Significance of fetal fibronectin and cytokine measurement in the cervicovaginal secretions of women at term in predicting term labor and post-term pregnancy

Abstract

Objective: To determine whether fetal fibronectin (FFN) or cytokine concentrations in cervicovaginal secretions can be used to predict term labor and post-term pregnancy.

Study Design: FFN and cytokines were assayed in cervicovaginal mucus from 122 pregnant women at 29–35 weeks and weekly from week 36 to parturition.

Results: FFN concentrations were elevated from about 3 weeks before parturition; a correlation was found between FFN levels and sampling-to-delivery intervals. Parturition was best predicted within 7 days of sampling when the FFN value was ≥50 ng/ml between 36 and 41 gestational weeks. Interleukin-1β (IL-1β) concentrations were elevated from 3 to 4 weeks before parturition; a correlation was found between IL-1β levels and sampling-to-delivery intervals. Parturition was best predicted within 7 days of sampling, with an IL-1β cut-off value of ≥100 pg/ml.

Conclusion: Term labor and post-term pregnancy can be predicted within 7 days of sampling, using FFN and IL-1β concentrations in cervicovaginal secretions of pregnant women.

Introduction

Fibronectins are ubiquitous, high molecular weight glycoproteins. Fibronectin is found in blood plasma and other bodily fluids, such as amniotic fluid, and is present in basement membranes and connective tissue between endothelial cells [1]. It plays important roles in coagulation and healing processes and functions as a structural protein that organizes and anchors the connective tissue system [1]. Using the monoclonal antibody FDC-6, it has become possible to identify minor structural differences, permitting differentiation between fetal and adult fibronectins [2], [3]. Fetal fibronectin (FFN) contains a specific epitope termed the “oncofetal” domain, and its molecular weight is higher than normal adult plasma fibronectin [2], [4]. FFN is thought to be produced by human trophoblast cells from 20 days post-conception to term [5]. FFN is found in large quantities in amniotic fluid (27.1±17.3 μg/ml [6]). It is also present in the amnion, in placental tissue, and in the area between the decidua parietalis and chorion [2], [5]. The presence of FFN in cervicovaginal secretions of pregnant women during the second and third trimesters has been suggested as a means of identifying women likely to experience threatened premature labor and premature rupture of membranes [6]. Blanch et al. and Lockwood et al. reported that a vaginal FFN increased in women at term and that a high value of vaginal FFN may be a predictor of a labor of short duration or a simple delivery [7], [8].

Recently cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) have been shown to be chemotactic factors involved in parturition. It has been reported that activation of IL-1β stimulates prostaglandin synthesis by uterine tissues [9] and in fetal membranes and decidua at the onset of parturition [10], [11]. IL-8, which is produced in the cervix at term, has strong chemotactic and activating effects on neutrophils [12], [13]. The cervix and lower segments of the uterus are known to produce large amounts of IL-8 in the final stages of pregnancy [14], [15]. IL-8 induces the activation and migration of neutrophils from vessels into the surrounding connective tissue and leads to the release of collagenase and elastase-containing granules in cervical ripening [16], [17]. Dramatically elevated levels of cytokines, including IL-1, IL-6, IL-8, and TNF, have been found in amniotic fluid, the chorionic-decidual interface, and cervical secretions of premature deliveries, in association with intrauterine infections [18], [19], [20], [21], [22].

Until now, the Bishop score has been the only way of estimating the probable time of birth [23]. Accurate determination of the actual onset of labor and delivery would be desirable, especially in women who are postmature.

This study was initiated to examine whether the presence of FFN or cytokines (IL-1β, IL-6, IL-8, TNF-α) in cervicovaginal secretions can be used as a marker to predict term labor and post-term pregnancy.