A new rapid bedside test to diagnose and monitor intra-amniotic inflammation in preterm PROM using transcervically collected fluid

Abstract Background Microbial invasion of the amniotic cavity, present in approximately 50% of patients with preterm prelabor rupture of membranes (PROM), is often associated with intra-amniotic inflammation, a risk factor for a short admission-to-delivery interval, early preterm delivery, and neonatal complications. We previously developed a cervical amniotic fluid collector, a device that allows collection of fluid noninvasively from the cervical canal when there is membrane rupture. Objective This study was designed to determine whether rapid analysis of an interleukin-8 (IL-8) concentration in fluid obtained non-invasively by the cervical amniotic fluid collector can be utilized to assess the risk of intra-amniotic inflammation. We also compared the diagnostic performance of this point-of-care test (POCT) for IL-8 in transcervically obtained fluid to that of a white blood cell (WBC) count determined in amniotic fluid retrieved by amniocentesis. Study Design This was a prospective cohort study performed between October 2011 and April 2017. Fluid was retrieved through both transabdominal amniocentesis and using a cervical amniotic fluid collector within 24 hours of amniocentesis in singleton pregnant patients with preterm PROM (16-35 weeks of gestation). Amniotic fluid obtained via amniocentesis was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas, and a white blood cell (WBC) count was determined. Intra-amniotic infection was diagnosed when microorganisms were identified by the culture of amniotic fluid. Intra-amniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/ml) assayed by ELISA. IL-8 in cervical fluid obtained by the collector was measured by the POCT which used a test strip and scanner based on the fluorescence immunochromatographic analysis in 2019. The diagnostic indices, predictive values, and likelihood ratios of the two different tests were calculated. Results 1) IL-8 concentrations ≥9.5 ng/ml in cervical fluid, determined by the POCT, was at the knee of the receiver operating characteristic (ROC) curve analysis and had a sensitivity of 98% (56/57, 95% confidence interval [CI] 91-99.96%), specificity of 74% (40/54, 95% CI 60-85%), positive predictive value of 80% (56/70, 95% CI 72-86%), negative predictive value of 98% (40/41, 95% CI 85-99.6%), positive likelihood ratio of 3.79 (95% CI 2.41-5.96), and negative likelihood ratio of 0.02 (95% CI 0.003-0.17) in the identification of intra-amniotic inflammation; a concentration of MMP-8 >23 ng/mL by ELISA had a prevalence of 51% (57/111). 2) Cervical fluid IL-8 concentrations ≥9.5 ng/ml had significantly higher sensitivity than a transabdominally obtained amniotic fluid WBC count in the identification of intra-amniotic inflammation (sensitivity: 98% [95% CI 91-99.96%] vs 84% [95% CI 72-93%]; p 23ng/mL; 91% [95% CI 82-97%] vs 75% [95% CI 63-85%]; p Conclusions The POCT based on IL-8 determination in fluid retrieved by a cervical amniotic fluid collector was predictive of intra-amniotic inflammation. Therefore, analysis of cervically obtained fluid by such POCT may be used to non-invasively monitor intra-amniotic inflammation in patients with preterm PROM.