The value of combined cervical length measurement and fetal fibronectin testing to predict spontaneous preterm birth in asymptomatic high-risk women LAUREN A. BOLT 1 , MANJU CHANDIRAMANI 1 , ANNEMARIE DE GREEFF 1 , PAUL T. SEED 1 , JAMES KURTZMAN 2 , & ANDREW H. SHENNAN 1 1 Division of Women’s Health, King’s Health Partners, King’s College London, London, SE1 7EH, UK, 2 Maternal-Fetal Medicine Diagnostic Treatment and Research Centre, Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Loma Linda University Medical Centre, Loma Linda, CA, USA Abstract Objectives. To determine the value of the combined use of fetal fibronectin (fFN) testing and transvaginal ultrasound measurement of cervical length (CL) for prediction of preterm birth (PTB) in asymptomatic high-risk women. Methods. One hundred and forty-seven asymptomatic women at high-risk of PTB were referred to specialist antenatal clinics and underwent CL and fFN testing over a 12-month period. Women had both tests undertaken between 22 þ0 and 30 þ0 weeks’ gestation, on one or more occasions. Results. In those who labored spontaneously (n ¼ 132), positive fFN and CL 25 mm was associated with a 53% risk of PTB at 537 þ0 weeks’ gestation, compared to a 10% risk in those with a negative fFN and CL 4 25 mm. With a known CL, the addition of positive fFN yielded significant hazard ratios regardless of CL (CL 4 25 mm-HR 2.78, CL 25 mm-HR 3.14, p 50.05). The hazard ratios were insignificant when CL results were added to a known fFN. Conclusions. In high-risk asymptomatic women, fFN may be used as a primary screening tool with CL measurement being reserved for those with a positive fFN result. Further prospective studies are needed to confirm our findings. Keywords: asymptomatic, cervical length, fetal fibronectin, high-risk, spontaneous preterm birth Introduction Despite advances in prenatal care, the rate of preterm birth (PTB) worldwide has not declined, and PTB remains the major contributor to neonatal morbidity and mortality. By identifying women at an increased risk for PTB, antenatal management may be individualized to potentially prevent early PTBs (32 þ0 weeks’ gestation) associated with significant long-term morbidities [1]. Past obstetric history is known to be a limited predictor of future PTB [2]. Other predictive tools with proven greater efficacy are increas- ingly being utilized in asymptomatic women to further identify those at an increased risk for PTB. The two most established, strongest, and clinically reliable predictors of PTB are transvaginal ultrasound assessment of cervical length (CL) and the detection of fetal fibronectin (fFN) in cervicovaginal secretions. The measurement of CL in asymptomatic high-risk women is becoming increasingly popular with good prediction of spontaneous PTB [3–7]. As the cervix shortens to 15 mm, there is almost a 50% risk of delivery at 32 þ0 weeks’ gestation, even in low risk women [8]. A CL 525 mm in asymptomatic high-risk women in the second trimester is deemed short [9]. fFN is a glycoprotein found in the choriodecidual interface. It can be detected in cervicovaginal secretions as the fetal membranes begin to separate from the uterine decidua. The presence of significant concentra- tions of fFN in these secretions at gestations between 22 þ0 –35 þ0 weeks’ gestation has been shown to be the greatest predictor of PTB [9]. In asymptomatic high-risk women, it has been determined that if a woman has a positive fFN result (a concentration of fFN 50 ng/ml), the likelihood of delivery at 30 þ0 weeks’ gestation is about 30% [10]. With a negative fFN result, the likelihood of delivery at 30 þ0 weeks’ gestation is known to be less than 1%. The use of combining fFN testing and CL assessment in women in threatened preterm labor has been investigated, with contradicting evidence showing that the addition of fFN testing does [11] and does not [12,13] provide greater prognostic information. In fact, the knowledge gained by using both predictors in threatened preterm labor has been associated with a reduction in the incidence of preterm labor [13], despite the uncertain efficacy of current interventions. The relative risks for PTB in high-risk asymptomatic women identified by poor obstetric history were calculated in the Preterm Prediction Study [9]. A positive fFN result with a CL 25 mm had a 50% and 60% risk of delivering before 32 þ0 and 37 þ0 weeks’ gestation, but rates were based on a small subgroup comprised of only 10 women. Therefore, the purpose of our study was to determine the efficacy of combined fFN and CL assessment for prediction of PTB in an asymptomatic high risk popula- tion. Correspondence: Lauren A. Bolt, Division of Women’s Health, King’s Health Partners, King’s College London, London, SE1 7EH, UK. Tel: þ44-(0)- 207- 188-3639. Fax: þ44-(0)- 207-620-1227. E-mail: lauren.bolt@kcl.ac.uk The Journal of Maternal-Fetal and Neonatal Medicine, July 2011; 24(7): 928–932 ISSN 1476-7058 print/ISSN 1476-4954 online Ó 2011 Informa UK, Ltd. DOI: 10.3109/14767058.2010.535872 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Kings College London on 11/08/11 For personal use only.