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

Molecular Diagnosis & Therapy volume 20, pages 135–149 (2016)Cite this article

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.

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Affiliations

  1. Department of Clinical and Chemical Pathology, Kasr Al-ainy School of Medicine, Cairo University, Kasr Al-Ainy Street, Cairo, 11562, Egypt

    Radwa Marawan AbdelHalim, Dalia Ibrahim Ramadan, Reham Zeyada & Iman Atef Mandour

  2. Department of Obstetrics and Gynecology, Kasr Al-ainy School of Medicine, Cairo University, Cairo, Egypt

    Ahmed Soliman Nasr

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  1. Radwa Marawan AbdelHalim
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  2. Dalia Ibrahim Ramadan
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Correspondence to Dalia Ibrahim Ramadan.

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Conflict of interest

Radwa Marawan AbdelHalim, Dalia Ibrahim Ramadan, Reham Zeyada, Ahmed Soliman Nasr and Iman Atef Mandour have no conflicts of interest to report.

Funding

The current study was funded by a grant from Cairo University (9 September 2013).

Ethical approval and informed consent

This study was approved by the local Ethics Committee of the Clinical and Chemical Pathology Department (February 2013). Written consents were obtained from participants prior to commencement of the study.

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AbdelHalim, R.M., Ramadan, D.I., Zeyada, R. et al. Circulating Maternal Total Cell-Free DNA, Cell-Free Fetal DNA and Soluble Endoglin Levels in Preeclampsia: Predictors of Adverse Fetal Outcome? A Cohort Study. Mol Diagn Ther 20, 135–149 (2016). https://doi.org/10.1007/s40291-015-0184-x

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  • DOI: https://doi.org/10.1007/s40291-015-0184-x

Keywords

  • Preterm Labor
  • Fetal Growth Restriction
  • Fetal Outcome
  • Preeclamptic Woman
  • Preeclamptic Patient