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

Abstract

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 α (TNF-α), 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-α, 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-α 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-α 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-α 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-α, 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-α 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-α 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.

The significance of TNF‐α and MMP‐8 concentrations in non‐invasively obtained amniotic fluid predicting fetal inflammatory response syndrome

“…10,11 During intra-amniotic bacterial invasion, this enzyme is responsible for the degradation of ECM of the chorioamnion, resulting in premature rupture of membranes (PROM), preterm birth, and is found in high levels in the amniotic fluid as well. 11 Amniotic fluid TNFα and MMP-8 are both associated with intraamniotic infection/inflammation, [11][12][13][14][15] FIRS, 16,17 and adverse neonatal outcomes. 16,[18][19][20][21] Although various amniotic fluid biomarkers have been extensively researched as predictive tools for intra-amniotic inflammation/infection and FIRS, most studies were sampling amniotic fluid obtained by transabdominal amniocentesis.…”

The Significance of Epidermal Growth Factor in Noninvasively Obtained Amniotic Fluid Predicting Respiratory Outcomes of Preterm Neonates

“…According to the kit’s inserts, the analytical sensitivity of human EGF was <1 pg/mL. Immunological AF assays of IL–6, TNF-α, and MMP–8 were performed by ELISA, as previously described [ 32 ].…”

“…The relationship between EGF and inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase-8 (MMP-8) were also evaluated. We previously reported the significance of inflammatory biomarkers in noninvasively obtained amniotic fluid predicting histological chorioamnionitis [ 32 ].…”

A value of soluble Toll‐like receptor 2 and 4 in vaginally obtained amniotic fluid for the prediction of histological chorioamnionitis

“…This is a part of the study “Significance of biochemical and immunological markers in amniotic fluid in predicting intrauterine infection,” which was approved by the Vilnius Regional Biomedical Research Ethics Committee on 4 July 2017 (No. 158200‐17‐931‐434) 12 …”