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.