Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

Abstract

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+0–14+6 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.

Cervical length at mid-gestation in screening for preterm birth in twin pregnancy

“…To date, there is evidence that both term and preterm labor are linked to an inflammatory process, and over the last few decades several biomarkers, including inflammatory cytokines, have been investigated for the prediction of PTB. Recently, Abbot et al . have shown that inflammation anticipates cervical shortening, thus questioning the utility of CL screening in asymptomatic women.…”

The impact of pregnancy on anti-HIV activity of cervicovaginal secretions

“…However, high levels of these mediators in CVL have been previously associated with adverse pregnancy outcomes such as cervical shortening and preterm birth suggesting that the concentrations we found were indicative of a response to some stimulus in vivo . 31,32 …”

Risk Prediction for Adverse Pregnancy Outcomes in a Medicaid Population

“…13,14,17,18 More recent efforts have focused on biomarkers such as pregnancy-associated plasma protein A, fetal fibronectin, and placental growth factor to augment the predictive capacity of demographic and clinical risk factors; however, this body of research has not yet yielded a clear approach for implementation in clinical practice. [19][20][21][22] As with prior studies, important risk factors in our model included race and obstetric history. Our inclusion of childhood abuse in the model is also consistent with recent literature demonstrating the importance of childhood history as a significant risk factor.…”

“…[13][14][15] More recently, risk models including cervical length as well as various biomarkers have shown promise in increasing prognostic performance. [16][17][18][19][20][21][22] However, this research has not yet yielded a risk assessment tool for use in clinical practice; moreover, the majority of these prediction models have been derived using a general population, which may overinflate their ability to discriminate risk within an a priori at-risk population of Medicaid recipients.…”