Cell-free DNA testing for Down syndrome explained

Learn about a new test to check for Down syndrome.

Cell-free DNA testing for Down syndrome explained

Cell-free DNA is a new lab test offered during pregnancy that is used to screen for Down syndrome. This test is also called NIPT, which stands for non-invasive prenatal test because it involves simply taking a sample of blood from the mom’s vein rather than inserting a needle into the uterus like an amniocentesis. Test results are generally available within seven to 10 days. NIPT has great potential as a screening test for genetic disorders in pregnancy, but there are some limitations that must be understood by patients so the test is used properly.

Fetal DNA

All pregnant women have small pieces of fetal DNA in their blood stream that comes from the baby. This DNA is released by the placenta and circulates in a woman’s blood from early in the first trimester until delivery. Scientists have discovered a method of counting the DNA fragments for each chromosome from the baby to determine if there are too many or too few. For example, if a fetus has Down syndrome, then the amount of DNA for that chromosome will be increased compared to the other chromosomes.

What does the test screen for?

NIPT is a screening test that provides information regarding only Down syndrome (trisomy 21), trisomy 18 and trisomy 13. A trisomy occurs when there is an extra copy of a particular chromosome in every cell. This can lead to intellectual disabilities and birth defects. Because it screens only for trisomy 21, 18, and 13, NIPT covers only 80 to 90 percent of chromosome abnormalities that would be detected using amniocentesis.

What does NIPT not screen for?

NIPT does not test for other genetic conditions like missing and duplicated pieces of chromosomes or chromosome abnormalities other than trisomy 21, 18 and 13. Currently, NIPT cannot detect genetic conditions like cystic fibrosis, beta-thalassemia or sickle cell anemia, which can only be identified by amniocentesis. In addition, NIPT does not screen for spina bifida or birth defects.

How accurate is the test?

NIPT is a screening test, not a diagnostic test, which means that sometimes the results are inaccurate. A screening test does not tell with 100 percent certainty whether or not a fetus will be affected by a given disorder. Unfortunately, marketing by the companies offering this test has sometimes been misleading in claiming that the test has greater than 99 percent accuracy, the same accuracy that is known with amniocentesis and chorionic villus sampling (CVS). It is certainly a good test for Down syndrome in women at risk but it is not correct to believe that NIPT has greater than 99 percent accuracy.

What other similar tests are available?

First trimester screen and quad screen are the other noninvasive screening tests that have been offered to all pregnant women for many years. The first trimester screen is done at 11 to 13 weeks gestation, which includes a measurement of fluid behind the neck of the fetus (nuchal translucency) by ultrasound and a blood test of the mother. The quad screen is a blood test (AFP) that is done at 15 to 20 weeks. These tests offer a wider range of screening than the NIPT as they also screen for birth defects, additional chromosome abnormalities and pregnancies at risk for complications like preeclampsia and poor fetal growth.

Limitations of NIPT

NIPT screens only for trisomy 21, 18 and 13 and not for other genetic conditions, birth defects or pregnancy complications. It is a good test for women wanting information about just these three trisomies with Down syndrome being the most common.

Studies have shown there can be false positive and false negative results with NIPT so any abnormal result should be followed-up by a diagnostic test like an amniocentesis. In addition, while the detection rates for trisomy 21 have been high, the test is much less accurate and effective for trisomy 18 and 13. That also means that women should be offered the more accurate invasive tests right away like CVS or amniocentesis when obvious birth defects are found on ultrasound or when they are at an especially high risk of a chromosome abnormality.

In addition to false positive and false negative results, sometimes the NIPT test cannot provide a result because the amount of fetal DNA is too low. Patients who want screening will then have to consider other screening tests or an amniocentesis.

A negative or normal NIPT test result means that it is very unlikely that the baby has trisomy 21, 18 or 13. However, these trisomies cannot be ruled out 100 percent and other abnormalities could still be present because NIPT does not test for other abnormalities.

When the NIPT test result is abnormal (positive), then the baby is at increased risk of the particular trisomy identified. However, there is still a chance that the baby is normal so a more accurate invasive test should always be performed. False positive results can occur from placental chromosome abnormalities, cancer cells, chromosome abnormalities of the mother, twins or triplets, use of donor egg, and miscarriage of one twin. A CVS can be done at 10 to 13 weeks gestation or an amniocentesis can be done at 15 to 24 weeks gestation. All of the fetal chromosomes, including chromosomes 21, 18 and 13 will be analyzed with these tests.

Research is still being done to determine if NIPT should be offered to all pregnant women and if the results can be made more accurate. In addition, many other genetic conditions could eventually be offered through this screening test.
Who should consider the NIPT test?

NIPT is currently offered only to woman at increased risk for trisomy 21, 18 and 13, which includes the following:

  • Women 35 years of age and older who do not want amniocentesis or CVS
  • Ultrasound findings consistent with a trisomy
  • Previous baby with a trisomy
  • Abnormal first trimester or quad screen test result

Based on what is currently known about this test, NIPT is not recommended in the following circumstances:

  • Low-risk women (age < 35, normal ultrasound)
  • Earlier than 10 weeks gestation
  • Twin or triplet pregnancies
  • Women over 250 pounds
  • To determine sex of the baby
  • Fetal birth defect seen on ultrasound

NIPT in low-risk patients

To date, studies have shown that NIPT is a good screening test for certain high-risk women but the test is not recommended for low-risk patients. The accuracy of screening tests depends on the background risk of the patient. Screening tests in women at high risk are more accurate than screening tests in women at low risk. Because the rate of trisomy is low in low-risk women, a positive test result is more likely to be false. A recent study in low-risk women found that more than half of the positive NIPT results were false positives. In other words, one in two positive test results in low-risk women is likely to be false positive.

Another limitation of NIPT screening in low-risk patients is that most of the genetic abnormalities in this population are conditions other than trisomy 21, 18 and 13. Therefore, first trimester screen and quad screen offer better detection rates of other genetic abnormalities and provide additional information about pregnancy risks involving high blood pressure and abnormal fetal growth.

What to do if you want NIPT

Women at risk of a trisomy who are interested in NIPT should see a genetic counselor to discuss testing options. Your family history should be reviewed to determine if other forms of screening or prenatal diagnosis are indicated. If you decide to have the NIPT test done, an ultrasound exam will be done at the same time to confirm viability, the number of fetuses and due date. The fluid behind the fetal neck (nuchal translucency) and the position of the heart in the fetal chest (cardiac axis) can also be measured as additional screening for birth defects.

NIPT screening does not assess risk of fetal birth defects such as spina bifida or other birth defects. Women undergoing NIPT screening should have an ultrasound later in the pregnancy (18 to 22 weeks) to rule these conditions out.

Posted In Children's, Health Information, Pregnancy, Women's