Author:

Keywords:

MMP, MMP:TIMP imbalance, Preterm labor, TIMP, biomarkers, cytokines, human parturition, maternal serum, sTREM-1

Abstract:

Preterm birth (PTB), defined as a delivery before 37 weeks of gestation, is the leading cause of perinatal morbidity and mortality worldwide. Diagnosis of preterm labour as well as accurate prediction of PTB is notoriously difficult. Preterm birth is initiated by multiple mechanisms including infection or inflammation which is the only pathological process for which a firm causal link with PTB has been established. Intrauterine infection evokes an immune response that involves the release of cytokines and chemokines, prostaglandins and matrix-degrading enzymes. These substances trigger uterine contractions, membrane rupture and cervical ripening. Most intra-uterine infections are chronic and subclinical in nature and consequently hard to diagnose before labour or rupture of the membranes. The best studied site of infection is amniotic fluid, but this requires an invasive procedure. A non-invasive approach seems to be more relevant to clinical practice. However, few studies have investigated the maternal inflammatory response during preterm labour. Therefore, the overall objective of this study was to determine several inflammatory markers in maternal serum from pregnant women in labour (either term or preterm) vs. non-labouring controls. We completed a nested case control study in which singleton pregnancies were recruited at Ghent University Hospital and divided into groups according to gestational age and labour status. Multiple proteins were evaluated in maternal serum using enzyme-linked or multiplex bead immunoassays including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), matrix metalloproteinases (MMP)-9 and MMP-3, tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 and a panel of 30 cytokines, chemokines and growth factors.