Performance of Massive Parallel Sequencing-Based Cell-Free DNA Testing in Compromised Pregnancies.

Area of Science:

• Genetics
• Reproductive Medicine
• Molecular Diagnostics

Background:

• Non-invasive prenatal testing (NIPT) is a key screening tool for common trisomies.
• NIPT can detect chromosomal anomalies beyond common trisomies.
• The utility of genome-wide NIPT (GWNIPT) in diverse prenatal settings requires further evaluation.

Purpose of the Study:

• To assess the performance of GWNIPT in detecting chromosomal abnormalities.
• To compare GWNIPT with reference diagnostic tests in fetal diagnostic studies (FDS).
• To evaluate GWNIPT's role in genetic diagnosis of early pregnancy losses (EPL).

Main Methods:

• VeriSeqTM NIPT Solution v2, a GWNIPT platform, was utilized.
• Testing was performed prior to invasive procedures in 155 FDS cases.
• GWNIPT was also applied to 68 EPL samples.

Main Results:

• In FDS, GWNIPT detected 61% of anomalies identified by diagnostic tests (QFPCR, array, karyotype).
• GWNIPT missed smaller deletions/duplications (<7 Mb) and balanced translocations.
• In EPL, GWNIPT identified anomalies in 46% of cases, with high concordance (16/18) to POC testing.

Conclusions:

• GWNIPT demonstrates clinical utility for prenatal genetic diagnosis.
• The test is valuable for EPL genetic diagnosis, especially with limited sample availability.
• GWNIPT complements traditional NIPT by offering broader genomic coverage.