Comparison between Cervicovaginal Fluid Interleukin-6 and Fetal Fibronectin in Combination with Cervical Ultrasound Characteristics for the Prediction of Spontaneous Preterm Delivery in Threatened Preterm Labor.

BACKGROUND: 80% of patients presenting with threatened preterm labor do not deliver preterm. Currently, cervical length and cervicovaginal fluid fetal fibronectin are tools used to predict spontaneous preterm birth. However, fetal fibronectin testing has been discontinued worldwide. OBJECTIVES: This study aimed to compare the predictive performance of cervicovaginal fluid interleukin-6 (IL-6) and fetal fibronectin, combined with cervical characteristics (cervical length, sliding sign, and elastography) and other maternal characteristics, for predicting spontaneous preterm delivery in patients with threatened preterm labor. METHODS: This was a prospective study involving 249 singleton pregnancies presenting at 20-36 weeks with threatened preterm labor. Upon admission, cervical length, cervical elastrography, cervical sliding sign, quantitative cervicovaginal fluid fetal fibronectin, and IL-6 were measured. The predictive performance of individual and combined biomarkers for predicting spontaneous preterm delivery < 37 weeks was calculated. RESULTS: The prevalence of spontaneous preterm delivery at <37 weeks of gestation was 10.04% (25/249). The spontaneous preterm delivery group had a significant shorter mean cervical length but higher mean fetal fibronectin and IL-6 concentrations than the term delivery group [cervical length: 2.31 cm (1.90-3.18) vs. 3.41 cm (6.89-11.42); fetal fibronectin: 100 ng/mL (21.50-461.0) vs. 7.50 ng/mL (3.00-59.50); IL-6: 98.63 pg/mL (18.04-258.43) vs. 18.41 pg/mL (11.02-38.91); p<0.001 for all]. The combination of cervical length and IL-6 yielded the highest AUC of 0.78, with a sensitivity of 72% at a specificity of 77.2%, and positive and negative predictive values of 26.1% and 96.1%, respectively, for predicting spontaneous preterm birth at <37 weeks. Such performance is significantly greater than fetal fibronectin (p=0.02) or cervical length alone (p=0.016) but comparable to IL-6 alone (p=0.13). There are no differences in cervical elastrography score (p=0.23) and the presence of cervical sliding sign (p=0.14) between term and preterm birth groups. CONCLUSION: In patients with threatened preterm labor symptoms, cervical length in combination with IL-6 had a moderate sensitivity but high specificity and negative predictive value; thus, these tests may be used as a rule-out test for spontaneous preterm delivery <37 weeks. Cervical length, in combination with IL-6, or IL-6 alone, can replace the fibronectin test.