Presence Of Fetal Fibronectin Research Articles

Management Dilemmas in Threatened Preterm Labor (TPTL) and its Impact: A Mini Review

Prematurity is a primary cause of neonatal mortality worldwide. The survivors also suffer long term complications and significant permanent neurodevelopmental disability. It contributes to about 70% of neonatal deaths and 36% of infant mortality. Neonatal mortality can be reduced by appropriate diagnosis, administration of corticosteroids, judiciary use of tocolytics and timely transfer to a centre with neonatal intensive care unit. Only about 10%-30% of cases with symptoms of preterm labor proceed to preterm delivery. Hence, it is necessary to differentiate between true preterm labor and threatened preterm labor (TPTL). The latter is diagnosed with onset of regular uterine contractions (at least one in ten minutes) with minimal or no cervical changes and intact membranes. There is no exact definition of TPTL and it varies between various institutions and countries. Over the last decade, there has been a tremendous development to aid in the prediction of preterm labor. Recently, transvaginal cervical length measurement and presence of fetal fibronectin (ffn) and/or phosphorylated insulin growth factor binding protein - 1 (phIGFBP - 1) in cervical fluid can be used to delineate between true and threatened preterm labor.

504: Serial collection of fetal fibronectin and the risk of spontaneous preterm birth among women with a sonographically short cervix

The presence of fetal fibronectin (FFN) in vaginal fluid is associated with risk for spontaneous preterm birth (SPTB). The effect of serial FFN samples on risk for SPTB is not known. We hypothesized that FFN status over gestation collected on serial exams is informative with respect to risk of SPTB <36wks for women with a short cervix (CL<25mm).

Sonographic Measurement of Cervical Length ad Fetal Fibronectin Testing in Threatened Preterm Labor

When measured in women with preterm contractions, both the presence or absence of fetal fibronectin in cervicovaginal secretions and sonographically measured cervical length have been reported to distinguish true from false labor, essentially between women who will and will not deliver within the next 7 days. The present study, which prospectively enrolled 195 women with singleton pregnancies who were seen at 24 to 36 weeks gestation, attempted to determine whether combining these 2 tests is more predictive than either test by itself. Participants presented with regular painful uterine contractions but were less than 3 cm dilated and had intact membranes. Fetal fibronectin concentrations were measured by immunoassay in cervicovaginal secretions taken from the posterior fornix or endocervix followed by digital assessment of cervical dilation. Transvaginal sonography was then performed to measure cervical length. The clinician caring for each patient was blinded to the test results. The women presented at a median gestational age of 31 weeks; 19 of them (9.7%) delivered within 1 week. The rate of preterm delivery was 51.4% in women whose cervical length was less than 15 mm and 0.6% in those having a longer cervix. Similarly, the preterm delivery rate for women with positive fetal fibronectin was 21.2% compared with 0.9% for fibronectin-negative women. The positive and negative likelihood ratios for delivery within 1 week were 9.8 and 0.05, respectively, for a cervical length less than 15 mm, and 2.6 and 0.08 for a positive fibronectin test. The rate of delivery within 7 days increased exponentially as cervical length decreased. Cervical length correlated inversely with positive fetal fibronectin; the shorter the cervix, the more likely that fibronectin was positive. On multiple logistic regression analysis, the only factor that independently and significantly predicted preterm delivery was cervical length. Excluding cervical length, positive fibronectin contributed significantly to predicting delivery within 1 week. Other predictive factors included Afro-Caribbean ethnicity and gestational age at the time of presentation. Analysis of receiver-operating characteristic curves indicated that predictions based on cervical length were better than those provided by the fibronectin test. In women presenting with threatened preterm labor, a short cervix on sonography more accurately identifies those at high risk than does the presence of fetal fibronectin in cervicovaginal secretions. Measurements of cervical length can provide a basis for hospitalizing women and administering a tocolytic agent or steroid. If sonography is not available, risk status may be inferred from ethnic origin, gestational age, and the results of a fetal fibronectin test.

A Randomized Controlled Trial of Metronidazole for the Prevention of Preterm Birth in Women Positive for Cervicovaginal Fetal Fibronectin: The PREMET Study

This double blind, randomized, placebo-controlled study was undertaken at 14 hospitals in the United Kingdom in asymptomatic women who were at high risk of preterm birth because of risk factors such as previous midtrimester pregnancy loss or preterm delivery, uterine abnormality, cervical surgery, or cerclage. The criterion for entry into the study was the presence of fetal fibronectin (fFN) in vaginal secretions in the second trimester of pregnancy. This factor appears to be more predictive of preterm birth than bacterial vaginosis or other putative biochemical markers. A total of 900 pregnancies were screened at 24 and 27 weeks gestation. Women with positive results were assigned to receive either oral metronidazole (400 mg 3 times a day) or a placebo for 1 week. The primary outcome was delivery before 30 weeks gestation, and secondary outcomes included delivery before 37 weeks. The study was stopped at an early stage when 21% of 53 women given metronidazole and 11% of 46 placebo recipients delivered before 30 weeks gestation. The risk ratio (RR) was 1.9, with an 85% confidence interval (CI) of 0.72-5.09. Preterm delivery (earlier than 37 weeks gestation) took place in 62% of women given metronidazole and in 39% of the placebo group (RR, 1.6; 95% CI, 1.05-2.4). The positive and negative predictive values of fFN for early preterm birth, estimated at 24 weeks gestation for the risk of delivery before 30 weeks, were 26% and 99%, respectively. The fFN reverted to negative in approximately half of the actively treated and placebo groups. Birth weights averaged 366 g lower for infants whose mothers received metronidazole, and 56% more infants in this group were smaller than 2.5 kg at birth compared with those who mothers received placebo. The proportions of low 1- and 5-minute Apgar scores were comparable in the metronidazole and placebo groups. This is the first prospective trial showing that metronidazole is not an effective means of preventing preterm delivery in high-risk women and that it may have adverse effects on the newborn infant. The investigators do not recommend the continued use of this drug with the intent of preventing preterm delivery.

Fetal fibronectin as predictor of successful induction of mid‐trimester abortion

Fetal fibronectin (FFN) in cervical secretion is one of the most effective markers of pre-term and term delivery. The presence of FFN in cervicovaginal secretions has recently been shown to reflect cervical state and an uncomplicated induction of labor at term. This study was designed to determine whether FFN could be a biochemical marker to predict the response to prostaglandins in early mid-trimester abortion. The presence of cervical FFN was evaluated by means of qualitative rapid immunoassay in 270 patients, who required second trimester termination of pregnancy at the Department of Gynecology and Obstetrics, University of Naples 'Federico II'. According to the standard protocol of our unit, women received 1.0 mg of gemeprost intravaginally at 3-hr intervals up to a maximum of five suppositories. The induction-to-abortion interval and the percentage of successful abortions within 24 hr in women in the positive FFN group (n=19) were compared with those in the negative FFN group (n=251). FFN in the cervical secretions was present in seven women (10.2%) at 16-weeks gestation, in seven women (7.5%) at 17-weeks gestation, and in five women (4.5%) at 18-week gestation. Final termination rates were 13 (68.4%) in the fibronectin-positive group and 177 (70.5%) in the fibronectin-negative group. The median abortion interval was similar (14.7 versus 15.1 hr) in both groups. A positive cervical fetal fibronectin test does not predict a successful medical termination of pregnancy in second trimester abortion. In this setting, the role of fetal cervical fibronectin in cervical ripening is, therefore, questionable.

Mesure échographique de la longueur du col de l’utérus dans les grossesses gémellaires avec menace d’accouchement prématuré : comparaison avec les grossesses uniques

Objective. – Our purpose was to assess the utility of ultrasonographic measurement of cervical length for predicting preterm delivery in pregnant women with twin pregnancy and preterm labor. Patients and method. – Prospective study in 192 singleton and 66 twin pregnancies with preterm labor before 34 weeks. Vaginal sonography for measurement of cervical length, and screening for fetal fibronectin in vaginal smears were performed at admission. The incidence of delivery before 34 weeks was compared with cervical length and the presence of fetal fibronectin. Results. – In singleton pregnancies, delivery before 34 weeks was significantly more frequent in women with a cervical length <30 mm (26.6 vs. 2.0%; P = 0.0004), or presence of fetal fibronectin (27.5 vs. 6.0%; P = 0.001). The corresponding negative predictive values (NPV) were 98% and 94%, respectively. In twin pregnancies, receiver characteristic curve analysis showed that a cervical length of 20 mm had the highest diagnostic performance in predicting preterm delivery. The corresponding NPV was 63%. In this group, delivery before 34 weeks showed no significant difference in women with a cervical length < 30 mm (43.7 vs. 38.8%), cervical length < 20 mm (52.0 vs. 36.6%, P = 0.219), or presence of fetal fibronectin (47.6 vs. 21.7%, P = 0.0705). Discussion and conclusion. – Ultrasonographic measurement of cervical length does not predict preterm delivery in twin pregnancies with preterm labor.

The Preterm Prediction Study: Prediction of preterm premature rupture of membranes through clinical findings and ancillary testing

Objective: Our objective was to determine the relative importance of demographic characteristics, clinical risk factors, and ancillary screening tests in the prediction of preterm birth as a result of premature rupture of membranes. Study Design: A total of 2929 women were evaluated in 10 centers at 23 to 24 weeks’ gestation. Demographic and clinical characteristics were ascertained. Cervicovaginal fetal fibronectin and bacterial vaginosis were evaluated. Cervical length was measured by vaginal ultrasonography. Patients were evaluated for spontaneous preterm birth caused by preterm premature rupture of membranes at <37 and <35 weeks’ gestation. Multivariate analyses were performed separately for nulliparous women and multiparous women. Results: Premature rupture of membranes at <37 weeks’ gestation complicated 4.5% of pregnancies, accounting for 32.6% of preterm births. Univariate analysis revealed low body mass index, pulmonary disease, contractions within 2 weeks, short cervix (≤25 mm), positive results of fetal fibronectin screening, bacterial vaginosis, and a previous preterm birth caused by premature rupture of membranes (in multiparous women) to be significantly associated with preterm birth caused by premature rupture of membranes in the current gestation. Short cervix, previous preterm birth caused by premature rupture of membranes in multiparous women, and presence of fetal fibronectin were the strongest predictors for both preterm birth caused by premature rupture of membranes at <37 and <35 weeks’ gestation. Women with positive fetal fibronectin screening results and a short cervix had greater risks both of preterm birth caused by premature rupture of membranes at <37 weeks’ gestation (relative risk, 4.9) and of preterm birth caused by premature rupture of membranes at <35 weeks’ gestation (relative risk, 13.5) than did those without these risk factors. Multiparous women with all three risk factors had a 31.3-fold increased risk of preterm birth caused by premature rupture of membranes at <35 weeks’ gestation. Conclusion: The combination of short cervical length, previous preterm birth caused by preterm premature rupture of membranes, and positive fetal fibronectin screening results was highly associated with preterm delivery caused by preterm premature rupture of membranes in the current gestation. (Am J Obstet Gynecol 2000;183:738-45.)

Prediction of Cervical Response to Prostaglandin E2 Using Fetal Fibronectin

Fetal fibronectin (FFN), a special form of the glycoprotein present in amniotic fluid and at the chorio-decidual interface, may be distinguished from adult fibronectin using monoclonal antibody FCD-6. Levels of the fetal form reportedly correlate strongly with the Bishop score, with positive fibronectin found more often where there is a favorable cervix. This study was an attempt to determine whether the presence of FFN in cervicovaginal secretions at term predicts the cervical response to prostaglandin E2 (PGE2) pessaries and successful induction of labor when the cervix is unfavorable. Secretions were tested before cervical ripening was attempted with PGE2 pessaries in 58 women with a singleton term or postterm pregnancy and a modified Bishop score less than 5 who were undergoing induction. Vaginal pessaries containing 3 mg of Prostin E2 were used. FFN was estimated by means of a solid-phase immunoassay using an anti-human fibronectin-gold colloid conjugate and FCD-6. Nineteen of the 58 women in the study (32 percent) had a positive result on the immunoassay for FFN. All but two of them had a modified Bishop score of 5 or greater or entered labor within 4 to 6 hours after vaginal placement of a single pessary. Two women required a second pessary but underwent cesarean delivery, one because of failed induction and the other because of failure to progress. Nearly half of the FFN-negative subjects had an improved Bishop score or entered labor after a single PGE2 pessary. Seven of the other 20 women delivered vaginally after a second dose. Eight women received a third or fourth pessary, and five of them delivered vaginally. Five women received oxytocin and had the membranes ruptured, but only one of them delivered vaginally. FFN-negative women required more PGE2 and had longer induction-delivery intervals than FFN-positive women, but there was no significant difference in the length of the active phase of labor. Fewer operative deliveries were performed in the FFN-positive group, but this trend was not statistically significant. These findings suggest that the FFN assay be part of assessing cervical status when labor is to be induced. Acta Obstet Gynecol Scand 1999;79:861–865

Fetal fibronectin as a predictor of preterm birth

Preterm delivery remains the leading cause of perinatal mortality and occurs in approximately 7-9% of pregnancies. The main problem for the obstetrician is the inability to detect women at risk from this complication. The presence of fetal fibronectin (fFN) in cervicovaginal secretions has been proposed as a specific predictor of preterm delivery. Immunohistochemical studies suggest that fFN is present in the extracellular matrix of the decidua basalis next to the intervillus space. It has been studied intensively in symptomatic patients and has a positive predictive value of 43-79%. It has also a negative predictive value of 99.7% for birth within 7 days and 93% for delivery before 37 weeks. Similarly, in high-risk asymptomatic women, it has been proved a useful screening tool for the prediction of preterm delivery, yielding a sensitivity of 43-92%, a specificity of 52-93%, a positive predictive value of 43-85% and a negative predictive value of 86-99%. In low-risk asymptomatic women, fFN has a sensitivity of 63-73%, a specificity of 80-98%, a positive predictive value of 13-36% and a negative predictive value of 95-97%. In women presenting with preterm contractions, a negative test may make one withhold potentially dangerous tocolytic therapy. In asymptomatic women this test can identify patients who have a very high risk for early delivery. Women identified as being high-risk can be offered steroid injections in order to improve lung maturity in preterm babies. Additionally, they can be counselled about the signs and symptoms of preterm labour, so that they can seek medical advice before labour is actually established. However, extensive research is still needed, as no clear benefit in preventing preterm birth using this test, has been shown so far.

Prediction of cervical response to prostaglandin E2 using fetal fibronectin

To determine whether presence of fetal fibronectin in cervico-vaginal secretions at term will predict the cervical response to prostaglandin E2 (PGE2) pessaries and successful induction of labor amongst subjects with unfavorable cervices. Cervico-vaginal secretion was tested for the presence of fetal fibronectin prior to cervical ripening with PGE2 pessaries in women with a singleton term or post-term pregnancy undergoing induction of labor. The total number of PGE2 pessaries, interval from induction to labor and induction to delivery, latent phase and active phase of labor and cesarean section rate were compared. Women with fetal fibronectin in their cervico-vaginal secretion had better cervical response to PGE2 pessaries and required fewer doses for induction of labor and they took a shorter time interval from induction to delivery. They tend to have a lower cesarean section rate but the figures did not reach statistical significance. The presence of fetal fibronectin from cervico-vaginal secretions in subjects with a Bishop score <5 is predictive of a favorable response to induction by prostaglandin pessary

Recent advances in the prediction of preterm labour

The sequence of biochemical events that lead to the initiation of human parturition at term are not understood, but there is even less understanding of the events that lead to the initiation of preterm labour. Presumably, it this lack of understanding of the underlying pathogenesis that has hampered progress, until recently, in the area of prediction of preterm labour. Various methods of predicting preterm labour have been studied. Home uterine activity monitoring has recently been shown to be of limited use, while risk scoring systems perform poorly in practice. Transvaginal ultrasound assessment of the cervix has a role to play in the prediction of preterm labour. The presence of fetal fibronectin in cervicovaginal fluid in the late second and early third trimesters is an important risk factor for preterm labour. The measurement of concentrations of certain pro-inflammatory cytokines in cervicovaginal secretions at similar gestations may also prove to be clinically useful. Additional potential biochemical markers are the subject of ongoing research. The ability to predict preterm labour will improve as knowledge of the pathophysiologies underlying preterm labour increases.

Fetal fibronectin in the cervical secretion predicts accurately the onset of labor at term

Objective: The objective of our study was to check if presence of fetal fibronectin in the cervical secretion of full term patient predicts accurately the onset of labour at term. Study design: 78 women in the term period were included in the study, serial samples for fetal fibronectin were assessed, each patient underwent spontaneous labor, delay between last sample and delivery were analysed. Results: Patient with positive fetal fibronectin delivered within 3 ± 1.9 days where as patient with negative fetal fibronectin delivered within 5.7 ± 3.9 days ( P = 0.01). Conclusion: Presence of fetal fibronectin in cervical secretions seems to be a powerful tool to predict in a short delay the onset of labour at term, it should be used in conjunction with clinical and fetal assessment data.

Fetal fibronectin as a predictor of preterm birth in patients with symptoms: A multicenter trial

OBJECTIVE: Our aim was to determine whether the presence of fetal fibronectin in vaginal secretions of patients with symptoms suggestive of preterm labor predicts preterm delivery. STUDY DESIGN: Patients who were examined at the hospital between 24 weeks' and 34 weeks 6 days' gestation with intact membranes, no prior tocolysis, symptoms suggestive of preterm labor, and cervical dilation <3 cm were recruited at 10 sites. Swabs of the posterior fornix were assayed for the presence of fetal fibronectin by monoclonal antibody assay, with a positive result defined as ≥50 ng/ml. Results were not available to the managing physicians. Tocolysis was used when clinically indicated after specimen collection. RESULTS: A total of 763 patients had fetal fibronectin results and pregnancy outcome data available for analysis. Fetal fibronectin was detected in specimens from 150 (20%) patients. Compared with patients who had negative results, patients who had positive results for fetal fibronectin were more likely to be delivered within 7 days (relative risk 25.9 [95% confidence interval 7.8 to 86]), within 14 days (relative risk 20.4 [95% confidence interval 8.0 to 53]), and before 37 completed weeks (relative risk 2.9 [95% confidence interval 2.2 to 3.7]). The negative predictive values for delivery within 7 days, within 14 days, and at <37 weeks were 99.5%, 99.2%, and 84.5%, respectively. When we used multiple logistic regression analysis to control for potential confounding variables among singleton pregnancies, only the presence of fetal fibronectin (odds ratio 48.8, 95% confidence interval 7.4 to 320), prior preterm birth (odds ratio 8.3, 95% confidence interval 1.5 to 46.6), and tocolysis (odds ratio 4.1, 95% confidence interval 1.0 to 16.0) were associated with birth within 7 days; fetal fibronectin (odds ratio 3.6, 95% confidence interval 2.2 to 5.9), prior preterm birth (odds ratio 2.5, 95% confidence interval 1.4 to 4.4), cervical dilatation >1 cm (odds ratio 2.9, 95% confidence interval 1.6 to 5.2), and tocolysis (odds ratio 4.5, 95% confidence interval 2.8 to 7.2) were all independently associated with delivery before 37 weeks. CONCLUSION: In a population of patients with symptoms, the presence of fetal fibronectin in vaginal secretions best defines a subgroup at increased risk for delivery within 7 days; the high negative predictive value of fetal fibronectin sampling supports less intervention for patients with this result.(Am J Obstet Gynecol 1997;177:13-8)

The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting preterm delivery: an overview.

To determine the accuracy with which cervico-vaginal fetal fibronectin predicts preterm delivery using systematic quantitative overview of the available literature. Online searching of MEDLINE database (1966 to April 1996), scanning of bibliography of known primary and review articles and review of recent journal issues. Study selection, assessment of study quality and data extraction were performed in duplicate under masked conditions. Likelihood ratios were generated in subgroups of symptomatic and asymptomatic pregnant women by pooling data from different studies. An LR of > 10 or < 0.1 indicated conclusive changes in the pretest probability of preterm delivery while an LR of 5-10 or 0.2-0.1 indicated only moderate changes. Seven hundred and twenty-three symptomatic women with threatened preterm labour included in nine studies and 847 asymptomatic women (635 low risk and 212 high risk) included in six studies selected for meta-analyses. Likelihood ratios for positive and negative test results using delivery at < 37 and < 34 weeks of gestation, and within one week of testing as outcome measures. In symptomatic women a positive test predicted delivery < 37 weeks of gestation with a pooled likelihood ratio (LR) of 4.6 (95% CI 3.5-6.1) while a negative test had a pooled LR of 0.5 (95% CI 0.4-0.6). For delivery < 34 weeks of gestation, the pooled LR was 2.6 (95% CI 1.8-3.7) for a positive test and 0.2 (95% CI 0.1-0.5) for a negative test. For delivery within one week of testing, the pooled LR was 5.0 (95% CI 3.8-6.4) for a positive test and 0.2 (95% CI 0.1-0.4) for a negative test. In asymptomatic women at low risk of delivery < 37 weeks of gestation the pooled LR was 3.2 (95% CI 2.2-4.8) for a positive test and 0.8 (95% CI 0.7-0.9) for a negative test. In high risk asymptomatic women using delivery < 37 weeks of gestation as an outcome measure the pooled LR was 2.0 (95% CI 1.5-2.6) for a positive test and 0.4 (95% CI 0.2-0.8) for a negative test. For delivery < 34 weeks of gestation in high risk, asymptomatic women the pooled LR was 2.4 (95% CI 1.8-3.2) for a positive test and 0.6 (95% CI 0.4-0.9) for a negative test. The presence of fetal fibronectin in cervico-vaginal mucus has limited accuracy in predicting preterm delivery as the likelihood ratios for positive and negative test results generated only minimal to moderate changes in the pretest probability of preterm birth.

Cervical fetal fibronectin in patients at increased risk for preterm delivery

OBJECTIVE: This study aimed to evaluate fetal fibronectin concentrations in cervical secretions measured by either a rapid immunoassay or an enzyme-linked immunosorbent assay as a tool for the screening of premature delivery in otherwise asymptomatic pregnant women at high risk for prematurity. STUDY DESIGN: One hundred two pregnant women at high risk for premature delivery were followed up. Samples of the cervical secretion were taken every 2 weeks between the twenty-fourth and the thirty-fourth weeks of pregnancy. The samples were obtained from the ectocervix with two swabs. One cervical sample was used for the immediate-reading membrane test, and the other one for the immunoenzyme test. The correlation between the presence of fetal fibronectin in the cervical secretions and preterm birth was evaluated. In addition, a comparison between tests was made. RESULTS: The rate of preterm birth was 37.25% (38/102). Membrane tests revealed a sensitivity of 73.68% and a specificity of 92.18%; its positive predictive value was 84.84% and the negative predictive value was 85.50%. The enzyme-linked immunosorbent assays revealed a sensitivity of 78.94% and a specificity of 85.93%; its positive predictive value was 76.92%, and the negative predictive value was 87.30%. When compared with each other, the tests were found essentially concordant ( p < 0.05). The elapsed time between the last sampling and the occurrence of preterm birth was 2.9 ± 1.8 weeks. CONCLUSION: The rapid result membrane test is comparable to the standard fetal fibronectin enzyme-linked immunosorbent assays for the detection of fetal fibronectin in cervical secretions between the twenty-fourth and thirty-fourth weeks of gestation. Moreover, both assays were found to be good tools for the prediction of premature delivery in asymptomatic pregnant women at high risk for prematurity. The availability of a rapid search for the presence of cervical fetal fibronectin should improve our ability to efficiently identify patients at risk for preterm delivery to discriminate between such patients and those with benign Braxton Hicks contractions. (Am J Obstet Gynecol 1996;175:178-81.)

Assessment of fetal fibronectin in cervical secretion in cases of equivocal rupture of the membranes at term

To evaluate if the presence of fibronectin in cervical secretion might provide information on the natural course of equivocal prelabor rupture of membranes (ROM) at term. One hundred and sixteen women with a history of prelabor ROM at term but without visible amniotic fluid leakage were included in the study. The presence of fetal fibronectin in cervical secretion was determined by a commercially available kit (ROM check; limit of detection 100 ng/ml). Women with (n=49) and without (n=67) a positive fibronectin test were compared with regard to time interval between presumed membrane rupture and delivery, mode of delivery and fetal distress rates. There was no significant difference in the time interval between presumed ROM and delivery between those with a negative fibronectin test (median: 80 hours) and those with a positive test (median: 64 hours; p=0.28, Mann-Whitney U-test). Neither were there any differences in complicated delivery or fetal distress rates. Determination of fetal fibronectin in cervical secretion with the present method is of limited value in the clinical management of patients with equivocal rupture of the membranes.

The presence of fetal fibronectin in the cervicovaginal secretions of women at term - Its role in the assessment of women before labor induction and in the investigation of the physiologic mechanisms of labor

OBJECTIVE: Our purpose was to determine whether the presence of fetal fibronectin in cervicovaginal secretions of patients undergoing induction of labor reflected the cervical state and ultimately the ease of induction of labor. STUDY DESIGN: A prospective observational study of 103 patients undergoing induction of labor at term was conducted at Liverpool Maternity Hospital, a large university teaching hospital. We studied the women after 37 completed weeks of pregnancy. A Dacron (Adeza Biomedical, Sunnyvale, Calif.) polyester swab specimen was first taken from the endocervix for assessment of the presence of the fetal fibronectin. The cervix was then assessed by digital vaginal examination and scored with a modified Bishop's score. The fetal fibronectin swab was processed at the bedside with a membrane immunoassay kit specific for fetal fibronectin. A score was ascribed depending on the strength of the fibronectin reaction determined by the intensity of the color change on the plate, the presence of fetal fibronectin resulting in a score of 1 to 4. The patient was subsequently managed according to the standard induction protocol of the unit. The clinicians involved in the patient's care were blind to the result of the fetal fibronectin swab. RESULTS: There was a good correlation between the modified Bishop's score and the fetal fibronectin score ( r = 0.58, p < 0.001). To predict a latent phase of <8 hours, a fetal fibronectin score of 3 or 4 has a sensitivity of 73% with a specificity of 83% and a modified Bishop score of ≥4 has a sensitivity of 75% and a specificity of 73%. For delivery within 12 hours of induction of labor a fetal fibronectin score of ≥3 has a sensitivity of 61% and specificity of 83% compared with the modified Bishop score of ≥4, which has a sensitivity of 76% and a specificity of 72.5%. CONCLUSIONS: The fetal fibronectin score is as good as the modified Bishop score as an index of the ease with which induction of labor may be performed. This would imply that it also reflects the proximity of the onset of labor. The presence of fetal fibronectinin cervicovaginal secretions is therefore a marker of the changes in the cervix and membranes that precede labor regardless of the gestational age. (A M J O BSTET G YNECOL 1996;174:262-6.)

Zuverlässigkeit des Nachweises von fetalem Fibronectin mit Hilfe des monoklonalen Antikörpers FDC-6

Detection of amniotic fluid in the vagina is commonly used to diagnosed rupture of amniotic membranes. In 1991 an immunoassay was introduced which is based on the detection of a fetal fibronectin isoform using the monoclonal antibody FDC-6. Fetal fibronectin is said to be absent from normal adult tissues and plasma, but present in fetal tissues. The low concentration of fetal fibronectin in maternal plasma is said not to interfere with the test results. Theoretically, demonstration of significant amounts of fetal fibronectin in vaginal secretions may be considered an unequivocal sign of leakage of amniotic fluid or, at least, of pre-rupture stretching of the membranes. We evaluated results of the membrane immunoassay and enzyme immunoassay, which are both based on the monoclonal antibody FDC-6. Fetal fibronectin has been determined in a clinically unambiguous context in amniotic fluid as well as in vaginal swabs and blood samples. In amniotic fluid, all membrane immunoassays performed were positive. The concentration of fetal fibronectin during the third trimester of pregnancy was lower than in the second trimester. Only 9/15 cases were positive for fetal fibronectin if vaginal swabs were taken 12 hours after unequivocal rupture of membranes and no amniotic fluid was visible in the vagina. Vaginal swabs of women with regular contractions showing cervical dilation of > 2 cm were positive for fetal fibronectin in all cases (20/20) whereas no fetal fibronectin could be determined in vaginal swabs obtained from clinically inapparent pregnant women. In all blood samples of pregnant women fetal fibronectin was detected and, surprisingly, also in blood samples of non-pregnant women, as well as in vaginal swabs of non-pregnant women with vaginal bleeding. In cases of unequivocal rupture or intactness of membranes, the results of both assays correspond well with the clinical findings. 12 hours after rupture of membranes the test may become negative if no amniotic fluid is visible in the vagina. As all blood samples had been positive for fetal fibronectin we conclude that vaginal bleeding will probably interfere with the test. The most surprising result is the apparent presence of fetal fibronectin in the blood samples of non-pregnant women. This observation can only be explained by a cross-reaction of the FDC-6 antibody with hepatic fibronectin.

Fetal fibronectin as a selection criterion for induction of term labor

OBJECTIVE: We examined whether the presence of fetal fibronectin in cervicovaginal secretions can be used as a selection criterion for induction of labor at term. STUDY DESIGN: Cervicovaginal secretions of 64 women who were scheduled for induction of labor were examined for fetal fibronectin and divided into group A (positive for fibronectin) and group B (negative for fibronectin). Both groups were examined for Bishop score, the number of prostaglandin tablets administered, and the interval between induction of labor and delivery. RESULTS: In group A the interval between induction of labor and delivery was significantly shorter ( p < 0.0001) than in group B. The number of prostaglandin tablets administered to group A was likewise significantly lower ( p < 0.0001). Unsuccessful induction of labor only occurred in women with fibronectin-negative cervicovaginal secretions. CONCLUSION: The assessment of the fibronectin content of cervicovaginal secretions constitutes a viable instrument in the decision-making process preceding induction of labor.

Fetal fibronectin as a marker to predict the onset of term labor and delivery

OBJECTIVE: We examined whether the presence of fetal fibronectin in cervicovaginal secretions may be a marker to predict the onset of term labor and delivery. STUDY DESIGN: A prospective study was performed in 100 primiparous and multiparous women having reached their expected date of confinement. Fetal fibronectin was assayed by taking samples of both the cervical and vaginal mucus with two different fetal fibronectin tests. The study population was divided into women delivering within 48 hours and women giving birth >48 hours after sampling. RESULTS: Seven patients had to be excluded from evaluation. Of the remaining 93 women, 37 were delivered within 48 hours; fetal fibronectin was detected in 30. Fifty-six women were delivered later than 48 hours; 51 of them had negative results for fetal fibronectin (positive accuracy 86%, negative accuracy 88%, p < 0.0001). CONCLUSION: Fetal fibronectin in the cervicovaginal secretions of women who have reached their expected date of confinement is a useful predictor of the onset of term labor and delivery.