As a prenatal genetic counselor, I spend a lot of time talking to expectant mothers who will be 35 years or older at delivery, or “advanced maternal age” (doesn’t that sound great?!). There is an increased chance with each passing year that our eggs will make an error with separation of the chromosomes (the packets of material that contain our genes) during fertilization. If this occurs, a baby could end up with an extra or missing copy of a gene or chromosome.
The most commonly known example of such an occurrence is Down syndrome. Fortunately, the odds are always in our favor that a baby is healthy and does not have a chromosomal, or genetic, condition. However, having a baby that has special needs has deep emotional, social, and financial impact on women and families. The women we encounter in our clinic often want to go beyond the known statistics. They want information specific to their baby and their pregnancy.
There are many screening tests out there, and Dr. Nathan Drever, M.D. has done a great job explaining what is available in his “What You Should Know About Antenatal Screening” series. I want to talk more specifically about Non-Invasive Prenatal Testing (NIPT), as it has quickly become a very popular screen over the last couple of years. It goes by many names including both generic (NIPT, cell-free DNA screening, NIPS) and brand names (MaterniT21, Panorama, Harmony, and Verifi).
It is important to understand that any test that is performed using a blood sample or ultrasound measurement alone during pregnancy is considered a screening test, which differs from testing by amniocentesis or chorionic villus sampling, both of which are considered diagnostic tests. Screening tests estimate risk, often times very well, but they cannot be considered confirmatory, as they do not sample cells directly from the baby. Diagnostic tests, on the other hand, do sample cells that come directly from the baby or placenta and are considered the “gold standard” when confirmation of the presence or absence of a genetic condition is recommended and desired by the patient and family.
A little bit of background information…
Historically, if a woman wanted to know her risk for common genetic conditions such as Down syndrome or Trisomy 18, we would measure levels of hormones and proteins in a blood sample from taken from the mother after 15 weeks of gestation, such as the “quad(ruple) screen”, or combine the results of this blood sample with an ultrasound measurement of the thickness of the skin behind the baby’s neck, or nuchal translucency, in the first trimester of pregnancy which is referred to as “first trimester screening.” Both of these types of screening tests give an estimated, calculated risk number for certain genetic conditions.
For example, the test might estimate that the chance of the baby having Down syndrome is 1 in 1,000. In other words, if I had a group of 1,000 women with that exact rest result, 1 woman would be expected to be carrying a baby with Down syndrome, while the other 999 women would be expected to be carrying babies without Down syndrome. Because age is part of this calculation and we know that risk goes up with age, women over age 35 have a higher chance of a false positive test result. This occurs when a screening test shows a high risk for a genetic condition that is not actually present in the baby. About 5% of women who have first trimester screening or a quad screen get a false positive result. If this happens a woman will be offered additional confirmatory testing typically with an amniocentesis, which can oftentimes cause extreme anxiety.
So What Is NIPT?
During pregnancy, the placenta, which originates from the fertilized embryo (yes, the placenta comes from the fetus, NOT the mother) is bathed by the mother’s blood, and allows oxygen and nutrients to reach the baby’s circulation. Just like skin cells shed as new ones grow, the placenta sheds cells too—right into a mother’s bloodstream! Eventually these cells break down and leave behind little pieces of the genetic code, or DNA, floating around in the mother’s blood stream (technically called “cell-free fetal DNA”). NIPT can identify these pieces of DNA that originate from the placenta. Since the baby and the placenta both came from the same fertilized egg, they have a lot in common genetically and we can get useful information with this form of testing.
Most forms of NIPT look for 5 common chromosomal conditions: trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), trisomy 21 (Down syndrome), and conditions where there may be an extra or missing copy of the sex chromosomes, such as Turner syndrome (a female with one X chromosome) and Klinefelter syndrome (a male with an extra X chromosome). The important thing to remember with NIPT is that it is a screening test—it is not a 100% yes or no answer. An abnormal NIPT result raises concern that the baby could have the genetic condition that results on a “positive” NIPT result, and follow-up testing is recommended to confirm. A normal NIPT gives reassurance that the baby likely does not have any the five genetic conditions that are included with this testing, but does not rule out the chance completely.
NIPT does not screen for all possible chromosomal or genetic disorders. It might be helpful to use a metaphor to illustrate this. Picture a crane with a magnet on the end. The crane has a large pile of metals that it needs to sort—tin, copper, silver, and brass, and maybe some other metals thrown in. The magnet is designed to only pick up tin, so if tin is in the pile the crane is really good at picking it out. Similarly, NIPT is really good at picking up Down syndrome when it is present. The crane wouldn’t be able to pick out copper or gold from the pile, even if they were there, and in the same way NIPT wasn’t designed to pick up all genetic and chromosomal conditions that can occur in a pregnancy.
You can go to www.NSGC.org and click on the “Find a Genetic Counselor” tool to find a genetic counselor near you!
Stay Tuned for Noninvasive Prenatal Testing Part 2!