What is the purpose of cell-free foetal DNA screening?

Thanks to new tests that analyse foetal DNA from a mother’s blood sample, prenatal screening has changed drastically in the last decade.

Evidence of circulating free DNA in the blood dates back to the late 1940s, but it wasn’t until the late 1990s that the existence of cell-free DNA from the foetus became clear. Also known as cell-free foetal DNA, it is found in pregnant women in addition to the aforementioned circulating free DNA.

What is cell-free foetal DNA?

Cell-free foetal DNA are small fragments of DNA from cells in the placenta, which then shed into the mother’s bloodstream when they rupture. This can be detected from the sixth week of pregnancy, although it is recommended to wait until there are sufficient concentration levels in the tenth week before getting tested. It has a size of approximately 150 base pairs, which is slightly smaller than the body’s cell-free DNA. This scientific breakthrough marks a milestone in prenatal screening. 

What is combined first-trimester screening, aka triple screening?

Prenatal screening tests are performed during pregnancy and aim to determine any possible alterations during the pregnancy. 

Pregnant women undergo numerous tests designed to inform them about their health and the health of their future baby. For expectant mothers, one of the biggest concerns is knowing whether their baby is at risk of having a chromosomal abnormality.

We know that certain factors such as the mother’s age increases this risk, the older the mother, the greater the risk of the baby exhibiting a chromosomal abnormality. Adding other parameters to this information improves our ability to determine which women are most and least at risk.

Hence the creation of the combined first trimester screening, which analyses biochemical and ultrasound data alongside the mother’s age to determine the risk of chromosomal disorders such as Down’s syndrome.

Computer software calculates the risk using this test data. The test provides information that is statistically based on risk. If the risk is high, it must be followed up by a diagnostic test to verify whether or not the foetus has a chromosomal abnormality.

Diagnostic tests require a sample taken directly from the foetus using either chorionic villus sampling or an amniocentesis, both of which are invasive and pose a potential risk to the pregnancy.

While combined first trimester screening has greatly improved in detecting at-risk and non-risk women, the detection rate is 90% which means that the test will leave 10% of babies with a chromosomal abnormality unidentified. Furthermore, it is important to note that this test has a 5% false positive rate, i.e. 1 in 20 women will undergo an unnecessary invasive procedure following a false positive result. 

Foetal DNA and non-invasive prenatal testing

Non-invasive prenatal testing (NIPT) has revolutionised the clinical management of detecting foetal chromosomal abnormalities.

Using the NGS sequencing method, NIPT tests analyse the cell-free DNA in a pregnant woman’s blood, which contains both foetal and maternal DNA. This technology allows us to identify the following types of chromosomal abnormalities:

• Trisomy: there are three copies of a chromosome instead of the usual two. 
• Monosomy: there is an absence of one of the two copies of a chromosome. 
• Microdeletion: there is an absence of a small part of a chromosome. 

The most common chromosomal disorders are: 

• Down’s syndrome or trisomy 21: this is caused by an extra copy of chromosome 21. It is the most common chromosomal disorder and occurs in approximately 1 in 750 newborns. Children with this syndrome may have mild to moderate learning disabilities, along with other impairments.
• Edward’s syndrome or trisomy 18: This is caused by an extra copy of chromosome 18. It is less common than Down’s syndrome, occurring in an estimated 1 in 7,000 newborns. This disease is more severe, given that most newborns do not survive past the age of one.
• Patau syndrome or trisomy 13: this is caused by an extra copy of chromosome 13. It occurs in approximately 1 in 15,000 newborns. Just like Edward’s syndrome, most newborns do not survive past one year of age.
• Alterations in the sex chromosomes X and Y . The clinical impact of these are generally much less severe than what we see in trisomies. 

As a result of the wide range of NIPT tests on the market, it’s sometimes difficult for people to find the most suitable test for their situation. For example, some tests analyse microdeletions or other less common trisomies. Your doctor will be able to recommend the most suitable option for you. 

Foetal DNA-based testing has a 99%+ detection rate, with a false positive rate of less than 0.1%, which cuts the number of women undergoing unnecessary invasive procedures to 1 in 1,000. In short, these tests represent a significant improvement in common chromosomal disorder (trisomies 21, 18 and 13) screening programmes and have penetrated many national public health systems as a result.

As we have highlighted, these screening tests have a much higher detection rate, with very few false positives. So today, thanks to NIPT, we can obtain far more accurate results and reduce the number of invasive procedures taking place.  

It is important to note that NIPT tests are still screening tests, so a positive result will always need to be confirmed by a follow-up invasive procedure. 

Other uses for cell-free DNA

Just like we can find both maternal and foetal DNA in pregnant women’s blood, research in the late 1980s found that cancer patients had cell-free DNA from tumours in their blood samples. This discovery has led to significant progress in cancer patient care as well. A blood sample provides much of the same information as a biopsy would, eliminating the need for a much more invasive procedure on the affected tissue.

As you can see, cell-free DNA is also useful in oncology.

Technological advances

Foetal DNA testing is available today as a result of cutting-edge technological advances. These tests have a much greater accuracy than the combined first-trimester screening, thereby reducing the need for so many invasive procedures. 

Sequencing methods have improved significantly in recent years and, with the help of automation, have made these non-invasive prenatal tests more accessible.

At Veritas, we hope that this post has helped you understand what foetal DNA is, and how analysing it has been ground breaking in medicine. You can also contact us if you would like to receive more information about our myPrenatal test.

This article is based on the original article written by Maria Moreno, Medical Science Liaison Manager at Veritas Intercontinental.