Prediction of invasive placenta through cell-free RNA analysis

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To develop the strategy predicting the invasive placenta, we have been collecting over 660 blood samples. However, since nobody have complicated with invasive placenta in the cases, we could not assess the predictive markers for invasive placenta. Therefore, we employed to predict the preeclampsia. The objective of this study is to predict occurrence of preeclampsia in a series of patients at gestational week 15-20 using a panel of cell-free or cellular mRNA markers. Data from 62 preeclamptic patients asymptomatic at the time of blood testing and 310 controls were analyzed. Multivariable analysis was performed using discriminant analysis. In the analysis of cell-free RNA, univariable analysis identified vascular endothelial growth factor receptor 1 (FLT1) as the marker with the highest detection rate, and placenta-specific-1 with the lowest. Mean estimated score for preeclampsia was 9.4 for controls and 72.5 for subjects who developed preeclampsia. An ROC curve obtained using the estimated score for preeclampsia as test variable yielded a DR of 84% (95%CI 71.8-91.5) at a 5% false-positive rate with an area under the curve of 0.927 (p<0.001). Again, DR and score for each patient for classification as preeclamptic correlated with severity. Next, in the cellular RNA analysis, the univariate ROC analysis identified soluble Flt-1 and endoglin as the markers with the highest sensitivity. The best multivariable model was obtained by combining Flt-1, Endoglin, placenta growth factor (PlGF) and parity. The relative ROC curve yielded a sensitivity of 66% at a 10% 1-specificity rate with an area under the curve of 0.884 (p<0.001). In conclusion, a panel of cell-free or cellular mRNA is able to detect subjects who will develop preeclampsia.