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

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).

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.

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).

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.