Prediction of pre-eclampsia by an analysis of placenta-derived cellular mRNA in the blood of pregnant women at 15-20 weeks of gestation

Objective A panel of cellular mRNA markers was used to predict the occurrence of pre-eclampsia in pregnant women at 15-20 weeks of gestation. Design Prospective cohort study. Setting The Department of Obstetrics and Gynaecology, University of Indonesia, Cipto Mangunkusumo National Hospital, Indonesia. Sample Peripheral blood samples from asymptomatic pregnant women. Methods Among 660 women, 62 developed pre-eclampsia at later gestation (pre-eclampsia group) and each case was matched with five controls. Therefore, the RNA expression levels in the cellular component of maternal blood in 62 women with pre-eclampsia were compared with those in 310 controls. Main outcome measures The cellular RNA expression levels of genes related to angiogenesis and oxidative stress were compared between pre-eclampsia and control groups. A receiver operating characteristic (ROC) curve was used to analyse the sensitivity of each available marker. A logistic regression analysis was performed to calculate the odds for each woman to be classified as a case. Results The univariate ROC analysis identified soluble vascular endothelial growth factor receptor-1 (Flt-1) and endoglin (ENG) as the markers with the highest sensitivity. The best multivariate model was obtained by combining Flt-1, ENG, placental 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). Conclusion A panel of cellular mRNA markers in maternal blood can predict the development of pre-eclampsia long before clinical onset.