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Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

Authors: Combs, C Andrew  Garite, Thomas J  Lapidus, Jodi A  Lapointe, Jerome P  Gravett, Michael  Rael, Julie  Amon, Erol  Baxter, Jason K  Brady, Kim  Clewell, William  Eddleman, Keith A  Fortunato, Stephen  Franco, Albert  Haas, David M  Heyborne, Kent  Hickok, Durlin E  How, Helen Y  Luthy, David  Miller, Hugh  Nageotte, Michael  Pereira, Leonardo  Porreco, Richard  Robilio, Peter A  Simhan, Hyagriv  Sullivan, Scott A  Trofatter, Kenneth  Westover, Thomas  Obstetrix Collaborative Research Network,  
Citation: Combs CA, etal., Am J Obstet Gynecol. 2015 Apr;212(4):482.e1-482.e12. doi: 10.1016/j.ajog.2015.02.007. Epub 2015 Feb 14.
Pubmed: (View Article at PubMed) PMID:25687566
DOI: Full-text: DOI:10.1016/j.ajog.2015.02.007

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually 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 of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2).
STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306).
RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 >=463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%.
CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, 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.


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CRRD Object Information
CRRD ID: 12792243
Created: 2017-03-13
Species: All species
Last Modified: 2017-03-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.