Development of FIRS RNA marker in maternal plasma

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It is well known that fetal inflammatory response syndrome(FIRS) causes severe multi-organ failures in the fetus or neonate. Although premature rupture of membrane and chorioamnionitis can be developed to the FIRS, the evaluation method to diagnose the onset of FIRS has not been established. To develop the method to predict the occurrence of FIRS is therefore very important. On the other hand, we have developed the prediction method for preeclampsia by using cell-free RNA and cellular RNA in maternal blood. We planned to apply this method to the prediction of FIRS.We obtained blood samples from admitted patients with threatened preterm birth, PROM, cervicitis, and chorioamnionitis. We further obtained the data of blood counts, CRP value, elastase and fibronectin values in the cervical mucus. In cases that were performed amniocentesis, the concentrations of elastase and fibronectin were also quantified. However, in the study period, we could not obtain samples from pregnant women with fetal infection.We expect inflammatory cytokines such as interleukin-6 and interleukin-8 as molecular markers for detecting the pathogenesis of FIRS. However, the preliminary study showed that the expression levels of these markers were already altered in such situation and these candidate markers could not be used for the prediction of FIRS.Therefore, we assessed the prediction of invasive placenta by using the analysis of cellular RNA in maternal blood. The expression levels of placenta specific-1(PLAC-1) and vascular endothelial growth factor A(VEGFA) in patients with invasive placenta were higher than those in normal pregnant women. In contrast, the level of KISS-1 was lower in the patients. These genes can be potential markers to predict the abnormal adherence of the placenta.It is thus revealed that the analysis of cellular RNA in maternal blood allowed the evaluation of fetal and/or placental pathophysiological alterations.