In less than a decade, prenatal screening has changed dramatically thanks to the introduction of tests that analyze fetal DNA in a blood sample from the mother.

The first evidence of the presence of free DNA circulating in the blood of any individual dates back to the late 1940s, but it was not until the late 1990s that it was discovered that in pregnant women in addition to their own free DNA, there was also free DNA from the fetus, also known as fetal free DNA.

What is fetal DNA?

The fetal DNA or fetal free DNA are small fragments of the DNA from cells of the placenta that, breaking, spill their contents into the bloodstream of the mother. It can be detected from week 6 of gestation, although it is recommended to wait until week 10 for the concentration to be sufficient to carry out tests. Its approximate size is about 150 base pairs, slightly smaller than the free DNA of the organism. This scientific advance has marked a before and after in prenatal screening.

What is combined first-trimester screening, also known as triple screening?

Screening or prenatal screening tests are carried out during pregnancy and are intended to determine the possibility of presenting any alteration during pregnancy.

Pregnant women undergo numerous tests that provide information about their health and that of the future baby. One of the biggest concerns that future mothers have is knowing the risk that the fetus has of presenting a chromosomal alteration.

In this sense, we know that certain factors increase this risk, such as maternal age, the older the mother is, the greater the risk that the future baby will present some chromosomal alteration. If we add other parameters to this maternal characteristic, the ability to determine which women are at higher risk and which are less at risk is improved.

This is the basis for the combined first-trimester screening, which analyzes biochemical and ultrasound factors along with the mother’s age to determine the risk of chromosomal abnormalities such as Down syndrome.

With the data obtained in the tests, a risk calculation is made using computer software. As we see, the information provided by this test is a risk-based on statistics and if it is a high risk, a diagnostic test must be performed to verify whether or not the fetus has the chromosomal alteration.

Diagnostic tests require obtaining a sample directly from the fetus through a chorionic villus biopsy or amniocentesis, both processes are invasive and are not without risk for pregnancy.

Although combined first-trimester screening has greatly improved the ability to detect women who are at risk and those who are not, the detection rate is 90% which means that 10% of women who have a fetus with a chromosomal abnormality will not be identified with the test. In addition, another important fact is that this test has a 5% false-positive rate, that is, 1 in 20 women undergoes an unnecessary invasive procedure.

Fetal DNA and Non-Invasive Prenatal Testing

The prenatal testing noninvasive or NIPT (of the English non-invasive prenatal test ) have revolutionized clinical management as it relates to the detection of chromosomal abnormalities in the fetus.

NIPT tests analyze free DNA in the pregnant woman’s blood, which contains DNA of both fetal and maternal origin, using the NGS sequencing technique. With this technology we can identify the following types of chromosomal alterations:

• Trisomies: the presence of three copies of a chromosome instead of the two expected copies.
• Monosomy: the absence of one of the two copies of a chromosome.
• Microdeletion: the absence of a small part of a chromosome.

The most frequent chromosomal alterations are:

• Down syndrome or trisomy 21: This is due to an extra copy of chromosome 21. It is the most common type of chromosome alteration and occurs in about one in every 750 newborns. Children with this syndrome may have mild to moderate intellectual disability, along with other disorders.
• Edwards syndrome or trisomy 18: This is due to an extra copy of chromosome 18. It is less common than Down syndrome since it is estimated to occur in 1 in 7,000 newborns. This pathology is more severe since most newborns do not survive the first year of life.
• Patau syndrome or trisomy 13: This is due to an extra copy of chromosome 13. The frequency is approximately 1 in 15,000 newborns. As in the previous case, most newborns do not survive the first year of life.
• Alterations on the sex chromosomes X and Y. The clinical consequences are generally much less severe than in the case of trisomies.

Today we can find a very wide range of NIPT tests on the market, which often makes it difficult to know which is the most appropriate. For example, there are some tests that include analysis for microdeletions or other less frequent trisomies. In these cases, your doctor will be the one who can best guide you on which is the most appropriate in your case.

Tests based on fetal DNA analysis have a detection rate greater than 99%, with a false positive rate of less than 0.1%, reducing the number of women who undergo an unnecessary invasive procedure to 1 in every 1,000. Ultimately, these tests represent a substantial improvement in the screening programs for the most frequent chromosomal diseases (trisomies 21, 18, and 13), which is why they have become part of many public health systems in different countries.

As we can see, these screening tests have a much higher detection rate, with very few false positives, so today, thanks to NIPT we can obtain much more precise results by reducing the number of invasive procedures. 

It is important to note that NIPT tests are still screening tests, therefore, in the event of a positive result, the result must always be confirmed by an invasive procedure.

Other applications of free DNA

In the same way that in the blood of pregnant women we can find DNA from both the mother and the fetus, in the late 1980s, it was discovered that cancer patients had free DNA from the tumor in their blood samples. This discovery has also meant an advance in the medical care of cancer patients since with a blood sample we can obtain much of the information obtained with a biopsy of the affected tissue but without the need to perform a procedure that is much more invasive for the patient.

As we can see, free DNA also has an application in the field of oncology. 

Technological advance

Technological advancement has been fundamental so that today we can have fetal DNA tests, much more accurate than the combined first-trimester screening, which reduces the number of invasive procedures.

In recent years, sequencing techniques have been significantly improved and, thanks to automation, have made these non-invasive prenatal tests more accessible