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Am J Perinatol 2024; 41(03): 290-299
DOI: 10.1055/a-1673-0280
Original Article

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

Subeen Hong   *
1   Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
,
Se Jin Lee   *
2   Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Korea
,
Yu Mi Kim
3   Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
,
Young Eun Lee
3   Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
,
Yehyon Park
3   Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
,
Hyeon Ji Kim
3   Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
,
Kyo Hoon Park
3   Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
› Author Affiliations 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.
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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

  • Elevated CVF levels of C3a, 4a and 5a are associated with IAI and SPTB.

  • CVF C3a, 4a and 5a have better predictability for SPTB, compared to AF WBC.

  • 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.


Supplementary Material



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.

Thieme Medical Publishers, Inc.
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