Clinical application of chromosomal microarray for pathogenic genomic imbalance in fetuses with increased nuchal translucency but normal karyotype

Abstract

Purpose: To evaluate the additive value of prenatal chromosomal microarray analysis (CMA) in assessing increased nuchal translucency (NT) (≥3.5 mm) with normal karyotype and the possibility of detecting clinically significant genomic imbalance, based on specific indications. Materials and Methods: Invasive samples from 494 pregnancies with NT ≥3.5 mm, obtained from the Research Center of Fertility & Genetics of Hamchoon Women's Clinic between January 2019 and February 2020, were included in this study and CMA was performed in addition to a standard karyotype. Results: In total, 494 cases were subjected to both karyotype and CMA analyses. Among these, 199 cases of aneuploidy were excluded. CMA was performed on the remaining 295 cases (59.7%), which showed normal (231/295, 78.3%) or non-significant copy number variation (CNV), such as benign CNV or variants of uncertain clinical significance likely benign (53/295, 18.0%). Clinically significant CNVs were detected in 11 cases (11/295, 3.7%). Conclusion: Prenatal CMA resulted in a 3% to 4% higher CNV diagnosis rate in fetuses exhibiting increased NT (≥3.5 mm) without other ultrasound detected anomalies and normal karyotype. Therefore, we suggest using high resolution, non-targeting CMA to provide valuable additional information for prenatal diagnosis. Further, we recommend that a genetics specialist should be consulted to interpret the information appropriately and provide counseling and follow-up services after prenatal CMA.

Chromosomal microarray analysis versus noninvasive prenatal testing in fetuses with increased nuchal translucency

“…Though the American College of Obstetricians and Gynecologists (ACOG) recommended that the usefulness of CMA in detecting chromosomal abnormalities remains ambiguous and conventional karyotype analysis remains the preferred method of prenatal diagnostic testing [ 23 ]. In the past years, more and more studies have demonstrated advantages of CMA over karyotype analysis in prenatal diagnosis [ 10 , 13 ]. In addition, a cut-off value of NT with 3.0 or 3.5 nm was used as the threshold in most investigations on the association between CMA and NT, the objective of this study was to determine whether CMA should be recommended on fetuses with NT ≥ 2.5 mm, but normal karyotypes.…”

“…CMA is a high-resolution and high-throughput molecular detection technology for detecting human genomic DNA copy number variation, which shows advantages over karyotyping both in postnatal diagnosis and prenatal diagnosis. According to the most recent research, applying of CMA in fetuses with elevated NT identified additional pathogenic copy number variants (CNVs) over that from karyotyping in 3.7% [ 10 ]. However, no global consensus on the cut-off value of NT for CMA has been reached currently.…”