Fetal Fibronectin Testing Research Articles

LB2: Opptimum

OPPTIMUM aimed to determine whether progesterone prophylaxis to prevent preterm birth in women at risk improves outcomes. In a double blind RCT, 1228 women at risk of preterm birth (due to a positive fetal fibronectin test, or a history of spontaneous preterm birth at ≤ 34+0 weeks gestation, or a cervical length ≤ 25mm) were randomized to vaginal progesterone, 200mg daily, or placebo, taken from 22-24 to 34 weeks gestation. Primary outcomes were (obstetric) preterm birth or fetal death before 34 weeks gestation, (neonatal) death or major morbidity (brain injury or bronchopulmonary dysplasia) and (childhood) Bayley III cognitive scores at 2 years of age, with values imputed for deaths. Analysis was by intention to treat using logistic, proportional hazards or linear regression, adjusting for previous pregnancy of ≥ 14 weeks (where possible), with study centre as a random effect. Progesterone had no statistically significant effect on either the primary obstetric or the childhood outcome (see table). Progesterone prophylaxis reduced the rate of the adverse neonatal composite outcome OR: 0.62 (95% CI 0.41, 0.94). However, following the pre-specified multiple comparisons procedure, this reduction was not statistically significant (adjusted p=0.072). Secondary analysis of the components of the neonatal outcome showed that progesterone reduced the risk of brain injury and neonatal death but not severe chronic lung disease. In the largest study of vaginal progesterone to date, we have not conclusively demonstrated reductions in preterm birth before 34 weeks or in neonatal morbidity. Progesterone appears to confer no long-term benefit or harm on cognitive and/or neurosensory outcomes in children at two years of age.

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.

Prescribing patterns of antenatal corticosteroids in women with threatened preterm labor

ObjectiveTo assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians’ decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor. Study designThis is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks’ gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10mm, group 2 CL 10–30mm and positive fFN, group 3 CL 10–30mm and negative fFN, group 4 CL>30mm. ResultsACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3–61 days), 44 days (IQR 17–69 days), 53 days (IQR 37–77 days) and 66 days (IQR 43–78 days) in group 1, 2, 3 and 4 respectively. ConclusionACS were prescribed frequently to women with a CL of 10–30mm and a negative fFN test or a CL>30mm. There is room for improvement in the prescription of ACS in these low risk women.

Risk factors for preterm delivery: do they add to fetal fibronectin testing and cervical length measurement in the prediction of preterm delivery in symptomatic women?

ObjectiveTo assess whether patient characteristics add to the fetal fibronectin test and cervical length measurement in the prediction of preterm delivery in symptomatic women. Study designA nationwide prospective cohort study was conducted in all ten perinatal centres in the Netherlands. Women with symptoms of preterm labour between 24 and 34 weeks gestation with intact membranes were invited. In all women qualitative fibronectin testing (0.050μg/mL cut-off) and cervical length measurement were performed. Only singleton pregnancies were included in this analysis. Logistic regression was used to construct two multivariable models to predict spontaneously delivery within 7 days: a model including cervical length and fetal fibronectin as predictors, and an extended model including all potential predictors. The models were internally validated using bootstrapping techniques. Predictive performances were assessed as the area under the receiver operator characteristic curve (AUC) and calibration plots. We compared the models’ capability to identify women with a low risk to deliver within 7 days. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25mm, was considered as low risk. ResultsSeventy-three of 600 included women (12%) had delivered spontaneously within 7 days. The extended model included maternal age, parity, previous preterm delivery, vaginal bleeding, C-reactive protein, cervical length, dilatation and fibronectin status. Both models had high discriminative performances (AUC of 0.92 (95% CI 0.88–0.95) and 0.95 (95% CI 0.92–0.97) respectively). Compared to the model with fibronectin and cervical length, our extended model reclassified 38 women (6%) from low risk to high risk and 21 women (4%) from high risk to low risk. Preterm delivery within 7 days occurred once in both the reclassification groups. ConclusionIn women with symptoms of preterm labour before 34 weeks gestation, a model that integrates maternal characteristics, clinical signs and laboratory tests, did not predict delivery within 7 days better than a model with only fibronectin and cervical length.

Gestational Age at Cervical Length and Fetal Fibronectin Assessment and the Incidence of Spontaneous Preterm Birth in Twins

To estimate the risk of spontaneous preterm birth in twin pregnancies based on transvaginal sonographic cervical length, fetal fibronectin (fFN) testing, and the gestational age at which these tests were performed. Women with twin pregnancies, cervical length assessment, and fFN testing between 22 weeks and 31 weeks 6 days in a single maternal-fetal medicine practice from 2005 to 2013 were included. All testing was done on asymptomatic women on an out-patient basis. Women with monochorionic monoamniotic twins and twin-twin transfusion were excluded. Logistic regression analysis was used to estimate the risk of spontaneous preterm birth before 35, 32, and 28 weeks. Six hundred eleven patients were included and underwent a total of 2406 cervical length measurements and 2279 fFN tests over the course of the study period. The likelihood values for spontaneous preterm birth before 35, 32, and 28 weeks were 19.1%, 6.3%, and 2.3%, respectively. The risk of spontaneous preterm birth before 35 weeks increased with a decreasing cervical length (coefficient for the log of the odds ratio [OR coefficient], -0.13; P < .01; 95% confidence interval [CI], -0.22 to -0.037), a positive fFN result (OR coefficient, 1.04; P < .01; 95% CI, 0.45 to 1.64), as well as earlier gestational ages at testing (OR coefficient, -0.214; P < .01; 95% CI, -0.33 to -0.10). Similar results were seen for spontaneous preterm birth before 32 and 28 weeks. In asymptomatic patients with twin pregnancies, the cervical length, fFN, and gestational age are all significantly associated with spontaneous preterm birth.

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.

Interleukin 6 and fetal fibronectin as a predictors of preterm delivery in symptomatic patients

Preterm delivery is the leading cause of neonatal mortality and morbidity. The rate of preterm births has been estimated to be about 15 million, which accounts for 11.1% of all live births worldwide. The purpose of this study was to evaluate the cervico-vaginal (CVF) cytokine IL-6 and fetal fibronectin (fFN) status as predictors of preterm delivery in patients with symptoms of preterm labor. Patients with symptoms suggestive of preterm labor were recruited from September 2013 to March 2014. Vaginal swabs were taken for fetal fibronectin test (fFN) and CVF IL-6. Antibiotics, steroids and tocolytics were administered, where appropriate. The outcome was measured by the occurrence of preterm delivery within 14 days from the day of hospital admission. Cut-off value of 1305 pg/mL for the concentration of IL-6 in the CVF was the best predictor of preterm delivery, with the sensitivity of 69.4% and specificity of 68.2%. Patients with positive fFN test had the OR of 6.429 (95%CI 1.991-20.758) to deliver prematurely. The multivariate analysis of combined fFN and CVF IL-6 tests resulted in risk of 86.7% to deliver prematurely, if both tests were positive. The combination of both tests performed better than the individual tests and decreased the false positive rate, which in turn reduced the chances for inappropriate patient treatment, bringing down the costs.

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)

Women's perspectives of the fetal fibronectin testing process: a qualitative descriptive study.

BackgroundIn 2009 the Ontario Ministry of Health and Long Term Care funded the implementation of province-wide fetal fibronectin testing in Ontario hospitals. This paper reports results from the provincial evaluation that sought to describe the experience of fetal fibronectin testing from the perspective of women with symptoms of preterm labour.MethodsA descriptive qualitative design was used, employing semi-structured telephone and face-to-face interviews with women who had fetal fibronectin testing.ResultsFive hospitals participated in recruiting women for the study and 17 women were interviewed. Women described their experiences of fetal fibronectin testing as an emotional process that moves from expecting, to feeling, to hoping for reassurance; and then to re-defining what is required to feel reassured. Women described feeling anxious while waiting for fetal fibronectin results. When test results were negative, women described feeling a sense of relief that their symptoms would not likely lead to an imminent preterm birth. Women with positive results expressed feeling reassured by the care decisions and quick action taken by the health care team.ConclusionFetal fibronectin testing was acceptable and beneficial to these women with symptoms of preterm labour. Implications for practice and future research are suggested.

PPO.05 Early fetal fibronectin testing at 18 weeks’ predicts spontaneous preterm birth, though accuracy is improved with combined CL testing

IntroductionCervical length measurement and fetal fibronectin (fFN) testing are recognised predictors of spontaneous preterm birth. Fetal fibronectin testing is traditionally used from 22 weeks’ gestation. Its value at earlier gestations...

Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor.

To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor. We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk. Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk. Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days. II.

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...

PPO.55 Full dilatation caesarean section and risk of subsequent preterm birth: a case series

Preterm birth (PTB) or mid-trimester loss is rare following term pregnancy. Caesarean section carried out at full dilatation (FDCS) is associated with increased clinical challenges1. The integrity of the cervix...

PLD.44 Evaluation of fetal fibronectin testing, subsequent management and outcomes in a London teaching hospital

Preterm birth (PTB) is a major cause of neonatal morbidity and mortality. Fetal fibronectin (FFN) is a valuable predictor of PTB allowing selection of women at risk of PTB, who...

Whole blood gene expression profile associated with spontaneous preterm birth in women with threatened preterm labor.

Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.

The NIFTY study: A multicentre randomised double‐blind placebo‐controlled trial of nifedipine maintenance tocolysis in fetal fibronectin‐positive women in threatened preterm labour

In an unselected group of women with signs of preterm labour, maintenance tocolysis is not effective in the prevention of preterm birth and does not improve neonatal outcome. Among women with signs of preterm labour, those who are fetal fibronectin positive have an increased risk of preterm birth. We investigated whether maintenance tocolysis with nifedipine would delay delivery and improve neonatal outcome in women with threatened preterm labour and a positive fetal fibronectin status. Women with a singleton pregnancy in threatened preterm labour (24(+0) to 33(+6) weeks) with a positive fetal fibronectin test were randomised to nifedipine or placebo. Study medication was continued until 36 completed weeks' gestation. The primary endpoint was prolongation of pregnancy of sevendays. Secondary endpoints were gestational age at delivery and length of NICU admission. Of the 60 participants, 29 received nifedipine and 31 placebo. Prolongation of pregnancy by >7days occurred in 22/29 (76%) in the nifedipine group and 25/31 (81%) in the placebo group (relative risks, RR 0.94 [0.72-1.2]). Gestational age at delivery was 36.1±5.1weeks for nifedipine and 36.8±3.6weeks for placebo (P=0.027). Length of NICU admission [median (interquartile ranges, IQR)] was 27 (24-41) days and 16 (8-37) days in nifedipine and placebo groups, respectively (P=0.17). In women with threatened preterm labour who are fetal fibronectin positive, maintenance tocolysis with nifedipine does not seem to prolong pregnancy, nor reduce length of NICU admission.

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

740: Comparison of the Actim Partus test and fetal fibronectin test in combination with cervical length in the prediction of spontaneous preterm delivery in symptomatic women: a post-hoc analysis

740: Comparison of the Actim Partus test and fetal fibronectin test in combination with cervical length in the prediction of spontaneous preterm delivery in symptomatic women: a post-hoc analysis

811: False-positive, false-negative and uninterpretable results in fetal fibronectin testing during the APOSTEL1 study; which factors do contribute?

811: False-positive, false-negative and uninterpretable results in fetal fibronectin testing during the APOSTEL1 study; which factors do contribute?