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

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.

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.

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.

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.