Prenatal detection of congenital heart defects (CHDs) is essential for risk stratification and perinatal planning. A retrospective cohort study published in the Taiwanese Journal of Obstetrics and Gynecology assessed the diagnostic value of combining prenatal imaging with stepwise genetic testing in fetuses diagnosed with CHDs over a 30-year period (1995–2024) at Taichung Veterans General Hospital.

The study included 423 fetuses with CHDs, all of whom underwent detailed fetal echocardiography. Genetic evaluation followed a tiered strategy beginning with karyotyping, with additional testing using chromosomal microarray analysis (CMA), targeted gene panels, or whole-exome sequencing (WES) when clinically indicated. Diagnostic yield was evaluated across testing modalities and CHD subtypes, including analyses according to the presence of extracardiac anomalies.

Among CHD categories, cyanotic CHDs were most frequent (39.5%), followed by miscellaneous anomalies (22.9%), left-to-right shunts (18.9%), obstructive lesions (11.6%), and arrhythmias (7.1%). Septal defects accounted for 18.7% of cases and increased to 26.5% when associated intracardiac anomalies were included. Extracardiac structural abnormalities were present in 22.2%, and fetal hydrops occurred in 5.0%.

Chromosomal abnormalities were detected in 12.3% (40/326) of tested fetuses, predominantly trisomies, and were significantly associated with left-to-right shunts (55%, P<0.001) and extracardiac anomalies (62.5%, P<0.001). Among 181 cases with normal karyotypes, CMA identified pathogenic or likely pathogenic copy number variants (CNVs) in 7.7%, including deletions involving 22q11.21 (TBX1), 7q11.23 (ELN), and 16q24.2–q24.3 (ZFPM1).
Addition of WES or targeted sequencing increased the overall diagnostic yield to 14.1% (27/191).

These findings support a clinically guided and resource-sensitive approach to prenatal genetic evaluation in fetal CHDs.