Noninvasive prenatal screening with conventional sequencing depth to screen fetal copy number variants: A retrospective study of 19 144 pregnant women.

Aim: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants.

Methods: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth.

Results: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases.

Conclusions: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.