Sunday, March 28, 2004

Tom Spears
The Ottawa Citizen

Doctors are poised to gather blood and DNA from thousands of pregnant Ottawa women, and later from their newborns, to learn how events in the womb influence people's health far later in their lifetimes.

In a $2.5-million study that may continue for decades, the Ottawa Hospital Research Institute will examine 8,000 mother-baby pairs (and trios), beginning with questions about why some pregnancies are healthy and others have unexpected complications. But the researchers hope for much more -- to follow the babies for their entire lives, and learn how their future health may be influenced by whether their mothers smoked, breathed pesticides, or carried certain genes.

With luck, they'll have early results about the pregnancy phase by Mother's Day of 2005, based on the first 3,000 births.

Insiders are calling it the mother of all studies, but it's also a study of all mothers.

It's loosely patterned on the famous study of ordinary residents of Framingham, a town near Boston. Beginning in 1948, family doctors there reported on the lifestyles and medical histories of 5,200 men and women, adding 5,000 more a generation later. Researchers combing through all the data made discoveries that are now taken for granted, but which were major breakthroughs at the time.

They found, for instance, that a high-fat diet and poor exercise led to high cholesterol, stroke and heart attacks, and that smoking damages the heart and blood vessels, too. These and other Framingham findings are basic to modern medicine.

"People are calling this (Ottawa study) the Fetal Framingham," said Dr. Mark Walker, the high-risk obstetrician and epidemiologist leading the study of mothers and babies.

"We're recruiting the subjects in utero, between 12 and 20 weeks" of pregnancy, he said. "At that time we're collecting information on mom's lifestyle, socio-economic factors and medical history. But as well we're collecting blood for vitamin levels -- folic acid is the most important one -- and DNA."

Doctors hope the information on physical factors, genes and social environment will give clues about why some pregnancies end in stillbirth, often with no warning. It may also help explain why some babies are born small and others large, and why some complications happen during pregnancy.

At birth, they'll collect placenta samples and babies' blood to see how the mother's and child's genes interact.

But that's just the start.

"Our hope is to follow this cohort (group) in perpetuity," Dr. Walker says. "We can start to look at some of the factors that may relate to childhood obesity, developmental delays, and ultimately to disease in adolescence and adulthood."

The inspiration for this approach is an exploding body of evidence that what happens in the womb has an enormous impact on a person's health for a lifetime.

"A lot of heart disease, diabetes, stroke, even some cancers probably have their origins in utero. It's that nine months in utero, and what's happening to the mom and what's happening to the baby, that determine what happens when you're 50 or 60 years old," he said.

One example: A study of thousands of Britons born in the 1920s showed that underweight babies had a higher risk of heart attacks, hypertension, stroke and Type 2 diabetes in later life. The increased risk "was as strong as from smoking or any lifestyle factors."

Long-term studies of this type are very expensive, and they're a big gamble for the agencies that fund them, says Dr. Andreas Wielgosz, an Ottawa cardiologist and spokesman for the Heart and Stroke Foundation of Canada. The foundation is a major supporter of the Walker team.

But Dr. Wielgosz says the risks -- of subjects moving away and losing touch, or doctors not continuing the work for enough years -- are balanced by extra-large payoffs when the study works.

Because they're so wide-ranging, long-term "cohort" studies raise new topics that no one ever dreamed of investigating, he said.

They're also less prone to bias that studies where patients or doctors have to depend on memories of their health patterns from many years in the past. There are fewer gaps in information.

"You get a much cleaner study. One has to remember that it takes a while before we get results," he cautions, but "you have a mine of data. You can ask all sorts of questions and come up with interesting answers.... I think it's exciting, but I think it's going to be very challenging."

The Ottawa team will also examine the mother's exposure to environmental contaminants such as pesticides and follow the children.

"To my knowledge there's no other cohort like this," Dr. Walker says.

Other researchers from around the country are already approaching him, wanting to get in on the work.

The women, however, will be restricted to those seen in hospitals in Ottawa and Kingston. In addition to OHRI, the study is supported by the Ottawa Hospital, University of Ottawa, Ontario Innovation Trust, Canada Foundation for Innovation and Canadian Institutes of Health Research.

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