Introduction

The confirmation of the presence of fetal cells in maternal circulation caused a stir in the current scientific community, because of its potential for the development of safer or even totally harmless antenatal diagnostic methods. However, this possibility requires collecting nucleate cells of fetal origin, which are present in maternal circulation, though in small amounts. Given this limitation and the absence of specific markers for these cells, other approaches have been explored which will allow testing fetal products.

In 1998, Lo and collaborators proved that there is free fetal DNA in the plasma of healthy pregnant women by quantifying this DNA through PCR (amplification chain reaction). Surprisingly, and unlike intact fetal cells which exist in maternal plasma (1 cell per ml of maternal blood), high levels of fetal DNA were found, amounting to approximately 5% of the total maternal DNA. The origin of free fetal DNA in circulation in maternal plasma is still unknown, but it will most probably come from the placenta (Wataganara and Bianchi, 2004).
Unlike fetal cells, which remain in maternal circulation after birth for long periods, free fetal DNA is rapidly eliminated after the child’s birth (Lo et al., 2003). This is essential for ensuring the accuracy of any antenatal test, because the assayed material does not come from previous pregnancies.

The development of new fetal DNA quantification and analysis in maternal blood opened new perspectives for diagnostics in antenatal medicine. Currently, it is possible to determine fetal sex for investigation of foetuses with high risk of developing diseases, such as congenital adrenal hyperplasia or X-linked hereditary diseases (Costa et al., 2002). On the other hand, it is also possible to investigate genetic disorders inherited from the father by testing whether maternal plasma contains mutated alleles. Another application for fetal DNA test in maternal blood is determining of the fetal RhD group in RhD-negative pregnant women for prevention of the haemolytic disease of the newborn. Finally, this technology will allow the non-invasive diagnostic of frequent aneuploidies, such as trisomy 21, trisomy 13, or trisomy 18. This opens up the possibility of developing other highly useful clinical applications of fetal DNA test technologies in maternal blood.