Screen-positive rate in cell-free DNA screening for microdeletion 22q11.2

Area of Science:

• Prenatal diagnostics
• Genetics
• Molecular biology

Background:

• Non-invasive prenatal testing (NIPT) screens for chromosomal abnormalities.
• Microdeletion 22q11.2 is a significant genetic condition.
• The fetal fraction (FF) is the proportion of cell-free DNA from the fetus in maternal plasma.

Purpose of the Study:

• To investigate the influence of fetal fraction (FF) on the screen-positive rate for 22q11.2 microdeletion screening.
• To determine optimal FF thresholds for reliable NIPT results.

Main Methods:

• Analysis of 52,019 singleton pregnancies using the Harmony® Prenatal Test.
• Logistic regression to identify factors affecting the screen-positive rate.
• Comparison of FF levels between high-risk and low-risk groups for 22q11.2 deletion.

Main Results:

• The overall screen-positive rate for 22q11.2 microdeletion was 0.59%.
• Lower FF (<11.0%) was linked to a higher screen-positive rate (0.92%) compared to higher FF (≥11.0%, 0.13%).
• A significant correlation was found between FF and the screen-positive rate.

Conclusions:

• The screen-positive rate in 22q11.2 microdeletion screening is dependent on the fetal fraction.
• Recommending analysis of samples with FF ≥11% can help maintain a low screen-positive rate.
• Optimizing FF thresholds enhances the reliability of NIPT for microdeletion screening.