Predictive value of quantitative fetal fibronectin for spontaneous preterm birth in asymptomatic pregnancies: a systematic literature review and meta-analysis

Abstract

Objective

Tests capable of accurate prediction of spontaneous preterm birth (sPTB) are crucial to inform clinical decisions to prevent neonatal deaths and reduce the risk of morbidity in surviving infants. A systematic literature review and meta-analysis were performed to assess the utility of the quantitative fetal fibronectin (fFN) test to predict sPTB at different test concentration thresholds.

Methods

Literature searches were conducted in MEDLINE, Embase, and the Cochrane Library in May 2022. Observational studies and clinical trials investigating the clinical utility of the quantitative fFN test in asymptomatic pregnancies prior to 37 weeks of gestation were eligible for inclusion. Meta-analysis quantified the risk of sPTB prior to four gestational age milestones (<28, <30, <34 and <37 weeks) based on quantitative fFN levels. No risk of bias assessment was performed however, clinical and methodological heterogeneity was explored to determine the feasibility of performing analyses.

Results

11 studies showed a quantitative assessment of fFN can differentiate between very high and very low risks of sPTB in asymptomatic pregnancies with <10% of women with very low fFN (<10 ng/mL) versus 37–67% of women with very high fFN (>200 ng/mL) delivering before 34 weeks. A meta-analysis of two studies showed, albeit with a low number of events, the odds of sPTB prior to 28 weeks was nine times higher in women testing positive at ≥50 ng/mL, whereas the odds of sPTB was 25 times higher in women with fFN concentrations >200 ng/mL (versus <50 ng/mL reference). Similarly, pooling three studies showed the odds of sPTB prior to 37 weeks was four times higher in women who tested positive at ≥50 ng/ml whereas the odds of delivery before 37 weeks was seven times higher for women with fFN concentrations ≥200 ng/ml (versus <50 ng/mL reference).

Conclusion

Quantitative fFN testing demonstrates increased predictive capabilities and utility of fFN testing in clinical practice, potentially preventing unnecessary intervention for women at very low risk and allowing an opportunity to optimize the management of asymptomatic patients at high risk of preterm delivery.

Keywords:

• Fibronectin
• preterm
• premature
• birth
• delivery
• pregnancy

Acknowledgements

We thank Shruti Nambiar for her contributions to the design and execution of the initial SLR, upon which this study was based. We also thank Allie Cichewicz and Heather Burnett for their contributions to the execution of the initial SLR and interim updates.

Disclosure statement

Sophie Dodman, Marissa Betts, and Binod Neupane are employed by Evidera, which provides consulting and other research services to pharmaceutical, medical device, and related organizations. In their salaried positions, they work with a variety of companies and organizations and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from Hologic, Inc. to participate in the study. Michael Ruma is a consultant and member of the Hologic speaker’s bureau and received funding from Hologic, Inc. to participate in the study. Hologic, Inc. did not participate in the data collection, analysis, nor interpretation of the research outcomes.

Data availability statement

Study protocol available upon request. The data used in the analyses are presented in Table 1.

Additional information

Funding

Evidera and Michael Ruma received funding from Hologic, Inc. to participate in the study. Hologic, Inc. did not participate in the data collection, analysis, nor interpretation of the research outcomes.