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

Objective: To determine the significance of tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-8 (MMP-8) in vaginally obtained amniotic fluid predicting fetal inflammatory response syndrome (FIRS) after preterm premature rupture of membranes (PPROM). Methods: In this prospective case-control study, TNF-alpha and MMP-8 concentrations were evaluated in vaginally obtained amniotic fluid from women with PPROM at 22-34 weeks of pregnancy. Biomarkers' concentrations were determined using an enzyme-linked immunosorbent assay. Patients were divided into two groups: the FIRS group (cord blood interleukin-6 > 11 pg/ml or histological funisitis) and the non-FIRS group (without these findings). The data were analyzed using R package (R-4.0.5). Results: The median TNF-alpha and MMP-8 concentrations in amniotic fluid from the 145 women included in the study were higher in the FIRS group than in the non-FIRS group. The area under the curve of TNF-alpha and MMP-8 was 0.77 and 0.75, respectively. The TNF-alpha concentration cut-off predicting FIRS was 89.20 pg/ml and was 170.76 pg/ml for MMP-8. In regression analysis, MMP-8 concentration was an independent predictor for FIRS. An MMP-8 concentration greater than 170ng/ml and a TNF-alpha concentration greater than 89 pg/ml increased the odds of FIRS 7.62 and 14.92 times, respectively. Conclusions: MMP-8 and TNF-alpha concentrations in vaginally obtained amniotic fluid may be good predictors for FIRS after PPROM before 34weeks of pregnancy. The non-invasive amniotic fluid analysis could be an alternative method to invasive amniocentesis.