Clinical applications of fetal DNA analysis in maternal plasma

Several applications of clinical interest to fetal DNA testing in maternal plasma have been described. These would be an alternative to invasive antenatal diagnostic methods, which generally carry a risk of fetal loss. In the future, it will be possible to non-invasively diagnose a number of diseases, such as ß-thalassemia (an hereditary type of anaemia), achondroplasia (nanism), and even Down Syndrome. It is believed that, in the future, this type of tests will replace amniocentesis (collection of amniotic fluid) for evaluation of the fetal status.
GeneLab is now developing a test for determining Rh (D) genotype by molecular techniques, which will be available in 2007.


Fetal RhD group determination

The determination of fetal RhD blood group in cases where the pregnant woman is RhD negative, with a risk of haemolytic disease of the newborn, is currently one of the most relevant clinical applications (Finning et al.,2004). Approximately 10-15% of the pregnant women are RhD-negative, and generally receive prophylactic treatment with human immunoglobulin to prevent anti-RhD antibodies that may be produced by the mother reacting with fetal erythrocytes. However, should fetal RhD group also be negative, prophylaxis with immunoglobulin is unnecessary and can be avoided. Determination of fetal RhD group by non-invasive procedures will make it possible to restrict antenatal prophylaxis to RhD-negative pregnant women who carry RhD-positive foetuses.


Preeclampsia

This pathology affects 6-8% of pregnant women and presents as high blood pressure and oedema in the beginning of the 2nd half of the pregnancy. It has been described that symptomatic pregnant women suffering from preeclampsia have 5 times more fetal DNA in their blood circulation. Further, asymptomatic pregnant women who subsequently developed preeclampsia have a higher amount of plasmatic DNA (Leung et al., 2001; Levine et al., 2004). Therefore, quantification of fetal DNA in maternal plasma may be a prognostic factor for preeclampsia in risk pregnancies.


Trisomy screening

A significant increase in fetal DNA concentration in maternal circulation was seen in pregnancies of foetuses with chromosomal anomalies, such as trisomy 21 and trisomy 13. This direct correlation may have implications in routine antenatal screening of these aneuploidies. In the future, this screening may have fetal DNA quantification included in the array of tests for the pregnant woman as a prognostic marker of risk situations (Farina et al.,2003).


Investigation of genetic disorders inherited from the father

By means of free fetal DNA testing in maternal plasma it is possible to identify alleles of paternal origin (which normally do not exist in maternal blood) and thereby identify foetuses at risk of developing genetic disorders inherited from the father. The detection of an allele of paternal origin with a mutation associated with Myotonic Dystrophy by means of fetal DNA in maternal blood testing was reported (Amicucci et al.,2000) In risk pregnancies for cystic fibrosis or beta-thalassaemia, the antenatal fetal assessment by fetal DNA testing in maternal plasma was also described (González et al.,2002; Chiu et al., 2002b). In another instance, the gene mutation which causes achondroplasia (nanism) was investigated in fetal DNA obtained from maternal blood (Chiu et al.,2002b).