Complementary role of echocardiography, karyotyping, and chromosomal microarray in congenital cardiac anomalies

Objective To assess the diagnostic efficacy of echocardiography, chromosome karyotyping, and chromosomal microarray analysis (CMA) in congenital cardiac anomalies. Methods This retrospective cohort study analyzed data from 3,386 pregnant women who underwent echocardiography and amniocentesis at the Sichuan Provincial Maternal and Child Health Care Hospital between January 2020 and August 2022. The study group included 697 women whose fetuses were diagnosed with congenital heart disease (CHD) by echocardiography, while the comparison group included 2,689 women with normal echocardiographic results. The diagnostic contributions of echocardiography, karyotyping, and CMA were compared between the two groups. Results Among the 697 cases diagnosed with CHD, the most common types were ventricular septal defect (44.45%) and valve abnormalities (40.66%). Chromosomal abnormalities were detected in 41 out of 629 CHD cases (6.52%) by karyotyping, with higher rates in complex CHD (16.36%) and CHD with extracardiac anomalies (23.08%) compared to the comparison group (4.71%). CMA identified 34 pathogenic copy number variations (CNVs) (5.28%) and 9 variants of unknown significance (VOUS) (1.40%) in 644 CHD cases, with higher CNV detection rates in complex CHD (7.69%) and CHD with extracardiac anomalies (7.69%) compared to the comparison group (1.38%). CMA further identified pathogenic CNVs in 4.42% (26/588) of CHD cases with a normal karyotype, yielding an incremental diagnostic rate of 4.42%. Conclusion Echocardiography remains the cornerstone for the prenatal detection of fetal heart malformations. When combined with karyotyping and CMA, this integrated approach achieves maximal detection of both macroscopic and submicroscopic genomic alterations—particularly in complex cardiac malformations or when extracardiac anomalies coexist—thereby delivering timely, comprehensive genetic information to guide early intervention and tailored perinatal counseling.