Cell Free Fetal DNA

Historically when there was a high risk of a child being born with a genetic disease, the options for prenatal testing were both invasive: chorionic villus sampling (CVS) and amniocentesis.

NIPT, non-invasive prenatal diagnostic testing, involves taking a blood sample from the mother and examining the small amounts of circulating fetal DNA that can be found in the mother’s blood.

Cell-Free DNA and Cell-Free Fetal DNA

When cells die, fragments of DNA are shed and can be found in the bloodstream- this is cell-free DNA (cf-DNA). Pregnant women have not only their own cf-DNA, the vast majority, but also some from dead placental cells which have fetal DNA, cell-free fetal DNA (cff-DNA). The challenge is differentiating what is the mother’s cf-DNA and what is fetal cf-DNA, as any testing relies on there being a difference between these.

The analysis of these off-DNA fragments is the basis of both Non-invasive prenatal diagnosis (NIPD) and Non-invasive prenatal testing (NIPT).

NIPD is the use of cff-DNA as a diagnostic test, a follow-up invasive test is not felt necessary. This can be used for certain single-gene disorders (e.g. CF and Huntington disease) and fetal sex determination for X-linked conditions (e.g. Duchenne Muscular Dystrophy, congenital adrenal hyperplasia).

NIPT is essentially the same process but the test isn’t considered diagnostic and subsequent confirmatory testing needs to be performed. (e.g. chromosomal number disorders like Down and Edwards trisomies).

Details of what tests are available and for what can be found in the National Genomic test directory for England.

This use of cell-free DNA for diagnosis relies on similar technology to cancer-cell free tumour DNA (ctDNA) liquid biopsies, as discussed in week 1.

Fetal Sex Determination

In families affected by serious X-linked conditions such as Duchenne muscular dystrophy, cff-DNA can be examined for the presence of certain genes that are only found on the Y chromosome. If a Y chromosome is found then the fetus is male.