Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study.

INTRODUCTION: CCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women. MATERIAL AND METHODS: In our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion. RESULTS: Sixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73-0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2. CONCLUSION: Low maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance. TRIAL REGISTRATION NUMBER (DRKS-ID): DRKS00010763, Registration date: September 02, 2016.

Prediction of Spontaneous Preterm Birth in At-risk Women Using Thrombospondin 1 from Cervicovaginal Fluid: A Prospective Observational Study.

Introduction Thrombospondin 1, desmoplakin and stratifin are putative biomarkers for the prediction of preterm birth. This study aimed to validate the predictive capability of these biomarkers in patients at risk of preterm birth. Materials and Methods We included 109 women with symptoms of threatened spontaneous preterm birth between weeks 20 0/7 and 31 6/7 of gestation. Inclusion criteria were uterine contractions, cervical length of less than 25 mm, or a personal history of spontaneous preterm birth. Multiple gestations were also included. Samples of cervicovaginal fluid were taken before performing a digital examination and transvaginal ultrasound. Levels of cervicovaginal thrombospondin 1, desmoplakin and stratifin were quantified by enzyme-linked immunosorbent assays. The primary endpoint was spontaneous preterm birth before 34 + 0 weeks of gestation. Results Sixteen women (14.7%) delivered before 34 + 0 weeks. Median levels of thrombospondin 1 were higher in samples where birth occurred before 34 weeks vs. ≥ 34 weeks of gestation (4904 vs. 469 pg/mL, p < 0.001). Receiver operator characteristics analysis resulted in an area under the curve of 0.86 (p < 0.0001). At an optimal cut-off value of 2163 pg/mL, sensitivity, specificity, positive predictive value and negative predictive value were 0.94, 0.77, 0.42 and 0.99, respectively, with an adjusted odds ratio of 32.9 (95% CI: 3.1 - 345, p = 0.004). Multiple gestation, cervical length, and preterm labor had no impact on the results. Survival analysis revealed a predictive period of more than eight weeks. Levels of desmoplakin and stratifin did not differ between groups. Conclusion Thrombospondin 1 allowed long-term risk estimation of spontaneous preterm birth.

Uterocervical angle as a predictor of preterm birth on a high-risk collective between 20 and 31 weeks of gestation: A cohort analysis.

INTRODUCTION: The cervical length (CL) measurement is a widely used method to estimate the risk of preterm birth. Due in particular to the high false-positive rate, the establishment of markers with improved test characteristics is a great challenge. A potential predictor of preterm birth is the uterocervical angle (UCA) and this additional measurement may improve the risk assessment. It was the aim of this study to compare the test properties of CL and UCA on patients at risk for preterm birth. MATERIAL AND METHODS: 109 patients with at least one of the following signs of threatening preterm birth between 20+0/7 and 31+6/7 weeks were included in a prospective cohort analysis: regular (>3/30 min) or painful uterine contractions, CL below 25 mm or a history of preterm birth. Exclusion criteria were premature rupture of membranes, hypertensive disorders, vaginal bleeding, surgical cerclage, Arabin pessary or cervical dilation of more than 30 mm. The determination of the UCA was carried out in a standardized manner using the image documents captured by vaginal sonographic CL measurement. The primary endpoint was preterm birth <34 weeks, secondary endpoints were delivery <37 weeks and within 7 days. RESULTS: The UCA was on average 103° and the mean UCA in preterm and term groups did not differ significantly (P = .924). The UCA was not predictive for threatened preterm birth, even if only singletons were considered. For CL the best predictive accuracy for preterm birth <34 weeks was observed at a cut-off value of 14 mm with sensitivity 0.50, specificity 0.80, positive predictive value 0.30, negative predictive value 0.90, positive likelihood ratio 2.4, negative likelihood ratio 0.6 and an odds ratio of 3.9 (95% confidence interval 1.3-11.7, P = .016). CONCLUSIONS: The assessment of UCA in patients at risk for preterm birth was not suitable to predict the probability of a threatened preterm birth. Measurement of UCA cannot be recommended in this situation.