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Complement activation fragments in cervicovaginal fluid are associated with intra-amniotic infection/inflammation and spontaneous preterm birth in women with preterm premature rupture of membranesComplement activation fragments in CVF, IAI and SPTBSupported by: the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) 2020R1F1A1048362
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 20+0 to 33+6 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, M-CSF, M-CSF-R, S100 A8, S100 A9, thrombospondin-2, VEGF, and VEGFR-1 by ELISA. 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. Conclusions: 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.
Received: 18 December 2020
Accepted after revision: 10 October 2021
19 October 2021 (online)
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