A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.

The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT–PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10−13–10−6 M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3.

Dalteparin, a low molecular weight heparin (LMWH), is given to pregnant women with thrombotic disorders. Clinical observations together with the documented changes of heparan sulfate proteoglycans in normal and protracted labor fostered the idea that LMWH shortens delivery time. Labor time was retrospectively determined among nulliparous pregnant women treated with dalteparin because of previous venous thromboembolism (VTE), thrombophilia or acute VTE during current pregnancy. Their labor time was compared to matched untreated controls. The proportion of instrumental deliveries and neonatal outcome was also compared. The dalteparin-treated group showed a significantly (30%) shorter labor time compared to matched controls. Total instrumental deliveries were the same in the two groups but operative intervention due to protracted labor was significantly less common in dalteparin-treated women. There was no difference in neonatal outcome. Dalteparin most likely shortens parturition time and may decrease the number of operative interventions due to protracted labor.

The changes in proteoglycan production in the human pregnant cervix can also be seen in corresponding cervical fibroblasts. Term partal and preterm partal cells differed from their non-pregnant counterpart, which suggests a role for proteoglycans in cervical ripening.

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