Stroke Risk Starts in Womb

Researchers from the UK's University of Southampton and the Medical University of South Carolina in Charleston recently proposed an unusual hypothesis to account for the abnormally high rate of stroke among elderly people living in some areas of England and the United States. According to their hypothesis, stroke occurs frequently in these areas not only because of the unhealthy eating and exercise habits of local residents, but also because of the poor living conditions of previous poverty-stricken generations.

A stroke occurs when there is a blockage or rupture of a blood vessel to the brain. This leads to brain damage, whose manifestations can include dizziness, slurred speech, and, in more severe cases, a loss of muscular control, sensation and consciousness. But David Barker, a Southampton researcher who led the study, believes that the foundation for stroke may be laid well before any dangerous blood clots form. "When living things develop, and human beings are no exception, they are very sensitive to the environment. And that includes the environment inside the womb," said Barker. This hypothesis is bolstered by the correlation, illustrated in Barker and his colleagues' study, between regions historically afflicted with devastating poverty and "stroke belts"-regions in which strokes occur frequently. The American Southeast and the northern regions of England and Wales have long been recognized as stroke belts. According to Barker, the current standard of living in those regions isn't bad enough to account for the abnormally high stroke rate, but during the mid-19th and early 20th centuries, both areas were plagued by extreme poverty and malnutrition. In the American Southeast, these problems began after the Civil War, and persisted until after the Depression. In Britain, they set in during the Industrial Revolution, when towns in the northern regions of England and Wales rapidly turned into crowded, unhealthy slums housing poor factory workers.

Barker and his team examined medical records of people who lived in stroke belts back then. Not unexpectedly, the general population's health had been extremely poor: infant and maternal death rates were high, and most people were malnourished, as indicated by their abnormally short statures. The researchers assert that these conditions caused women to give birth to children who were likely to suffer from stroke in later life. This would explain why the stroke belts began to emerge around the middle of the 20th century-the time when those children began reaching old age (when strokes typically occur). Thus, the researchers present a strong case that a person's lifetime health may be traceable back to the nine months he or she spent in the womb.

The researchers' study, published in the July 2003 issue of the American Heart Association's journal Stroke, constitutes part of a small but growing body of research suggesting that conditions in the womb significantly impact a person's health in ways that may not be evident until later life. This theory goes far beyond acknowledging that babies can suffer physical and developmental disabilities when their mothers drink, smoke, use drugs, or take certain medicines during pregnancy. Instead, it suggests that healthy babies with no genetic defects and no history of disease in their families can still be destined for future health problems because of conditions they experienced in the womb.

Researchers began seriously studying the health effects of the uterine environment after the end of World War II. As the war drew to a close, the Germans blocked off supply channels to Denmark's largest cities, creating a famine. The Danes were badly malnourished, and two decades later, when boys who had been in their mothers' wombs during the famine underwent their military physicals, it was found that they were surprisingly prone to obesity. Scientists believed this health problem was related to the famine 20 years before. Similarly, during the Dutch Hunger Winter of 1944 to 1945, Germans cut off the food supply to parts of the Netherlands. Later, researchers determined that children who had been severely malnourished while in the womb had a predisposition for conditions such as schizophrenia, obesity and diabetes. And, they found correlations between malnutrition at different periods in a fetus's development and specific medical conditions. For example, fetuses that suffered from malnourishment early on in their development were prone to obesity, while those who suffered later in their development were prone to decreased glucose tolerance.

The theory that stress, poor nutrition and other factors affecting a pregnant woman can also affect her growing fetus and predispose it to future health problems is now becoming more accepted. Heart disease, diabetes, stroke, cancer, and perhaps even psychiatric conditions such as bipolar disorder and schizophrenia could all be related to the environment in the womb. "When the fetus is at specific, critical points in development, different organs in the body-the pancreas, the brain-are more vulnerable than others to a stressful situation," is what Kent Thornburg of the Oregon Health Sciences University told the Washington Post. If these organs receive too many stress hormones or do not get enough food from the mother, they will undergo a process called programming. "Assuming" that stress is natural and that the body will have to live under stress for its whole life, the organs adjust to survival under stressful conditions. "But that modifies their gene expression for life in ways that may not in fact be advantageous," said Thornburg.

Barker is a leading proponent of the "fetal origins of adult disease" (FOAD) hypothesis. In addition to laying the groundwork for strokes, prenatal environmental factors seem to predispose people to heart disease. His original studies found that babies who were born small-weighing about six or seven pounds-were more likely to develop heart disease as adults. This result has been confirmed by other studies. "The mom early on signals to the fetus what the environment is really like. 'You're going to grow up in a poor environment, so you'd better slow down your growth trajectory,'" Arye Stein of Emory University told the Post. If the environment remains poor after birth, the child is well adapted because of the preparations in the womb. But if the environment improves so that there is plenty of food and work is sedentary, the child will be poorly adapted, and will end up depositing fat too easily. There is also evidence that abnormally large babies, who may have been exposed to abnormally high or low levels of hormones or growth factors in the womb, may have an increased risk of developing cancer. Karin Michels of Harvard Medical School found that women who had been large babies, possibly due to high concentrations of such chemicals in the mother's body, had twice the usual risk of breast cancer.

Other problems could arise when events during pregnancy affect a fetus's nervous system, possibly leading to mental illness. For example, when a pregnant woman's body fights off an infection, her activated immune system could affect the fetus's brain, leading to increased risk of schizophrenia, a mental illness characterized by delusions, confused thinking, and unusual behavior that makes social interaction difficult.

Sources

"A Pregnant Mother's Diet May Turn the Genes Around." Sandra Blakeslee. New York Times , October 7, 2003, page F1.

"Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation." Robert Waterland and Randy Jirtle. Molecular and Cell Biology, August 2003, page 5293.

"Exposure at Ground Zero Is Linked to Smaller Babies." Patricia Callahan. Wall Street Journal, August 6, 2003, page D3.