Fetal aneuploidy screening: Clinical sciences

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Introduction0:00–0:44

Fetal aneuploidy screening refers to non-invasive testing that assesses the risk of chromosomal abnormalities present in a fetus.
Many gestations affected by aneuploidy result in nonviable pregnancies and subsequent miscarriages. However, for pregnancies that result in live-born neonates, aneuploidy may lead to congenital birth defects, intellectual disability, failure to thrive, infertility, and a shortened lifespan.
Fetal aneuploidy screening should be offered to all patients during their pregnancy. Also keep in mind that aneuploidy screening is not required and some patients may decline screening, even after thorough counseling.
When your patient presents for fetal aneuploidy screening, start by obtaining a focused history and ultrasound.Starting with the history, assess your patient's age, particularly noting if they are over 35 years old, which is considered advanced maternal age, as the risk of chromosomal abnormalities increases in this group.

History and US0:44–2:11

Also, confirm your patient's estimated delivery date, or EDD, as screening tests must be performed during specific gestational times.
Some patients may report a history of early pregnancy loss or a prior pregnancy affected by a chromosomal abnormality, both of which can increase the risk of aneuploidy.
Additionally, assess if your patient has a personal history of a chromosomal abnormality. Next, obtain an ultrasound and confirm the presence of a viable intrauterine pregnancy, or IUP.
If a viable IUP is not confirmed, you may choose to hold off on aneuploidy counseling until early pregnancy loss is ruled out.
Here’s a clinical pearl: The most common autosomal chromosomal aneuploidies in live-born infants are Down syndrome or trisomy 21; Edward syndrome, also known as trisomy 18; and Patau syndrome, or trisomy 13.
Klinefelter syndrome, or 46XYY, is the most common sex chromosome aneuploidy, while Turner syndrome, or 45 X, is the only viable monosomy.
Now it’s time to counsel your patient on the available aneuploidy screening options. Remember, screening should be offered to all patients regardless of their age or individual risk of aneuploidy.

Counseling2:11–7:26

Begin by educating your patient on their specific risk of carrying a fetus affected by aneuploidy and counsel them that positive screening results require further diagnostic testing for confirmation with chorionic villus sampling or amniocentesis, both of which are invasive tests.
Explain all available screening options, which include ultrasound assessment of nuchal translucency, either alone or in conjunction with serum screening; single point-in-time testing, or one-step screens; and combined screening tests in which samples are obtained in the first and second trimesters.
The choice of which test to perform depends on many factors including the patient’s age, gestational age, cost, availability, and preference, as well as positive and negative predictive value of each option.
Okay let’s start with the nuchal translucency, or NT scan, which is sonographic measurement of the fluid-filled space normally seen on the dorsal aspect of the fetal neck.
An enlarged NT scan measuring at least 3 millimeters or above the 99 percentile for crown-rump-length are associated with fetal aneuploidy and structural abnormalities.
NT evaluation is performed between 10 and 14 weeks and can be used either as a solo test or as part of a serum screen. NT testing can assess individual fetuses in multifetal gestations, providing an opportunity to screen for additional fetal anomalies.Next, let’s look at one-step screening options starting with cell-free DNA.
Cell-free DNA testing is based on the fact that fetal cells circulate within the maternal bloodstream. The test involves obtaining a maternal blood sample and then analyzing small segments of fetal DNA.
In addition to screening for aneuploidy, this test can also determine fetal sex, Rh status, and certain autosomal dominant conditions.
Cell-free DNA testing is performed as early as 9 weeks of gestation and can be continued throughout the pregnancy. First trimester screening measures serum analytes, specifically free beta-hCG and pregnancy-associated plasma protein A analyte, or PAPP-A, in conjunction with NT testing.
The final risk assessment is calculated based on the test results along with maternal factors such as age, history of aneuploidy, weight, race, and number of fetuses.
This test is performed between 10 and 14 weeks gestation. Lastly, the quadruple screen, or quad screen, assesses four serum analytes including hCG; alpha fetoprotein, or AFP; inhibin A; and unconjugated estriol.
It provides information on the risk of aneuploidy and open neural tube defects such as spina bifida. This test is performed between 15 and 23 weeks of gestation.
Now, there are also combined first and second trimester screens. Integrated screening involves completing NT testing and a serum analyte screen for free beta-hCG and PAPP-A in the first trimester; then a quad screen is done in the second trimester.
The patient receives the combined results in the second trimester. If ultrasonography is not available to perform the NT or if the measurements are inaccurate due to maternal body habitus or fetal position, you can offer a serum integrated screen instead, which is a combination of the first and second trimester serum analytes.
Another combined test is the contingent screen, which offers the patient the results after each lab draw. Specifically, it starts with NT measurement and first trimester analyte screening for free beta-hCG and PAPP-A.
Then, based on the results, patients are classified as low, intermediate, or high risk of aneuploidy. Follow-up testing involves either a quad screen in the second trimester, diagnostic testing, or cell-free DNA testing.
Lastly, a similar combined test is the sequential stepwise screen. This test includes a first trimester NT testing and serum analyte screening for free beta-hCG and PAPP-A.
Assessment of first trimester results determines the next step which is either a second trimester screening via the quad screen or additional diagnostic testing.
Okay, let’s talk about some considerations to keep in mind when counseling your patient about these tests. Tests with the highest detection rates include cell-free DNA, integrated, contingent, and sequential stepwise screening.
Tests that provide results in the first trimester, have the advantage of allowing more time for confirmatory testing and subsequent management; these include NT only, cell-free DNA, first trimester screening, and some combined screening tests.
However, keep in mind that NT alone has both poor sensitivity and specificity. Tests that avoid the use of ultrasound include cell-free DNA, quad, or serum integrated screening.
After adequate counseling and through shared decision making, your patient will decide which screening option is best for them, including opting out of screening if desired.Now, if your patient prefers the NT only option, obtain the NT measurement.

NT only7:26–8:01

If the result is normal, or negative, counsel your patient on the residual risk of aneuploidy, which is the probability that aneuploidy is present despite the negative test.
Due to its poor sensitivity and specificity, your patient may want to consider additional screening as well. If the result is positive, you should definitely refer your patient for genetic counseling, obtain a comprehensive ultrasound to assess for other structural abnormalities, and consider further screening or confirmatory diagnostic testing.
Well, what if your patient prefers one-step serum testing? If your patient prefers a one-step test be sure to obtain their blood work for cell-free DNA, first trimester serum analyte screening for free beta-hCG and PAPP-A, and a quad screen at the correct gestational age and then interpret the results.

One-step8:01–8:34

If the result is negative, counsel them on the residual risk of aneuploidy; if the result is positive, refer them to genetic counseling, obtain a comprehensive ultrasound, and offer confirmatory diagnostic testing.
Now if your patient prefers a combined screen, assess which specific option they’d like to pursue. If either integrated or serum integrated screening is chosen, review results after the second trimester lab evaluation.

Combined8:34–9:41

Negative results of either screening option require counseling on the residual risk of fetal aneuploidy; whereas positive results require referral to genetic counseling, a comprehensive ultrasound, and consideration for confirmatory diagnostic testing.If your patient prefers contingent screening, begin by assessing their first trimester results.
For low risk results, no further testing is indicated. For intermediate risk results, proceed with a second trimester screen.
For high risk results, consider diagnostic testing or cell-free DNA; and offer genetic counseling. Finally, if your patient prefers sequential stepwise screening, begin by assessing their first trimester results.
Patients with a negative result will proceed with second trimester screening, while those with positive results should consider diagnostic testing and genetic counseling.Alright, as a quick recap… Fetal aneuploidy screening assesses the risk of an individual pregnancy having a chromosomal abnormality.

Review9:41–10:14

These non-invasive screening tests may include measurement of the nuchal translucency on ultrasound, a one step serum analyte test, or a combined first and second trimester assessment.
Positive results need a comprehensive ultrasound, referral to genetic counseling, and consideration for invasive diagnostic testing for confirmation.
Patients with negative results need counseling on their residual risk, and they may also choose diagnostic testing.
Fetal aneuploidy screening: Video, Steps, and Uses | Osmosis