Cervical Fetal Fibronectin Research Articles

Preterm labor with intact membranes: a simple noninvasive method to identify patients at risk for intra-amniotic infection and/or inflammation

Objective To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis. Methods This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20–34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system. Results Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0–2), maternal serum CRP concentration (score 0–2), cervical dilatation (score 0-2), and gestational age at presentation (score 0–1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92–0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation (p < .001, for all); 4) the risk score with a cutoff of 4 had a sensitivity of 94.9% (37/39), a specificity of 90.9% (90/99), a positive predictive value of 80.4% (37/46), a negative predictive value of 97.8% (90/92), a positive likelihood ratio of 10.4 (95% CI, 5.6–19.5), and a negative likelihood ratio of 0.06 (95% CI, 0.15–0.22) in the identification of intra-amniotic infection/inflammation. Conclusions (1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.

Fetal Fibronectin as a Predictor of Preterm Delivery: A Nigerian Cohort Study.

Background Fetal fibronectin is a useful biomarker in the diagnosis and management of preterm labour. Objectives To evaluate the relationship between cervical fetal fibronectin and preterm delivery and the association between cervical fetal fibronectin level and gestational age at delivery. Materials and Methods A prospective cohort study was performed in a tertiary hospital in Nigeria, involving equal number of pregnant women with (96) and without (96) preterm labour. Fetal fibronectin assay was done using solid-phase immunogold assay. The data were analysed using IBM SPSS version 24. Descriptive and inferential statistical analyses were done. The level of significance was p-value <0.05. Results Less than half (47.9%) of the women in the study group had preterm delivery while 13.09% of the women in the control group delivered preterm. Fetal fibronectin test had a sensitivity, specificity, positive predictive value and negative predictive value of 78%, 86.5%, 71.9%, and 89.0%, respectively, a positive likelihood ratio and negative likelihood ratio of 5.76(95% CI, 3.67 – 9.64) and 0.26(95% CI, 0.16 – 0.41), respectively. Conclusion The findings in our study value of fetal fibronectin in predicting preterm delivery. Its use will support less intervention for patients with negative results.

A Combination of Cervicovaginal Fluid Glutamate, Acetate and D-Lactate Identified Asymptomatic Low-Risk Women Destined to Deliver Preterm: a Prospective Cohort Study

Due to the modest predictive capacities and limited clinical application of transvaginal ultrasonographic cervical length (CL) and quantitative fetal fibronectin (qfFN) in pregnant women at low risk of preterm birth (PTB), we sought to determine the utility of cervicovaginal fluid (CVF) metabolites (by-products of host-microbial metabolism) for prediction of spontaneous PTB in asymptomatic low-risk women at mid-gestation. This was a prospective sub-cohort study from the ECCLIPPx study cohort. CVF from asymptomatic singleton women (20–22 weeks, n = 168) without a prior history of PTB were analysed for metabolites by enzyme-based spectrophotometry. CL, vaginal pH and qfFN were also measured. Correlation and predictive analyses were performed by Spearman’s correlation, and binary logistic regression and area under receiver operating characteristic curve (AUC), respectively. Of the 168 women enrolled, only CVF samples from 135 (80.4%) women were analysed. There were 6/135 (4.4%) spontaneous PTB (sPTBs), with two of these pregnancies ending ≤ 28 weeks’ gestation. Individually (AUC, 95% CI), only glutamate (0.72, 0.64–0.80) and CL (0.69, 0.60–0.77) were predictive of PTB. However, five multivariable models that more accurately predicted sPTB were also identified, i.e. a combination of: glutamate, acetate and D-lactate (GAD, 0.82, 0.74–0.89); CL and qfFN only (0.78, 0.70–0.85); CL, qfFN, glutamate and acetate (0.88, 0.81–0.93); CL, qfFN and GAD (0.94, 0.88–0.98); and GAD and pH (0.86, 0.79–0.92). Correlations between CL, pH and qfFN and metabolites were also observed. In this cohort, a midtrimester combination of CVF glutamate, acetate and D-lactate predicted preterm birth more accurately than individual metabolites, cervical length and fetal fibronectin with a very low false-positive rate and high positive predictive value. Further testing in populations with higher preterm birth rates is required.

Self-reported pain scores as a predictor of preterm birth in symptomatic twin pregnancy: a retrospective study

BackgroundTo evaluate the self-reported pain scores as a predictor of preterm birth (PTB) in symptomatic twin pregnancy and to develop a nomogram for the prediction model.MethodsWe conducted a retrospective study of 148 cases of symptomatic twin pregnancies before 34 weeks of gestation visited at Seoul national university hospital from 2013 to 2018. With other clinical factors, self-reported pain score was evaluated by the numerical rating scale (NRS) pain scores for pain intensity. By multivariate analyses and logistic regression, we developed a prediction model for PTB within 7 days. Using the Cox proportional hazards model, the curves were plotted to show the predictability of the PTB according to NRS pain score, while adjusting the other covariates.ResultsTwenty-three patients (15.5 %) delivered preterm within 7 days. By a logistic regression analysis, higher NRS pain score (OR 1.558, 95 % CI 1.093–2.221, P < 0.05), shorter cervical length (OR 3.164, 95 % CI 1.262–7.936, P < 0.05) and positive fibronectin results (OR 8.799, 95 % CI 1.101–70.330, P < 0.05) affect PTB within 7 days. Using the variables, the area under the receiver operating characteristic curve (AUROC) of the prediction model was 0.917. In addition, we developed a nomogram for the prediction of PTB within 7 days.ConclusionsSelf-reported pain scores combined with cervical length and fetal fibronectin are useful in predicting impending PTB in symptomatic twin pregnancy.

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

561: A high cervical fetal fibronectin concentration increases the risk of intra-amniotic infection/inflammation in preterm labor

561: A high cervical fetal fibronectin concentration increases the risk of intra-amniotic infection/inflammation in preterm labor

Rationale & design of the PROMISES study: a prospective assessment and validation study of salivary progesterone as a test for preterm birth in pregnant women from rural India

BackgroundIn India, 3.6 million pregnancies are affected by preterm birth annually, with many infants dying or surviving with disability. Currently, there is no simple test available for screening all women at risk of spontaneous PTB in low income setting, although high resource settings routinely use cervical length measurement and cervico-vaginal fluid fetal fibronectin for identification and care of women at risk due to clinical history. In rural India, where the public health system has limited infrastructure, trained staff and equipment, there is a greater need to develop a low-cost screening approach for providing early referral, treatment and remedial support for pregnant women at risk of preterm birth. There is interest in the use of a salivary progesterone test as a screening tool preliminary evidence from India, Egypt and UK has shown promise for this type of test. The test requires further validation in a low resource community setting.MethodsThe Promises study aims to validate and test the feasibility of introducing a low-cost salivary progesterone preterm birth prediction test in two rural districts in India with high rates of prematurity. It is a prospective study of 2000 pregnant women recruited from Panna and Satna in Madhya Pradesh over approximately 24 months. Demographic and pregnancy outcome data will be collected, and pregnancies will be dated by ultrasound sonography. Saliva progesterone will be measured by ELISA in samples obtained between 24–28 weeks of gestation. The association between salivary progesterone and preterm birth will be determined and the utility of salivary progesterone to predict preterm birth < 34, as well as < 30 and < 37 weeks assessed. Additional qualitative data will be obtained in terms of acceptability and feasibility of saliva progesterone testing and knowledge of PTB.DiscussionA validated cost-effective saliva test, which has potential for further adaptation to a ‘point of care’ setting will allow early identification of pregnant women at risk of preterm birth, who can be linked to an effective pathway of care and support to reduce preterm birth and associated adverse consequences. This will reduce both economic and emotional burden on the affected women and their families.

Cervical Evaluation in Pregnancy: Proper Measurement, Evaluation, and Management.

Preterm birth is the leading cause of perinatal morbidity and mortality in developed nations. The heterogeneous causes of spontaneous preterm birth make prediction and prevention difficult. The primary importance of transvaginal cervical sonography and cervicovaginal fetal fibronectin lies in their high negative predictive values in assessing risk for preterm birth. Cervical length may be useful in identifying women who are candidates for cervical cerclage or progesterone therapy for preterm birth prevention. Together, cervical length and fibronectin can be used in the triaging of women symptomatic for preterm labor.

The Case Against Measuring Cervical Length and Fetal Fibronectin to Predict Preterm Birth

Although a history of preterm birth raises risk for recurrence in subsequent pregnancies, most early deliveries occur in first-time mothers without

Biomarkers for predicting spontaneous preterm birth: an umbrella systematic review

Objective: To identify all systematic reviews investigating the role of maternal and fetal biomarkers for predicting spontaneous preterm birth (SPTB).Methods: Medline and Web of Sciences databases were searched electronically. Studies exploring the association between maternal biomarkers and spontaneous delivery were considered suitable for inclusion. A synthesis of the systematic reviews was performed with the umbrella methodology. Statistical measures of association (Odd ratio, OR, relative risk, RR) and predictive accuracy (sensitivity, specificity, positive and negative likelihood ratios were used to synthesize results of the included studies.Results: 21,614 articles were identified, 542 were assessed with respect to their eligibility for inclusion and 14 systematic reviews included. Cervical fibronectin was the biomarkers which showed the highest strength of association with the occurrence of SPTB (delivery within 24 h OR 7, 95%CI 3–17; delivery <7 days (OR 12, 95%CI 8–16). Maternal serum alpha fetoprotein, was associated with an OR of 4 and 3 for early and late SPTB. C-reactive protein had an OR of 2 (95%CI 1–2) and 8 (95%CI 4–16) when detected in maternal plasma and amniotic fluid, respectively. Among cytokines, interleukin-6 had an OR and an LR + for SPTB of 2 and 12 when detected in maternal serum.Conclusions: Cervical fetal fibronectin, alpha fetoprotein, C- reactive protein and interleukin 6 can have an overall good diagnostic accuracy in identifying pregnancies at risk of SPTB. Large prospective studies in different sub-set of women are needed to ascertain whether the combination of different serological and imaging marker can improve antenatal prediction of this condition.

Clinical study of Jiawei Bazhen decoction combined with oxytocin for cervical ripening of qi and blood deficiency type of pregnant women

To study preliminarily the effect of Jiawei Bazhen decoction combined with oxytocin in promoting cervical ripening of full-term pregnancy women who were in the deficiency of qi and blood type through the syndrome differentiation of traditional Chinese medicine (TCM). 180 patients that met the inclusion criteria of the study were randomly divided into three groups: the control group(oxytocin group), the treatment group (Jiawei Bazhen decoction combined with oxytocin group), the blank control group (expected and observation group). Cervical maturity score (Bishop score), vaginal and cervical secretions fetal fibronectin (FFN), the result of induced labor, the result of mother and baby were observed in each group before and after treatment. The result comes out that the cervical Bishop score of pregnant women for treatment group were significantly higher than the control group and blank control group after treatment (P < 0.05). The FFN of pregnant women for the treatment group were significantly different from the control group and blank control group after treatment (P < 0.05). The pregnancy outcome of the three groups: the labor rate and rate of vaginal delivery of the treatment group were higher than the other two groups, and the difference was statistically significant (P < 0.05). The cesarean section rate of the treatment group was significantly lower than the other two groups, the difference was also statistically significant (P < 0.05). The three groups did not appear the phenomenon of neonatal asphyxia. Jiawei Bazhen decoction combined with oxytocin is effective in producing cervical ripening and induce labor. It is convenient, safe and reliable, for it is no obvious adverse effects on mother and fetus, but effective in reducing the rate of cesarean section, and playing a positive role in promoting natural delivery.

The association between maternal biomarkers and pathways to preterm birth in twin pregnancies

Objective: We sought to estimate the association between cervical length (CL) and fetal fibronectin (fFN) and each pathway leading to preterm birth in twin pregnancies.Methods: Cohort study of 560 patients with twin pregnancies who underwent routine serial CL and fFN screening from 22 to 32 weeks in one maternal fetal medicine practice during 2005–2013. We calculated the association between a short CL (≤20 mm) or positive fFN with overall preterm birth <32 weeks, and then subdivided the analysis into preterm birth <32 weeks from preterm labor, preterm premature rupture of membranes (PPROM) and indicated causes. We excluded cases of monochorionic-monoamniotic placentation, vasa previa, twin–twin transfusion and patients with cerclage.Results: The overall rate of preterm birth <32 weeks was 6.9% (3.9% from preterm labor, 1.6% from PPROM and 1.4% indicated). A short cervix was associated with preterm birth <32 weeks arising from preterm labor (12.4% versus 2.0%, p < 0.001), but not PPROM (1.9% versus 1.3%, p = 0.651). Positive fFN was associated with preterm birth <32 weeks both from preterm labor (17.0% versus 2.4%, p < 0.001) as well as from PPROM (5.7% versus 1.0%, p = 0.034). Neither was significantly associated with preterm birth <32 weeks from indicated causes.Conclusions: The mechanism leading toward preterm influences the accuracy of screening tests chosen to assess risk in twin pregnancies. A shortened cervical length and positive fFN is associated with spontaneous preterm labor and birth <32 weeks. However, PPROM does not appear to be preceded by a short cervix, but is preceded by a positive fFN. Neither test is associated with an indicated preterm birth.

Evaluation of the ability of cervical length and fetal fibronectin measurement to predict preterm delivery in asymptomatic women with risk factors

Objective: To evaluate the power of transvaginal ultrasound cervical length (CL) and fetal fibronectin (fFN) measurement for the prediction of preterm delivery (PTD) in asymptomatic women with risk factors.Methods: Between January 2010 and October 2012, 218 women with singleton pregnancies and a high risk for PTD (i.e. prior history of PTD, cervical surgeries, late miscarriages, uterine abnormalities or premature rupture of the membranes) were selected. CL was measured by transvaginal ultrasonography between 14 and 22 weeks, and a CL < 2.5 cm was considered to be short. The fFN was measured with a sterile speculum examination. The primary outcome was the spontaneous PTD rate at <34+0 and <37+0 weeks, and the PTD rate was analyzed by either of two methods alone or combined.Results: There were 213 cases included in the analysis, and 47 women (22.1%) had positive fFN. The average CL of women with positive fFN (2.3 ± 0.9 cm) was significantly shorter than that of women with negative fFN (3.1 ± 0.8 cm; p = 0.02). There were 25 (11.7%) and 38 (18.8%) cases with PTD at <34+0 and <37+0 weeks, respectively. By individual analyses, the highest PTD rate was 51.2% in women with positive fFN at <37+0 weeks. The sensitivity and diagnostic efficiency values for PTD prediction by CL were low at <34+0 and <37+0 weeks. The values of diagnostic efficiency by fFN were >80% at <34+0 and <37+0 weeks. In the combined analysis, the highest PTD rate was 57.1% in women with CL ≤ 2.5 cm and positive fFN at <37+0 weeks. The Kaplan–Meier curve indicated that there were significant differences among the four groups (χ2 = 54.261; p = 0.000).Conclusions: These results indicate a significant correlation between fFN and PTD prediction. The PTD prediction could be enhanced by combined CL and fFN measurement.

Management of vasa praevia: A potential role for cervical length and quantitative fetal fibronectin measurement

A 37-year-old Caucasian woman presented to the Pre-term Surveillance Clinic in her second pregnancy, at 18 + 6 weeks’ gestation. Her previous pregnancy had resulted in spontaneous pre-term birth (s...

Combination of cervical sonoelastography with cervical length measurement and fetal fibronectin to improve prediction of preterm birth

Combination of cervical sonoelastography with cervical length measurement and fetal fibronectin to improve prediction of preterm birth

Routine cervical length and fetal fibronectin screening in asymptomatic twin pregnancies: is there clinical benefit?

Objective: To determine whether routine cervical length (CL) and fetal fibronectin (fFN) screening is associated with improved clinical outcomes in asymptomatic patients with twin pregnancies.Study design: We compared outcomes between two large cohorts of twin pregnancies who delivered in New York City from 2003 to 2012. One cohort (n = 532) was managed by a single group practice, delivered at one large academic medical center, and underwent routine serial CL and fFN screening. The second cohort (n = 456) delivered at a second large academic center and only underwent CL and fFN testing as clinically indicated. Outcomes measured include cerclage placement, preterm birth (PTB), spontaneous PTB (sPTB), and antenatal corticosteroid (ACS) exposure.Results: Rates of cerclage placement, PTB, and SPTB were similar between the two groups. However, routine CL and fFN screening was associated with improved rates of ACS exposure in patients who delivered <34 weeks (91.3% versus 74.7%, p = 0.005) and 34–36 6/7 weeks (41.3% versus 13.9%, p < 0.001) without increased ACS exposure in women who delivered at term. In patients who delivered <34 weeks, routine CL and fFN screening was significantly associated with improved rates of ACS exposure within 1–14 days of delivery and within 1–7 days of delivery.Conclusion: In twin pregnancies, routine CL and fFN screening does not reduce the risk of PTB or SPTB. However, the routine use of these tests is associated with significantly improved ACS exposure and timing for women who deliver preterm without increasing ACS exposure to women who deliver at term.

527: Routine cervical length and fetal fibronectin screening in asymptomatic twin pregnancies: is there clinical benefit?

Twin gestations are at an increased risk of preterm birth (PTB). A short cervical length (CL) and a positive fetal fibronectin (fFN) are both significantly associated with PTB in twin pregnancies. However, it is uncertain if the routine use of these screening tests in asymptomatic twin pregnancies leads to improved outcomes. Our objective was to assess whether routine CL and fFN screening in twin gestations is associated with improved outcomes.

Prevention and Management of Preterm Birth

Prevention and treatment of preterm delivery is not one of the success stories of modern medicine, preterm birth constitutes the major determinant of perinatal mortality and morbidity, and the long-term results of being born too early often lead to a shorter, less healthy life and a more difficult school and professional career. Different methods have been introduced to predict the advent of preterm labour in asymptomatic women, including fetal fibronectin and transvaginal ultrasound cervical length measurement. R. Arisoy and M. Yayla present data on the evaluation of the cervix in asymptomatic singleton pregnancies; they also address the most frustrating issue: what measures to take once a short cervix has been detected. They restrict their study to singleton pregnancies; although both cervical length and fetal fibronectin are good predictors of preterm delivery in twins, no intervention has proven useful in twins: vaginal progesteron makes no difference and cerclage even worsens the outcome. Possibilities for real primary prevention are rare and include treatment of asymptomatic bacteriuria and periodontal disease. O. Huck et al. elaborate this last issue and present an excellent overview on both epidemiologic and pathophysiologic data. Another method proposed for primary prevention of preterm birth is the use of progesteron, including vaginal progesteron and systemic 17-hydroxyprogesterone caproate. Starting progesterone treatment can be based not only on cervical length or vaginal fibronectin but also on past obstetrical history. C. E. Ransom et al. comment on the use of 17-hydroxyprogesterone caproate and the influence of obstetric history. Some newer methods are on the border of being introduced to clinical practice; one such candidate is near-infrared spectroscopy. K. M. Power and colleagues present the use of near-infrared spectroscopy of amniotic fluid to assess preterm delivery. Once preterm labour has been established, tocolytics are (all too) often used, and what their exact place in treatment is remains open for discussion. Hubinont and F. Debieve present a concise update on tocolysis. In case preterm delivery seems unavoidable, the optimal mode of fetal monitoring and the mode of delivery have to be chosen. Fetal heart rate monitoring in the preterm period constitutes a special challenge and is further commented by K. Afors and E. Chandraharan, while S. R. Bhatta and C. R. Keriakos discuss the optimal way of delivering the preterm baby in vertex position. As the articles in this issue demonstrate, preterm labour and delivery constitute one of the major challenges of obstetrics in the 21st century. Yves Jacquemyn Ronnie Lamont Jerome Cornette Hanns Helmer

OC26.02: Validating a prediction model of spontaneous preterm birth using ultrasound cervical length measurement and fetal fibronectin immunoassay

OC26.02: Validating a prediction model of spontaneous preterm birth using ultrasound cervical length measurement and fetal fibronectin immunoassay

OP22.01: Markers for labour induction success in nullipara. Do cervical length and fetal fibronectin have any predictive value?

OP22.01: Markers for labour induction success in nullipara. Do cervical length and fetal fibronectin have any predictive value?