What is the clinical significance of a positive fetal fibronectin (FFN) test in the setting of vaginal bleeding?

Fetal Fibronectin Testing in the Setting of Vaginal Bleeding

Fetal fibronectin (FFN) testing is contraindicated in the presence of vaginal bleeding, as bleeding is a known interferent that invalidates the test results and makes interpretation unreliable.

Key Testing Requirements and Contraindications

The ACOG guidelines explicitly state that FFN testing requires intact amniotic membranes and should only be performed under specific conditions 1. Vaginal bleeding represents a critical exclusion criterion because:

• Blood contamination interferes with the immunoassay, producing false-positive results that cannot be reliably interpreted 1
• The test is only validated for use between 24 weeks, 0 days and 34 weeks, 6 days of gestation with intact membranes and minimal cervical dilatation 1

Clinical Approach When Both Bleeding and Preterm Labor Concerns Exist

When a patient presents with vaginal bleeding in the second or third trimester, the diagnostic approach must prioritize identifying the bleeding source rather than relying on FFN:

Immediate Imaging Assessment

Transvaginal ultrasound is the primary diagnostic modality for evaluating vaginal bleeding, as it can identify life-threatening conditions while simultaneously assessing cervical length and preterm labor risk 1:

• Evaluate for placenta previa, vasa previa, and placental abruption—conditions that carry significant maternal and fetal mortality risk 1
• Assess cervical length from external to internal os, which provides preterm delivery risk stratification independent of FFN 1
• Avoid digital cervical examination until placenta previa, low-lying placenta, and vasa previa are excluded 1

Cervical Length as Alternative Risk Stratification

In the presence of bleeding, transvaginal cervical length measurement becomes the primary tool for preterm birth risk assessment 1:

• A short cervix identified on transvaginal ultrasound is associated with increased preterm delivery risk 1
• When vaginal bleeding accompanies a short cervix, the risk of preterm delivery is significantly increased compared to short cervix alone 1
• This provides actionable risk stratification without requiring FFN testing 1

Understanding FFN Performance in Complicated Pregnancies

Research demonstrates that FFN is frequently positive in pregnancies complicated by bleeding, but this reflects the pathophysiology rather than providing useful clinical discrimination 2:

• Studies show elevated FFN rates in women with bleeding, preterm labor, and PPROM compared to controls 2
• The presence of FFN in bleeding patients may indicate choriodecidual disruption, but cannot distinguish between different etiologies or predict outcomes reliably when blood is present 2

Clinical Utility of FFN (When Appropriately Used)

Understanding FFN's proper role helps clarify why it fails in bleeding scenarios:

Negative Predictive Value (Primary Clinical Utility)

The main clinical value of FFN is its negative predictive value in symptomatic women without bleeding 1, 3:

• Negative FFN has 99.7% negative predictive value for delivery within 7 days and 93% for delivery before 37 weeks in appropriate candidates 3
• This allows clinicians to avoid unnecessary tocolysis, hospitalization, and steroid administration in symptomatic women 1, 4

Limited Positive Predictive Value

Even in ideal testing conditions, positive FFN has modest predictive performance 3, 5:

• Positive predictive value ranges from 43-79% in symptomatic patients 3
• A 2020 systematic review and meta-analysis found that summary likelihood ratios were never >10 or <0.1, indicating only moderate prediction even in optimal circumstances 5

Common Pitfalls to Avoid

• Do not attempt FFN testing in any patient with vaginal bleeding—the results will be uninterpretable and may lead to inappropriate clinical decisions 1
• Do not perform digital cervical examination before excluding placenta previa in bleeding patients—this can precipitate catastrophic hemorrhage 1
• Do not rely on FFN screening in asymptomatic low-risk women—it has limited clinical utility in this population even without bleeding 1, 5
• Remember that FFN testing requires results available within 24 hours to guide clinical decision-making effectively 1

Recommended Diagnostic Algorithm for Vaginal Bleeding with Preterm Labor Concerns

1. Perform transabdominal ultrasound first to evaluate placental location and fetal status 1
2. Proceed to transvaginal ultrasound (safe even with placenta previa) to assess cervical length and exclude vasa previa 1
3. Use cervical length measurement (<25 mm indicates increased risk) as your preterm birth risk stratification tool 1
4. Add color/power Doppler to evaluate for placental abruption if clinically suspected 1
5. Reserve FFN testing only for symptomatic patients without bleeding who have intact membranes and meet all other testing criteria 1