When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes

Objective: To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate optimal screening or action with a NT 95th percentile-3.50 mm. Methods: A retrospective analysis 2,328 pregnancies ≥ percentile through ultrasound-guided transabdominal chorionic villus sampling (CVS), amniocentesis, cordocentesis obtained clinical samples (chorionic villi, amniotic fluid, cord blood), real-time quantitative fluorescent PCR (QF-PCR), chromosome karyotyping (CS), microarray (CMA), whole exome sequencing (WES) were provided identify genetic etiologies. Results: In this study, incidence chromosomal defects increased thickness. When 6.5 mm, 71.43% attributed abnormalities. The 994 gravidas fetal underwent short tandem repeat (STR), CS, CMA. 804 fetuses normal karyotypes, CMA detected 16 (1.99%) extra pathogenic likely copy number variations (CNVs). incremental yield was only 1.16% (3/229) 3.37% (10/297) in group percentile-2.99 mm 3.0–3.49 separately. Among 525 who STR, CMA, WES, WES 4.09% (21/513). there no additional single-nucleotide (SNVs) while 143 cases 5.59% (8/143). Conclusion: percentile-3.0 since aneuploidy variation primary causes contribution not significant, we recommend NIPT-Plus pregnant women first. addition, comprehensive testing involving can benefit