The mother decided—against her earlier leaning—to have a non-invasive prenatal test (NIPT) for the top three most common genetic abnormalities: Down syndrome (also called trisomy 21), trisomy 18, and trisomy 13. NIPT tests DNA in maternal blood to screen for those three anomalies.
The test indicated that her fetus was at increased risk for trisomy 21, or Down syndrome. But that was hardly the end of the story: Clinicians advised performing diagnostic testing because an increased risk for Down syndrome was not conclusive. The only way to be sure, one way or the other, was to do diagnostic testing. The parents chose to have further testing done.
Danielle LaGrave, MS, LCGC
“The good thing is, there’s nothing irreversible about deciding to get a screening. [Clinicians should] just make sure that patients are making medical decisions based on diagnostic information, meaning further tests, and not just screening information.”
The amniocentesis revealed trisomy 21. The parents chose to have their baby, but they had gained knowledge and preparation time they would not have had when learning in the delivery room while exhausted, says ARUP genetic counselor Danielle LaGrave, MS, LCGC. The mother and father were then counseled by a genetic counselor and given information about that syndrome. They learned what medical issues might affect their child and determined that they wanted to deliver at a specialized hospital—where the staff was prepared to treat their baby and ensure the best possible outcome. Knowing the diagnosis ahead provided time to ensure that their pediatrician knew the medical needs of their child or to find a doctor with those skills. They were also able to inform friends and family and set the scene. “That way, when they have the baby, the news that the baby has this disorder does not supersede this joyous occasion,” notes LaGrave.
We’ll talk here with LaGrave about non-invasive prenatal testing.
- What is NIPT?
It’s in a new generation of screening for fetal chromosome abnormalities. A sample of the mother’s blood is drawn, and the test screens for the most common genetic abnormalities. The blood contains cell-free DNA—that is, DNA that is not enclosed in a cell, and which is produced by the natural growth and destruction of our cells. Most of the cell-free DNA present in a pregnant woman’s blood is maternal in origin, but some is fetal in origin. This is called the “fetal-fraction”. As the fetus grows, the amount of fetal versus maternal DNA increases. NIPT looks at the DNA and tries to distinguish whether there is an extra copy of specific chromosomes present in the fetus. Both the mother and the fetus should have 46 chromosomes. The test looks for a small increase in the fetal chromosome complement, a 47th chromosome.
“It is important to remember that NIPT is still a screening test,” says ARUP genetic counselor Danielle LaGrave.
- What is the general accuracy of NIPT?
The screening has a detection rate of above 99 percent for the three most common chromosome abnormalities, trisomy 21, trisomy 18, and trisomy 13. The false-positive rate is well under 1 percent. This is far more sensitive than the various maternal serum screening tests that were all that was available until 2011 or so. The maternal serum screens also have a much higher rate of false positives.
- What are the limitations of NIPT?
Because NIPT is highly sensitive, people sometimes mistakenly conclude that if the test says a fetus screens positive for a disorder, that the fetus will have that disorder. But it is important to remember that NIPT is still a screening test. There are biological reasons that might lead to a false positive result—the placenta could have a chromosome abnormality, but the baby does not. Sometimes the mother may have a cell line that has a chromosome abnormality. This does not cause her any problems, but it may be picked up by the test and interpreted as an increased risk for that abnormality in the fetus. Because of these and other limitations, we recommend that women who have a positive NIPT result undergo fetal diagnostic testing, fetal ultrasound, or possibly other testing. You definitely want to test in some way beyond the screening, especially before deciding to terminate a pregnancy. It is a patient’s choice whether they want to end a pregnancy or not. If they choose to do so, we want to make sure they are doing so with correct and complete information, not because they are scared and stressed and thinking the initial screening provided all the information needed.
- How can genetic counselors help in the case of difficult screening results?
If any provider is unsure what to tell their patients regarding NIPT results, the genetic counselors at ARUP are happy to go over the results with them to make sure they feel very comfortable before having these conversations with their patients. If a clinician wants percentages on false positives or other helpful statistics, we can pull up calculators to show useful numbers. Our NIPT brochure covers additional information, too. The good thing is, there’s nothing irreversible about deciding to get a screening. Just make sure that patients are making medical decisions based on diagnostic information, meaning further tests, and not just screening information.
Catherine Arnold, Science Communications Writer
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