Current methods of fetal diagnostic testing involve obtaining samples of amniotic fluid (amniocentesis), placenta (chorionic villus sampling) or fetal blood or tissues. However, fetal blood or tissue is rarely used as it puts the fetus at risk of injury. Due to this risk, development of rapid, safe, effective and non-invasive prenatal tests have been an area of research. Fetal genetic material can be found in maternal circulation as early as the first trimester and this discovery has been very promising in the abilities to screen for fetal disease.
Cell free fetal DNA testing, also known as noninvasive prenatal testing (NIPT) has been commercially available since 2011. Current tests on the market include verifi ®, harmony ®, and MaterniT21 ®. These tests require a simple blood draw at 10 weeks gestation or later. Routine testing includes an assessment for Down’s syndrome (Trisomy 21) and two other genetic abnormalities considered to be more severe than Down’s syndrome called trisomy 18 and trisomy 13. Aneuploidy is the term used to describe the presence of an abnormal number of chromosomes in a cell. These tests can also provide an assessment of sex chromosomes/gender and some rare disorders associated with sex chromosomes such as Turners Syndrome. The results are usually available within two weeks and there is a 2-4 % chance that there will not be a sufficient amount of fetal genetic material resulting in a “no-call” result.
It is important to understand that these tests are considered “screening” tests or a risk assessment rather than a “diagnostic” test. Any abnormal result should be confirmed by a diagnostic test such as amniocentesis. The laboratories that initially developed noninvasive testing conducted their research in a population of women over the age of 35. Women age 35 and older are considered to be at increased risk for a chromosomal abnormality. The rationale for this was to improve the likelihood of detecting the condition and avoiding a false positive or a false negative test result. A false negative result is when the test is falsely interpreted to be negative when indeed the fetus is positive. A false positive test result is when the test is falsely interpreted as positive when indeed the fetus is negative. It is also very important to understand that these tests have not been studied as extensively in the lower risk population (e.g., women under the age of 35). Conventional screening tests such as the first trimester (nuchal translucency) or quadruple screen are better validated in the low risk population. Because of these principles, the American College of Obstetrics and Gynecology governing body (ACOG) has just released an update opinion on the appropriate use of cell free fetal DNA testing. The recommendations are as follows:
- Given the performance of conventional screening methods, the limitations of cell-free DNA screening performance, and the limited data on cost-effectiveness in the low-risk obstetric population, conventional screening methods remain the most appropriate choice for first-line screening for most women in the general obstetric population.
- Although any patient may choose cell-free DNA analysis as a screening strategy for common aneuploidies regardless of her risk status, the patient choosing this testing should understand the limitations and benefits of this screening paradigm in the context of alternative screening and diagnostic options.
- The cell-free DNA test will screen for only the common trisomies and, if requested, sex chromosome composition.
- Given the potential for inaccurate results and to understand the type of trisomy for recurrence-risk counseling, a diagnostic test should be recommended for a patient who has a positive cell-free DNA test result.
- Parallel or simultaneous testing with multiple screening methodologies for aneuploidy is not cost-effective and should not be performed.
- Management decisions, including termination of the pregnancy, should not be based on the results of the cell-free DNA screening alone.
- Women whose results are not reported, indeterminate, or uninterpretable (a “no call” test result) from cell-free DNA screening should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy.
- Routine cell-free DNA screening for microdeletion syndromes should not be performed.
- Cell-free DNA screening is not recommended for women with multiple gestations.
- If a fetal structural anomaly is identified on ultrasound examination, diagnostic testing should be offered rather than cell-free DNA screening.
- Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy.
- Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects; patients who are undergoing cell-free DNA screening should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment.
Patients may decline all screening or diagnostic testing for aneuploidy.
Simply put, this is exciting technology- but as with any test there are limitations. Furthermore, as it introduced into practice more information is gathered to help modify guidelines and appropriate usage. Talk to your provider to see if cell free DNA testing is a consideration for you and your pregnancy.
Kathryn Goralski, M.D., F.A.C.O.G
American College of Obstetrics and Gynecology Committee Opinion #640, ”Cell-Free DNA Screening for Fetal Aneuploidy” July 2015