Microbial invasion of the amniotic cavity (MIAC), which complicates PPROM in approximately 30% of cases, may induce intraamniotic inflammatory response [11], selleck kinase inhibitor [12]. Specific motifs on the bacterial surface as well as endogenous molecules, released from damaged tissue and cells, are recognized by pattern recognition receptors. Their activation leads to increasing levels of inflammatory mediators in the amniotic fluid followed by the recruitment of neutrophils and other immune cells from the uterine wall to the placenta and fetal membranes. The neutrophil infiltration of the placenta and fetal membranes is then called histological chorioamnionitis (HCA).
The parallel presence of both MIAC and HCA, determining an infectious phenotype of PPROM, is responsible for serious neonatal morbidity, including chronic pulmonary diseases [13], [14] and adverse neurodevelopmental outcome [15], [16], both of which have long-term consequences on quality of life and health care costs [1]. This suggests that the identification of the infectious phenotype of PPROM is crucial for improving outcome in expectant management and parental counseling of women at risk [17]. Regrettably, there is no robust diagnostic tool currently available for identifying this phenotype. Aside from the hypothesis-based research approach widely used in the quest for new diagnostic biomarkers, proteomics offers an unbiased alternative view on the protein changes associated with diseases [18].
The possibility of identifying hundreds of proteins combined with the ability to quantify changes in their abundance across multiple samples makes proteomics a very appealing approach for the exploratory phase of the biomarker discovery process. Promising candidate proteins, selected upon completing Dacomitinib this phase, should then be targeted using complementary methods to verify the initial findings and to further validate their diagnostic potential in larger independent patient cohorts [18]. Two pieces of pioneering work, by Gravett et al. and Romero et al., presented the potential of proteomics in the discovery of novel biomarkers of intraamniotic infection in spontaneous preterm birth patients [19], [20]. Unfortunately, the validation step of the exploratory proteomic phase findings is frequently neglected. Without these data, the translation of these candidate markers into subsequent preclinical and ultimately clinical trials is substantially limited.