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Cell-free DNA (cfDNA) prenatal screening for chromosomal aneuploidies
Cell-free DNA (cfDNA) testing is used for prenatal screening for common chromosome abnormalities. There is uncertainty about the appropriateness of cfDNA screening for some populations, including those at low risk for common fetal genetic abnormalities. This topic was selected for a health technology assessment because of medium concerns for the safety and efficacy of cfDNA screening in the general population and high concern for cost.
Primary criteria ranking
- Safety = Medium
- Efficacy = Medium
- Cost = High
- Draft key questions published: July 9, 2019
- Public comment period: July 10 to 23, 2019
- Final key questions updated: August 26, 2019
- Draft report published: October 22, 2019
- Public comment period: October 23 to November 21, 2019
- Final report published: December 13, 2019
- HTCC public meeting: January 17, 2020
Cell-free fetal DNA (cfDNA) screening is a form of noninvasive prenatal testing (NIPT) used to determine the risk that a fetus will be born with certain genetic abnormalities.1 cfDNA testing analyzes fragments of fetal DNA that are present in maternal blood1 and is considered noninvasive compared with traditional testing methods such as amniocentesis or chorionic villus sampling. The cfDNA in a sample of a woman’s blood can be screened for trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), and problems with the number of sex chromosomes such as Klinefelter syndrome and Turner syndrome.2 Results of maternal blood screening tests for fetal aneuploidy are reported as the level of risk that the disorder might be present:
- A positive screening test result for aneuploidy means that the fetus is at higher risk of having the disorder compared with the general population. It does not mean that the fetus definitely has the disorder.2
- A negative result means that the fetus is at lower risk of having the disorder compared with the general population. It does not completely rule out the possibility that the fetus has the disorder.2
The use of cfDNA screening has mainly been evaluated in people who are already known to be at a higher risk of pregnancies with a chromosomal abnormality.3 The evidence for people at low or unknown risk is much more limited.3 The American College of Obstetricians and Gynecologists (ACOG) has stated that cfDNA screening works best for individuals who already have an increased risk of having a baby with a chromosomal disorder.2 ACOG recommends that for a woman at low risk of having a baby with a chromosome disorder, conventional screening remains the most appropriate choice.2 However, obstetric care providers should be prepared to discuss the benefits, risks, and limitations of the available screening tests (Table 1).2
In the U.S., cfDNA screening for people with a high risk of fetal aneuploidy is covered by most commercial and public insurance plans.4 Some insurance companies, including Anthem Blue Cross Blue Shield and Cigna, now cover cfDNA for all pregnancies.4 However, clinical practice guideline authors vary in their recommendations, citing challenges with cost and the positioning of cfDNA in the screening and diagnostic pathways.2,5,6 Therefore, questions remain as to whether cfDNA tests should be used universally in the general obstetric population, or only in cases of increased risk of genetic anomaly (e.g., increased maternal age, family history of a particular genetic disorder).