Prenatal Diagnostic Value of Chromosomal Microarray in Fetuses with Nuchal Translucency Greater than 2.5 mm

Objective. To assess the clinical value of prenatal diagnosis using quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA) for the examination of genomic imbalances in prenatal amniotic fluid samples from fetuses with a nuchal translucency (NT) greater than or equal to 2.5 mm. Materials and Methods. A total of 494 amniotic fluid samples and 5 chorionic villus samples were included in this study, with a fetal NT ≥ 2.5 mm at 11–13+6 weeks of gestation from November 2015 to December 2018. All cases were examined with QF-PCR, and those with normal QF-PCR results were then analyzed by CMA. Results. Of the 499 cases, common aneuploidies were detected by QF-PCR in 61 (12.2%) cases. One case of triploidy, one case of trisomy 21 mosaicism, and two cases of X/XX mosaicism were further confirmed by fluorescence in situ hybridization (FISH). Among the 434 cases with normal QF-PCR results, microarray detected additional pathogenic copy number variants (CNVs) in 4.8% (21/434) of cases. Six cases would have been expected to be detectable by conventional karyotyping because of large deletions/duplications (>10 Mb), leaving fifteen (3.5%, 15/428) cases with pathogenic CNVs only detectable by CMA. Pathogenic CNVs, especially those <10 Mb, were centralized in cases with an NT < 4.5 mm, including 5 pathogenic CNVs in cases with an NT of 2.5–3.5 mm and 7 pathogenic CNVs in cases with an NT of 3.5–4.5 mm. Conclusions. It is rational to use a diagnostic strategy in which CMA is preceded by a less-expensive, rapid method, namely, QF-PCR, to detect common aneuploidies. CMA allows for the detection of a number of pathogenic chromosomal aberrations in fetuses with an NT ≥ 2.5 mm.