these findings, according to the authors' 2001 paper in the Proceedings of the National Academy of Sciences, is that the seasonality of infectious disease and the availability of nutrients caused some fetuses to suffer more in the womb or shortly after birth, which in turn led to increased disease susceptibility later--and hence, shorter lives. Although the study demonstrates that conditions in the womb and in infancy influence subsequent health, it revealed that longevity shifted by only a matter of months. "All the evidence I know about suggests that early-life events are only modestly important," says Vaupel. Barker, by contrast, has suggested that malnutrition in utero can damage health even more than smoking does. Regardless of how much early-life events imperil future well-being, researchers will not be in a position to devise treatments that might reverse prenatal damage until they understand the biological mechanisms that underlie the effect. "I don't think we're to the point of giving advice yet, because we don't really know the causal pathways," says Matthew Gillman, a Harvard epidemiologist and leading fetal origins researcher. Some scientists remain unconvinced that maternal malnutrition causes the kinds of findings turned up by Barker and others. The real culprit could be social class, says epidemiologist Kaare Christensen of the University of Southern Denmark in Odense. After all, poverty tends to go hand in hand with numerous negative health outcomes and acts over the course of a lifetime. Christensen also points out that the Barker hypothesis provides a purely environmental explanation for disease--the environment in this case being the mother's womb. But "genetic factors that affect your [weight at] birth may also affect you later in life," he says. Even if prenatal events turn out to significantly influence later-life health, we might still have the capacity to control our fates. When it comes to health and life span, "adult behavior trumps fetal origins," says Nevin Scrimshaw, institute professor emeritus at the Massachusetts Institute of Technology and president of the International Nutrition Foundation. Those investigating fetal origins have now begun to move beyond epidemiological studies to investigate the underlying processes--for example, whether particular genes are switched on or off in response to varying nutrition in utero. In the meantime, pregnant women should certainly keep themselves well nourished, but there's no reason for middle-aged adults to stop paying visits to the stair climber. Chris Mooney is a freelance writer living in Berkeley, California, a situation that may or may not have something to do with what his mother was eating 26 years ago.