Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia

Abstract

The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta.

Quantification of Cell-Free DNA in Normal and Complicated Pregnancies: Overcoming Biological and Technical Issues

“…Samples obtained from women with IUGR, preeclampsia and/or in late-gestation (but not pregnancies complicated with NTD in fetus) revealed the highest placental cfDNA concentrations, which all exceeded one SD from the mean for that assay using both PCR methods (Figure 1). These results are in agreement with previously published data [9], [10], [21], [24], [27] but do not provide enough evidence to establish conclusions as only a few pathological samples were available for the study. We detected a positive association between gestational age and the concentration of placental fraction for both qPCR results ( SRY , R = 0.49, p  = 0.04, n = 18; RASSF1A , R = 0.45, p  = 0.013, n = 30) and ddPCR RASSF1A data (R = 0.47, p  = 0.022, n = 24), (Table S7).…”

Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes

“…Shedding of cfpDNA in the maternal circulation may very well also play a role in the pathogenesis of adverse pregnancy outcomes . So far, studies analyzing associations between cfpDNA levels and adverse pregnancy outcomes have mostly been performed in mid or late pregnancy, and only few as early as the first trimester . The largest study that analyzed first trimester cfpDNA levels did not find an association with PE or sPB .…”

Placenta-derived exosomes: potential biomarkers of preeclampsia

“…46 Cell-free fetal DNA cfDNA and cffDNA are also probable combined biomarkers of PE, mainly due to their sensitivity and specificity in biological fluids. 47,48 The identification of the methylated RASSF1A promoter gene, which is elevated in early-PE pregnancies, [49][50][51] offers a promising alternative to the quantification of cffDNA, using Y-chromosome-specific sequences. 52 Notably, high doses of human cffDNA did not induce PE-like symptoms in a murine in vivo model, 53 reinforcing the notion that the increase in RASSF1A methylation is a consequence rather than a cause of PE.…”