Fetal RhD typing with free DNA in maternal plasma

Abstract

The finding of free fetal DNA (ffDNA) in the plasma of pregnant women was first reported by Lo et al in 1997. Considerable research has aided our understanding of this phenomenon. The source of the fetal DNA is probably the result of apoptosis of villous trophoblasts, either in situ or after they have entered the maternal circulation. The breakdown of intact fetal cells in the maternal circulation may also contribute to ffDNA. Total cell-free DNA is higher in maternal serum than plasma; however, similar levels of ffDNA are detected in both. FfDNA is demonstrable as early as 32 days of gestation and increases to comprise 3% of the total DNA pool in maternal plasma in the second trimester and increases to 6% in the late third trimester. After delivery by cesarean section, the mean half-life of ffDNA is 16 minutes, with no detectable levels by 2 hours after delivery in virtually all patients. FfDNA is elevated above norms in a variety of conditions, which include fetal trisomy 21 (2-fold increase), fetal trisomy 13, hyperemesis gravidarum, polyhydramnios, preeclampsia (5-fold increase), and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Levels in patients who ultimately have preeclampsia have been found to be elevated at 13 to 17 weeks of gestation, with a second rise 3 weeks before the onset of clinical symptoms. In the case of a heterozygous paternal genotype, pregnant women who are alloimmunized to the RhD red cell antigen are at risk to carry an affected fetus in only 50% of cases. Because, in the past, a method for the determination of the RhD type of the fetus was not