Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism.

F etal cells are consistently found in the maternal circulation, and polymerase chain reaction based studies have led to the identification of cell free fetal DNA (fetal DNA) in maternal blood. Approximately 1.2 nucleated fetal cells/ml of whole blood from women carrying a male fetus were detectable, and relative enrichment of fetal DNA was detected in the maternal plasma and serum. The amount of fetal DNA in the maternal blood increases with progression of pregnancy, and 3.4–6.2% of the total maternal plasma DNA during pregnancy was of fetal origin. Therefore, cell free fetal DNA in pregnant women’s plasma is useful for noninvasive prenatal diagnosis, especially for detection of fetal sex, 4 RhD blood type, and gene mutations of paternal origin. Previous studies indicated that pregnant women with pre-eclampsia, placenta previa and fetal chromosome abnormalities tend to have elevated levels of fetal DNA in their plasma. Since functional or structural abnormalities of the placenta and destruction of the trophoblast may be associated with these diseases, it is suggested that cell free fetal DNA is of placental origin. This implies that quantitative analysis of fetal DNA may be valuable to screen for placental dysfunction. Ng et al recently reported that placental mRNA is present in the maternal circulation, and suggested that the same might occur for placental DNA, However, no direct evidence has been given for placenta derived cell free fetal DNA in the maternal blood, although its clinical use is growing. Confined placental mosaicism, which is defined by the presence of abnormal karyotypes only in the placenta while the fetus itself is usually diploid, may occur through a loss of the extra chromosome in a trisomic zygote during an early mitotic cell division in only the embryonic progenitor cells (trisomic rescue) or through a postzygotic mitotic duplication of one chromosome in only the progenitors of the placenta cell lineage in the developing normal diploid conceptus. Confined placental mosaicism has been reported to be detected in 1–2% of chorionic villus samples at 10–11 weeks of gestation, and in over 20% of pregnancies with intrauterine growth retardation of unknown cause. If a trisomic allele is detected in maternal plasma with confined placental mosaicism, this is direct evidence for placental DNA in the maternal circulation. Here we report the result of a study that supports the presence of placental DNA in maternal plasma.