Fetal fibronectin: The impact of a rapid test on the treatment of women with preterm labor symptoms

doi:10.1067/mob.2003.390

American Journal of Obstetrics and Gynecology

Volume 188, Issue 6, June 2003, Pages 1588-1595

Presented at the Sixty-Ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, October 22−27, 2002, Rancho Mirage, Calif.

https://doi.org/10.1067/mob.2003.390 Get rights and content

Abstract

Objective: The purpose of this study was to determine whether knowledge of the results of a rapid fetal fibronectin test affects treatment decisions during the evaluation and treatment of possible preterm labor. Previous observational studies have suggested that a negative test might help to avoid unnecessary intervention. Study Design: This was a randomized study of women who were between 24 weeks and 34 weeks 6 days of gestation with symptoms of preterm labor and who were seen in three community hospitals. A rapid fetal fibronectin test was performed on all subjects. Patients were assigned randomly to a group whose results were known to physician or to a group whose results were not known. Treatment decisions were at the discretion of the physician. Results: One hundred eight samples were collected between September 2000 and December 2001. There were 10 positive fetal fibronectin tests. The overall prevalence of delivery within 2 weeks for the study population was 2.8%. For women who had negative fetal fibronectin test results, the hospital stay was not significantly shorter when the result was known (6.8 hours) than when it was not known (8.1 hours, P =.35). However, when the physician knew the fetal fibronectin status of women with a negative test result who were observed for >6 hours, the hospital stay was shortened 40%, to 22.7 hours from 37.8 hours (P =.04). Conclusion: Fetal fibronectin testing may be able to supplement clinical judgment in the evaluation of the condition of patients with symptoms of preterm labor. The greatest benefit of fetal fibronectin testing might be for the patient whom the physician judges to be at high risk for imminent delivery. In such patients, the knowledge of a negative fetal fibronectin may shorten the hospital stay.

Section snippets

Material and methods

The study was conducted at four community hospitals in the Portland, Ore, and Vancouver, Wash, metropolitan area. One site was excluded from analysis because only one subject was enrolled during the study period. All patients were members of a staff-model health maintenance organization and were cared for by these staff physicians or certified nurse-midwives. The protocol was approved by the human subjects review board at each institution. Women were eligible for the study if they arrived at

Results

Consent was obtained from 114 patients. Six patients were excluded for the following reasons: the patient was evaluated in the clinic rather than on labor and delivery area (3 patients), no data about the labor and delivery visit were available (2 patients), the specimen was too bloody and was rejected by the laboratory (1 patient). This left 108 swabs, from 100 different patients. Eight patients were entered into the study twice, because this was allowed under study protocol if >2 weeks had

Comment

Few medical tests tell us absolutely whether a patient has a disease. Rather, they increase or decrease the probability of having that disease for a specific patient or for the whole population that is being considered. In this case, the “disease” we are interested in is whether the patient is likely to be delivered within the next 1 to 2 weeks; if this likelihood is high enough, we will consider tocolytics, corticosteroids, and possibly transport to a tertiary care center. This concept of a

References (27)

JD Iams et al.
Fetal fibronectin improves the accuracy of diagnosis of preterm labor
Am J Obstet Gynecol
(1995)
J Bartnicki et al.
Fetal fibronectin in vaginal specimens predicts preterm delivery and very-low-birth-weight infants
Am J Obstet Gynecol
(1996)
BK Rinehart et al.
Pregnancy outcome in women with preterm labor symptoms without cervical change
Am J Obstet Gynecol
(2001)
W Giles et al.
The effect of fetal fibronectin testing on admissions to a tertiary maternal-fetal medicine unit and cost saving
Am J Obstet Gynecol
(2000)
AS Lukes et al.
Predictors of positivity for fetal fibronectin in patients with symptoms of preterm labor
Am J Obstet Gynecol
(1997)
RL Goldenberg et al.
The preterm prediction study: fetal fibronectin testing and spontaneous preterm birth
Obstet Gynecol
(1996)
CJ Lockwood et al.
The presence of cervical and vaginal fetal fibronectin predicts preterm delivery in an inner-city obstetric population
Am J Obstet Gynecol
(1993)
MP Nageotte et al.
Fetal fibronectin in patients at increased risk for premature birth
Am J Obstet Gynecol
(1994)
JD Iams et al.
Fetal fibronectin improves the accuracy of diagnosis of preterm labor
Am J Obstet Gynecol
(1995)
DR Burrus et al.
Fetal fibronectin, interleukin-6 and C-reactive protein are useful in establishing prognostic subcategories of idiopathic preterm labor
Am J Obstet Gynecol
(1995)

JC Morrison et al.

Prediction of spontaneous preterm birth by fetal fibronectin and uterine activity

Obstet Gynecol

(1996)

GM Joffe et al.

Am J Obstet Gynecol

(1999)

RL Lopez et al.

Am J Obstet Gynecol

(2000)

Cited by (44)

Randomized clinical trials are not always the best way to assess diagnostic tests: the case of fetal fibronectin testing
2018, American Journal of Obstetrics and Gynecology
Predicting preterm birth: Cervical length and fetal fibronectin
2017, Seminars in Perinatology
Citation Excerpt :
Therefore, it is debatable whether these findings provide additional needed guidance in clinical management. Despite observational studies that suggested FFN testing may help reduce the use of unnecessary resources,47,48 RCTs have not confirmed these findings.49,50 In a systematic review and cost-analysis of five RCTs and 15 diagnostic test accuracy studies,51 FFN testing had moderate accuracy for predicting PTB, but no RCT reported a significant improvement in maternal or neonatal outcomes.
Spontaneous preterm birth remains the leading cause of neonatal morbidity and mortality worldwide, and accounts for a significant global health burden. Several obstetric strategies to screen for spontaneous preterm delivery, such as cervical length and fetal fibronectin measurement, have emerged. However, the effectiveness of these strategies relies on their ability to accurately predict those pregnancies at increased risk for spontaneous preterm birth (SPTB). Transvaginal cervical shortening is predictive of preterm birth and when coupled with appropriate preterm birth prevention strategies, has been associated with reductions in SPTB in asymptomatic women with a singleton gestation. The use of qualitative fetal fibronectin may be useful in conjunction with cervical length assessment in women with acute preterm labor symptoms, but data supporting its clinical utility remain limited. As both cervical length and qualitative fetal fibronectin have limited capacity to predict preterm birth, further studies are needed to investigate other potential screening modalities.
Prediction of preterm delivery in symptomatic women (preterm labor)
2016, Journal de Gynecologie Obstetrique et Biologie de la Reproduction
Évaluer les outils de prédiction d’accouchement prématuré spontané en cas de menace d’accouchement prématuré.
Recherche bibliographique dans les bases de données Medline et Cochrane et les recommandations de sociétés savantes internationales. Sélection des études réalisées sur une population de femmes en situation de menace d’accouchement prématuré.
La menace d’accouchement prématuré est une situation clinique survenant entre 22 et 36 SA + 6 jours, dans laquelle sont observées des modifications cervicales et des contractions utérines, évoluant spontanément ou non vers un accouchement prématuré (accord professionnel). Les contractions utérines peuvent être détectées par la tocométrie et par la patiente elle-même. La fréquence des contractions utérines ne permet pas de prédire avec fiabilité un accouchement prématuré spontané (NP3). Les modifications cervicales peuvent être appréciées par la mesure échographique de la longueur de col et par le toucher vaginal (score de Bishop). La longueur du col est significativement corrélée au risque d’accouchement prématuré spontané (NP1). Les seuils de 15 mm et de 25 mm sont les plus pertinents pour respectivement prédire et écarter un risque d’accouchement prématuré spontané à 48 heures et à 7 jours (accord professionnel). Chez les patientes symptomatiques, la mesure échographique systématique de la longueur de col à l’admission n’est pas associée à une réduction significative du taux d’accouchement prématuré spontané (NP3). L’évaluation clinique du col utérin (score de Bishop) par le toucher vaginal est également un paramètre performant pour la prédiction d’un accouchement prématuré spontané (NP2). Plus le score de Bishop est élevé, plus le risque d’accouchement prématuré spontané est important (NP3). Il n’est pas possible de recommander l’emploi d’un outil plus qu’un autre (échographie du col ou toucher vaginal) en situation de menace d’accouchement prématuré (grade B). Cependant, du fait de l’excellente valeur prédictive négative de la mesure échographique du col, et d’une moindre variabilité interobservateur, il est proposé de mesurer par échographie la longueur cervicale du col avant de décider d’un transfert in utero pour menace d’accouchement prématuré (accord professionnel). Le dépistage de la fibronectine fœtale chez les patientes en situation de menace d’accouchement prématuré a une excellente valeur prédictive négative pour prédire l’absence d’accouchement prématuré spontané à 48 heures et à 7 jours. (NP2). La détection de la fibronectine fœtale chez les patientes en menace d’accouchement prématuré ne permet cependant pas de définir une stratégie permettant de réduire le taux d’accouchement prématuré spontané (NP2) et n’est donc pas recommandée (accord professionnel).
Les outils de prédiction d’un accouchement prématuré spontané en cas de menace d’accouchement prématuré sont performants mais leur usage ne permet pas de réduire le taux d’accouchement prématuré spontané. La valeur prédictive négative élevée de ces outils (mesure échographique du col, détection de la fibronectine fœtale dans les voies génitales) constitue un atout dans le choix de la prise en charge des femmes en situation de menace d’accouchement prématuré (transfert in utero, corticothérapie).
To evaluate the predictors of spontaneous preterm birth in case of preterm labor.
Literature search in Medline and Cochrane databases and recommendations of international societies. Selection of studies in symptomatic women (with preterm labor).
Preterm labor is defined as a clinical situation occurring between 22 and 36 weeks + 6 days, in which cervical changes are observed associated with uterine contractions, evolving spontaneously or not to preterm delivery (Professional consensus). Uterine contractions can be detected by the cardiotocometry and by the patient herself. Uterine contractions frequency does not reliably predict spontaneous preterm birth (NP3). Cervical modifications may be appreciated by ultrasonographic measurement of cervical length and vaginal examination (Bishop score). Cervical length is significantly correlated with the risk of spontaneous preterm birth (NP1). The 15 and 25 mm thresholds are the most relevant to respectively predict and rule out spontaneous premature birth at 48 hours and 7 days (professional consensus). In symptomatic patients, routine ultrasonographic measurement of cervical length at admission is not associated with a significant reduction of spontaneous preterm birth rate (NP3). Clinical evaluation of the cervix (Bishop score) by vaginal examination is an effective parameter for the prediction of preterm birth (NP2). The higher the Bishop score, the higher the risk of preterm birth (NP3). It is not possible to recommend the use of a tool more than another (cervix ultrasound versus vaginal examination) in women experiencing preterm labor (grade B). However, due to the excellent negative predictive value of cervical ultrasound measurement and the lower interobserver variability, we suggest to perform a cervical ultrasonographic measurement before an in utero transfer for preterm labor (professional consensus). Screening for fetal fibronectin in the genital tract of patients with preterm labor has an excellent negative predictive value for predicting the absence of spontaneous preterm birth at 48 hours and 7 days (NP2). Nevertheless, its use in symptomatic women is not associated with a reduction of preterm birth rate (NP2) and is therefore not recommended (professional consensus).
Predictors of preterm birth in women with preterm labor are effective but do not allow a reduction of the preterm birth rate. The high negative predictive value of these predictors (Bishop score, ultrasound measurement of the cervix, fetal fibronectin detection in the genital tract) is an asset in the choice of an appropriate management in women with preterm labor (in utero transfer or corticosteroids).
Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials
2016, American Journal of Obstetrics and Gynecology
Citation Excerpt :
All randomly assigned women were included in an intention-to-treat analysis. In 3 studies, laboratory personnel who performed the FFN test were blinded to women’s characteristics and outcomes (ie, blinding of outcome assessment).8,9,12 Physicians were not blinded to the FFN assay result.
Fetal fibronectin is an extracellular matrix glycoprotein that is produced by amniocytes and cytotrophoblasts and has been shown to predict spontaneous preterm birth.
The aim of this systematic review and metaanalysis of randomized clinical trials was to evaluate the effect of the use of fetal fibronectin in the prevention of preterm birth in singleton pregnancies with threatened preterm labor.
The research was conducted with the use of MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library as electronic databases from the inception of each database to February 2016. Selection criteria included randomized clinical trials of singleton gestations with threatened preterm labor that were assigned randomly to management based on fetal fibronectin results (ie, intervention group) or not (ie, comparison group). Types of participants included women with singleton gestations at 23 0/7 to 34 6/7 weeks with threatened preterm labor. Studies that included management that was also based on the use of sonographic cervical length were excluded. The primary outcome was preterm birth at <37 weeks of gestation. The summary measures were reported as relative risk or as mean differences with 95% confidence interval.
Six trials that included 546 singleton gestations with symptoms of preterm labor were included in the metaanalysis. The overall risk of bias of the included trials was low. Women were eligible for the random assignment in case of symptoms that suggested preterm labor at 23–34 weeks of gestation. During admission, before digital examination, a Dacron swab was rotated in the posterior fornix for 10 seconds to absorb cervicovaginal secretions that were then analyzed for the fetal fibronectin qualitative method, with results reported as either positive or negative. Women who were assigned randomly to the fetal fibronectin group had a similar incidence of preterm birth at <37 weeks of gestation (20.7% vs 29.2%; relative risk, 0.72; 95% confidence interval, 0.52–1.01), at <34 weeks of gestation (8.3% vs 7.9%; relative risk, 1.09; 95% confidence interval, 0.54–2.18), at <32 weeks of gestation (3.3% vs 5.6%; relative risk, 0.64; 95% confidence interval, 0.24–1.74), and at <28 weeks of gestation (1.1% vs 1.7%; relative risk, 0.74; 95% confidence interval, 0.15–3.67) compared with the control group. No differences were found in the number of women who delivered within 7 days (12.8% vs 14.5%; relative risk, 0.76; 95% confidence interval, 0.47–1.21), in the mean of gestational age at delivery (mean difference, 0.20 week; 95% confidence interval, –0.26 to 0.67), in the rate of maternal hospitalization (27.4% vs 26.9%; relative risk, 1.07; 95% confidence interval, 0.80–1.44), in the use of tocolysis (25.3% vs 28.2%; relative risk, 0.97; 95% confidence interval, 0.75–1.24), antenatal steroids (29.2% vs 29.2%; relative risk, 1.05; 95% confidence interval, 0.79–1.39), in the mean time in the triage unit (mean difference, 0.60 hour; 95% confidence interval, –0.03 to 1.23) and in neonatal outcomes that included respiratory distress syndrome (1.3% vs 1.5%; relative risk, 0.91; 95% confidence interval, 0.06–14.06), and admission to the neonatal intensive care unit (19.4% vs 8.1%; relative risk, 2.48; 95% confidence interval, 0.96–6.46). Management based on the fetal fibronectin test required higher hospitalization charges (mean difference, $153; 95% confidence interval, 24.01–281.99).
Fetal fibronectin testing in singleton gestations with threatened preterm labor is not associated with the prevention of preterm birth or improvement in perinatal outcome but is associated with higher costs.
Comparison of rapid bedside tests for phosphorylated insulin-like growth factor-binding protein 1 and fetal fibronectin to predict preterm birth
2016, International Journal of Gynecology and Obstetrics
To compare the accuracy of rapid bedside tests for phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP-1) and fetal fibronectin (fFN) to predict preterm delivery among women with threatened preterm labor.
A prospective observational study was conducted among women with a singleton pregnancy of 28–36 weeks, intact membranes, and symptoms suggestive of preterm labor who attended a center in New Delhi, India, between April 1, 2011, and March 31, 2014. Rapid bedside tests were performed at presentation to measure the levels of phIGFBP-1 and fFN in cervicovaginal secretions. All patients were managed as per the standard hospital protocol and followed up until delivery.
Data were available for 468 participants. For delivery before 37 weeks, the phIGFBP-1 test exhibited a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81.1%, 97.1%, 95.2% and 87.7%, respectively. The sensitivity, specificity, PPV, and NPV for the fFN test were 19.4%, 99.4%, 97.4%, and 63.2%, respectively. The phIGFBP-1 test displayed higher sensitivity and NPV than did the fFN test for delivery before 34 weeks and within 7 days of testing (P < 0.05 for all).
The rapid bedside test for phIGFBP-1 was more reliable in the prediction of preterm delivery than was the equivalent test for fFN.
Prescribing patterns of antenatal corticosteroids in women with threatened preterm labor
2015, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
Unfortunately these results are not significant since our study was not powered for this outcome. Negative findings concerning the clinical utility of fFN have been reported [36–40] which might be due to the absence of a fixed protocol in relation to the fFN results. Therefore clinicians might not have incorporated the test results into their decision making [40].
To 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.
This 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 < 10 mm, group 2 CL 10–30 mm and positive fFN, group 3 CL 10–30 mm and negative fFN, group 4 CL > 30 mm.
ACS 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.
ACS were prescribed frequently to women with a CL of 10–30 mm and a negative fFN test or a CL > 30 mm. There is room for improvement in the prescription of ACS in these low risk women.

View all citing articles on Scopus

^☆: Supported by Adeza Biomedical, Sunnyvale, Calif.

^☆☆: Reprints not available from the authors.

View full text

Transactions Of The Sixty-Ninth Annual Meeting Of The Pacific Coast Obstetrical And Gynecological SocietyFetal fibronectin: The impact of a rapid test on the treatment of women with preterm labor symptoms☆,☆☆

Abstract

Section snippets

Material and methods

Results

Comment

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Transactions Of The Sixty-Ninth Annual Meeting Of The Pacific Coast Obstetrical And Gynecological Society
Fetal fibronectin: The impact of a rapid test on the treatment of women with preterm labor symptoms☆,☆☆