Fetal cell-free plasma DNA concentrations in maternal blood are stable 24 hours after collection: analysis of first- and third-trimester samples.

Abstract

The discovery of intact fetal cells in maternal blood has led to the possibility of noninvasive prenatal genetic testing. Although extensive work has been performed on maternal blood in the hope of developing a reliable method for the recovery of intact fetal cells, the total number of recoverable cells is quite small, averaging 19 nucleated fetal cells in 16 mL of blood (1)(2). This is contrasted by a relatively large amount of cell-free fetal DNA detectable in maternal plasma (3). Recent studies suggest that cell-free fetal DNA in maternal plasma can be used as a diagnostic tool for diseases of pregnancy, such as preeclampsia or preterm labor, or for fetal anomalies, such as Down syndrome (4)(5)(6)(7). Because of these potential applications, it is of great importance to determine whether cell-free fetal DNA concentrations remain stable in a test tube after phlebotomy. In this report we evaluate the effects of time after phlebotomy on the quantity of cell-free fetal DNA in blood samples from a pregnant woman and a woman who has just undergone termination of pregnancy. The post-termination samples were used because in the first trimester, there are relatively few fetal cells present in maternal blood. The termination procedure increases fetomaternal transfusion (8). We hypothesized that after phlebotomy, apoptotic fetal cells that die in the venipuncture tube would release their DNA. We also asked whether more fetal cells undergo apoptosis as a result of exposure to the maternal bloodstream and cytokines. In both cases, we hypothesized that cell-free fetal DNA concentrations would increase in the blood samples over time. This study was performed with Institutional Review Board approval and with informed consent from participants at Tufts-New England Medical Center. For early-gestation samples, 29 women who were 6–17 weeks pregnant were recruited from …