82: Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in preterm labor with intact membranes

Abstract

Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor (PTL) and is associated with maternal and neonatal infectious morbidity. MIAC is often occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort with PTL and to validate the test in an independent cohort. Prospective study of women with PTL who had amniocentesis to screen for MIAC. MIAC was defined as a positive culture and/or 16S-rDNA by PCR. Nine candidate CVF proteins were analyzed by ELISA. Logistic regression was used to identify combinations of up to 3 CVF proteins that could accurately classify the Phase 1 cohort (N=108) into those with or without MIAC. The best models were selected based on ROC area-under-curve (AUC) in Phase 1. Model performance was then tested in a second cohort (Phase 2, N=306). MIAC was present in 15% of cases in Phase 1, 9% in Phase 2. A 3-marker CVF model using IL6, Gro-α, and IGF-BP1 had AUC 0.87 in Phase 1 and AUC 0.78 in Phase 2. Two-marker CVF models using IL6+Gro-α or AFP+Gro-α performed similarly in Phase 2 (AUC 0.78, 0.75 respectively), but were not superior to CVF-IL6 alone (AUC 0.80, Figure). A cut-off value of CVF-IL6 >463 pg/ml (which had 81% sensitivity in Phase 1) predicted MIAC in Phase 2 with sensitivity 79%, specificity 78%, PPV 38%, NPV 97%, +LR 3.6, -LR 0.27. CVF-IL6 was also a strong predictor of severely elevated amniotic fluid IL6 (≥11.3 ng/mL) in phase 2 (AUC 0.83). Cervicovaginal fluid IL-6, alone or in combination with Gro-α, is strongly associated with MIAC. If developed into a bedside test or rapid lab assay, a test based on cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.