(537) Cell-Free-DNA based tests for prenatal diagnosis of fetal anomalies: what is the diagnostic yield?

To identify diagnostic yield of whole genome cell free DNA (cfDNA) for prenatal diagnosis of fetal anomalies and compare to diagnostic yield of direct DNA testing.

Study Design:
Retrospective review of pregnancies between 2020 to present that had MaterniTGenome™ sent at a quaternary care referral center. Participants were identified through the institution’s LabCorp Portal. All participants received genetic counseling per institutional guidelines. Charts were reviewed for participant demographics, indication for testing including ultrasound findings and type(s) of fetal anomaly, types of test sent and results, and neonatal testing. Primary outcomes include: (1) frequency in which cfDNA based assessment provided a diagnosis, (2) correct diagnostic yield corroborated by direct DNA. Descriptive statistics were performed using STATA18.

Results:
108 patients had a MaterniTGenome test  (Table 1). Of those, 86 (79.6%) had testing due to an ultrasound detected fetal anomaly, and 49 (45%) had testing for single gene disorders via cfDNA (Vistara™). 8 patients had positive MaterniTGenome™ results and 2 had positive Vistara™ results. Of the 8 with positive results, 4 (50%) had true positives by direct DNA and 1 (12.5%) had a false positive; 3 patients were lost to follow up. Notably, 2 of 4 with true positives had a diagnosis of Trisomy 21. 13 patients had diagnostic testing after a negative MaterniTGenome™: amniocentesis (8), CVS (1), cord blood (2), products of conception (2). Of those, 5 (38.5%)  received a genetic diagnosis based on further direct DNA testing, and 8 (61.5%) had testing that confirmed true negative results (Table 2). The sensitivity of MaterniTGenome™ was calculated to be 44.4% compared to diagnostic yield of invasive testing.

Conclusion:

CfDNA based assays offer an alternative to invasive diagnostic testing in the setting of fetal anomalies, but with significant limitations compared to direct fetal DNA assessment. This should be further evaluated in larger cohorts to determine best practice and counseling for use of cfDNA in these settings.