Quantitative fetal fibronectin and cervical length in symptomatic women: results from a prospective blinded cohort study^*

Abstract

Objectives: Our objectives were to determine whether quantitative fetal fibronectin (fFN) and cervical length (CL) screening can be used alone or in combination as prognostic tests to identify symptomatic women at the highest or lowest risk for spontaneous preterm birth (sPTB).

Methods: A prospective, blinded cohort study of women presenting with a singleton gestation to our triage unit between 22-33w6d with preterm labor symptoms was performed. Women with ruptured membranes, moderate/severe bleeding, and dilation >2 cm were excluded. The primary outcome was sPTB <37 weeks. We evaluated test characteristics of quantitative fFN and CL assessment, both separately and in combination, considering traditionally reported cut-points (fFN ≥50 and CL <25), as well as cut-points above and below these measures. We found interactions between fFN >50 and CL <25 and sPTB by parity and obstetric history (p < .05) and therefore stratified results. Test characteristics are presented with positive predictive value (PPV) and negative predictive value (NPV).

Results: Five hundred eighty women were enrolled and 537 women were available for analysis. Overall sPTB rate was 11.1%. Among nulliparous women, increasing levels of fFN were associated with increasing risk of sPTB, with PPV going from 26.5% at ≥20 ng/mL to 44.4% at ≥200 ng/mL. A cut-point of 20 ng/mL had higher sensitivity (69.2%) and higher NPV (96.8%) and therefore identified a “low-risk” group. fFN was not informative for multiparous women regardless of prior obstetrical history or quantitative level chosen. For all women, a shorter CL was associated with an increased sPTB risk. Among nulliparas and multiparas without a prior sPTB, a CL <20 mm optimized test characteristics (PPV 25 and 20%, NPV 95.5, and 92.7%, respectively). For multiparas with a prior sPTB, CL <25 mm was more useful. Using fFN and CL in combination for nulliparas did not improve test characteristics over using the individual fFN (p = .74) and CL (p = .31) components separately.

Conclusions: This study identifies the importance of stratifying by parity and obstetrical history when using screening modalities for risk assessment in symptomatic women. For nulliparous women, either quantitative fFN or cervical length assessment can be utilized, depending on resources available, but a lower cut-point of 20 ng/mL should be used for quantitative fFN. For multiparous women, fFN is not useful and cervical length assessment should be the main screening tool utilized when there is clinical uncertainty. Regardless of parity, the PPV of fFN and CL is low and therefore the greatest clinical utility remains in its NPV.

Keywords:

• Cervical length
• preterm birth
• quantitative fetal fibronectin
• symptomatic preterm labor

Disclosure statement

This study was an investigator-initiated study sponsored by Hologic. The sponsor did not have access to any results at any time during the study or at the conclusion of the study. The sponsoring organization did not preview of any of the data included in this manuscript. No potential conflict of interest was reported by the authors.

Additional information

Funding

Hologic USA (Marlborough, MA, United States of America) provided financial and equipment assistance.

This study was funded in part by a career development award in Women’s Reproductive Health Research: K12-HD001265-15. Hologic USA (Marlborough, MA) provided financial and equipment assistance.