Fetal DNA in Maternal Plasma: Biology and Diagnostic Applications (Minireview‪)‬

During pregnancy, the fetal and maternal circulations are separated by the placental membranes. However, a variety of evidence has pointed toward the incompleteness of this barrier to cellular trafficking. Of special relevance to this review, fetal nucleated cells have been demonstrated in maternal circulation (1, 2) and have been widely pursued as potential substrates for noninvasive prenatal diagnosis (3). However, the rarity of such fetal cells in maternal blood has been a major obstacle to the routine application of this concept. Recently, there has been much interest in the use of the noncellular portion of blood, namely plasma, for molecular analysis. This interest has been stimulated mainly by the finding of tumor-derived DNA in the plasma and serum of cancer patients (4-6). These findings thus open up the possibility that circulating DNA may also be found in other clinical scenarios. In particular, there is much similarity between the placenta and a malignant tumor, leading some investigators to term the placenta "pseudomalignant" (7). Such a similarity suggests that just as tumor DNA can be found in the circulation of cancer patients, fetal DNA may also be found in maternal plasma.