Maria Sennström

Interleukin-8 is a mediator of the final cervical ripening in humans

OBJECTIVE The aim of the present study was to investigate the presence of interleukin-8 (IL-8) in the human cervix and whether the levels of interleukin-8 could be related to the ripening process during pregnancy. STUDY DESIGN Cervical biopsies were obtained in twelve term pregnant and in eight vaginally delivered women. Seven non-pregnant fertile women served as controls. After homogenisation and centrifugation, IL-8 levels were determined in the supernatant by an enzyme-immunoassay (EIA). RESULTS In women at term, the concentration of IL-8 increased six-fold from median 330 pg/ml to median 2190 pg/ml (P < 0.001). After the final cervical ripening it increased in additional 11-fold to median 26,100 pg/ml (P < 0.001). These changes are highly significant. CONCLUSION To our knowledge, this is the first time IL-8 has been identified in human cervix. Our results support the involvement of IL-8 in the connective tissue remodelling during the final cervical ripening just before onset of labour.

Matrix metalloproteinase‐8 correlates with the cervical ripening process in humans

Background.  To determine levels of matrix metalloproteinases MMP‐1, ‐3 and ‐8 and localize them and the tissue inhibitors of metalloproteinases TIMP‐1 and ‐2 in human cervical tissue during the cervical ripening process.

Cervical fetal fibronectin correlates to cervical ripening

Aim of study. It is well established that the cervical ripeness is of great prognostic value at labor induction. The available methods of measuring the cervical ripeness are not satisfactory. This study was therefore initiated to investigate if there is any correlation between cervical fetal fibronectin and cervical ripening at term.

Protein gene product 9.5‐immunoreactive nerve fibers and cells in human cervix of late pregnant, postpartal and non‐pregnant women

BACKGROUND The aim of this study was to examine the occurrence and distribution of the general neuronal marker protein gene product (PGP) 9.5 in the cervix uteri. METHODS Cervical biopsies were obtained from late pregnant (n=5), postpartal (n=5) and non-pregnant (n=5) women. The samples were prepared for immunohistochemistry using antibodies to PGP 9.5. RESULTS Nerve fibers were found consistently in all biopsies. There were differences in the occurrence and distribution of PGP 9.5 immunoreactive nerve fibers and cells between the three groups. Immunoreactive nerve fibers were observed at a moderate to abundant frequency in the stroma and around arterial vessel walls, in all groups. Immunoreactive nerve fibers were also observed at high frequency within and around glandular epithelium in the late pregnant and postpartal groups. PGP 9.5 immunoreactive cells were seen occasionally in the stroma of the non-pregnant group, but at a high frequency in the stroma, around arterial blood vessel walls, around and within the glandular epithelium in the late pregnant and postpartal groups. The total frequency of immunoreactive nerve fibers and cells was the highest in the late pregnant group, slightly lower in the postpartal group, and the lowest in the non-pregnant group. CONCLUSIONS These findings show that changes in the general innervation take place during human cervical ripening until late pregnancy and parturition.

Cervical fetal fibronectin correlates to prostaglandin E2–induced cervical ripening and can be identified in cervical tissue

OBJECTIVE Our purpose was to investigate whether prostaglandin E2-induced cervical ripening can be related to changes in fetal fibronectin levels and whether fetal fibronectin can be detected by immunohistochemistry in amniotic and cervical tissue. STUDY DESIGN Fetal fibronectin levels in cervical mucus were quantitated in 28 nulliparous term pregnant women with unfavorable cervical states before and after intracervical application of prostaglandin E2 gel. The concentration of fetal fibronectin was determined with use of an enzyme immunoassay. Cervical biopsy specimens and amniotic tissue for immunohistochemical analysis were obtained from three term pregnant women and after parturition in three women. Cervical biopsy specimens from two nonpregnant women served as controls. Immunohistochemical analysis was performed with antibodies directed toward fetal fibronectin. RESULTS The fetal fibronectin level in cervical mucus was low in all women before prostaglandin E2 application. In women with a successful prostaglandin E2-induced ripening (i.e., an increase of cervical score with > or =3 points), a tenfold increase in the fetal fibronectin level was registered. In women with an insufficient cervical ripening after prostaglandin E2 treatment no significant increase in the fetal fibronectin level was registered. The immunohistochemical analyses have identified fetal fibronectin in the epithelial cells of the cervix uteri. CONCLUSION Successful prostaglandin E2-induced cervical ripening seems to be related to a significant increase in cervical fetal fibronectin levels. Fetal fibronectin can be detected immunohistochemically in the pregnant human cervix.

Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio and Time to Delivery in Women With Suspected Preeclampsia.

OBJECTIVE: To assess the association of a serum soluble fms-like tyrosine kinase 1-to-placental growth factor (sFlt-1-to-PlGF) ratio of greater than 38 with time to delivery and preterm birth. METHODS: Secondary analysis of an observational cohort study that included women 18 years of age or older from 24 to 36 6/7 weeks of gestation at their first study visit with suspected (not confirmed) preeclampsia. Participants were recruited from December 2010 to January 2014 at 30 sites in 14 countries. A total of 1,041 women were included in time-to-delivery analysis and 848 in preterm birth analysis. RESULTS: Women with an sFlt-1-to-PlGF ratio greater than 38 (n=250) had a 2.9-fold greater likelihood of imminent delivery (ie, delivery on the day of the test) (Cox regression hazard ratio 2.9; P<.001) and shorter remaining time to delivery (median 17 [interquartile range 10–26] compared with 51 [interquartile range 30–75] days, respectively; Weibull regression factor 0.62; P<.001) than women with an sFlt-1-to-PlGF ratio of 38 or less, whether or not they developed preeclampsia. For women who did not (n=842) and did develop preeclampsia (n=199), significant correlations were seen between an sFlt-1-to-PlGF ratio greater than 38 and preterm birth (r=0.44 and r=0.46; both P<.001). Among women who did not develop preeclampsia, those who underwent iatrogenic preterm delivery had higher median sFlt-1-to-PlGF ratios at their first visit (35.3, interquartile range 6.8–104.0) than those who did not (8.4, interquartile range 3.4–30.6) or who delivered at term (4.3, interquartile range 2.4–10.9). CONCLUSIONS: In women undergoing evaluation for suspected preeclampsia, a serum sFlt-1-to-PlGF ratio greater than 38 is associated with a shorter remaining pregnancy duration and a higher risk of preterm delivery.

Neurochemical and cellular markers in human cervix of late pregnant, postpartal and non-pregnant women

Background. The aim was to evaluate the peptidergic innervation and the dendritic cell content in the cervix uteri.