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; birth; delivery; pregnancy; premature; preterm.