عفونت مایع آمنیوتیک در بارداری های زودرس با غشاهای غیر قابل کنترل Amniotic Fluid Infection in Preterm Pregnancies with Intact Membranes

1. Introduction Intra-amniotic infection (IAI), defined as microbial invasion of the amniotic cavity (MIAC) with intra-amniotic inflammation, is common in women with preterm labor and exists with or without preterm prelabor rupture of membranes (PPROM) [1]. MIAC often leads to IAI [2]. However, intraamniotic inflammation in the absence of MIAC also occurs [3]. Amniocentesis and amniotic fluid (AF) rapid biomarker testing may help in optimal timing of delivery. Infection may induce the degranulation of interleukin- (IL-) 6 and matrix metalloproteinases (MMP), from polymorphonuclear neutrophils (PMNs) [4]. MMP-8 has been linked to MIAC [5–7], inflammation [8–10], histological chorioamnionitis (HCA) [11], and adverse neonatal outcome [12, 13]. Several AF biomarkers form proteolytic cascades. They are formed in inflammatory conditions after recruitment and activation of neutrophils, which release their subcellular granules, that is, degranulating tissue destructive enzymes (for example, MMP-8, MMP-9, and neutrophil elastase (HNE)). Those and other such enzymes can form cascades by activating each other. The process leads to degradation of extracellular matrix components and modulation of cytokines [4], which may lead in obstetrics to membrane rupture or ripening and softening of the cervix. MPO is the activator of MMP-8 and MMP-9, while IL6 can act as their inducer (Cascade 1). HNE is an activator of MMP-9, and elafin is an antiprotease of HNE [14]. Elafin is produced not only by neutrophils but also by epithelial cells [14]. Thus, HNE and MMP-9 form another PMNderived proteolytic cascade (Cascade 2), to which elafin associates. The third cascade comprises MMP-2, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), MMP-8/TIMP-1 molar ratio, and C-reactive protein (CRP) (Cascade 3). MMP2 and TIMP-1 are not produced by PMNs. While many reports on AF biomarkers in PPROM pregnancies exist, such studies of MIAC and IAI in preterm pregnancies with presumed intact membranes are only few [3, 15, 16].