Prenatal diagnosis refers to the process of diagnosing anomalies, genetic disorders, and certain other conditions present in the fetus during pregnancy using various methods such as ultrasound, Doppler, and genetic testing.

Today, a definitive diagnosis of chromosomal abnormalities such as Down syndrome is made through genetic testing of fetal or placental tissue obtained via invasive procedures. Because invasive procedures carry certain risks, screening tests are used to identify fetuses at high risk for chromosomal abnormalities such as Down syndrome, trisomy 13, and trisomy 18.

During pregnancy, screening tests for certain genetic disorders are performed to identify affected fetuses and, with the family’s consent, terminate these pregnancies. If the family does not wish to terminate the pregnancy, it is possible to manage the pregnancy and delivery in the best possible way for both the mother and the fetus, since the fetal abnormality is known. Furthermore, a normal screening test result reassures the family—especially in cases where the risk of chromosomal abnormalities is high, such as advanced maternal age or a family history of such conditions—and provides assurance that the fetus is normal with respect to the condition being screened for. The higher the detection rate of the screening test for the specific condition being screened for, the more effectively the family’s concerns will be alleviated.

With the introduction of screening tests for chromosomal abnormalities, it has become easier for families at high risk of having a baby with a chromosomal abnormality to have a healthy baby, and the burden on society of chromosomal abnormalities compatible with life—such as Down syndrome—has been reduced.

If a chromosomal abnormality screening test yields a positive result—that is, if a high risk is identified for the condition being screened for—this must be confirmed through invasive procedures such as chorionic villus sampling (CVS) or amniocentesis. These procedures carry a risk of causing a miscarriage in about 0.5–1% of cases and, although rare, may harm the fetus. Additionally, they impose a financial burden and cause anxiety for the pregnant woman and her family. In particular, amniocentesis can be performed at a later stage of pregnancy. These drawbacks of invasive procedures have driven the search for highly reliable, non-invasive tests, leading to the development of non-invasive prenatal testing (NIPT).

NIPT is a new genetic testing method that uses cell-free fetal DNA (cffDNA) obtained from the pregnant woman’s plasma. For this reason, NIPT is also known as the cell-free fetal DNA test or fetal DNA test. Cell-free fetal DNA can be detected in the pregnant woman’s bloodstream as early as the 7th week, and the test can be performed starting at the 9th week of pregnancy. Commercial kits recommend performing the test starting at the 10th week.

The amount of cell-free fetal DNA (ffDNA) and cell-free fetal RNA (ffRNA) found in the mother’s blood constitutes a small fraction of the total cell-free nucleic acids. However, this amount is sufficient for diagnostic purposes. By isolating and amplifying the low levels of fetal DNA in the mother’s blood and performing next-generation sequencing, genetic abnormalities in the fetus can be identified. This process currently takes 7 to 14 days.

NIPT is commercially used to detect trisomies 13, 16, 18, 21, and 22; sex chromosome abnormalities; fetal sex; fetal blood type (RHD); and certain microdeletions.

One of the most significant advantages of NIPT is that, as a screening test, it has very high detection rates for abnormalities and therefore significantly reduces the need for invasive procedures; when used as a diagnostic test, the Non-Invasive Prenatal Test (NIPT) is a screening test performed during the period when fetal DNA is present in the mother’s blood. Unlike invasive and risky procedures such as amniocentesis, this test—which is performed by simply drawing a tube of blood from the expectant mother—enables the detection of chromosomal abnormalities such as Patau syndrome, Edwards syndrome, and Down syndrome in the early stages of pregnancy.

It eliminates the need for invasive procedures. For this reason, it is recommended that NIPT be used as a second-line screening test to reduce the need for invasive procedures—such as amniocentesis and CVS—which are required for definitive diagnosis in pregnancies where the risk of chromosomal abnormalities is assessed as high based on indicators such as serum biochemical tests, ultrasound, or maternal age.

Another key advantage of NIPT as a screening test is that it provides results early in pregnancy. It is clear that obtaining information about the fetus’s genetic makeup through NIPT during the first three months of pregnancy will give families more time to decide how to manage the pregnancy or whether to terminate it; and it is clear that it will allow families to have more time to prepare for the care of a baby requiring special care.

Reference:

Atar S, Yalım NY. Turkish Journal of Bioethics, 2019, Vol. 6, No. 1, pp. 26–33.