Topic: Information Point: Screening Copy

Screening Tests for Down syndrome

First Trimester Screening Tests

The patient in this video had a first trimester screening involving the assessment of the levels of one or more analytes (PAPP-A and typically free beta HCG) and a measure of “nuchal translucency” through the use of ultrasound. The nuchal translucency is simply a normal aspect of the fetal anatomy, which is determined in the neck and under a very carefully controlled set of anatomic and technical circumstances. The sensitivity of first trimester nuchal translucency in conjunction with analytes is thought to be in the range of 82 to 87%, set for a false positive rate of 5% (ACOG, 2016).

Non-Invasive Prenatal Screening Tests

There are also newer non-invasive prenatal screening tests that can be done after 9 or 10 weeks. These tests have the highest detection rates among all screening tests for Down syndrome, Edward syndrome, Patau syndrome, and the sex of the fetus, specifically for women who have already learned their pregnancy has greater chances for a genetic condition. These tests look at pieces of genetic material from the placenta in the woman’s blood to find chromosome conditions. These tests are still considered screening tests because false negatives and false positives do occur. The accuracy is improved but varies depending on the condition, so diagnostic testing is recommended for patients who want to know with certainty. In addition, these tests do not detect many other genetic conditions or factors that might be present in a pregnancy. These tests also might not be as reliable in some situations, such as with twins or multiples. ACOG (2016) has thus noted that pregnancy management decisions should not be made on the basis of these screening tests alone.

Testing companies note that non-invasive prenatal screens have both high levels of sensitivity and specificity (> 99%).  However, sensitivity and specificity are not the same thing as positive predictive value (PPV), which is an estimation that the baby actually has the condition being tested for, and is of course, the primary screening result patients have asked to know. To see how positive predictive value can vary by both condition and maternal age, you can refer to the NIPS PPV calculator: https://www.perinatalquality.org/Vendors/NSGC/NIPT/

For example, for a sensitivity set at 99.2% and a specificity set at 99.91% for a 30-year-old patient whose NIPS test is positive for Down syndrome, the PPV is calculated at 61%.  This means that there is a 61% chance that the fetus actually does have Down syndrome.  Further diagnostic testing is available to determine the actual presence of the condition. PPV varies with maternal age and tested condition, and PPV is generally less for younger patients and for rarer conditions.

Reference:

American College of Obstetricians and Gynecologists (2016, May).  Practice bulletin 162: Prenatal diagnostic testing for genetic disorders.  Washington, DC: American College of Obstetricians and Gynecologists.

For accessible explanations of prenatal screening and ultrasound for patients, see the following online resources:

  1. Maternal Serum Screening (MSS) by the Washington State Department of Health and Genetic Support Foundation:  https://youtu.be/TOdEbBlhIgU?list=PL82Z-swK0-4lq6SaKF_lCRquP15gJ3VG0               
  2. Ultrasound in the Second Trimester by the Washington State Department of Health and Genetic Support Foundation: https://youtu.be/b9Ug23X0voc?list=PL82Z-swK0-4lq6SaKF_lCRquP15gJ3VG0 

For a discussion of cell-free DNA screening suitable for both medical providers and patients, you can view this short video from the Washington State Department of Health and the Genetic Support Foundation.

Prenatal Cell-Free DNA Screening (cfDNA Screening):  https://www.youtube.com/watch?time_continue=64&v=e86_l_UqecU&feature=emb_logo