Gestational Age Assessment by Methylation and Size Profiling of Maternal Plasma DNA: A Feasibility Study

To the Editor: The discovery of circulating cell-free fetal DNA in maternal plasma in 1997 (1) has transformed the practice of prenatal testing (2). The biological properties of the fetal-derived DNA in the plasma of a pregnant woman have been demonstrated to exhibit a number of differences from the maternal-derived DNA. Of note is that cell-free fetal DNA molecules are shorter than the maternal DNA molecules (3) and their overall methylation levels are lower than their maternal counterparts (4). However, the understanding of how the methylation and size profiles would change across different gestational ages remains incomplete. In this study, we investigated whether one could use the temporal changes in maternal plasma DNA to obtain information regarding the gestational age. We obtained peripheral blood samples with informed consent and institutional approval from 10 pregnant women from each of the first (12–14 weeks), second (20–23 weeks), and third (38–40 weeks) trimesters and harvested the plasma and maternal buffy coat from each case. Fetal samples were also obtained by chorionic villus sampling, amniocentesis, or sampling of the placenta, depending on whether a case was from the first, second, or third trimester, respectively. The maternal buffy coat and fetal samples …