CELL-FREE FOETAL DNA IN NIPT

What is cell-free DNA?

Cell-free DNA (cfDNA) is the population of DNA that circulates in the bloodstream, but which is not contained within a cell. Cell-free DNA arises from the lysis of cells undergoing apoptosis, which occurs naturally in all humans.

What is cell-free foetal DNA?

Cell-free foetal DNA (cffDNA) originates from apoptosing trophoblastic cells of the placenta. These apoptosing cells release foetal DNA into the maternal bloodstream, which is referred to as cell-free foetal DNA. Foetal fraction is the amount of the cell-free DNA in the maternal bloodstream that is of foetal origin. The American College of Obstetricians and Gynaecologists noted that 3–13% of circulating cell-free DNA is of foetal origin at 10 weeks’ gestation. Several studies have noted that there is a large variance in the fraction of cffDNA between patients (see graph below).

Low Foetal Fraction

Low foetal fraction is associated with high maternal body-mass index and certain foetal aneuploidies.² Not all Non-Invasive Prenatal Testing (NIPT) technologies can detect aneuploidies at low foetal fractions.

The power of Whole Genome Sequencing (WGS), the technology used by TriScreen NIPT, can detect aneuploidy at foetal fractions as low as 2%.3 In a recent study, comparing WGS and SNP based NIPT technologies, the WGS method maintains high specificity and can detect a higher proportion of aneuploidies in low foetal fraction samples.²

Further studies have shown that the sensitivity and specificity of WGS NIPT were not influenced by low foetal fraction.³

1. References:

1. Wang et al. Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma. Prenat Diagn. 2013 Jul;33(7):662-6. doi: 10.1002/pd.4119. Epub 2013 May 9.
2. Artieri et al. Noninvasive prenatal screening at low fetal fraction: comparing whole-genome sequencing and single-nucleotide polymorphism methods. Prenat Diagn. 2017 May;37(5):482-490. doi: 10.1002/pd.5036. Epub 2017 Apr 26.
3. Fiorentino et al. The importance of determining the limit of detection of non-invasive prenatal testing methods. Prenat Diagn. 2016 Apr;36(4):304-11. doi: 10.1002/pd.4780. Epub 2016 Feb 21.