Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes [RNA-seq]

Although analysis of maternal plasma cell-free content has been employed for screening of genetic abnormalities within a pregnancy, limited attention has been paid to its use for the detection of adverse pregnancy outcomes (APOs) based on placental function. We investigated the cell-free RNA content of 102 maternal, 25 cord plasma samples and 7 non pregnant women as control. using cell-free RNA sequencing, APOs revealed seventy-one differentially expressed genes early in pregnancy. We noticed the upregulation of S100A8, MS4A3 and MMP8 that have been already associated with APOs but also the upregulation of BCL2L15 and the downregulation of ALPL that have never been associated with APOs. We constructed a classifier with a positive predictive ability (AUC) of 0.91 for APOs, 0.86 for preeclampsia alone and 0.64 for GDM. We conclude that placenta-specific cell-free nucleic acids during early gestation provide the possibility of predicting APOs prior to the emergence of characteristic clinical features. Overall design: cell-free RNA profile from plasma of pregnant women with normal pregnancies or with adverse pregnancy outcomes (APOs) such as gestational diabetes, preeclampsia or gestational hypertension. The samples have been collected at 1st, 2nd and 3rd trimester during pregnancy and again at delivery. The cord blood has been collected as well. We analyzed the cell-free RNA content of 102 maternal, 25 cord plasma samples and 7 non pregnant women as control.