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Objectives: to assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 and premature delivery and fetal inflammation., Methods: maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations., Results: maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6., Conclusion: our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA.

Objective: Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC)., Methods: In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis., Results: 1) The median AF concentration of visfatin was significantly higher in patients at term than in mid-trimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC., Conclusions: 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the membrane status, suggesting that visfatin participates in the host response against infection.

Objective: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3., Study Design: A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value < 0.05 was considered statistically significant., Results: (1) MMP-3 was detected in 99.5% (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3., Conclusions: (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.