The assessment of combined karyotype analysis and chromosomal microarray in pregnant women of advanced maternal age: a multicenter study

Abstract

Background: Retrospectively analyzed the results of prenatal diagnosis and hoped to provide scientific clinical guidance of prenatal screening and diagnosis for the women in advanced maternal age (AMA). Methods: In total, 4,224 women of AMA who accepted prenatal diagnosis by amniocentesis (AC) from two prenatal diagnosis centers were recruited for this study. After genetic counseling and informed consent, 3,475 women received karyotype analysis only, 703 were examined by both karyotype analysis and chromosomal microarray (CMA), while 46 cases selected CMA only. Both centers used the same detection platform, experimental scheme, and quality control standards. Results: A total of 164 women with chromosomal abnormal results were found, the abnormality rate was 3.88% (164/4,224). Among them, 145 (3.4%, 145/4,224) cases were detected as abnormal chromosome number, 19 cases (0.4%, 19/4,224) as abnormal chromosome structure. Compared with simple AMA women, the abnormality rate was significantly increased in the AMA women who combined with other indications, particularly in number abnormalities (22.5% vs. 1.0%, P<0.001). Forty-eight copy number variations (CNVs) were detected, moreover 10 cases (0.24%, 10/4,224) were proved as pathogenic or likely pathogenic CNVs. With the CMA technology, the rate of additional abnormalities with clinical significance was 1.42% (10/703). Chromosome number abnormalities significantly increased with age (P<0.001), while there were no such trends in chromosomal structural abnormalities (P=0.624). Conclusions: About 3.88% fetuses of AMA women had chromosomal abnormalities, the abnormality rate increased with their age. The application of CMA could increase the diagnostic rate by about 1.4% for AMA women, and greatly reduce their tension.

Prenatal diagnosis of 2193 pregnant women with invasive indications for chromosomal abnormalities in southern China: a retrospective study

“…Besides, follow up data showed that 169 (45.5%) women terminated pregnancy based on ultrasonic outcomes, which highlighted the importance of ultrasonography in prenatal screen. Previous studies exploring the effect of maternal age on self-generating abortion found that AMA was a crucial factor related to fetal chromosome aneuploidy (21,22). Consistently, we con rmed AMA as an important risk factor of chromosome abnormalities.…”

Chromosomal Abnormality in Fetuses with Isolated Antenatal Hydronephrosis: Update for Prenatal Diagnosis and Genetic Counseling

“…In case 2 (table3), the deleted region on chromosome15q11. characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature [15] .In case 10 (table 3), a de novo deletion fragment in 17q12 region covered 99.97% region of RCAD (renal cysts and diabetes) syndrome.…”

“…Moreover, we incorporated fetuses with APRPD of 10 mm and progressed to determine the cutoff value for application of CMA. Because the value of 10 mm and less measured at 2nd Trimester was also the cutoff value for fetal mild bilateral pyelectasis, which was a benign condition especially when the renal pelvis regressed [18] [19] . Based on these ndings, we suggest that cases with APRPD of 10 mm and further progressed could be offered for invasive procedures.…”

“…Human cyto12 SNP array (Illumina, San Diego, CA) comprising approximately 300,000 SNP probes with average marker spacing of roughly one probe every 10 kb was applied for the whole-genome scan. SNP array experiments were performed as previously described in our laboratory [13] and molecular karyotype analysis was performed by KaryoStudio V 1.4.3.0 (Illumina). Copy number variations (CNVs) were called at an effective minimal resolution of 100 kb involving at least 10 contiguous probes.…”

“…CNVs that did not t any of the above criteria were considered as VOUS. All above experimental and analytical methods were performed based on the previous report as reference in our laboratory [13] . In this study, we reported only pathogenic CNVs and VOUS.…”