Noninvasive prenatal testing based on massively parallel sequencing (MPS) of cell-free DNA in maternal plasma has become rapidly integrated into clinical practice for detecting fetal chromosomal aneuploidy.
Whenever screening for trisomy is based on cell free fetal DNA (cfDNA), the fetal fraction should be above 10%. If it is less then 4%, the labs won't give a result but if it is between 4 and 10% you will still get a result which, however, is less reliable. A chromosome 21 comprises about 0.75% of the genome, disomy 1.5% and trisomy 21 2.25%, respectively. If the cfDNA concentration is 15% and if there is fetal trisomy 21, then 85% will be of maternal origin and disomic while 15% will be trisomic: 85% x 1,5% + 15% x 2,25% = 1.61% compared to 1.50%. If the fetal fraction is only 5%, then there will be only 1.54% of chromosome 21 DNA. That clearly indicates why the detection rates goes down. Wright et al. recently demonstrated that the detection rate for trisomy 21 in cases with fetal fractions of 9,8,7,6, 5% and 4% is 100%, 100%, 99,8%, 97,6%, 87,4% and 62,1%. On the webpage of Natera there is a graph indicating that about a fourth of all tests have a cfDNA concentration of less than 10%.
Thats why it is so important to focus on the fetal fraction when reading the report.
Hope this helps,
Best wishes
Oliver
and what do you think about confined placental mosaicism? because the (cfDNA) could be from placental tissue and not fetal? Is it ok or not?
All "fetal" or pregnancy DNA in the maternal system comes from the placenta. That's one of the main weaknesses of cfDNA testing. It cannot be better than a CVS. CVS was fully acceptable for now. But now as we discuss detection rates of more than 99% for a false positive rate of 0,1% these issues become relevant. That why the ideal would be to deal with fetal cells but that is still too far away.
Best wishes
Oliver
Karl Oliver do you have experience with fetal cells in transcervical cell
samples collected in the first trimester of pregnancy by two different procedures mucus collection and intrauterine lavage ?
Unfortunatelly not. I am more into first trimester screening based on ultrasound, serum biochemistry and nowadays cell free fetal DNA.
Only drawback i feel is that its screening & not diagnostic test ( though sensitivity is almost 99%)
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