The Implementation and Clinical Validation of a Whole-Genome Sequencing Non-Invasive Prenatal Test in a High-Complexity Clinical Laboratory: A Retrospective Analysis of 11,235 Pregnancies.

Background

Cell-free DNA non-invasive prenatal testing (NIPT) is recommended by the American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics and Genomics (ACMG) for fetal aneuploidy screening in all pregnancies, yet most testing is performed by centralized reference laboratories. We evaluated whether a whole-genome sequencing (WGS) NIPT assay implemented in a high-complexity clinical laboratory can achieve a performance consistent with established reference laboratories.

Methods

We retrospectively analyzed 11,235 evaluable clinical NIPT samples processed in a single Clinical Laboratory Improvement Amendments (CLIA)-certified, College of American Pathologists (CAP)-accredited laboratory using the Illumina VeriSeq NIPT Solution v2, which reports trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), and sex chromosome aneuploidies (SCA). Results were compared with the diagnostic and clinical follow-up; the performance was calculated overall and by maternal age with 95% confidence intervals (CIs).

Results

Of 11,318 accessioned samples, 83 (0.73%) were not reportable and excluded. The sensitivity was 100% for all conditions (T21 95% CI 92.1-100%); per-condition specificity exceeded 99.9% (99.81% for any reported aneuploidy overall), with no false-negative results among cases with available follow-ups. Observed positive predictive values (PPVs) were 91.8% (T21), 85.7% (T18), 63.6% (T13), and 79.3% (SCA), consistent with published ranges for this routine, unselected screening population.

Conclusions

A high-complexity clinical laboratory can deliver WGS-based NIPT at this level of performance, supporting broader, more timely access to guideline-recommended screening. NIPT remains a screening test, and high-risk results require diagnostic confirmation.