Chromosomal microarray analysis for pregnancies with or without ultrasound abnormalities in women of advanced maternal age

Abstract

Background: Chromosomal microarray analysis (CMA) has been suggested to be routinely conducted for fetuses with ultrasound abnormalities (UA), especially with ultrasound structural anomalies (USA). Whether to routinely offer CMA to women of advanced maternal age (AMA) without UA when undergoing invasive prenatal testing is inconclusive.Objective: This study aimed to evaluate the efficiency of CMA in detecting clinically significant chromosomal abnormalities in fetuses, with or without UA, of women with AMA.Methods: Data from singleton pregnancies referred for prenatal CMA due to AMA, with or without UA were obtained. The enrolled cases were divided into AMA group (group A) and AMA accompanied by UA group (group B). Single nucleotide polymorphism (SNP) array technology and conventional karyotyping were performed simultaneously.Results: A total of 703 cases were enrolled and divided into group A (N = 437) and group B (N = 266). Clinically significant abnormalities were detected by CMA in 52 cases (7.4%, 52/703; the value in group A was significantly lower than that in group B (3.9% vs 13.2%, P < .05); no statistic difference was observed with respect to submicroscopic variants of clinical significance between the two groups (0.9% vs 2.6%, P > .05). Conclusions:Chromosomal microarray analysis should be available to all women with AMA undergoing invasive prenatal testing, regardless of ultrasound findings. K E Y W O R D S advanced maternal age, chromosomal microarray analysis, conventional karyotyping, ultrasound abnormalities How to cite this article: Wu X, An G, Xie X, et al. Chromosomal microarray analysis for pregnancies with or without ultrasound abnormalities in women of advanced maternal age. J Clin Lab

Clinical Application of Chromosomal Microarray Analysis in Pregnant Women with Advanced Maternal Age and Fetuses with Ultrasonographic Soft Markers

“…In our study, CMA results proved that the detection rate of clinically significant CNVs was 2.37% in group 1, which is higher than the 0.92% reported by Wu et al [ 14 ]. Previous research reports showed that the incremental diagnostic rate of CMA in the group of pregnant women with AMA alone ranged from 0.29% to 1.73%, as shown in Table 6 .…”

“…However, previous studies had shown that the fetus with USG soft markers is related to an increased risk of chromosomal abnormalities. Previous studies have shown that the incremental diagnostic rate of CMA for fetuses with USG soft markers and a normal karyotype ranged from 2.60% to 4.95% ( Table 6 ) [ 7 , 9 , 14 , 16 – 24 ]. In this study, the rate was 2.0% and the lower detection rate may be caused by the types of soft markers.…”

“…Moreover, this study also analyzed the CMA results of the AMA pregnant women with the fetal USG soft markers and a normal karyotype (group 3). There is only 1 previous study that assessed this issue, showing a detection rate of 1.49% (2/134) for abnormal CMA findings with clinical significance [ 14 ]. In our study, the detection rate was 5.07% (7/138), which was higher than that reported by Wu et al and similar to that of fetuses with structural anomalies [ 14 ].…”

“…However, the interpretation of VUS results has become a difficult problem in the clinical application of CMA. The rate of VUS detected by CMA is quite variable [ 14 , 28 , 29 ]. In our study, VUS was detected from the 3 research groups and had a comparatively higher detection rate of 15.78% than that in the previous literature.…”

The difference between karyotype analysis and chromosome microarray for mosaicism of aneuploid chromosomes in prenatal diagnosis

“…These results are consistent with those reported in the literature (Table 2). [16][17][18][19][20][21] Chen et al 22,23 reported that the calculated level of trisomy mosaicism in amniocytes was higher from fluorescent in situ hybridization (FISH) analysis (using uncultured amniocytes) compared with karyotype analysis. As mentioned above, these results may reflect the poor genetic stability and elimination of cells with trisomy during long-term cell culture (required for karyotype analysis), leading to the relatively reduced levels of trisomy mosaicism from karyotype analysis.…”