Correlation of maternal plasma total cell-free DNA and fetal DNA levels with short term outcome of first-trimester vaginal bleeding

Abstract

The current methods using sonographic parameters and/or maternal serum beta-HCG levels to predict spontaneous abortion are not satisfactory. The aim of this study was to determine whether maternal plasma fetal DNA and total DNA levels could be used to predict spontaneous abortion. We prospectively studied pregnant women who presented with vaginal bleeding in the first trimester of pregnancy, and those who had no vaginal bleeding (controls). DYS14 and the beta-globin gene were used to measure the maternal plasma levels of fetal and total DNA, respectively, by real-time PCR. A total of 1114 women were studied. Both maternal plasma fetal and total DNA concentrations increased with gestation from 6 to 11.6 weeks in the controls. The multiple of medians (MoMs) of fetal and total DNA concentration in those who miscarried were significantly greater (P < 0.001) than in the normal controls by about 5- and 4-fold respectively. Using a cut-off value of 1.6 MoMs for total DNA to predict spontaneous abortion, the sensitivity was 98.2% and false positive rate was 4.7%. However, using a cut-off value of 1.8 MoMs for fetal DNA, the corresponding figures were 97% and 44.3%, respectively. Both maternal plasma fetal and total DNA concentrations increased throughout the first trimester. Significantly high levels of fetal and total DNA were found in those who miscarried.