Circulating Maternal Total Cell-Free DNA, Cell-Free Fetal DNA and Soluble Endoglin Levels in Preeclampsia: Predictors of Adverse Fetal Outcome? A Cohort Study

Abstract

Background: The diagnosis of preeclampsia (PE) is based on the measurement of maternal blood pressure and proteinuria; however, these parameters are not used in the prediction of adverse fetal outcomes that may occur due to fetal stress. The plasma concentrations of total cell-free DNA (cf-DNA), cell-free fetal DNA (cff-DNA) and soluble endoglin (sEng) are higher in women with established PE than in normotensive controls, and the increase is particularly marked in those with severe PE. We aimed to evaluate the levels of cf-DNA, cff-DNA and sEng in pregnant Egyptian women with PE in order to assess the severity of the disease and to detect their potential utility in the future prediction of time of delivery and adverse fetal outcome.

Subjects and methods: The study included 107 pregnant females with established PE during their third trimester (51 with mild PE and 56 with severe PE), together with 93 normotensive pregnant women. Absolute quantitation of the hemoglobin subunit beta (HBB) and testis-specific protein, Y-linked 1 (TSPY1) genes for the measurement of cf-DNA and cff-DNA in maternal blood, respectively, was carried out using real-time polymerase chain reaction (PCR) together with the measurement of serum sEng using ELISA.

Results: An almost twofold increase in cf-DNA and cff-DNA was detected in the severe PE group over the mild group, and both were significantly different from the control group. Significantly higher levels of cf-DNA, cff-DNA and sEng, with variable magnitudes, were detected in the preterm labor and unfavorable fetal outcome groups compared with the term and favorable outcome groups, respectively. The three markers were almost equivalent with regard to the area under the curve for predicting adverse fetal outcome in the severe PE group. The same was also true for cf-DNA and cff-DNA within the mild PE group.

Conclusions: Incorporation of cf-DNA, cff-DNA and sEng into the prenatal care service should be considered as a serious addition for the screening and detection of adverse pregnancy outcomes in view of their significant elevations in cases of preeclamptic women whose babies ultimately suffered a poor outcome.