ProteoGenix Publishes Key Study of Intra-amniotic Infection in Journal of the American Medical Association

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Despite improvements in prenatal care, preterm birth occurs in 11.8% of births in the United States and remains the major obstetrical problem in developed countries. Recently, intraamniotic infection (IAI) has been implicated as a major cause of preterm birth. Intraamniotic infections cause more than 50% of very low birth-weight neonates born before 30 weeks of gestation, in which neonatal mortality and morbidity are high. ProteoGenix scientists, led by Drs. Michael Gravett and Srinivassa Nagalla, report a breakthrough diagnostic test to detect IAI using a novel proteomics based technology.

Most women in preterm labor with intact membranes and a positive AF microbial culture are refractory to standard tocolytic therapy and rapidly deliver compared to women in preterm labor with sterile amniotic fluid . Moreover, antibiotic therapy has not prevented preterm delivery in most studies possibly because the patient subgroup with early IAI that might benefit from antibiotic treatment is identified too late or not at all. The objective of this study was to discover novel biomarkers for subclinical or occult IAI by proteomic profiling methods. We utilized surface-enhanced laser desorption-ionization/time-of-flight (SELDI-TOF) mass spectrometry (MS), gel electrophoresis, and tandem mass spectrometry (MS/MS) to characterize amniotic fluid peptides in pregnant rhesus monkeys with experimental IAI. The proteome profile that was identified in infected monkeys was then tested for specificity and sensitivity in detecting sub-clinical IAI among women in preterm labor.

This proteomics-based characterization of the differential expression of AF proteins in IAI identified a distinct proteomic profile in an experimental primate chorioamnionitis model that was 100% sensitive and 91% specific in detecting sub-clinical IAI among a human cohort with preterm labor. These diagnostic protein expression signatures, complemented by immunodetection of specific biomarkers in AF and in maternal serum, have application in the early detection of IAI.