دانلود رایگان مقاله انگلیسی عفونت مایع آمنیوتیک در بارداری های زودرس با غشاهای غیر قابل کنترل - هینداوی 2018

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 Creactive 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.

4. Discussion

We demonstrated that, among IAI suspected cases, all AF biomarkers from Cascades 1 and 2 were associated with MIAC, which was documented in one-fourth of our IAI suspected cases despite presumed intact membranes. The association persisted even after adjusting by gestational age at amniocentesis. Furthermore, in IAI cases AF biomarkers produced by neutrophils were associated with general inflammatory biomarker CRP [19] in AF. Additionally, neutrophil based biomarkers were able to both discriminate cases from controls after adjusting by gestational age at amniocentesis and associate with MIAC.

The problem with biomarkers commonly used, that is, AF-Gluc and AF-LD, is the limited accuracy for MIAC [15,20, 21]. AF-MMP-8 and AF-IL-6 have been demonstrated to provide better accuracy [22] but are not commonly used in clinical practice. Rapid AF biomarkers are needed for optimal timing of delivery in women with suspected IAI.

We studied several AF biomarkers which form inflammation related proteolytic cascades. One can identify increased levels of PMN-derived biomarkers in MIAC cases. IL-6 can induce PMN extravasation at the site of inflammation, often triggered by microorganisms or virulence factors associated [4], and also act as a degranulation inducer.

Proinflammatory neutrophil-derived AF biomarkers (Cascade 1) associated with general inflammatory biomarker CRP in IAI cases though suggesting that activated and degranulating neutrophils are the major source of MMP-8 and MMP-9, MPO (Cascade 1), and HNE (Cascade 2) in the AF affected by MIAC. AF neutrophils are of maternal origin [1] reflecting maternal host response to infection. Cascade 3 biomarkers did not detect this since these biomarkers, MMP2 and TIMP-1, are not produced and released by neutrophils [4, 23]. Furthermore, HNE and MPO can proteolytically and oxidatively inactivate TIMP-1, respectively, thus reducing the antiproteolytic defensive shield in AF [4, 23]. Infection leading to imbalance of MMP-8 and TIMP-1 may be related to initiation of preterm delivery [24].