Prenatal Cell-Free DNA Screening

What Is Prenatal cfDNA Screening?

Prenatal cfDNA screening, previously referred to as noninvasive prenatal testing (NIPT) or noninvasive prenatal screening (NIPS), is a prenatal screening test that assesses the risk that a fetus will be born with an abnormal number of chromosomes. Resulting disorders, also known as aneuploidies, include trisomy 13, trisomy 18, trisomy 21 (Down syndrome), and sex chromosome aneuploidies (SCAs).

Prenatal cfDNA screening tests are not considered diagnostic; however, they can be used as a safe, cost-effective screening option as early as 10 weeks of gestation. Prenatal cfDNA screening is a blood-based test that will determine whether the patient is at high or low risk of aneuploidy of the fetus; the risk level will indicate whether additional confirmatory testing is recommended. If patients receive a high-risk screening result or if a result cannot be generated, additional confirmatory testing will be recommended.

For detailed information about prenatal cfDNA screening, refer to the ARUP Consult Prenatal Testing for Chromosomal Abnormalities and Neural Tube Defects topic.

Why Use Prenatal cfDNA Screening?

Prenatal cfDNA screening is the most sensitive and specific prenatal screening option for trisomy 13, trisomy 18, and trisomy 21 (Down syndrome). It offers improved testing performance compared with traditional maternal serum screening (MSS) tests, with fewer false-positive and false-negative results. Prenatal cfDNA screening is noninvasive, requires a single tube of blood from the pregnant individual, and can be performed as early as 10 weeks of gestation and as late as the end of the pregnancy. The screening result is normally returned to the provider within 5–7 days.

• For more detailed information about the performance of ARUP’s prenatal cfDNA screening test, refer to the Noninvasive Prenatal Aneuploidy Screen by Cell-Free DNA Sequencing Test Fact Sheet.
• For more information on testing options, refer to the ARUP Consult Prenatal Testing for Chromosomal Abnormalities and Neural Tube Defects topic.

Impact on Patient Care

Autosomal aneuploidies such as trisomy 13, trisomy 18, and trisomy 21 (Down syndrome) disrupt the normal course of development and cellular function in a fetus and are associated with congenital malformations, intellectual disability, and increased risk for fetal/infant mortality.

Prenatal cfDNA screening offers a noninvasive way to screen for these conditions, thereby reducing the risk of miscarriage associated with prenatal diagnostic procedures such as amniocentesis and chorionic villus sampling (CVS). Prenatal cfDNA screening results provide information to inform further testing and clinical decision-making. High-risk screening results merit prompt, appropriate follow-up, as critical clinical decisions should be based on diagnostic rather than screening test results.

Prenatal cfDNA screening tests can also determine fetal sex. Although parents can opt out of learning the baby’s sex, SCAs will be reported regardless of the opt-out status.

Improved Method

ARUP’s test is performed on the Illumina VeriSeq NIPT Solution platform, which uses massively parallel whole genome sequencing of cfDNA derived from maternal whole blood samples. The generated paired-end sequencing data are then aligned to a reference genome and bioinformatically counted for over- or underrepresentation of the interrogated chromosomes. 

Benefits of this improved method include:

• Lower sample quantities required
• Reduced turnaround time (5–7 days)
• Fully automated workflow, which reduces risk of human error and improves turnaround times

To review specific metrics on test performance, including clinical and analytic sensitivity/specificity and positive predictive value, please refer to the Noninvasive Prenatal Aneuploidy Screen by Cell-Free DNA Sequencing Test Fact Sheet.

Why Use ARUP Laboratories?

ARUP offers the following:

• A comprehensive suite of testing for women’s health
• Clinician support from our integrated team of board-certified laboratory geneticists and genetic counselors, who specialize in prenatal genetics and can aid in test selection and result interpretation
• Results interfaced with the electronic medical record (EMR), which streamlines workflow for hospital laboratory sendout testing staff
• Diagnostic testing, including chromosome analysis, fluorescence in situ hybridization (FISH), or genomic microarray on amniocentesis or chorionic villus samples, available following a high-risk screen result

Professional Guidelines

The American College of Obstetricians and Gynecologists (ACOG), American College of Medical Genetics and Genomics (ACMG), and Society for Maternal-Fetal Medicine (SMFM) recommend that prenatal genetic screening, including prenatal cfDNA screening, and prenatal diagnosis be offered to all pregnant individuals, regardless of maternal age or fetal risk of chromosomal abnormality.

Based on these guidelines, insurance reimbursement rates have significantly improved. Many national payers cover prenatal cfDNA screening for women in any risk category, whereas some cover prenatal cfDNA screening only for women considered high risk. Preauthorization may be required.

Additional Resources

ACOG Practice Bulletin: Screening for Fetal Chromosomal Abnormalities

ARUP Consult

Refer to ARUP Consult for information on ordering recommendations, Test Fact Sheets, and testing algorithms.

• ARUP Consult Prenatal Testing for Chromosomal Abnormalities and Neural Tube Defects topic

Educational Brochures

These brochures offer information for both clinicians and patients on why prenatal cfDNA screening is important, the conditions that are screened for, and important test metrics.

• Noninvasive Prenatal Aneuploidy Screen by Cell-Free DNA Sequencing (Patient)
• Noninvasive Prenatal Aneuploidy Screening Test (Physician)

Other Content

Women’s Health: A comprehensive suite of testing for women’s health

Spotlight Video on Testing Technology: Noninvasive Prenatal Aneuploidy Screening by Cell-Free DNA by Shelly Bosworth, MS, LCGC