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DOI: 10.1055/a-1673-0280
Complement Activation Fragments in Cervicovaginal Fluid Are Associated with Intra-Amniotic Infection/Inflammation and Spontaneous Preterm Birth in Women with Preterm Premature Rupture of Membranes
Funding This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1F1A1048362). The funders had no role in the design of the study, data collection, analysis, data interpretation, or writing the manuscript.![](https://www.thieme-connect.de/media/ajp/202403/lookinside/thumbnails/10-1055-a-1673-0280_201093-1.jpg)
Abstract
Objective We sought to determine whether the levels of complement and other inflammatory and angiogenic mediators in cervicovaginal fluid (CVF) are independently associated with intra-amniotic infection and/or inflammation (IAI) and imminent spontaneous preterm birth (SPTB, £48 hours of sampling) in women with preterm premature rupture of membranes (PPROM).
Study Design This was a retrospective study consisting of 85 singleton pregnant women with PPROM at 200/7 to 336/7 weeks. Amniotic fluid (AF) obtained via amniocentesis was cultured and assayed for interleukin-6. CVF samples collected at the time of amniocentesis were assayed for complement C3a, C4a, and C5a, HSP70 (heat shock protein 70), M-CSF (macrophage colony-stimulating factor), M-CSF-R (macrophage colony-stimulating factor-receptor), S100 A8, S100 A9, thrombospondin-2, VEGF (vascular endothelial growth factor-receptor), and VEGFR-1 (vascular endothelial growth factor-receptor 1) by enzyme-linked immunosorbent assay.
Results Multivariate logistic regression analyses revealed that elevated CVF concentrations of complement C3a, 4a, and 5a were significantly associated with an increased risk of IAI and imminent SPTB, whereas those of M-CSF were associated with IAI, but not imminent SPTB (p = 0.063), after adjustment for baseline covariates (e.g., gestational age at sampling). However, univariate, and multivariate analyses showed that the CVF concentrations of angiogenic (thrombospondin-2, VEGF, and VEGFR-1) and inflammatory (HSP70, M-CSF-R, S100 A8, and S100 A9) proteins were not associated with either IAI or imminent SPTB.
Conclusion In women with PPROM, elevated CVF concentrations of complement C3a, C4a, and C5a are independently related to an increased risk of IAI and imminent SPTB. These findings suggest that complement activation in CVF is significantly involved in mechanisms underlying preterm birth and in the host response to IAI in the context of PPROM.
Key Points
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Elevated CVF levels of C3a, 4a and 5a are associated with IAI and SPTB.
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CVF C3a, 4a and 5a have better predictability for SPTB, compared to AF WBC.
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Elevated CVF levels of M-CSF were associated with IAI, but not SPTB.
Keywords
cervicovaginal fluid - complement activation - intra-amniotic infection - preterm premature rupture of membranes - proteins - spontaneous preterm birth* These two authors contributed equally to this work.
Publication History
Received: 18 December 2020
Accepted: 10 October 2021
Accepted Manuscript online:
19 October 2021
Article published online:
28 November 2021
© 2021. Thieme. All rights reserved.
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