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

Stubert, Johannes; Gründler, Kathleen; Gerber, Bernd; Richter, Dagmar; Dieterich, M.

doi:10.1055/a-1486-7148

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Our robust marker selection process took into account the performance of individual markers, combinatorial effects with other markers, and stability. Many markers that were identified, such as A1BG 24 , ALB 34,44 , FN1 35,49 , GC 34,36,50 , TF 24,49 , TIMP1 36,39 , and THBS1 37,51 , align with previous findings, while novel markers, like LUM, AMBP, B2M, PRG2, ZG16B, and PSG1 were discovered. Function analysis revealed that proteins significantly upregulated in sPTB samples were associated with abnormal activation of the complement system, extracellular matrix remodeling, and serine protease inhibitor activity.…”

Section: Discussionsupporting

confidence: 85%

Noninvasive cervicovaginal proteomic biomarkers for spontaneous preterm birth

Zhao,

Hou,

Cheng

et al. 2024

Preprint

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Preterm birth (PTB), a leading cause of neonatal mortality, presents challenges in prediction with current methods focusing on traditional risk factors or biomarkers, particularly for spontaneous preterm birth (sPTB). Here, we developed a machine-learning framework based on untargeted cervicovaginal fluid proteomics from 707 individuals (136 sPTB and 571 FTB, Full-term birth) across five hospitals. Our analysis identified 293 proteins with potential predictive value, subsequently distilled into a robust predictive model composed of five protein markers (LUM, AMBP, B2M, FN1, and TIMP1) demonstrating outstanding performance in predicting the risk of sPTB. It achieved area under the receiver operating characteristic curve values of 0.89, 0.90, 0.92, and 0.94 in independent validation datasets from four hospitals, with an overall sensitivity = 0.73 and specificity = 0.92. Moreover, we reproduced the predictive performance of these five biomarkers using enzyme-linked immunosorbent assay (ELISA). At system level, integrating proteomics data from all hospitals, we delineated two distinct molecular subtypes of sPTB, revealing functional differences. Concurrently, we conducted a drug target analysis, unveiling potential preventative drugs for sPTB. In summary, this research expands the repertoire of sPTB prediction biomarkers, offers a novel non-invasive predictive model for sPTB and provides valuable data resources for further investigation into the pathogenesis of preterm birth.

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Section: Discussionsupporting

confidence: 85%

Noninvasive cervicovaginal proteomic biomarkers for spontaneous preterm birth

Zhao,

Hou,

Cheng

et al. 2024

Preprint

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“…The study was conducted as part of the “Analysis of diagnostic accuracy of predictive biomarkers in risk assessment of threatening preterm birth” (ADAPROB) study, parts of which have already been published [ 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

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

Hoffmann,

Gründler,

Richter

et al. 2023

BMC Pregnancy Childbirth

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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.

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“…Around 10.6% of all deliveries worldwide are premature 4 . The number of premature deliveries in Germany has remained almost the same in recent years; in 2008, it was 8.0% and in Austria it was 7.9% in 2016 5 .…”

Section: Introductionmentioning

confidence: 99%

Hexoprenaline Compared with Atosiban as Tocolytic Treatment for Preterm Labor

Kirchhoff

Schneider

Pichler³

et al. 2022

Geburtshilfe Frauenheilkd

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Introduction Preterm birth is defined as a live birth before 37 weeks of gestation and is associated with increased neonatal morbidity and mortality. The aim of this study is to compare the efficacy of hexoprenaline and atosiban for short- and long-term tocolysis and their effects on neonatal and maternal outcomes. Methods This retrospective cohort study included women with threatened preterm labor between 24 + 0 and 34 + 0 weeks of gestation without premature rupture of membranes. The tocolytic efficacy of hexoprenaline and atosiban was compared in women receiving one of the two medications for short- and long-term tocolysis. Continuous variables were compared using t-test or Mann–Whitney U test, as appropriate. Comparison of categorical variables between the two groups was done with χ2 test after Pearsonʼs and Fisherʼs exact test. Results 761 women were enrolled in this study; 387 women received atosiban and 374 women received hexoprenaline as their primary tocolytic agent. Atosiban showed a higher efficacy as a primary tocolytic agent (p = 0.000) within 48 hours. As regards long-term tocolysis, there were no differences between the treatment groups (p = 0.466). Maternal side effects such as tachycardia (p = 0.018) or palpitations (p = 0.000) occurred more frequently after the administration of hexoprenaline, while there were no differences between the two drugs administered with regard to any other maternal or neonatal outcome parameter. Conclusion Our retrospective study shows a significantly higher efficacy of atosiban in the first 48 hours, especially when administered at an early gestational age. There were no significant differences in terms of neonatal outcome but significantly more maternal adverse effects during the administration of hexoprenaline.

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

Cited by 3 publications

References 45 publications

Noninvasive cervicovaginal proteomic biomarkers for spontaneous preterm birth

Noninvasive cervicovaginal proteomic biomarkers for spontaneous preterm birth

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

Hexoprenaline Compared with Atosiban as Tocolytic Treatment for Preterm Labor

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