Fig. 2: Simulated risk modification with genome-wide noninvasive prenatal screening (NIPS).

Flow diagram, moving left to right, depicts the change in baseline risk for a patient referred to our institution. (a) Entire cohort, in which 23.8% of patients enrolled had a clinically significant chromosomal abnormality. A hypothetical patient referred to us with a positive genome-wide NIPS would have their residual risk increased from 23.8% to 80.6%, which may serve to support confirmatory diagnostic testing for patients of a given risk preference profile. In contrast, a negative genome-wide NIPS serves to reduce residual risk from 23.8% to 6.1%, which for patients of a given risk profile may serve as a measure of reassurance. (b) Subset of patients who did not have a common aneuploidy or sex chromosome aneuploidy diagnosed by NIPS. In this group, 50% of patients with a positive genome-wide NIPS result were found to have a clinically relevant finding on chromosomal microarray. Those with a negative genome-wide NIPS result had their risk of a clinically significant finding on microarray reduced from 8.7% to 5.2%. (c) Subset of subjects with an abnormal fetal ultrasound. Note that the baseline risk of 18.8% is lower than in the first simulation likely because aneuploidy is screened out in the first trimester. A hypothetical patient referred with an abnormal fetal ultrasound who was found to have a positive genome-wide NIPS test would have their risk of a clinically significant chromosomal abnormality increased from 18.8% to 55.6%, which may serve to support confirmatory diagnostic testing for patients of a given risk preference profile. In contrast, a negative genome-wide NIPS in this population serves to reduce residual risk only marginally from 18.8% to 12.7%.