Proteomic analysis of plasma to identify novel biomarkers for intra-amniotic infection and/or inflammation in preterm premature rupture of membranes

Abstract

This study aimed to identify potential plasma biomarkers associated with microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in women with preterm premature rupture of membranes (PPROM). This retrospective cohort study included 182 singleton pregnant women with PPROM (23–33 weeks) who underwent amniocentesis. Plasma samples were analyzed using label-free liquid chromatography-tandem mass spectrometry for proteome profiling using a nested case-control study design (cases with MIAC/IAI vs. non-MIAC/IAI controls [n = 9 each]). Three identified target molecules for MIAC/IAI were further verified by ELISA in the study cohort (n = 182). Shotgun proteomic analysis revealed 17 differentially expressed proteins (P < 0.05) in the plasma of MIAC/IAI cases. In particular, the levels of FCGR3A and haptoglobin, but not LRP1, were found to be increased in the plasma of patients with MIAC, IAI, and both MIAC/IAI compared with those without these conditions. Moreover, these differences remained significant after adjusting for gestational age at sampling. The area under the curves of plasma FCGR3A and haptoglobin ranged within 0.59–0.65 with respect to each of the three outcome measures. Plasma FCGR3A and haptoglobin were identified as potential independent biomarkers for non-invasively detecting MIAC/IAI in women with PPROM.

Exploratory study on the mechanism of necrotic effect of nourishing cells in the context of genital tract infection in premature rupture of membranes

“…This leads to cellular swelling and rupture, resulting in the release of cellular contents into the extracellular space. [17,18] In addition, cell apoptosis is accompanied by nuclear condensation and degradation of DNA into fragments. In the context of genital tract infections associated with preterm PROM, impaired invasion of trophoblast cells can affect spiral artery remodeling, thereby affecting blood supply at the maternalfetal interface and leading to placental hypoxia.…”

Potential of plasma inflammatory and angiogenic mediators for predicting spontaneous preterm delivery, intraamniotic infection/inflammation, and composite neonatal morbidity/mortality in women with early preterm premature rupture of membranes

“…This hypothesis is even more appealing as evidence shows that there is a significant increase in various proinflammatory cytokines and chemokines that are simultaneously expressed in the maternal blood and AF compartments, specifically in the context of SPTD and MIAC 14,20,21 . Previous studies have identified several inflammatory‐ and immune‐related proteins in maternal plasma as potential biomarkers for MIAC, IAI, and acute HCA in pregnancies complicated by PPROM 14,22–25 ; however, the relationship between their altered plasma expression and gestational latency (SPTD) or CNMM in women with early PPROM remains unclear. Furthermore, selected potential inflammatory AF biomarkers (e.g., complement fragment C4a [C4a], MMP‐9, and S100 calcium‐binding proteins A8, A9, and A8/A9 complex [S100A8, S100A9, and S100A8/A9, respectively]), which were shown to be useful for detecting PPROM‐related complications, 26–30 have not yet been fully studied in maternal plasma samples from women with PPROM.…”