ASK THE EXPERT
From the desk of:
Stephen T. Vermillion, M.D. Assistant Professor
Division of Maternal-Fetal Medicine
Department of Obstetrics and Gynecology
Medical University of South Carolina
Get the facts on Fetal Fibronectin (fFN) testing
Background:
Preterm birth complicates almost 11% of all pregnancies, yet it accounts for a disproportionate share of the neonatal mortality and morbidity in the United States. At least 75% of neonatal deaths that are not caused by birth defects result from complications arising from preterm birth. Additionally, prematurity is responsible for the vast majority of neonatal and chronic childhood morbidity. Complications include chronic lung disease, visual and hearing disabilities, neurobehavioral impairment, and cerebral palsy.
Despite modest advances in traditional antenatal therapies, the incidence of preterm birth has continued to increase over the past decade. This increase in prematurity is in part due to the increase successes in assisted reproductive techniques resulting in increased frequencies of multiple gestations and due to the rise in adolescent pregnancies, both of which are at increased risk for preterm birth.
Fortunately, we are rapidly developing an understanding of the complexity of the pathways that lead to preterm birth. The process of preterm birth is not as simple as once hypothesized, but more likely to include a series of pathways that may be intertwined. Potential mechanisms for preterm birth may include uterine and cervical weakening, uterine reactivity manifested as contractions, infectious processes, hormonal variations, and varying degrees of interactions of these processes.
Recognizing that a sophisticated process exists makes it obvious that one therapy for all is not appropriate. More importantly, we now have the ability to identify many women with the greatest risks with several newer diagnostic modalities used in the prediction of preterm birth. These exciting newer techniques for preterm birth prediction include transvaginal cervical sonography and fetal fibronectin (fFN) testing.
What is fetal fibronectin (fFN)?
Fetal fibronectin (fFN) is a multifunctional protein substance that is located within the choriodecidual interface and is presumed to have “glue-like” responsibilities. Fetal fibronectin is normally present in the cervicovaginal secretions when the deciduas capsularis and parietalis fuse. It is presumed that the presence of fFN in cervicovaginal secretions between 22 and 35 weeks is an abnormal finding and may signify a disruption of the membranes surfaces either from uterine contractions or inflammation from infection.
How is the fFN test performed?
Testing for fFN is very simple and safe. It is imperative that the specimen be obtained prior to procedures that may disrupt the cervix and erroneously release fFN and more than 24 hours after previous manipulation (digital or ultrasonographic cervical examination). Additionally, the specimen should not be obtained in the presence of the following:
* Cervical dilation > 3 cm
* Rupture of the membranes
* Recent use (< 24 hours) of soaps, gels, lubricants
* Moderate or gross vaginal bleeding
* Coitus within 24 hours
A sterile speculum free of lubricants is placed into the vagina and the special dacron swab from the fFN kit is used to collect a small sample of secretions from the posterior fornix, not in the cervical os. The sample should be obtained prior to collection of any vaginal wet preparations or cervical cultures. The swab is then placed into the special tube from the collection kit (Adeza® Biomedical) that is very similar to a genprobe kit. The collection tube is then labeled and sent to the laboratory and reported qualitatively and positive or negative.
How is a fFN used in clinical practice?
Studies have been performed using fFN in two specific clinical scenarios involving either asymptomatic or symptomatic patients. The first and less recognized is the patient who is at an increased risk for preterm birth, but who is currently asymptomatic or without contractions. The FDA currently has approved fFN for these patients between 22 and 30 weeks based on previous screening studies. Secondly, and probably the most widely accepted role for fFN testing is with the symptomatic patient with contractions prior to 35 weeks, intact membranes, and with < 3 cm of cervical dilation. The FDA has approved fFN testing in this subset of patients between 24 and 35 weeks gestation.
What does a negative fFN mean?
A negative fFN assay provides the clinician with the most compelling prediction of preterm birth afforded to the fFN test. Specifically, in symptomatic patients with a negative fFN the likelihood of not delivering within the next 14 days is greater than 99%. Presented another way is that 124 out of 125 symptomatic women with a negative fFN will not deliver within the next 14 days. Roughly 1 in 3 asymptomatic women with significant risk factors for preterm birth will deliver before 37 weeks. However, if these same asymptomatic women have a negative fFN test then 15 out of 16 will not spontaneously deliver before 37 weeks. The power of the fFN test lies within the negative prediction.
What does a positive fFN mean?
A positive fFN assay has less positive prediction for a preterm delivery, but does signify an increased risk for preterm birth. In symptomatic patients with a positive fFN, 1 out of 6 women (17%) will deliver within 14 days of the test collection. For asymptomatic women with significant risk factors for preterm birth roughly 1 in 3 will deliver prior to 37 weeks. However, this risk is increased to 1 in 2 with a positive fFN test in this same subset of patients.
How is a negative test utilized clinically?
Based on the high negative prediction for preterm birth after a negative fFN test result the clinician can use this information to avoid unnecessary hospitalization and eliminate unnecessary interventions. The clinician should educate the patient regarding the fFN testing and provide reassurance of the unlikely chance of preterm delivery to occur in the next 14 days. Further, the patient can be further educated about the signs and symptoms of preterm labor and retested should symptoms change after a 2 week interval.
What do I do with a positive test?
Management of patients with a positive fFN is not as straightforward as it is with those with negative tests. While the positive prediction (the chance that one will deliver in 14 days after a positive fFN test) is 1 in 6, these patients still are at a significantly increased risk for preterm birth. Management should be individualized and may include but is not limited to the following:
• Increased intensity of surveillance
• Modification of activities of daily living (ADLs)
• Consideration of hospitalization or transfer to a tertiary care facility
• Administration of antenatal corticosteroids if not previously treated
• Screening for cervicovaginal infections and appropriate treatment
• Tocolytic therapy
Studies have indicated that patients who remain undelivered after a positive fFN are more likely to convert to a negative test. Thus it may be appropriate to retest these patients after 1-2 weeks to help guide clinical management.
What are the economic consequences of fFN testing?
Joffe et al. (Am J Obstet Gynecol 1999; 180:581-586) more recently evaluated the financial impact of routine fFN testing in a population of patients presenting with signs and symptoms of preterm labor. In this prospective cohort analysis, admissions, costs for the management of preterm labor and threatened preterm labor, and perinatal outcomes for one year were compared with the same outcomes in the subsequent year after the introduction of routine fFN testing. These authors noted that there were no differences in the number of deliveries, incidence of deliveries < 35 weeks, admissions to neonatal intensive care units (NICU), length of NICU stay, or any other neonatal outcomes between the two study years. However, after introduction of the fFN in the second year there was a significant reduction in the incidence of admissions for preterm labor and prescriptions written for tocolytic agents at a cost savings of $486,000 for the study period.
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