Background Harmony™ Prenatal Test uses an assay method, Digital Analysis of Selected Regions (DANSR™), for analysis of chromosomes 13, 18, 21, X and Y as well as other chromosomes to measure fetal fraction (FF). Products from the DANSR assay are then analysed with Fetal fraction Optimised Risk of Trisomy Evaluation (FORTE™) algorithm to assess patient-specific risk of trisomy. Alternative tests, such as those using massively parallel shotgun sequencing, use a Z-statistic or Normalised Chromosome Value (NCV) to discriminate between normal and abnormal chromosomal counts without accounting for FF.

Methods A general pregnancy population cohort of 15,841 women between 10.0 to 14.3 weeks gestation were followed to pregnancy outcome. Z-statistics were computed using previously described standard Z-test of proportions and compared to FORTE risk scores generated by Harmony. A Z-statistic of ≥3 was ‘Positive’ for trisomy and a FORTE risk score of ≥1% was ‘High Risk’ for trisomy.

Results See Table 1. Cumulative test discordant rate for non-trisomies with FORTE was 0.08% compared to 1.07% with Z-statistic.

Conclusion Analysis using FORTE to incorporate FF in cfDNA testing yields >10 fold reduction in discordant results This will become increasingly relevant as cfDNA testing gets more broadly used in the general pregnancy population.