13: Development of a noninvasive test for intraamniotic infection using proteomic analysis of cervicovaginal fluid in women with preterm labor


      To develop a noninvasive test for intraamniotic infection (IAI) in women with preterm labor, intact membranes (PTL-I).

      Study Design

      Among 105 cases of PTL-I before 37 wks, IAI was defined by amniocentesis results: positive amniotic fluid culture and/or 16S ribosomal DNA PCR (16S-rDNA), a highly sensitive & specific test for presence of eubacteria, Mycoplasma, and Ureaplasma sp. Immunoassays were used to quantitate proteins in cervicovaginal fluid (CVF). Candidate CVF proteins were entered individually and in combination into logistic regression models.


      IAI was present in 13% (14/105), 11 by both 16S-rDNA & culture, 3 by 16S-rDNA alone. From 75 candidate CVF proteins associated with IAI, 5 were included in a final model: 1 plasma protein, 2 cytokine/chemokines, 1 cell adhesion protein, 1 peroxidase. Final model had area under ROC 0.983. A dichotomous classification rule based on these 5 proteins had sensitivity 93%, specificity 93%, PPV 72%, NPV 99% for prediction of IAI, and screen positive rate 19%. Test performance was not impaired by blood in the CVF specimen (present in 12 cases without IAI, none with IAI.)


      In PTL-I, the CVF proteome is measurably altered by IAI. A prototype multiple-marker test based on the concentrations of 5 distinct proteins in CVF appears to discriminate between IAI and non-infected cases, potentially reducing need for amniocentesis. Such a test could be very useful in the management of PTL-I. Research regarding the role of various proteins in CVF may yield insight into the pathophysiology of PTL.