"Preterm births are a major public health problem and are common in the United States with more than 10 percent of births taking place prematurely," explained Michael Gravett, M.D., chief of maternal-fetal medicine; a professor of obstetrics and gynecology in the OHSU School of Medicine and an associate scientist at the OHSU Oregon National Primate Research Center. "Premature births are responsible for a startling 80 percent of newborn deaths that are not associated with birth defects. By finding a method for quickly detecting one of the major cases of preterm labor and then treating it, we believe this finding could have a very significant impact and likely save young lives."
To conduct this research, Gravett and his colleague Srinivasa Nagalla, M.D., teamed animal and human studies with state-of-the-art proteomics research. The scientist's utilized cutting-edge mass spectrometry and bioinformatics methods to find biomarkers associated with detectable biological signs, for intra-amniotic infection.
"The result was the identification of proteins and peptides in both human and non-human primate amniotic fluid that signal an infection exists," said Nagalla, an associate professor of pediatrics in the OHSU School of Medicine and director of the Center for Biomarker Discovery. "The likely outcome of this finding is that a simple test may be developed to detect the presence of these biomarkers, thereby signaling the pregnant woman has an infection that needs treatment."
Previous research in non-human primates by Gravett and his colleagues demonstrates that when detected and treated with the correct combination of drugs, intra-amniotic infections can be suppressed and premature birth prevented.
In conducting this current research, the scientists used mass spectrometry analysis of non-human primates amniotic fluid to not only identify the protein biomarkers for intra-amniotic infections, but also the length of time between infection and the appearance of these biomarkers.
"Biomarkers for infection were detected in a very short amount of time, within only 12 hours of infection," explained Nagalla.
"In addition to animal studies, we studied pregnant women to confirm that the data gathered about non-human primate biomarkers correlates to humans," added Gravett. The biomarkers identified in the animal studies was also identified in 11 of the 11 patients with infections. In addition, testing of patients without infections resulted in no false positives."
While this research may result in significant health benefits, there are also likely economic impacts. The breakthrough technology is licensed to ProteoGenix, an Oregon biotechnology company founded by OHSU, Nagalla, Gravett, and other collaborators in 2002. The company employs proteomic and functional genomics technology to discover, develop, manufacture, and commercialize biomarkers for fetal, maternal, pediatric and adult applications.
The ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International.
OHSU includes the schools of dentistry, medicine, nursing and science and engineering; OHSU Hospital and Doernbecher Children's Hospital; numerous primary care and specialty clinics; multiple research institutes; and several outreach and community service units.
Note: OHSU and Drs. Gravett and Nagalla have a significant financial interest in ProteoGenix, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by the OHSU Conflict of Interest in Research Committee.
Journal
JAMA