Fetal aneuploidy screening: Clinical sciences

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. 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 46XXY, 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. 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.