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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2021; 81(09): 1055-1064
DOI: 10.1055/a-1486-7148
GebFra Science
Original Article

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

Thrombospondin 1 im Zervikovaginalsekret als Prädiktor einer spontanen Frühgeburt bei Frauen mit erhöhtem Risiko: eine prospektive Observationsstudie
Johannes Stubert
1   Department of Obstetrics and Gynecology, Rostock University Medical Center, Rostock, Germany
,
Kathleen Gründler
2   Department of Obstetrics and Gynecology, HELIOS Hospital Schwerin, Schwerin, Germany
,
Bernd Gerber
1   Department of Obstetrics and Gynecology, Rostock University Medical Center, Rostock, Germany
,
Dagmar-Ulrike Richter
1   Department of Obstetrics and Gynecology, Rostock University Medical Center, Rostock, Germany
,
Max Dieterich
1   Department of Obstetrics and Gynecology, Rostock University Medical Center, Rostock, Germany
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Abstract

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.

Zusammenfassung

Einleitung Thrombospondin 1, Desmoplakin und Stratifin sind putative Biomarker für die Vorhersage einer Frühgeburt. Ziel dieser Studie war es, das prädiktive Potenzial dieser Biomarker in Patientinnen mit erhöhtem Frühgeburtenrisiko zu überprüfen.

Material und Methoden Insgesamt wurden 109 Frauen mit Symptomen einer drohenden spontanen Frühgeburt im Zeitraum zwischen 20 0/7 und 31 6/7 SSW in die Studie aufgenommen. Einschlusskriterien waren uterine Kontraktionen, eine Zervixlänge von weniger als 25 mm oder spontane Frühgeburt in der Anamnese. Mehrlingsschwangerschaften wurden auch eingeschlossen. Es wurde ein zervikovaginaler Abstrich entnommen, gefolgt von einer manuellen und einer Ultraschalluntersuchung. Die zervikovaginalen Konzentrationen von Thrombospondin 1, Desmoplakin und Stratifin wurden mithilfe von ELISA quantifiziert. Der primäre Endpunkt war eine spontane Frühgeburt vor 34 + 0 SSW.

Ergebnisse Bei 16 Frauen (14,7%) kam es vor 34 + 0 SSW zur Entbindung. Die mittleren Thrombospondin-1-Konzentrationen waren höher in den Proben, bei denen die Geburt unter 34 SSW stattfand, verglichen mit einer Geburt ≥ 34 SSW (4904 vs. 469 pg/ml, p < 0,001). Die ROC-Analyse ergab eine AUC von 0,86 (p < 0,0001). Für den optimalen Cut-off von 2163 pg/ml betrugen die Sensitivität, Spezifität sowie der positive und negative prädiktive Wert jeweils 0,94, 0,77, 0,42 und 0,99 bei einer adjustierten Odds Ratio von 32,9 (95%-KI 3,1 – 345, p = 0,004). Mehrlingsschwangerschaft, Zervixlänge und vorzeitige Wehen hatten keinen Einfluss auf die Ergebnisse. Bei der Überlebensanalyse zeigte sich ein prädiktiver Zeitraum von mehr als 8 Wochen. Es gab keine Unterschiede zwischen den Gruppen hinsichtlich der Desmoplakin- und Stratifin-Konzentrationen.

Schlussfolgerung Thrombospondin 1 erlaubt die langfristige Risikoabschätzung für eine spontane Frühgeburt.

Key words

biomarker - cervical length - desmoplakin - preterm birth - preterm labor - stratifin - test characteristics - thrombospondin 1

Schlüsselwörter

Biomarker - Zervixlänge - Desmoplakin - Frühgeburt - vorzeitige Wehen - Stratifin - Testcharakteristika - Thrombospondin-1

Supporting Information

    ELISA assays used for protein quantification in CVF with coefficients of variability (CV) and detection limits.

  • Table S1


Publication History

Received: 04 December 2020

Accepted after revision: 16 April 2021

Article published online:
13 September 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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