Assessment of a Simplified Cell-Free DNA Method for Prenatal Down Syndrome Screening

Area of Science:

• Genetics
• Molecular Biology
• Prenatal Diagnostics

Background:

• Current cell-free DNA (cfDNA) prenatal screening for trisomies relies on complex technologies like massively parallel sequencing.
• Rolling circle amplification (RCA) presents a simpler alternative methodology requiring further evaluation.

Purpose of the Study:

• To assess the performance and requirements of a simplified cfDNA-based prenatal screening system using RCA.
• To determine the detection and false-positive rates for common trisomies using the RCA method.

Main Methods:

• A prospective study involving 16 sites and women 10-20 weeks pregnant.
• Collection of 2-3 blood samples for RCA testing, with diagnostic results determining clinical truth.
• Analysis of detection rates for trisomic pregnancies and false-positive rates in unaffected pregnancies.

Main Results:

• Achieved a 95.9% detection rate for common trisomies with an overall false-positive rate of 1.00%.
• Demonstrated a low test failure rate of 0.04% and high fetal sex call accuracy (99.7%).
• Observed a significantly lower false-positive rate (0.30%) when assay precision was high.

Conclusions:

• The simplified cfDNA-based system using RCA is encouraging for prenatal screening in laboratory settings.
• Collecting two samples improved detection, reduced failure rates, and enabled rapid reporting.
• Future work should focus on enhancing run precision with single-tube collection.