Prenatal Genetic Testing for Fetal Chromosomal Differences: What is the Right Test for You?
Shannon M. Clark, MD
September 27, 2022
* UPDATED 10/2022
I know OBGYN appointments can sometimes be overwhelming or too short on time to get all of your questions answered about certain pregnancy-related topics. The topic of prenatal testing for fetal chromosomal differences (abnormalities) is one that definitely deserves more discussion!
If you have been offered this testing (via prenatal genetic screening or diagnostic testing), but declined because you were concerned about risks, fearful of the results, or even unsure of how the results would be used, this discussion is for you. If you are age 35 or over and considering trying to conceive or are newly pregnant, this information is also for you! I will try to answer questions that you might have to help you make an informed decision.
What is prenatal genetic testing?
Prenatal genetic testing for chromosomal differences is offered to all pregnant individuals in order to provide an assessment of the risk of carrying a fetus with a chromosomal difference (aka chromosomal abnormality, aneuploidy or disorder). This can involve prenatal genetic screening with a fetal ultrasound evaluation and maternal blood sampling, or prenatal genetic diagnostic testing with an amniocentesis (amnio) or chorionic villus sampling (CVS). The results can give parents-to-be and the obstetrical care team valuable information about whether the fetus has certain genetic disorders, chromosomal differences, or fetal abnormalities.
You are well within your rights to decline this testing, and you might even feel that they are not right for you because having a fetus with a chromosomal difference wouldn’t change your pregnancy decisions. Some feel that they shouldn’t do the testing because they would not terminate the pregnancy even if abnormalities were found. However, I highly recommend prenatal genetic screening because it is much easier to counsel a patient and discuss potential impact on the pregnancy, as well as future management options, by having this piece of information in the event that an abnormality is found on fetal ultrasound. It can also help you decide if you want to pursue prenatal genetic diagnostic testing via an amniocentesis or CVS. To discuss all the ins and outs of prenatal genetic screening, I spoke with genetic counselor, Liz Sheehan.
Timing: Can be done at any time but is ideally performed before pregnancy
Tests use blood or tissue sample
Detects whether you and/or your partner carry a mutation for a certain genetic disorder
First-Trimester Screening (NT +/- serum analytes)
Timing: 10–13 weeks
Blood test plus nuchal translucency (NT) ultrasound exam of the fetus
Screens for Down syndrome (trisomy 21) and trisomy 18
Integrated Screening and Sequential Screening
Timing: 10–22 weeks
Combines first-trimester and second-trimester screening
Screens for Down syndrome, trisomy 13, trisomy 18, and neural tube defects (NTDs)
Cell-free DNA Screening
Timing: 10 weeks and beyond
Screens for Down syndrome, trisomies 13 and 18, and sex chromosome abnormalities (like Turner Syndrome)
Second-Trimester Screening (quad screen)
Timing: 15–22 weeks
Screens for Down syndrome, trisomy 18, and NTDs
Basic or Detailed Ultrasound Exam
Timing: 18–22 weeks
Screens for some fetal physical defects
Types of prenatal genetic diagnostic testing
These tests are considered definitive, meaning they can tell you with certainty if the fetus has a chromosomal difference. These tests are invasive tests and do carry certain risks. Be sure to discuss these risks with your obstetrical care provider or a genetic counselor.
Timing: 10–13 weeks
Tests fetal cells in a sample of chorionic villi from the placenta
Detects Down syndrome, trisomy 13, trisomy 18, and inherited disorders
Does not test for NTDs
Timing: 15+ weeks
Tests fetal cells in a sample of amniotic fluid
Detects Down syndrome, trisomy 13, trisomy 18, and inherited disorders
Detects certain types of NTDs
Characteristics, advantages and disadvantages of prenatal genetic screening tests
Let’s talk about Down Syndrome
Why is age 35 significant? A person is born with all the eggs one will ever carry. As the eggs age with the individual, the higher the likelihood that the chromosomes will not split apart correctly once the egg has been fertilized, thus screening is highly recommended for those age 35 and over. Down Syndrome occurs when there are 3 instead of 2 copies of chromosome 21 in the fetus. We know that age plays a factor in some chromosomal differences, and you might already be familiar with age 35 and older being the age at which we start to see the chance chromosomal differences, like Down Syndrome, increase.
By understanding prenatal genetic testing for fetal chromosomal differences via prenatal genetic antenatal screening and diagnostic testing, I believe patients are more empowered and can better understand the situation if something is found on testing or ultrasound.
Summary of Recommendations from ACOG PB 226: "Screening for Fetal Chromosomal Abnormalities"
The following recommendations and conclusions are based on good and consistent scientific evidence (Level A):
Prenatal genetic screening (serum screening with or without nuchal translucency [NT] ultrasound or cell-free DNA screening) and diagnostic testing (chorionic villus sampling [CVS] or amniocentesis) options should be discussed and offered to all pregnant women regardless of maternal age or risk of chromosomal abnormality. After review and discussion, every patient has the right to pursue or decline prenatal genetic screening and diagnostic testing.
If screening is accepted, patients should have one prenatal screening approach, and should not have multiple screening tests performed simultaneously.
Cell-free DNA is the most sensitive and specific screening test for the common fetal aneuploidies. Nevertheless, it has the potential for false-positive and false-negative results. Furthermore, cell-free DNA testing is not equivalent to diagnostic testing.
All patients should be offered a second-trimester ultrasound for fetal structural defects, since these may occur with or without fetal aneuploidy; ideally this is performed between 18 and 22 weeks of gestation (with or without second‐trimester maternal serum alpha‐fetoprotein).
Patients with a positive screening test result for fetal aneuploidy should undergo genetic counseling and a comprehensive ultrasound evaluation with an opportunity for diagnostic testing to confirm results.
Patients with a negative screening test result should be made aware that this substantially decreases their risk of the targeted aneuploidy but does not ensure that the fetus is unaffected. The potential for a fetus to be affected by genetic disorders that are not evaluated by the screening or diagnostic test should also be reviewed. Even if patients have a negative screening test result, they may choose diagnostic testing later in pregnancy, particularly if additional findings become evident such as fetal anomalies identified on ultrasound examination.
Patients whose cell-free DNA screening test results are not reported by the laboratory or are uninterpretable (a no‐call test result) should be informed that test failure is associated with an increased risk of aneuploidy, receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing.
If an enlarged nuchal translucency or an anomaly is identified on ultrasound examination, the patient should be offered genetic counseling and diagnostic testing for genetic conditions as well as a comprehensive ultrasound evaluation including detailed ultrasonography at 18–22 weeks of gestation to assess for structural abnormalities.
The following recommendations and conclusions are based on limited or inconsistent scientific evidence (Level B):
The use of cell-free DNA screening as follow-up for patients with a screen positive serum analyte screening test result is an option for patients who want to avoid a diagnostic test. However, patients should be informed that this approach may delay definitive diagnosis and will fail to identify some fetuses with chromosomal abnormalities.
In clinical situations of an isolated soft ultrasonographic marker (such as echogenic cardiac focus, choroid plexus cyst, pyelectasis, short humerus or femur length) where aneuploidy screening has not been performed, the patient should be counseled regarding the risk of aneuploidy associated with the finding and cell-free DNA, quad screen testing, or amniocentesis should be offered. If aneuploidy testing is performed and is low-risk, then no further risk assessment is needed. If more than one marker is identified, then genetic counseling, maternal–fetal medicine consultation, or both are recommended.
No method of aneuploidy screening that includes a serum sample is as accurate in twin gestations as it is in singleton pregnancies; this information should be incorporated into pretest counseling for patients with multiple gestations.
Cell-free DNA screening can be performed in twin pregnancies. Overall, performance of screening for trisomy 21 by cell-free DNA in twin pregnancies is encouraging, but the total number of reported affected cases is small. Given the small number of affected cases it is difficult to determine an accurate detection rate for trisomy 18 and 13.
Because preimplantation genetic testing is not uniformly accurate, prenatal screening and prenatal diagnosis should be offered to all patients regardless of previous preimplantation genetic testing.
The following recommendations and conclusions are based primarily on consensus and expert opinion (Level C):
The use of multiple serum screening approaches performed independently (eg, a first-trimester screening test followed by a quad screen as an unlinked test) is not recommended because it will result in an unacceptably high positive screening rate and could deliver contradictory risk estimates.
In multifetal gestations, if a fetal demise, vanishing twin, or anomaly is identified in one fetus, there is a significant risk of an inaccurate test result if serum-based aneuploidy screening or cell-free DNA is used. This information should be reviewed with the patient and diagnostic testing should be offered.
Patients with unusual or multiple aneuploidies detected by cell-free DNA should be referred for genetic counseling and maternal–fetal medicine consultation.
With space and time to process the findings, many find a feeling of relief while feeling less worry and panic. Ask questions of your OBGYN, and if they cannot answer, ask to be referred to an MFM or genetic counselor.
Shannon M. Clark, MD, MMS is a double board certified ObGyn and Maternal-Fetal Medicine Specialist, and founder of Babies After 35. In her roles as a clinician, educator and researcher at UTMB-Galveston, she focuses on the care of people with maternal and/or fetal complications of pregnancy. Dr. Clark has taken a special interest in pregnancy after the age of 35, which according to age alone, is considered a high-risk pregnancy.