A Retrospective Study of Noninvasive Prenatal Testing for Chromosome Aneuploidies and Sub-Chromosomal Copy Number Variations in 24359 Single Pregnancies

Abstract Background: With the development of whole-genome sequencing, small sub-chromosomal deletions and duplications could be found by non-invasive prenatal testing(NIPT). This study aimed to review the efficiency of NIPT as a screening test for aneuploidies and sub-chromosomal copy number variations (CNVs) in 24359 single pregnancies.Methods: A total of 24359 single pregnancies with different clinical indications were retrospectively analyzed. The positive predictive value （PPV）of chromosome aneuploidies and subchromosomal CNVs were analyzed. Pathogenicity of abnormal NIPT results were assessed according to American College of Medical Genetics and Genomics(ACMG). Results: A total of 442 pregnancies (442/24359,1.9%) were with abnormal NIPT results. PPV for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), and sex chromosome aneuploidies (SCAs) was 84.8%, 54.2%, 11.1% an 40.5% respectively. The PPV for sub-chromosomal CNVs was 59.0% (46/78). The PPV for CNVs ≤5 Mb was 68.9% (31/45), for CNVs within 5-10 Mb was 83.3%(5/6) and for CNVs ≥10 Mb was 37.1% (10/27) respectively. The clinical information, prenatal diagnosis results and follow-up results of 46 true positive cases, 6 cases with sub-chromosomal CNVs inconsistent with NIPT and 1 false negative case were also described in detail.Conclusions: Our data have potential significance in demonstrating the significance of NIPT not only for common whole chromosome aneuploidies but also for sub-chromosomal CNVs. Besides, the clinical information, prenatal diagnosis results and follow-up results of 52 cases with sub-chromosomal CNVs and 1 false negative case would provide important guidance for genetic counseling.