Cell-Free Foetal DNA as a Useful Marker for Preeclampsia Prediction

Preeclampsia (PE) is a leading cause of maternal complications and is diagnosed by clinical manifestation. The aim of the study was to evaluate changes of cell-free DNA (cfDNA) and cell-free foetal DNA (cffDNA) concentration during uncomplicated pregnancy and PE in one group of women, and define the predictive value for PE. A total of 580 women were prospectively evaluated, 20 of them developed PE and were included in laboratory analysis, and 22 healthy pregnant with uncomplicated pregnancy were included as the laboratory control group. We determined cfDNA and cffDNA in maternal blood at 11-14, 24-26, and 30-32 weeks. Level of cfDNA was evaluated by determining the RASSF1A gene using PCR analysis, cffDNA-by determining the hypermethylated part of RASSF1A gene. The concentration of cfDNA did not differ in the first and second trimesters but significantly increased at 30-32 weeks in both groups. During uncomplicated pregnancy, median cffDNA level increased from 14.15 GE/ml to 24.87 GE/ml (p = 0.002) and 32.62 GE/ml (p = 0.005). In the PE group, an elevation in cffDNA level was significant only in the second half of pregnancy (from 54.85 to 96.72 (p > 0.05) and 158.30 GE/ml (p = 0.031) at 11-14, 24-26, and 30-32 weeks, respectively). At all studied periods, cffDNA level in the PE group was significantly higher compared to uncomplicated pregnancy (р < 0.001). ROC analysis showed that a cut-off value of cffDNA concentration 22.54 GE/ml in maternal blood at 11-14 weeks of pregnancy had the greatest predictive value for PE prediction, with 85.0% sensitivity and 81.8% specificity. CffDNA is a promising marker for PE prediction from the first trimester of pregnancy.