Inflammatory proteins in maternal plasma, cervicovaginal and amniotic fluids as predictors of intra-amniotic infection in preterm premature rupture of membranes

Abstract

ObjectiveWe aimed to assess the correlations among multiple cytokine concentrations in the maternal plasma, cervicovaginal fluid (CVF), and amniotic fluid (AF) compartments in women with preterm premature rupture of membranes (pPROM), and to develop a prediction model based on non-invasive measures, having better sensitivity and specificity for the identification of microbial invasion of amniotic cavity (MIAC).MethodThis retrospective study included 75 consecutive women with pPROM (20+0–34+0 weeks), who underwent amniocentesis. Both maternal plasma and CVF samples were collected at the time of amniocentesis. Stored AF, plasma and CVF samples were assayed for cytokine levels [interleukin (IL)-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β] using a multiplex immunoassay kit.ResultsLevels of inflammatory proteins measured in the CVF were significantly correlated with AF proteins levels, whereas none of the proteins in plasma correlated significantly with any in the AF or CVF. Proteins levels measured in the AF and CVF were significantly higher in women with MIAC compared to those without, whereas only high levels of IL-6 in plasma were significantly associated with MIAC. By using stepwise regression analysis, a non-invasive model (using clinical factors and CVF cytokine levels) for the prediction of MIAC was developed; the area under curve of this non-invasive model was similar to that of the invasive model (using clinical factors and AF cytokines).ConclusionsThe levels of inflammatory proteins in the CVF correlated with those in the AF, whereas those in the plasma showed no correlation. A non-invasive model using clinical factors and CVF cytokine levels predicted the risk of MIAC in women with pPROM.

Identification of Cultivable Bacteria in Amniotic Fluid Using Cervicovaginal Fluid Protein Microarray in Preterm Premature Rupture of Membranes

“…MIP-1α, also referred to as chemokine ligand 3 (CCL3), plays a role in inflammatory responses [31] and its role in relation to MIAC has been evaluated in several studies [12,24,32]. Consistent with the biological functions of MIP-1α [31], an elevated MIP-1α level was found in the AF of women with MIAC in whom a diagnosis of PPROM or preterm labor was made.…”

“…Consistent with the biological functions of MIP-1α [31], an elevated MIP-1α level was found in the AF of women with MIAC in whom a diagnosis of PPROM or preterm labor was made. [12,32] However, there is currently a paucity of data on the altered expression of MIP-1α in CVF associated with MIAC in women with PPROM. In CVF, we found a significant correlation between increased MIP-1α and MIAC in PROM.…”

“…In the setting of PPROM, cervicovaginal fluid (CVF), obtainable via non-invasive methods, could be a possible alternative to AF because the ruptured membrane causes spillage of AF into the cervicovaginal cavity. In fact, our group and others have demonstrated that cytokine levels in CVF were significantly and positively correlated with those in AF samples, and have been associated with MIAC in women with PPROM [6][7][8][9][10][11][12]. Presently, however, CVF cytokines when measured alone have not been found to be sensitive or specific enough at predicting MIAC to replace AF testing, including AF white blood cell counts (WBC) [6,7,10,11].…”

Cervicovaginal fluid cytokines as predictive markers of preterm birth in symptomatic women

“…MIP-1α and MIP-1β are produced in the macrophages in response to infection and inflammation. They subsequently activate human granulocytes and the level of MIP-1α in the CVF is associated with amniotic fluid infection [21,36,37]. MIP-1α has been studied in the CVF of patients with pPROM, but not PTL.…”

“…Thereafter, the objective of our study was to determine whether inflammatory cytokines could be measured using non-invasive methods. Recent studies have shown that IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and MIP-1β levels in the CVF of patients with pPROM were correlated with those in the amniotic fluid [21]. IL-1β, IL-6, IL-8, and TNF-α levels were also elevated in patients with intact membranes in PTL [22].…”