Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA

Area of Science:

• Genetics
• Molecular Biology
• Biochemistry

Background:

• Prenatal trisomy 21 (T21) screening typically uses fetal DNA analysis from maternal blood.
• Current DNA-based screening methods are reliable but present a significant cost barrier to widespread adoption.

Purpose of the Study:

• To investigate the potential of maternal plasma RNA screening as a reliable and cost-effective alternative for prenatal T21 detection.
• To identify RNA markers in maternal plasma that can accurately predict embryonic T21.

Main Methods:

• Discovery phase: RNA and miRNA microarrays followed by qRT-PCR on plasma from 20 women (11-13 weeks gestation).
• Validation phase: qRT-PCR and machine learning analysis on plasma from 998 pregnancies (including 50 T21 cases).
• Machine learning algorithms were trained and tested to evaluate predictive performance.

Main Results:

• Initial analysis identified potential mRNA and small RNA markers.
• Machine learning models using 6-10 RNAs achieved high predictive accuracy (AUC up to 1.00).
• The RNA-based approach demonstrated significant potential for T21 prediction.

Conclusions:

• Maternal plasma RNA analysis, combined with qRT-PCR and machine learning, can accurately predict T21.
• This RNA-based screening method offers a potentially lower-cost alternative to DNA-based methods.
• The findings support the development of universal prenatal T21 screening.