A retrospective study for diagnostic value of chromosomal microarray analysis in fetuses with high-risk prenatal indications

Abstract

Abstract Objective The aim of this study was to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with high risk for various conditions on chromosomal abnormalities. Methods 8560 clinical samples were collected from pregnant women between Feb 2018 and June 2022, including 75 villus, 7642 amniotic fluid, and 843 umbilical cord blood samples. This retrospective analysis included pregnancies with high-risk indications for invasive prenatal diagnosis, mainly including ultrasound anomalies, high-risk for maternal serum screening(MMS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA). All samples were evaluated by both CMA and karyotyping. The rate of clinically significant genomic imbalances between the different groups was compared. Results The success rate of CMA was 99.95% (8556/8560). A total of 1037 samples (12.11%, 1037/8560) presented with chromosomal abnormalities by using CMA, whereas 803 samples (9.38%, 803/8560) presented with chromosomal abnormalities by using karyotyping. The overall prenatal diagnostic yield was 1040 (12.14%) of 8560 pregnancies. Clinically significant genomic aberrations were identified in 153 (6.21%) of 2463 patients with non-structural ultrasound anomalies, 79(6.38%) of 1238 with structural ultrasound anomalies, 37 (4.26%) of 868 at high-risk for MSS, 395(42.29%) of 934 at high-risk for NIPT, 16 (2.94%) of 544 with a family history, 7 (1.89%) of 369 with AMA, 1 (1.56%) of 64 with history of adverse exposure, 10 (4.46%) of 224 with parental chromosome anomalies and 9 (2.99%) of 301 with other indications. Conclusion CMA has a better diagnostic value for screening chromosomal abnormalities, especially for pregnant women with normal karyotypes. The diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, hydrops fetalis, cystic hygroma and thickened nuchal translucency or nuchal fold.