Can the quantity of cell-free fetal DNA predict preeclampsia: a systematic review

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Previous studies have demonstrated an increase in the quantity of cell-free fetal DNA (cffDNA) before the onset of preeclampsia. It would be beneficial if the quantity of cffDNA predicted preeclampsia in order to implement preventative trials and strategies to decrease maternal and fetal morbidity. Our objective was to review the literature on using cffDNA levels as a predictor of preeclampsia.


We performed a systematic review following the Meta-analyses and Systematic Review of Observational Studies guidelines. Included studies evaluated cffDNA levels in pregnant women before the clinical onset of preeclampsia.


Thirteen studies met inclusion criteria. There was considerable heterogeneity between included studies, and all received a quality grade of C on the Grading of Recommendations Assessment, Development, and Evaluation scale. Of the 13 studies, 11 found an increase in cffDNA among pregnant women who subsequently developed preeclampsia. In addition, all four studies analyzing early-onset or severe preeclampsia found significantly elevated cffDNA levels prior to disease onset.


Cell-free fetal DNA quantification is a promising marker for preeclampsia prediction, especially for the development of early-onset or severe preeclampsia. However, because of the heterogeneity in published studies, a precise conclusion about the statistical and clinical relevance cannot be made. © 2014 John Wiley & Sons, Ltd.

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