Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks’ gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (,25 mm) by 24 weeks’ and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/ elafin from 14 weeks’ versus those who did not (CI 1.94–3.79, p,0.0005). CVF trappin2/elafin before 24 weeks’ was 1.79 times higher in women who had a spontaneous preterm birth ,37 weeks’ (CI: 1.05–3.05, p = 0.034). Trappin2/elafin (. 200 ng/ml) measured between 14–14 weeks’ of pregnancy predicted women who subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort. Citation: Abbott DS, Chin-Smith EC, Seed PT, Chandiramani M, Shennan AH, et al. (2014) Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth. PLoS ONE 9(7): e100771. doi:10.1371/journal.pone. 0100771 Editor: Alan Landay, Rush University, United States of America Received March 21, 2014; Accepted May 22, 2014; Published July 30, 2014 Copyright: 2014 Abbott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and any additional information required can be obtained by contacting the author for correspondence. Funding: Action Medical Research, grant number S/P/4113 (Registered Charity No: 208701; www.action.org.uk) to RMT AHS. Tommy’s Charity (Registered Charity No: 1060508; http://www.tommys.org/) to RMT AHS. The Sutton Place Foundation General Charitable Trust (Registered Charity No: 1136264) RMT AHS. Wellbeing of Women (Registered Charity No: 239281; http://www.wellbeingofwomen.org.uk) to DSA AHS RMT. British Maternal and Fetal Medicine Society (http://www. rcog.org.uk/content/british-maternal-fetal-medicine-society) to DSA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * Email: rachel.tribe@kcl.ac. uk " These authors are joint first authors on this work.