Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study.

Objective: To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency.

Methods: Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities.

Results: There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05).

Conclusion: The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.