Residual Risks of Fetal Chromosome Aberrations When Cell-Free DNA Prenatal Screening Is Normal: A Retrospective Study

Area of Science:

• Prenatal diagnostics
• Genetics
• Obstetrics

Background:

• Cell-free DNA (cfDNA) screening is a common method for detecting fetal chromosomal abnormalities.
• Interpreting cfDNA screening results requires understanding residual risks, especially in specific clinical scenarios.

Purpose of the Study:

• To estimate the residual risk of fetal chromosomal aberrations following normal cfDNA screening.
• To refine prenatal counseling by providing accurate risk figures.

Main Methods:

• A retrospective study of 46,007 pregnant women with normal cfDNA screening results.
• Cohort divided into targeted (chromosomes 13/18/21) and genome-wide cfDNA groups.
• Cytogenomic follow-up using chromosomal microarray (CMA) for risk assessment.

Main Results:

• Overall residual risk for pathogenic chromosomal aberrations was low (0.15% for targeted, 0.14% for genome-wide cfDNA).
• In cases with ultrasound anomalies, residual risk increased significantly (13.3% for targeted, 8.1% for genome-wide cfDNA).
• Majority of CMA referrals (511/806) were due to ultrasound anomalies.

Conclusions:

• Normal cfDNA screening indicates a low residual risk of pathogenic copy number variations (CNVs).
• Ultrasound anomalies in conjunction with normal cfDNA screening substantially elevate the risk of chromosomal aberrations.
• Invasive testing may be justified in cases with ultrasound anomalies despite normal cfDNA results, aiding informed prenatal counseling.