Quantitative Fetal Fibronectin Testing Research Articles

A prospective, double-blinded cohort study using quantitative fetal fibronectin testing in symptomatic women for the prediction of spontaneous preterm delivery

BackgroundSpontaneous preterm birth (PTB) affects 6.5% of deliveries in Hong Kong. Quantitative fetal fibronectin (fFN) is under-utilised as a test for PTB prediction in Hong Kong. Our objective was to evaluate the effectiveness of quantitative fFN in predicting spontaneous PTB in women with symptoms of threatened preterm labour (TPTL) in our population.MethodsA prospective, double-blinded cohort study of women with a singleton gestation and TPTL symptoms presenting to a tertiary hospital in Hong Kong between 24 + 0 to 33 + 6 weeks was performed from 1st October 2020 and 31st October 2021. Women with vaginal bleeding, ruptured membranes, and cervical dilation > 3 cm were excluded. The primary outcome was to test the characteristics of quantitative fFN in predicting spontaneous PTB < 37 weeks. Secondary outcome was to investigate the relationship between fFN value and time to PTB. Test characteristics of quantitative fFN at different thresholds were evaluated.Results48 women with TPTL were recruited. All had fFN testing at admission with the results being concealed from the obstetrician managing the patient. 10 mothers had PTB (< 37 weeks’ gestation). 7/48 (15%) had a subsequent PTB within 14 days from testing and 5 (10%) delivered within 48 h. The negative predictive value (NPV) of predicting delivery within 14 days was 97.3% and 100% when using a cut-off of < 50ng/ml and < 10ng/ml respectively. Using > 200 ng/ml as cut-off can also reliably predict delivery within 48 h – 7 days with positive predictive value PPV of 100%; as well as PTB before 37 weeks.ConclusionsQuantitative fFN has predictive value for spontaneous PTB prediction in symptomatic women in a Hong Kong population. fFN concentration could help clinicians rule out PTB and avoid unnecessary interventions and hospitalisation.

Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly

Congenital uterine anomalies are associated with late miscarriage and spontaneous preterm birth. Our aim was 1) to determine the rate of spontaneous preterm birth in each type of congenital uterine anomaly, and 2) to assess the performance of quantitative fetal fibronectin and cervical length measurement by transvaginal ultrasound in asymptomatic women with congenital uterine anomalies for the prediction of spontaneous preterm birth at <34 and <37 weeks of gestation. This was a retrospective cohort of women with congenital uterine anomalies asymptomatic for spontaneous preterm birth, from 4 tertiary referral centers in the United Kingdom (2001-2016). Congenital uterine anomalies were categorized into fusion (unicornuate, didelphic, and bicornuate uteri) or resorption defects (septate, with or without resection, and arcuate uteri), based on prepregnancy diagnosis. All women underwent serial transvaginal ultrasound cervical length assessment in the second trimester (16 to 24 weeks' gestation); a subgroup underwent quantitative fetal fibronectin testing from 18 weeks' gestation. We investigated the relationship between congenital uterine anomalies and predictive test performance for spontaneous preterm birth at <34 and <37 weeks' gestation. A total of 319 women were identified as having congenital uterine anomalies in our high-risk population. Of the women, 7% (23/319) delivered spontaneously at <34 weeks' gestation and 18% (56/319) at <37 weeks' gestation. Rates of spontaneous preterm birth by type were asfollows: 26% (7/27) for unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for septate, and 31% (4/13) for arcuate. In all, 80% (45/56) of women who had spontaneous preterm birth at <37 weeks did not develop a short cervical length (<25 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short cervical length had a low sensitivity (20.3) for predicting spontaneous preterm birth at <34 weeks. Cervical length had an area under the receiver operating curve of 0.56 (95% confidence interval, 0.48-0.64) and 0.59 (95% confidence interval, 0.55-0.64) for prediction of spontaneous preterm birth at <34 and <37 weeks, respectively. The area under the curve for cervical length to predict spontaneous preterm birth at <34 weeks was 0.48 for fusion defects (95% confidence interval, 0.39-0.57) but 0.78 (95% confidence interval, 0.66-0.91) for women with resorption defects. Overall quantitative fetal fibronectin had an area under the curve of 0.63 (95% confidence interval, 0.49-0.77) and 0.58 (95% confidence interval, 0.49- 0.68) for prediction of spontaneous preterm birth at <34 and <37 weeks, respectively. The area under the curve for prediction of spontaneous preterm birth at <37 weeks with quantitative fetal fibronectin for fusion defects was 0.52 (95% confidence interval, 0.41-0.63) but 0.79 (95% confidence interval, 0.63-0.95) for women with resorption defects. Results were similar when women with intervention were excluded. The commonly used markers cervical length and quantitative fetal fibronectin have utility in prediction of spontaneous preterm birth in resorption congenital uterine defects but not in fusion defects. This is contrary to findings in other high-risk populations. These findings need to be accounted for when planning antenatal care, and have potential implications for predictive tests used in spontaneous preterm birth surveillance and intervention.

The efficacy of quantitative fetal fibronectin in predicting spontaneous preterm birth in symptomatic women: A retrospective cohort study.

Recent data suggest that quantitative measurements of fetal fibronectin can be used accurately to predict increased risk of preterm birth. The purpose of this study was to demonstrate that the quantification of fetal fibronectin improves diagnostic accuracy in women who present with symptoms suggestive of threatened preterm labour (TPL) using a quantitative fetal fibronectin (qfFN) bedside analyser. This was a retrospective cohort study of pregnant women who presented between 22+6 and 32+6 weeks gestation with symptoms of TPL who had qfFN measured using the Rapid fFN Q10 system. The ability to predict spontaneous preterm birth (sPTB) within 48h, 14days and <34weeks gestation at qfFN thresholds of 10, 50 and 200ng/mL was assessed. The overall rate of sPTB <34weeks was 4.1% (n=373). For deliveries within 48h, within 14days and <34weeks, a qfFN threshold of 200ng/mL had positive predictive values of 26.7%, 42.9% and 46.7%, respectively, when compared to patients with qfFN values of 0-9ng/mL. The corresponding relative risks were 68.5, 53.8 and 38.0, respectively CONCLUSION: Quantitative fetal fibronectin testing with thresholds of 10, 50 and 200ng/mL allows for more accurate prediction of preterm birth in symptomatic women. This higher degree of discrimination allows for more directed interventions for high-risk patients and reduces the cost and burden of unnecessary treatment for low-risk patients.

Evaluation of the quantitative fetal fibronectin test and PAMG-1 test for the prediction of spontaneous preterm birth in patients with signs and symptoms suggestive of preterm labor

Objective: The objective of this study is to compare the qualitative fFN test at 50 ng/ml threshold to novel methods for assessing risk of imminent sPTB in women with symptoms of preterm labor (PTL): (1) quantitative fetal fibronectin (qfFN) at four thresholds: 10, 50, 200, and 500 ng/ml; and (2) qualitative PAMG-1 test.Study design: Consecutive patients presenting with singleton pregnancies, signs of PTL, gestational age 23.1–34.6, intact membranes, no coitus within 24 h, and cervical dilation ≤3 cm. fFN was performed as standard of care, while clinicians were blinded to the qfFN and PAMG-1 test results. qfFN accuracy was evaluated at four thresholds of 10, 50, 200, and 500 ng/ml for its ability to predict imminent spontaneous preterm delivery (sPTD) ≤ 7 and ≤14 d from the time of sample collection. The PAMG-1 test was evaluated based on its qualitative result for the same delivery endpoints.Results: Seventy-two patients were analyzed. Fifty-seven percent of patients had an fFN concentration of <10 ng/ml fFN; 75% < 50 ng/ml; 92% < 200 ng/ml; 97% < 500 ng/ml. The SN, SP, PPV, and NPV for fFN at each of the four cutoffs for sPTB ≤7 d: 10 ng/ml: 67%, 58%, 6%, 98%; 50 ng/ml: 67%, 77%, 11%, 98%; 200 ng/ml: 33%, 93%, 17%, 97%; 500 ng/ml: 0%, 97%, 0%, 96%. The PAMG-1 test was positive in 7% of patients. SN, SP, PPV, and NPV for PAMG-1 for sPTD ≤7 d were 67%, 96%, 40%, and 99%, respectively.Conclusion: Compared with qfFN, the PAMG-1 test is a better predictor of spontaneous delivery within 7 d while maintaining a very high negative predictive value. The PAMG-1 test is an easy-to-use bedside test that provides rapid results, does not require a speculum examination, can be used after vaginal exam and coitus and does not require specialized equipment to analyze results. As to be expected, compared with the conventional cutoff of fFN (50 ng/ml), a higher fFN cutoff of 200 ng/ml does seem to increase the PPV of the test, but this comes at a cost to the fFN test’s SN and NPV, rendering it of little to no advantage in clinical practice.

Quantitativer Fibronectin-Nachweis zur Risikoabschätzung für eine Frühgeburt

Bruijn M et al. Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women. BJOG 2016; 123: 1965 – 1971

The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women

The combination of the qualitative fetal fibronectin test and cervical length measurement has a high negative predictive value for preterm birth within 7 days; however, positive prediction is poor. A new bedside quantitative fetal fibronectin test showed potential additional value over the conventional qualitative test, but there is limited evidence on the combination with cervical length measurement. The purpose of this study was to compare quantitative fetal fibronectin and qualitative fetal fibronectin testing in the prediction of spontaneous preterm birth within 7 days in symptomatic women who undergo cervical length measurement. We performed a European multicenter cohort study in 10 perinatal centers in 5 countries. Women between 24 and 34 weeks of gestation with signs of active labor and intact membranes underwent quantitative fibronectin testing and cervical length measurement. We assessed the risk of preterm birth within 7 days in predefined strata based on fibronectin concentration and cervical length. Of 455 women who were included in the study, 48 women (11%) delivered within 7 days. A combination of cervical length and qualitative fibronectin resulted in the identification of 246 women who were at low risk: 164 women with a cervix between 15 and 30 mm and a negative fibronectin test (<50 ng/mL; preterm birth rate, 2%) and 82 women with a cervix at >30 mm (preterm birth rate, 2%). Use of quantitative fibronectin alone resulted in a predicted risk of preterm birth within 7 days that ranged from 2% in the group with the lowest fibronectin level (<10 ng/mL) to 38% in the group with the highest fibronectin level (>500 ng/mL), with similar accuracy as that of the combination of cervical length and qualitative fibronectin. Combining cervical length and quantitative fibronectin resulted in the identification of an additional 19 women at low risk (preterm birth rate, 5%), using a threshold of 10 ng/mL in women with a cervix at <15 mm, and 6 women at high risk (preterm birth rate, 33%) using a threshold of >500 ng/mL in women with a cervix at >30 mm. In women with threatened preterm birth, quantitative fibronectin testing alone performs equal to the combination of cervical length and qualitative fibronectin. Possibly, the combination of quantitative fibronectin testing and cervical length increases this predictive capacity. Cost-effectiveness analysis and the availability of these tests in a local setting should determine the final choice.

Quantitative fetal fibronectin and cervical length to predict preterm birth in asymptomatic women with previous cervical surgery

Quantitative fetal fibronectin testing has demonstrated accuracy for prediction of spontaneous preterm birth in asymptomatic women with a history of preterm birth. Predictive accuracy in women with previous cervical surgery (a potentially different risk mechanism) is not known.We sought to compare the predictive accuracy of cervicovaginal fluid quantitative fetal fibronectin and cervical length testing in asymptomatic women with previous cervical surgery to that in women with 1 previous preterm birth.We conducted a prospective blinded secondary analysis of a larger observational study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women measured with a Hologic 10Q system (Hologic, Marlborough, MA). Prediction of spontaneous preterm birth (<30, <34, and <37 weeks) with cervicovaginal fluid quantitative fetal fibronectin concentration in primiparous women who had undergone at least 1 invasive cervical procedure (n = 473) was compared with prediction in women who had previous spontaneous preterm birth, preterm prelabor rupture of membranes, or late miscarriage (n = 821). Relationship with cervical length was explored.The rate of spontaneous preterm birth <34 weeks in the cervical surgery group was 3% compared with 9% in previous spontaneous preterm birth group. Receiver operating characteristic curves comparing quantitative fetal fibronectin for prediction at all 3 gestational end points were comparable between the cervical surgery and previous spontaneous preterm birth groups (34 weeks: area under the curve, 0.78 [95% confidence interval 0.64-0.93] vs 0.71 [95% confidence interval 0.64-0.78]; P = .39). Prediction of spontaneous preterm birth using cervical length compared with quantitative fetal fibronectin for prediction of preterm birth <34 weeks of gestation offered similar prediction (area under the curve, 0.88 [95% confidence interval 0.79-0.96] vs 0.77 [95% confidence interval 0.62-0.92], P = .12 in the cervical surgery group; and 0.77 [95% confidence interval 0.70-0.84] vs 0.74 [95% confidence interval 0.67-0.81], P = .32 in the previous spontaneous preterm birth group).Prediction of spontaneous preterm birth using cervicovaginal fluid quantitative fetal fibronectin in asymptomatic women with cervical surgery is valid, and has comparative accuracy to that in women with a history of spontaneous preterm birth.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7days compared with qualitative fFN and CL. Post hoc analysis of frozen fFN samples of a nationwide cohort study. Ten perinatal centres in the Netherlands. Symptomatic women between 24 and 34weeks of gestation. The risk of PTD<7days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7days using a reclassification table. Spontaneous delivery within 7days after study entry. We studied 350 women, of whom 69 (20%) delivered within 7days. The risk of PTD in <7days ranged from 2% in the lowest fFN group (<10ng/ml) to 71% in the highest group (>500ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7days with rising fFN concentration [10-49ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199ng/ml: OR 3.2, 95% CI 0.79-13; 200-499ng/ml: OR 9.0, 95% CI 2.3-35; >500ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7days. In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Quantitative fetal fibronectin to predict preterm birth in asymptomatic women at high risk.

To evaluate the diagnostic accuracy of cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth before 34 weeks of gestation. We conducted a prospective masked observational cohort study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women at high risk of spontaneous preterm birth (n=1,448; 22-27 6/7 weeks of gestation) measured using a rapid bedside analyzer. The routine qualitative result (positive-negative) was made available to clinicians at the time of testing, but the quantitative result remained blinded until after delivery. Spontaneous preterm birth (less than 34 weeks of gestation) increased from 2.7%, 11.0%, 14.9%, 33.9%, and 47.6% with increasing concentration of fetal fibronectin (less than 10, 10-49, 50-199, 200-499, and 500 ng/mL or greater, respectively). A threshold of 200 ng/mL had a positive predictive value of 37.7 (95% confidence interval [CI] 26.9-49.4) with specificity 96% (95% CI 95.3-97.3). Women with a fetal fibronectin concentration of less than 10 ng/mL had a very low risk of spontaneous preterm birth at less than 34 weeks of gestation (2.7%), no higher than the background spontaneous preterm birth rate of the general hospital population (3.3%). The quantitative fetal fibronectin test predicted birth at less than 34 weeks of gestation with an area under the curve (AUC) of 0.78 (95% CI 0.73-0.84) compared with the qualitative test AUC 0.68 (95% CI 0.63-0.73). Quantitative fetal fibronectin discriminated risk of spontaneous preterm birth at less than 34 weeks of gestation among women with a short cervix (less than 25 mm); 9.5% delivered prematurely less than 10 ng/mL compared with 55.1% greater than 200 ng/mL (P<.001). Alternative risk thresholds (less than 10 ng/mL and greater than 200 ng/mL) improve accuracy when using quantitative fetal fibronectin measurements to define risk of spontaneous preterm birth. This is particularly relevant for asymptomatic women with a short cervix. II.

362: Does quantitative fetal fibronectin testing add to cervical length measurement and qualitative fetal fibronectin testing; (I) Identification of low risk women with threatened preterm labor (EUFIS study)

To evaluate whether quantitative fetal fibronectin (fFN) testing adds to cervical length (CL) and qualitative fetal fibronectin testing in the identification of women at low risk (<5%) for spontaneous preterm delivery (PTD) < 7 days.

363: Does quantitative fetal fibronectin testing add to cervical length measurement and qualitative fetal fibronectin testing; (II) absolute probability of preterm delivery

363: Does quantitative fetal fibronectin testing add to cervical length measurement and qualitative fetal fibronectin testing; (II) absolute probability of preterm delivery <7 days in women with threatened preterm labor (EUFIS study)

PFM.07 Quantitative fetal fibronectin testing as a predictor of spontaneous preterm delivery after cervical surgery

IntroductionQuantitative fetal fibronectin (qfFN) testing has demonstrated accuracy at predicting sPTB in high-risk asymptomatic women (previous preterm birth or late miscarriage). It is not known whether qfFN has predictive accuracy...

741: Does quantitative fetal fibronectin testing improve the prediction of spontaneous preterm delivery as compared to qualitative fetal fibronectin testing in symptomatic women: a post-hoc analysis

741: Does quantitative fetal fibronectin testing improve the prediction of spontaneous preterm delivery as compared to qualitative fetal fibronectin testing in symptomatic women: a post-hoc analysis

PM.61 The Use of Quantitative Fetal Fibronectin to Predict Obstetric Outcome: A Comparison of a New and Established Quantitative Bedside Analyser in Asymptomatic High-Risk Women

Background Preterm birth (PTB) remains a significant cause of neonatal morbidity and mortality. The most accurate predictors of PTB are ultrasound determined cervical length (CL) and fetal fibronectin (fFN)1. Quantitative...

Evaluation of a quantitative fetal fibronectin test for spontaneous preterm birth in symptomatic women

The purpose of this study was to determine whether quantification of cervicovaginal fluid fetal fibronectin (fFN) improves diagnostic accuracy of spontaneous preterm birth (sPTB) in symptomatic women. A prospective blinded predefined secondary analysis of a larger study of cervicovaginal fluid fFN concentration (nanograms per milliliter) in women symptomatic of preterm labor (n =300 women; 22-35 weeks' gestation) with a Hologic 10Q system (Hologic, Marlborough, MA). Clinicians were blinded to the result until after the delivery, but the qualitative Hologic TLI(IQ) fFN result was made available. The positive predictive value for sPTB (<34 weeks' gestation) increased from 19%, 32%, 61%, and 75% with increasing thresholds (10, 50, 200, and 500 ng/mL, respectively). Compared with <10 ng/mL fFN, the relative risk of delivery was 5.6 (95% confidence interval [CI], 1.05-29.57), 7.9 (95% CI, 1.38-45.0), 22.8 (95% CI, 3.84-135.5), and 51.3 (95% CI, 12.49-211.2; P < .01). Quantitative fFN provides thresholds (10 and 200 ng/mL) in addition to the qualitative method (50 ng/mL) to discriminate the risk of sPTB in symptomatic women.

Sexual intercourse increases the likelihood of a false positive fetal fibronectin test

IntroductionFetal fibronectin (fFN) is an excellent predictor of preterm birth. Seminal fluid may cross react with the fFN assay. Sexual intercourse on quantitatively measured concentration of fetal fibronectin (fFN) in...