Prognostic Markers for Chorioamnionitis: IL-6, TNF-α, and MMP-8 in Vaginally Obtained Amniotic Fluid

Background. Earlier chorioamnionitis diagnosis is crucial to improve maternal and neonatal health outcomes. This study was conducted to evaluate the inlerleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and matrix metalloproteinase 8 (MMP-8) levels in vaginally obtained amniotic fluid to investigate their prognostic value and to determine the most appropriate cut-off values for the prediction of chorioamnionitis. Methods. This case control study included women who were diagnosed with preterm premature rupture of the membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free-leaking amniotic fluid was obtained vaginally with a sterile speculum less than 48h before delivery. Amniotic fluid IL-6, TNF-alpha, and MMP-8 levels were determined by the Enzyme Linked Immunosorbent Assay. Diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. Results. The study included 156 women, 65 patients in the histological chorioamnionitis group (Group I) and 91 in a group without diagnosed histological chorioamnionitis (Group II). The median concentrations of IL-6, MMP-8, and TNF-alpha in amniotic fluid were statistically significantly higher in Group I than in Group II (p-value < 0.001). The area under the curve of TNF-alpha and MMP-8 were higher than the area under the curve of IL-6 (0.91, 0.89, and 0.81, respectively). No statistically significant difference was found when comparing the receiver operating characteristic (ROC) curves of TNF-alpha and MMP-8. The optimum cut-off values for the prediction of chorioamnionitis were found to be 1389.82 pg/mL for IL-6, 21.17 pg/mL for TNF-alpha, and 172.53 ng/mL for MMP-8. The sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV) of the IL-6 cut-off for chorioamnionitis were 88%, 70%, 67%, and 89%, respectively. The sensitivity, specificity, PPV, and NPV of the TNF-alpha cut-off were 88%, 84%, 79%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV of the MMP-8 cut-off were 80%, 87%, 81%, and 86%, respectively. Conclusions. The vaginally obtained amniotic fluid IL-6, MMP-8, and TNF-alpha seem to be good predictors for chorioamnionitis of patients with preterm premature rupture of membranes before 34 weeks of gestation. The noninvasive technique of sampling amniotic fluid could be alternative method to invasive amniocentesis.

Automated summary

This study evaluated IL-6, TNF-alpha, and MMP-8 levels in vaginally obtained amniotic fluid as predictors for chorioamnionitis in patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid could be an alternative method to invasive amniocentesis.