Evaluation of additive effect of quantitative fetal fibronectin to cervical length for prediction of spontaneous preterm birth among asymptomatic high-risk women.

Objective: To determine if quantitative fetal fibronectin (qFFN) in addition to transvaginal ultrasound (TVU) cervical length (CL) measurement between 180/7 and 236/7 weeks would be predictive of spontaneous preterm birth (sPTB) at <350/7 weeks among asymptomatic high-risk women as defined by those with prior sPTB > 200/7 weeks.Material and methods: A prospective observational study of asymptomatic women with singleton gestations between 180/7 and 236/7weeks and one or more prior SPTB was performed. Women at their anatomy scan who opted into universal CL screening were enrolled. At enrollment, a vaginal speculum exam was performed to collect cervico-vaginal fluid from the posterior fornix using fetal fibronectin (FFN) swab. These women were then followed until delivery. Women with multiple gestations, rupture of membranes, vaginal bleeding, intercourse, or vaginal exam within 48 h of enrollment were excluded. Physicians were blinded to the qFFN levels, but the CL measurements were made available. The primary outcome was sPTB < 350/7 weeks.Results: Of the 105 asymptomatic women with prior sPTB who were prospectively enrolled, 19 (18.1%) had recurrent sPTB < 370/7 weeks. None of the sPTB were iatrogenic. Using receiver-operating characteristic curves, qFFN ≥ 10 ng/mL had the highest sensitivity with subsequent lowest false negative rate, while FFN ≥ 50 ng/mL was identified as being the best balance of sensitivity and false positive rate for predicting sPTB < 350/7 weeks. As compared with CL ≤ 25 mm alone, with the use of CL ≤ 25 mm or qFFN ≥ 50 ng/mL as screening criteria for prediction of SPTB < 350/7 weeks, sensitivity improved from 18.2 to 63.6%, specificity decreased from 96.8 to 82.1%, positive predictive value (PPV) decreased from 40.0 to 29.2%, negative predictive value (NPV) marginally improved from 91.1 to 95.1%.Conclusion: In women with singleton gestations with prior SPTB, qFFN can be used as an adjunct to triage patients who are found to have a shortened cervix. Sensitivity and NPVs improved with the addition of qFFN to TVU CL screening alone in women with singleton gestations with prior SPTB. However, specificity and PPVs decreased.

Evaluation of additive effect of quantitative fetal fibronectin to cervical length for prediction of spontaneous preterm birth among asymptomatic low-risk women.

INTRODUCTION: Our objective was to evaluate the possible additive effect of quantitative fetal fibronectin to transvaginal ultrasound cervical length measurement between 18(0/7) and 23(6/7)  weeks for prediction of spontaneous preterm birth at <37(0/7)  weeks among asymptomatic low-risk women. MATERIAL AND METHODS: A prospective observational study was performed of asymptomatic women with singleton gestations between 18(0/7) and 23(6/7)  weeks and no prior spontaneous preterm birth. Women with multiple gestations, rupture of membranes, vaginal bleeding, intercourse or vaginal exam within 48 h of enrollment were excluded. Physicians were blinded to the quantitative fetal fibronectin levels, but the cervical length measurements were made available. The primary outcome was spontaneous preterm birth at <37(0/7)  weeks. RESULTS: Of the 528 asymptomatic low-risk women who were prospectively enrolled, 36 (6.82%) had spontaneous preterm birth at <37(0/7)  weeks. Using the receiver-operating characteristic curve, fetal fibronectin value of ≥5 ng/mL was identified as the optimal cut-off for predicting spontaneous preterm birth at <37(0/7)  weeks. As compared with cervical length ≥20 mm alone, with the use of cervical length ≤20 mm or quantitative fetal fibronectin ≥5 ng/mL as screening criteria for prediction of spontaneous preterm birth at <37(0/7)  weeks; sensitivity improved from 11.11 to 61.11%, specificity decreased from 99.59 to 55.08%, positive predictive value decreased from 66.67 to 9.05%, negative predictive value marginally improved from 93.87 to 95.09% and predictive accuracy decreased from 93.56 to 55.49%. CONCLUSIONS: Although the sensitivity improved, other predictive statistics and predictive accuracy did not improve by the addition of mid-trimester quantitative fetal fibronectin to cervical length measurement. Therefore, addition of mid-trimester quantitative fetal fibronectin to cervical length measurement cannot be recommended at this time for prediction of spontaneous preterm birth at <37(0/7)  weeks in asymptomatic low-risk women.