A Mouthful of Evidence:
A Little Help from Baboons
In collaboration with the University of Texas Health Sciences Center at San Antonio and The Forsyth Institute in Boston, Ebersole is attacking the problem from another direction, too. He is studying samples from pregnant baboons.
"Baboons were chosen for several reasons," Ebersole says. "They develop periodontal disease similar to humans, they are a tough animal, the mother/child bond is stronger than with many other primates, and there is an available colony of about 3,500 baboons at the National Primate Research Center in San Antonio."
Ebersole and his collaborator, Lakshmyya Kesavalu, a veterinary researcher at UK's Center for Oral Health Research, are studying the effects of periodontal disease on pre-term birth in the animals.
Research began in July 2002, with samples from a group of 37 baboons. Ebersole will be making three or four trips to San Antonio each year during this project to collect clinical, microbiological and blood samples. The blood samples will then be brought to UK for study. Ebersole expects the study to be completed in 2007.
Mothers-to-be take a research role
Ebersole's UK colleague John Novak, professor and associate director of the Center for Oral Health Research, is the principal investigator at UK for a $7 million study, a human-subjects counterpart to the work Ebersole is doing with baboons. In this first-ever national, multi-center study, Novak and his team will examine pregnant women who already have periodontal disease in a project being funded by the National Institute of Dental and Craniofacial Research.
Jeffrey Ebersole (left) and John Novak in are investigating the link between periodontal disease in expectant mothers and low birthweight of their babies.
The University of Minnesota is leading this study, with research partners at UK, the University of Mississippi and Columbia University. Each university is recruiting 200 patients into the study. Half of the mothers will be treated for periodontal disease during their second trimester and the other half treated after giving birth.
At UK, the research is being done in collaboration with the Department of Obstetrics and Gynecology's High-Risk Maternal Fetal Medicine Clinic. James Ferguson, department chair of obstetrics and gynecology, is a co-investigator on the study. It is the first large, federally funded study to be done as part of the new Delta Dental Plan of Kentucky Clinical Research Center located in the College of Dentistry.
"This is primarily an intervention study," says Novak. "We will be treating periodontal disease as an infection, then seeing what effect that has on the delivery of the child relative to the adverse outcomes that are associated with pre-term delivery." He says the primary question is, "Does the mother deliver prematurely?" The secondary question is, "What impact does it have on the baby?"
The researchers began recruiting patients in March 2003 for the study, which will take two to three years to complete. "What we really don't understand is what types of oral infection are associated with pre-term birth," says Novak. "Is every woman who has an infection in her mouth, who has plaque in her mouth, liable to deliver her baby pre-term? Well, we know this isn't true. Most women deliver normally. So we are also very interested in the types of infections that make up their dental plaque and the types of bacteria that are colonizing their mouth."
Novak is targeting seven or eight bacteria, the same ones implicated in many other problems. Interestingly, one of the oral bacterial species may be associated with early fetal loss in horses, a condition called Mare Reproductive Loss Syndrome. Novak and Ebersole are also planning collaborative studies with the College of Agriculture's Department of Veterinary Science to look at the potential contribution of oral infections to fetal deaths in horses.
"Veterinarians have identified a specific organism in the horse that is very closely related to an oral organism in humans," Novak says. "They don't know how this organism gets from the horse's mouth to the fetus and may create this problem, but they have already isolated the organism from the fetal membranes."
Novak says this organism, a member of the bacterial family Actinobacillius, is closely related to an organism in humans that causes severe periodontal disease in young people. "It appears that similar biologic processes may be occurring in some pregnant mares," he says.
Ebersole reiterates that the overall goal in his study and Novak's is to identify if there is a link between periodontal disease and pre-term, low-birthweight infants and, if so, how strong this link is. The next step, he says, is to intervene in that process to lower the risk of pre-term birth. "Eventually we hope to have this treated as a public health measure so that every expectant mother receives dental care as part of her prenatal care," he says.
Delta Dental ensuring further clinical research
The Delta Dental Plan of Kentucky Clinical Research Center was created in October 2002 with a $750,000 endowment from Delta Dental, an amount matched by the Kentucky Research Challenge Trust Fund. The center will combine the expertise of medical and dental researchers with research groups around the country, and will serve as a focal point for interdisciplinary research.
The University of Louisville received a similar gift, boosting Delta Dental's investment in oral health research in Kentucky to $1.5 million. At UK, the center will be the clinical arm of the Center for Oral Health Research, which Jeffrey Ebersole directs.
"The establishment of these centers immediately gives us a greater opportunity to develop and implement collaborative clinical and translational research with investigators in Kentucky, across the country and around the world," Ebersole says.
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