Heart disease in adulthood is preprogrammed in the womb, epidemiological studies suggest, and the chief culprit appears to be the mother's nutritional health, but it is not clear yet exactly what the biological mechanism at fault is. Scientists with Oregon Health & Science University's Heart Research Center have launched the first phase of a large study to find the answer.

One hundred fifty Klamath Falls, Ore., women of child-bearing age are being recruited for the initial phase of the Oregon Women's Study -- 50 who are in the first trimester of pregnancy, 50 in the last trimester and 50 who are not pregnant. The study will test methodology for a much larger study for which OHSU is expected to seek funding support from the National Institutes of Health.

The objective of the Oregon Women's Study is to determine how the nutrition, metabolism and lifestyle of pregnant women influences the growth pattern of the fetus and later the infant in its first year.

Epidemiological studies long have shown that low-birth-weight babies are more prone to developing cardiovascular disease, coronary disease, type 2 diabetes, osteoporosis and even cognitive deficits and certain kinds of mental illnesses later in life. Poor nutrition has been suspected to be the chief cause.

"We know a lot about the associations between being born small and the diseases for which you are at risk, but what we're missing are the biological causes of this effect," said Kent L. Thornburg, Ph.D., director of the OHSU Heart Research Center, M. Lowell Edwards Chair of Research in Clinical Cardiology and professor of medicine (cardiovascular medicine) in the OHSU School of Medicine.

"Very early in a pregnancy, it is thought, the embryo reads chemical signals from the mother that tell it how fast to grow and how it should configure its cellular anatomy," said Thornburg. "Eggs are fertilized up in the fallopian tube creating the blastocyst which works its way down to the womb and, as it does so, it is undergoing cell divisions. The nutritional environment before the blastocyst implants in the womb influences the growth and pattern of cell formations that form the actual embryo and those that end up as the placenta around it."

Nutritional deprivation in critical periods during gestation triggers adaptive mechanisms, it is suspected, that cause the fetus to reduce its demand for nutrients and redistribute blood flow to protect the embryonic brain and other key organs. These adaptations help keep the fetus alive but, after birth, appear to have lifetime consequences for the body's structure and metabolism.

"These kids are born small and they grow up to be more vulnerable to diseases," said Thornburg. "They are physiologically different. The origins of chronic diseases that were once thought to be almost wholly genetic are now known to be largely environmental and the nature-versus-nurture debate has taken a new twist."

The cohort of women in the Klamath Falls study who are not pregnant but later become pregnant will be a prized source of base-line information for drawing inferences about their diets and body compositions before pregnancy and the subsequent growth and composition of their embryos during the first trimester. These women will be followed through the gestation period and their progeny will be tracked for several years after birth.

Why Klamath Falls? This rural southern Oregon community of 42,000 (a count that includes the city, its suburbs and surrounding communities) was chosen for the pilot study for both scientific and practical reasons. "There are distinct cultural and regional differences in the way people eat," said Thornburg. "We don't know much about the diets of people in Oregon's rural communities and we don't know much about how their babies grow. Eventually, we want to repeat this work in as many of Oregon's subcultures as we can find. Klamath Falls also has a relatively stable population which makes it simpler to track women over a long period of time."

Among the practical reasons: Many Klamath Falls family physicians are part of the Oregon Rural Practice-based Research Network, a collaboration of researchers and health professionals both at OHSU and in rural communities throughout the state dedicated to community-based research.  Also, OHSU's Cascades East Family Medicine Residency Program - which is co-sponsored by Merle West Medical Center, Klamath Falls' largest employer, and the Oregon Area Health Education and Training Center - is based there.

The Oregon Women's Study grows out of the award-winning epidemiological research of David Barker, M.D., Ph.D., adjunct professor of medicine (cardiovascular medicine), OHSU School of Medicine and also professor at the University of Southampton in the United Kingdom. Barker's "early origins hypothesis," put forth more than 15 years ago, said that restrictions on fetal growth are associated with a range of disabling adult medical disorders, most notably coronary heart disease. Numerous large-scale studies in Europe, Asia and the United States have lent further support to his hypothesis in the years since. Barker, a fellow of the Royal Society, was honored for his work in 2005 with the Danone International Prize for Nutrition.

The Klamath Falls study is being conducted under the leadership of Cynthia D. Morris, Ph.D., M.P.H., professor and vice chairwoman of medical informatics and clinical epidemiology, OHSU School of Medicine; Sally Y. Segel, M.D., assistant professor of obstetrics and gynecology, OHSU School of Medicine; and Robert G. Ross, M.D, assistant professor of family medicine, OHSU School of Medicine, and director of the Cascades East Family Medicine Residency Program. Diane Davina, R.N., a Klamath Falls nurse, is the study's Heart Research Center coordinator.

The Northwest Health Foundation, the Collins Medical Trust and the Audrey Love Charitable Foundation, along with many individuals, are providing financial support for the study.

For more information about the Oregon Women's Study, go to http://www.ohsu.edu/heart/ , e-mail Lisa Rhuman at rhumanl@ohsu.edu, or call the OHSU Heart Research Center at (503) 494-2382.

About OHSU
Oregon Health & Science University is the state's only health and research university, and only academic health center. It is Portland's largest employer and the fourth largest in Oregon (excluding government), with nearly 12,000 employees. It serves 189,000 patients, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to each county in the state.