Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes.

INTRODUCTION: Intra-amniotic inflammation is defined by elevated inflammatory biomarkers in the amniotic fluid (AF), either due to microbial invasion of the amniotic cavity (MIAC) or sterile inflammation. Amniocentesis being an invasive procedure, we wanted to investigate whether elevated matrix metalloproteinase-8 (MMP-8) or interleukin-6 (IL-6) concentrations could be detected from cervical fluid samples. MATERIALS AND METHODS: This prospective study included 67 women with singleton nondiabetic pregnancies with or without preterm premature rupture of membranes (PPROM) between 22+0 and 37+0 weeks of gestation. Simultaneous AF and cervical samples were obtained. RESULTS: In women without PPROM, cervical MMP-8 concentrations correlated with AF MMP-8 concentrations (rS = 0.466, p = 0.002), but cervical IL-6 did not correlate with AF IL-6 (rS = 0.277, p = 0.076). In PPROM cases no correlations were found. Women with MIAC had higher concentrations of AF MMP-8 and AF IL-6 compared to women without MIAC regardless of membrane status. However, only women without PPROM had higher concentrations of cervical MMP-8 in proven MIAC. CONCLUSION: In women without PPROM, cervical MMP-8 concentration reflects the magnitude of AF MMP-8, thus potentially guiding the selection of patients benefitting from amniocentesis.

Amniotic Fluid Infection in Preterm Pregnancies with Intact Membranes.

Introduction. Intra-amniotic infection (IAI) is a major cause of preterm labor and adverse neonatal outcome. We evaluated amniotic fluid (AF) proteolytic cascade forming biomarkers in relation to microbial invasion of the amniotic cavity (MIAC) and IAI in preterm pregnancies with intact membranes. Material and Methods. Amniocentesis was made to 73 women with singleton pregnancies; 27 with suspected IAI; and 46 controls. AF biomarkers were divided into three cascades: Cascade 1: matrix metalloproteinase-8 (MMP-8), MMP-9, myeloperoxidase (MPO), and interleukin-6; Cascade 2: neutrophil elastase (HNE), elafin, and MMP-9; Cascade 3: MMP-2, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), MMP-8/TIMP-1 molar ratio, and C-reactive protein (CRP). MMP-8 was measured by an immunoenzymometric assay and the others were measured by ELISA. Standard biochemical methods, molecular microbiology, and culture techniques were used. Results. MMP-8, MMP-9, MPO, elafin, and TIMP-1 concentrations were higher in IAI suspected cases compared to controls and also in IAI suspected cases with MIAC compared to those without MIAC when adjusted by gestational age at amniocentesis. All biomarkers except elafin and MMP-2 had the sensitivity of 100% with thresholds based on ROC-curve. Odd ratios of biomarkers for MIAC were 1.2-38 and 95% confidential intervals 1.0-353.6. Conclusions. Neutrophil based AF biomarkers were associated with IAI and MIAC.

Vaginally obtained amniotic fluid samples in the diagnosis of subclinical chorioamnionitis.

INTRODUCTION: Preterm birth is often caused by infection or inflammation. High concentration of lactate dehydrogenase and low concentration of glucose in amniotic fluid obtained by amniocentesis are associated with subclinical chorioamnionitis. We evaluated amniotic fluid lactate dehydrogenase and glucose concentrations in relation to histologic chorioamnionitis in vaginally obtained samples. MATERIAL AND METHODS: In a prospective study, vaginally obtained amniotic fluid samples were collected from 53 women with preterm prelabor rupture of membranes at 23(+4) to 34(+5) weeks of gestation at University Hospital, Helsinki, Finland. Amniotic fluid lactate dehydrogenase and amniotic fluid glucose were measured by immunochemiluminometric assays. Histopathologic examination of placenta was performed. The main outcome measure was histologic chorioamnionitis. RESULTS: Median concentration of vaginally obtained amniotic fluid lactate dehydrogenase was higher in women with histologic chorioamnionitis than in women without (1400 IU/L vs. 784.5 IU/L, p = 0.005). By receiver operating characteristics curve the optimal cut-off for amniotic fluid lactate dehydrogenase in relation to histologic chorioamnionitis was 1029 IU/L (sensitivity 65%, specificity 69%, positive predictive value 83% and negative predictive value 46%). Amniotic fluid lactate dehydrogenase concentrations showed striking fluctuation in repeat samples. Amniotic fluid glucose concentrations did not differ among women with or without histologic chorioamnionitis (0 mmol/L vs. 0.65 mmol/L, p = 0.20). CONCLUSION: Elevated amniotic fluid lactate dehydrogenase was associated with histologic chorioamnionitis, but decreased amniotic fluid glucose was not. However, the clinical value of vaginally obtained amniotic fluid lactate dehydrogenase is limited because of high sample-to-sample variability. Better biomarkers for optimal timing of delivery in women with preterm prelabor rupture of membranes are needed.