cfDNA vs. Routine Screening – How Do They Compare?

FINDINGS:

• Cell free DNA (cfDNA / NIPS / NIPT) screening tests for fetal Trisomy 21 (Down syndrome) are more sensitive, have lower false positive rates and higher positive predictive values regardless of maternal age, than standard first trimester screening
• Despite improved performance compared to standard screening, cfDNA tests should be considered screening tests only. Further counseling and diagnostic confirmation should be sought prior to acting on a positive cfDNA screening test result

SYNOPSIS:

Norton and colleagues (NEJM, 2015) reported findings from the NEXT study comparing performance between new prenatal screening tests using cfDNA, compared to first trimester standard screening (serum pregnancy-associated plasma protein A, and total or free beta subunit of human chorionic gonadotropin measurements, with nuchal translucency).

KEY POINTS:

• In a general population of  women in the first trimester of pregnancy, cfDNA testing detected 38/38 fetuses affected with Trisomy 21 compared to 30/38 with standard screening
• The positive predictive value (PPV) was 80.9% using cfDNA compared to 3.4% using standard screening
• cfDNA screening did result in some false positives for Trisomy 21
  • confirmatory/diagnostic testing is therefore required before acting on cfDNA or standard screening tests
• cfDNA screening is less ideal for obese patients as suggested in previous studies
• “No results” cfDNA reports require additional follow-up to rule out fetal aneuploidy
• This study was focused on Trisomy 21 detection only; however results for Trisomy 18 and Trisomy 13 suggest cfDNA provides more accurate screening for these disorders as well

Learn More – Primary Sources:

The NEXT study: Cell-free DNA Analysis for Noninvasive Examination of Trisomy