Using Cell-Free DNA Analysis to Test for Fetal Aneuploidy

Screenings for fetal aneuploidy have seen some significant advances in recent years. Fetal aneuploidy occurs when there is an abnormal number of chromosomes present, rather than the usual 23 pairs. One of the most common types of fetal aneuploidy is trisomy, where there are three copies of a chromosome instead of two, such as Tisomy 21, also known as Down Syndrome.

Routine screenings for several trisomies include ultrasounds and blood tests in the first trimester, but conventional prenatal diagnosis is determined via chorionic villus sampling or amniocentesis, invasive procedures that can increase a woman’s chance of miscarriage. However, in 2011, cell-free DNA analysis became clinically available, giving women a non-invasive prenatal screening option. Both the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine now recommend cell-free DNA analysis to screen for fetal aneuploidy for women who have an increased risk of fetal aneuploidy.

What Does Cell-Free DNA Screening Tell Us?

During pregnancy, there are cell-free DNA fragments from both the mother and the fetus present in maternal circulation. Cell-free DNA analysis can detect increased amounts of chromosomal material in maternal blood, with testing possible as early as 10 weeks of pregnancy. The test will only screen for the common trisomies (trisomy 13, 18 and 21), and can screen for sex chromosome composition if requested.

The use of cell-free DNA as a screening test for fetal aneuploidy has been validated by a number of laboratories using different techniques. It’s important to note that regardless of which molecular technique is used, all tests have a high sensitivity and specificity for trisomy 18 and trisomy 21.

In cases where the woman’s cell-free DNA screening test results are uninterpretable, not reported or indeterminate, further genetic counseling and testing should be offered to the patient because of an increased risk of aneuploidy. The testing would include a comprehensive ultrasound evaluation along with diagnostic testing.

How To Counsel Patients On Cell-free DNA Screenings

When discussing cell-free DNA analysis with patients, it should be carefully explained that the screening does not replace the precision that is obtained with diagnostic tests. To be more specific, this includes tests such as chorionic villus sampling or amniocentesis. As a result, the cell-free DNA test has limitations, such as a limited ability to identify all chromosome abnormalities.

Additionally, cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. It is wise to inform patients who are undergoing cell-free DNA screening that they should also have a maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment.

The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Therefore, decisions including the termination of a pregnancy, should not be strictly based on the results of a cell-free DNA screening alone. Patients should be informed that a negative cell-free DNA test result does not ensure a normal pregnancy.

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