Fetal fibronectin is a large glycoprotein located in the extracellular matrix surrounding the extravillous trophoblast at the uteroplacental junction and in the chorion. Fetal fibronectin levels reach their peak of approximately 4000 ng/mL between 10 and 12 weeks gestation, fall to below 50 ng/mL by 18 weeks, and remain at undetectable levels until 36 to 37 weeks. Mechanical stress caused by uterine contractions and local inflammation lead to separation of the choriodecidiual interface and release of fetal fibronectin into the vagina. Between 20 and 37 weeks gestation, fetal fibronectin should normally not be present in the cervix and vagina. Detection of fetal fibronectin in cervicovaginal secretions at a concentration of >50 ng/mL indicates the patient is at high risk for preterm labor and subsequent early birth.
The FFN test is most useful in differentiating "true" preterm labor from false labor in women presenting with contractions between 22 to 32 weeks gestational age. Patients who present with contractions but insignificant cervical dilation or effacement can often have their therapy modified based on the presence or absence of fetal fibronectin. A negative test is associated with a very low risk of delivery in the next 7 to 14 days. The negative predictive value is >95%. FFN works well for predicting when a symptomatic woman will not deliver, but not for predicting when she will deliver.
The American College of Obstetrics and Gynecology has recommended the use of this test if the following criteria are met (Int'l J Obstet Gynecol 1997; 59:164):
- Amniotic membranes are intact
- Cervical dilatation < 2 cm and effacement < 80%
- Sampling is performed no earlier than 24 weeks, 0 days and no latter than 34 weeks, 6 days of gestation (using a swab of the vaginal vault)
FFN is not recommended as a general screening test for preterm labor in asymptomatic women. The main problem in using the FFN test in women without prior history or symptoms of preterm labor is that no treatment is effective in preventing preterm births if no symptoms are present.
Multiple pregnancies cause elevated FFN concentrations. FFN testing is valid only at 28 to 30 weeks instead of the usual 21 weeks.
Reference value is negative. The optimal cutoff for FFN is 50 ng/mL to determine preterm delivery. A negative test indicates that the FFN level is < 50 ng/mL.
Fetal fibronectin is sampled from cervical and vaginal secretions. Serum samples are not used due to the presence of fFN produced by hepatocytes. FFN should be collected at the beginning of the speculum examination before any lubricants are used and before the digital examination. A special Dacron polyester swab and transport tube must be used. Any cervical vaginal mucus can be used; however, the best sampling site is the cervical os. During a sterile speculum examination, the swab is gently rolled over the exocervix and dipped into the posterior fornices, but not placed into the cervical canal. Testing is usually done biweekly from 24 to 36 weeks.
Lubricating ointments and Betadine should be avoided because they can cause false negative results.
False Negative Results |
False Positive Results |
Lubricants |
Blood |
Soaps |
Amniotic fluid |
Disinfectants |
Recent intercourse |
Cerclage |
Digital exam within 24 hours |
Specimens should not be collected from patients with known placental abruption, placenta previa, ruptured membranes, vaginal bleeding, or intercourse in the last 24 hours because these factors can cause false positive results.
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