Repeated Quantitative Fetal Fibronectin Assessments for Preterm Birth Prediction in Pregnant Women with Cervical Insufficiency

Background/Objectives: Preterm birth remains the leading cause of neonatal morbidity and mortality, with cervical insufficiency being a major risk factor. Quantitative fetal fibronectin (qfFN) and the QUiPP App version 2.0 are established tools for preterm birth prediction; however, the value of repeated assessments remains unclear. This study aimed to evaluate the prognostic accuracy of longitudinal qfFN measurements and QUiPP risk assessment in women with progressive cervical insufficiency and to evaluate the prognostic performance of repeated assessments. Methods: In this retrospective cohort study, 88 women with progressive cervical insufficiency who underwent repeated qfFN measurements were included. Cervical length, qfFN, and QUiPP risk were assessed at diagnosis and at subsequent time points. Prognostic performance for delivery within one week and before 34 and 37 gestational weeks was evaluated. Results: The prognostic performance represented by the area under the curve increased from 0.71 to 0.75 for qfFN and from 0.74 to 0.82 for QUiPP from the first to the final assessment, although neither difference reached statistical significance (qfFN p = 0.522; QUiPP risk p = 0.135). For imminent preterm birth, qfFN demonstrated excellent rule-out performance, with a negative predictive value of 100% at <10 ng/mL. QUiPP risk provided superior risk stratification and achieved excellent prognostic accuracy for delivery before 34 weeks at the final assessment (area under the curve = 0.82). Receiver operating characteristic analysis identified optimal cutoffs of approximately 40 ng/mL for qfFN and 23% for QUiPP risk in predicting delivery before 34 weeks. Conclusions: Repeated qfFN assessment combined with QUiPP risk estimation was associated with numerically higher discriminatory performance at the final assessment. While the identified optimal cutoff values need to be validated in prospective trials, they might have the potential to safely reduce unnecessary interventions in the future. qfFN functioned as an effective rule-out test, whereas QUiPP enhanced risk stratification, supporting their combined repeated use to guide clinical management before 34 + 0 weeks of gestation.