Increased MMP-3 levels were found in amniotic fluid during term as well as preterm parturition and in cases of IUI. A fully functional TIMP network has been demonstrated in fetal membranes, decidua and placenta, irrespective of labor status. The majority of studies focused only on TIMP-1 and TIMP- 2. TIMP-1 concentrations in amniotic fluid were increased in the presence of IUI and in patients with rupture of the membranes either term or preterm, but not in those with spontaneous labor. In contrast, TIMP-2 levels were decreased in women with IUI, rupture of the membranes and spontaneous labor. Furthermore, it has been shown that amniotic fluid levels of TIMP-1 decrease with advancing gestational age while those of TIMP-2 do increase. We hypothesized that aberrant MMP expressions at local level implicated in ECM degradation of the amniochorion and cervix, are associated with aberrant changes in circulating MMPs, resulting in imbalanced MMP:TIMP ratios and leading to preterm labor. We therefore sought to determine the maternal serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as the MMP:TIMP ratios during term and preterm labor. Blood samples of laboring women were collected by the attending midwife upon admission to the labor and delivery ward. Women at term not in labor were sampled prior to their Caesarean section. GA matched controls were enrolled from the prenatal clinic. These pregnant women were screened at 20�C22 weeks to verify whether they fulfilled the inclusion criteria. When they were eligible for participation, the study was explained and they were matched for week of gestation with a PTB case. Sampling was performed during a subsequent prenatal consultation at the appropriate gestational age. Because these key GP 1a covariates were the focus of our investigation, they remained in the models regardless of their significance. To adjust for possible confounding effects, the following covariates were considered in the model selection procedure: maternal age, education level, marital status, smoking, body mass index, history of PTB, storage time and time delay between sampling and processing. This set of covariates was included in the initial model of the selection GR 135531 procedure for each outcome. Model selection was carried out for each outcome independently and occurred in two steps. First, a backward selection of main terms was applied in which covariates were sequentially removed in order of increasing significance until only terms with p-value below 0.10 remained. In the second step, first order interactions were considered between the covariates remaining in the model. The forward selection of interaction terms was performed with an inclusion criterion of p = 0.05. When no further interactions met this criterion, the final model was obtained for that outcome.