Noninvasive Prenatal Testing Becomes a Reality

285 BreastQ&ABy Kari Bohlke, ScD


Since the 1970s pregnant women have had the option of being tested for chromosomal abnormalities in the fetus (such as trisomy 21, also known as Down syndrome). Screening typically involves blood tests and ultrasound; if these tests—which have somewhat limited accuracy—produce an abnormal finding, women often proceed to invasive testing with amniocentesis or chorionic villus sampling for a definitive diagnosis. Risks of invasive testing include a small chance of miscarriage, but the need for invasive testing may be substantially reduced by a new generation of prenatal tests.

Noninvasive prenatal testing (NIPT) is a new approach to screening for trisomies of chromosomes (three copies) that involves evaluation of fetal DNA collected from the mother’s blood. The first tests to hit the market rely on “cell-free DNA,” which are fragments of fetal genetic material that circulate in maternal blood during pregnancy. These fragments do not last for long in the mother’s blood and provide information about the current pregnancy only. An advantage of this type of testing is that it provides more-accurate information than standard blood tests about aneuploidies, an abnormal number of chromosomes, such as three copies of chromosome 21 instead of the normal two copies.

Optimal use of these tests is still being explored, but they may be used as a follow-up to abnormal results on standard blood and ultrasound tests or as an initial screening tool. Due to the lower number of false-positive test results, they have reduced the need for invasive, diagnostic testing for aneuploidies of whole chromosomes. Women who receive an abnormal result based on cell-free DNA, however, are still referred for invasive testing to confirm the result (NIPT is currently a screening test only, not a diagnostic test). The cell-free DNA assays test for only about one-third of the possible chromosome abnormalities.

Another type of NIPT that is expected to become available in the next year or two analyzes the DNA from intact fetal cells (specifically, fetal nucleated red blood cells). Like cell-free DNA fragments, these cells circulate in maternal blood and have a limited life span. In contrast to cell-free DNA fragments, however, intact cells contain the fetus’s entire genome; this would make it possible to test for a much broader range of genetic abnormalities. Furthermore, because these cells come from the fetus itself, rather than from the placenta, as most cell-free DNA fragments do, it avoids the potential problem of confined placental mosaicism, a situation in which the chromosomal makeup of the placenta differs from that of the fetus.

Currently, the American Congress of Obstetricians and Gynecologists recommends offering NIPT as part of screening for women who are at increased risk of having a fetus with certain chromosomal abnormalities.8 Women should be counseled carefully, however, so that they understand that most of the risk of genetic abnormalities remains even after such screening. There is still limited information about how these tests perform in low-risk pregnancies. The National Society of Genetic Counselors also supports NIPT as an option when there is an increased risk of a chromosomal abnormality, and it stresses the importance of informed consent, education, and counseling by a qualified provider, such as a certified genetic counselor.9

As prenatal testing continues to evolve, it is likely to raise some difficult questions for families and physicians. Women will have the option of receiving ever-expanding information about their pregnancy but will need to think carefully about the types of information that they actually want. These decisions are extremely personal, and they highlight the importance of education and counseling both before and after testing. When women want to receive a particular piece of information, however, the ability to receive it early, accurately, and noninvasively is an important advance.  _