Cell-Free Fetal DNA
A blood sample drawn from a vein in the mother's arm
Cell-free fetal DNA (cffDNA) is genetic material that is released by the placenta and circulates in a woman's blood during pregnancy. CffDNA generally reflects the genetic makeup of the developing baby (fetus). Cell-free fetal DNA prenatal screening, called non-invasive prenatal screening (NIPS) by some, detects defects in fetal DNA after it is purified from the pregnant woman's blood.
CffDNA is present in a pregnant woman's blood in small quantities starting in the first trimester and increases throughout pregnancy. The cffDNA test is a relatively new, non-invasive method of screening that can be performed as early as the tenth week of pregnancy for women.
The test can identify chromosome disorders in a developing baby, including the presence of extra chromosomes (trisomies) such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). The extra genetic material present in these conditions affects the development of the baby and causes characteristic signs, symptoms, and complications.
Down syndrome is the most common of the three trisomies detected by cffDNA testing and varies significantly in severity from person to person. Edwards syndrome and Patau syndrome are more rare and more severe, with most affected babies dying within weeks to months of birth. This test may be used to identify other rare conditions resulting from an extra chromosome or missing piece of chromosome (microdeletion).
CffDNA testing can also detect an extra sex chromosome. One example is Klinefelter syndrome, resulting from two X chromosomes and one Y chromosome. For more on this and other rare chromosome disorders, see the Related Pages section of this article.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the mother's arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
The cell-free fetal DNA (cffDNA) test is a relatively new test that may be used to assess the risk of a pregnant woman's developing baby (fetus) having a chromosome disorder, such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). It may be used to identify other rare conditions resulting from an extra chromosome or missing piece of chromosome (microdeletion).
Non-invasive prenatal screening (NIPS) that uses cffDNA testing is one of the options that may be offered for prenatal screening for chromosome disorders. Conventional testing options include the first trimester Down syndrome screen and the second trimester maternal serum screen. The screening approach a woman chooses depends on what technology is available and when she first seeks prenatal care. Also, pregnant women may wish to check with their insurance companies, as not all policies may cover cffDNA.
Currently, two major health organizations differ in their recommendations on the use of cffDNA testing. Talk to your healthcare practitioner about your prenatal screening options and what may be best for you.
- According to the American College of Medical Genetics and Genomics (ACMG), NIPS using the cffDNA test is the most sensitive screening option for Down syndrome. ACMG recommends that healthcare practitioners inform their pregnant patients about this screening option, regardless of age and whether or not they are at increased risk for carrying a baby with a chromosome disorder. CffDNA screening is more sensitive than conventional first or second trimester screening tests, according to ACMG, and can replace those tests to screen for pregnancies at risk for Down, Edwards, and Patau syndromes.
- The American College of Obstetricians and Gynecologists (ACOG) currently states that any pregnant woman may choose cffDNA regardless of her risk for carrying a baby with a chromosome disorder but cautions that she understand the limitations and benefits of this screening option. Considering the performance of conventional screening methods and the limitations of cffDNA testing as well as other factors, ACOG recommends that conventional screening methods remain the most appropriate choice for most pregnant women. ACOG does recommend that the cffDNA test be offered to women at an increased risk for fetal defects after genetic counseling. Factors that increase risk include:
- Advanced maternal age: 35 years or older
- A fetal ultrasound result that indicates an increased risk of a chromosome abnormality
- A previous pregnancy with a trisomy
- A positive first-trimester or second trimester maternal screening test
- A known balanced chromosome translocation (switched chromosome pieces) in the mother or father that is associated with trisomy 13, 18, or 21
The cffDNA test is used as a screening test, not a diagnostic test. If there are abnormal findings in routine prenatal testing or in cffDNA testing, then more invasive confirmatory testing using procedures such as chorionic villus sampling (CVS) or amniocentesis may be indicated to diagnose a chromosome abnormality.
When is it ordered?
What does the test result mean?
A negative cffDNA test result means that it is very unlikely that the baby has trisomy 13, 18, or 21. If the test is negative for other chromosomal abnormalities that the laboratory tested for, then it is unlikely that the baby is affected by those. However, these trisomies or genetic defects cannot be entirely ruled out, and other chromosome abnormalities could still be present.
If a cffDNA screen is positive, then the fetus is at an increased risk of having the identified abnormality. However, the test is not diagnostic. The performance of more invasive procedures, including chorionic villus sampling (CVS) between the tenth and twelfth week of pregnancy or an amniocentesis procedure between 15 and 20 weeks of pregnancy, and subsequent chromosome analysis is required to rule out or diagnose a chromosome disorder.
In some cases, the laboratory that performs the DNA analysis will return an "indeterminate" or "no call" result when there is an insufficient amount of cell-free fetal DNA in the maternal blood sample. This can occur, for example, when the woman is obese (weighing more than 250 pounds) or when the blood sample is collected too early in the pregnancy (prior to the tenth week of pregnancy). ACMG and ACOG recommend that women with a "no call" result be offered diagnostic testing using amniocentesis or CVS if the maternal blood sample was drawn at an appropriate gestational age. ACMG also recommends offering a screening test other than NIPS in cases of significant maternal obesity.
Questions on interpreting the results of a cffDNA are usually best answered by someone experienced in genetic counseling.
Is there anything else I should know?
The full clinical utility of cffDNA testing has yet to be established. As research progresses, use of the test may be expanded.
Should I ask my healthcare practitioner about having a cffDNA test performed?
You may choose to discuss this screening option as well as others with your healthcare practitioner to make an informed decision. You may also be referred to a genetic counselor who will help you understand the limitations and benefits of screening as well as the meaning and implications of your results.
If I have a negative cffDNA test with my current pregnancy, will I need to repeat it with the next baby?
Yes, you may be offered the test with subsequent pregnancies. Since it is the baby that is being assessed, each pregnancy would be tested and evaluated separately.
How long does it take for cffDNA testing results?
This depends on the laboratory performing the test. It may take one to two weeks for results.
Does cffDNA test for neural tube defects such as spina bifida?
Will this test tell me the sex of my baby?
Yes, this test can reveal the sex of your baby and your healthcare practitioner may provide you with this information if you request it. However, if you don't want to know the sex of your baby, you can usually request that this information be suppressed in the report.
On This Site
Conditions: Down Syndrome
Screening: Pregnancy & Prenatal Testing
In the News: Genetic Experts Update Recommendations on Non-invasive Prenatal Screening (2016), New Study: Genetic Blood Test Better than Standard Prenatal Screening, Still Not Perfect (2015)
Elsewhere On The Web
National Society of Genetic Counselors: Before and During Pregnancy
National Human Genome Research Institute: Chromosome Abnormalities
National Institutes of Health, Office of Rare Diseases Research: Chromosome Disorders
National Association for Down Syndrome
National Down Syndrome Society
Trisomy 18 Foundation
MedlinePlus Medical Encyclopedia: Trisomy 13