Clinical Application of Chromosomal Microarray Analysis in Fetuses with Congenital Heart Disease

Background: Congenital heart disease (CHD) is an important birth defect, but its mechanism is still unclear. In recent years, genetic causes including chromosomal abnormalities are associated with the occurrence of congenital heart disease. In this study, CMA technology is applied to explore the genetic causes of congenital heart disease, so as to further clarify the correlation between genotype and phenotype and prepare for late pregnancy intervention and postnatal diagnosis and treatment. Objective: To explore the chromosomal abnormalities and copy number variation (CNVs) of fetuses with CHD by CMA technology, and to clarify the clinical application value of CMA technology as a detection method of first-tier antenatal CHD. Methods: : Amniotic fluid sample from 155 pregnant women diagnosed with fetus CHD by prenatal ultrasound from 2018 to 2021 are collected for SNP-array detection and karyotype analysis. According to the detected CNVs results, FISH, CMA or karyotype analysis are further selected for parental verification. Results: Among the 155 fetuses with CHD, a total of 32 (20.6%) cases of chromosomal abnormalities are detected, of which 31.3% are chromosome number abnormalities. CNVs of likely pathogenicity and unknown significance are 2.5% and 5.2% respectively. The detection rate of chromosomal abnormalities in CHD of different subtypes is different, among which the high detection rate is complex CHD (31.2%), right ventricular outflow tract obstruction (30.7%) and conotruncal defects (25%). The detection rate of chromosomal abnormalities in CHD with extracardiac structural abnormalities is significantly higher than that in isolated CHD (52.4% vs 11.3%, p<0.05). In addition, the detection rate of CHD with abnormal extracardiac structure is significantly higher than that of CHD with soft markers (52.4% vs 17.8%, p<0.05), which is statistically significant. There is no significant difference in detection rate between CHD with soft markers and isolated CHD (17.8% vs 11.3%). Of the 155 pregnant women with fetus CHD, 59 chose to terminate their pregnancies, some of which were terminated according to the results of SNP-array, and some of which were terminated according to the severity of CHD. Conclusion: SNP-array technology can be used to detect chromosomal abnormalities of first-tier antenatal CHD fetuses, with high resolution, short reporting period and high efficiency. Meanwhile, pregnancy intervention can be taken according to the results.