Maternal Plasma Cell-Free DNA in the Prediction of Pre-Eclampsia. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Rolnik, D. L.; O'Gorman, N.; Fiolna, M.; van den Boom, D.; Nicolaides, K. H.; Poon, L. C.
• Is Part Of: Obstetrical & gynecological survey. Volume 70:Issue 6(2015)
• Publication Date: 2015-06
• Subjects: Obstetrics -- Periodicals; Gynecology -- Periodicals; Generative organs, Female -- Surgery -- Periodicals; 618
• DOI: 10.1097/01.ogx.0000467225.91373.46
• Languages: English
• ISSNs: 0029-7828

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>ABSTRACT</title> <p>In both developed and developing countries, preeclampsia (PE) is among the most common causes of perinatal and maternal morbidity and mortality. Studies have reported higher serum or plasma concentrations of total and fetal cell-free DNA (cfDNA) in women with PE compared with normotensive controls. This has been associated with accelerated apoptosis of trophoblastic cells due to placental ischemia, although recent studies have not been able to find whether these high levels antecede PE. This case-control study aims to further explore if fetal fraction at 11 to 13 and 20 to 24 weeks' gestation and maternal plasma concentrations of total cfDNA can help predict PE and if those measurements are increased with pregnant women who develop PE.</p> <p>This study looked at 20 pregnant women with PE who delivered before 34 weeks and 20 with PE who delivered at or after 34 weeks. In the first trimester, the study group was compared with 200 controls, and in the second, 100 controls. Plasma samples were taken during first and second trimesters of pregnancy, and pregnancy outcome data were collected from hospital records and the women's general practitioners. Venous blood was collected and centrifuged at 2000<italic>g</italic> for 10 minutes and then again at 16, 000<italic>g</italic> for 10 minutes. Laboratory staff were blinded to the diagnosis of PE. The cfDNA was then evaluated using both a targeted sequencing polymorphism-dependent method and also a fetal fraction assessment from whole-genome random sequencing. The data were further analyzed, converting distributions of cfDNA and fetal fraction at 11 to 13 weeks to multiples of median. The Mann-Whitney <italic>U</italic> test was used to make comparisons between the outcome groups.</p> <p>The control group saw a significant increase (10%) in median fetal fraction and its MoM (multiples of the median) values between the first and second trimesters but did not find significance in the difference in the median total of cfDNA and its MoM values over gestation. Compared with the control group, the early PE group saw a significant increase in median total cfDNA (2104 genome equivalents [GE]/mL vs 1590 GE/mL), a significant decrease in median fetal fraction (6.8% vs 8.7%), but no significant change in MoM values. The late PE group had no significant difference in median total cfDNA, in fetal fraction, or in MoM values, but compared with controls, median fetal fraction decreased at 20 to 24 weeks' gestation (8.2% vs 9.6%). The late PE group saw no significant difference in MoM values compared with controls.</p> <p>The study found that at 11 to 13 weeks' gestation, the median maternal plasma concentration of total cfDNA is increased, and fetal fraction decreased in pregnancies that develop early PE. In late PE pregnancies, the median fetal fraction at 20 to 24 weeks reduced. However, when maternal characteristics are taken into account, the MoM in PE are not significantly different from those in normotensive controls. These results suggest that neither measurements of total cfDNA nor fetal fraction in maternal plasma is useful in predicting PE at 11 to 13 or 20 to 24 weeks' gestation.</p> </sec> </abstract>