OHSU test targets premature births
Printed in the The Oregonian, July 28, 2004 by Patrick O'Neill

Scientists are developing a simple blood screening that could cut the number of risky early births nearly in half

Infections of the amniotic fluid and fetus result in thousands of babies with very low birth weight in the United States, costing billions of health care dollars a year. But scientists at Oregon Health & Science University say they're close to developing a test that could reduce the number of premature babies by 175,000 a year from the current 400,000. A study in today's issue of the Journal of the American Medical Association shows that doctors can detect amniotic infections -- a major cause of prematurity -- with a simple blood test that pinpoints protein biomarkers. Researchers hope the test, developed at OHSU, could replace riskier and less-accurate means of diagnosis, such as amniocentesis, in which a needle is used to take amniotic fluid through the abdominal wall. Dr. Michael G. Gravett, chief of maternal-fetal medicine at OHSU and the study's lead author, predicted that a test will be on the market within a year to determine if pregnant women have infections that could lead to premature birth. Those who have such infections could receive antibiotics earlier than is now possible to prevent premature delivery, he said. "This is potentially very important," said Dr. Robert Goldenberg, an obstetrics/gynecology professor at the University of Alabama at Birmingham who was not involved in the study. Other doctors noted that the study involved only 33 women and said further research is needed to confirm that certain proteins are, in fact, a universal indicator of the infections. Gravett said the test wouldn't be used on all pregnant women -- just those who have fevers after the 20th week of gestation.

Development of such a test could be a boon to OHSU's hopes of becoming a biomedical powerhouse. The study was funded in part by ProteoGenix Inc., an OHSU spinoff company of which Gravett is director of maternal and perinatal research. The technology used in the study is licensed to the company, which was founded by OHSU and some of the study's researchers in 2002. The company aims to use the study of proteins to find biomarkers for fetal, maternal, pediatric and adult illnesses. Gravett said ProteoGenix is working with a Texas company to develop kits that would be used in doctors' offices. He said he has no estimate of the number of kits that might be sold. Dr. Srinivasa Nagalla, director of the Center for Biomarker Discovery at OHSU's Doernbecher Children's Hospital and a study co-author, said the ability to identify proteins that are associated with specific diseases comes from field of study called "proteomics." Nagalla also is a founder of ProteoGenix. Using techniques developed in that field, he said, researchers can build a computerized profile of proteins that the body produces in response to certain illnesses. By identifying those proteins in a pregnant and feverish patient, doctors can to tell whether the woman has a uterine infection. Nagalla said a test likely would cost $200 to $300.

The study combined research on both monkeys and humans to look at the behavior of live cells.

Researchers at OHSU's Oregon National Primate Research Center infected 19 pregnant monkeys with infection-causing bacteria and found that within 12 hours, they produced telltale biological protein markers for the infection. The biomarkers were found in a study group of 11 women who were admitted to Seattle-area hospitals in premature labor and who were also found to have amniotic infections. The biomarkers were not present in another group of 11 women who gave birth prematurely but showed no evidence of infection. A third group of 11 women had no infection and delivered near-term. Gravett said preterm births occur about 10 percent of the time but account for 80 percent of newborn deaths -- apart from those caused by birth defects.

Until now, amniotic infections have been difficult to detect at an early stage. Symptoms, including early labor, tend to appear late in the course of the infections. Scientists hope future studies will determine whether antibiotics will really help stop premature labor.

"It would be a great thing if that's the case," said Dr. Glenn Markenson, a maternal-fetal medicine specialist at Baystate Medical Center in Springfield, Mass., who was not involved in the study. Gravett and Nagalla both have a significant financial interest in ProteoGenix. But Jim Newman, OHSU spokesman, said the potential conflict of interest has been reviewed by the OHSU Conflict of Interest in Research Committee. The Associated Press contributed to this report. Patrick O'Neill; 503-221-8233; poneill@news.oregonian.com