[Genetic characteristics and prognostic analysis of 162 fetal cardiac abnormalities]

Objective: To analyze the type and characteristics of fetal cardiac abnormalities and their relationships with genetic abnormalities and clinical prognosis. Methods: The clinical data of 162 pregnant women with fetal cardiac abnormalities who came to the prenatal diagnosis center of Peking University First Hospital and performed genetic tests from February 2013 to February 2021 were reviewed. Genetic testing methods included chromosome karyotype analysis, array-based comparative genomic hybridization (aCGH) and pathogenic gene detection. Fetuses with isolated cardiac abnormalities and no fatal genetic abnormalities were assessed using the fetal cardiac birth defects clinical outcome score and followed up. Results: (1) Ultrasonography results: among the 162 fetuses, 86 cases (53.1%, 86/162) had isolated cardiac abnormalities, and 76 cases (46.9%, 76/162) had extra-cardiac abnormalities; single cardiac abnormalities were in 84 (51.9%,84/162) cases, and multiple cardiac abnormalities occurred in 78 cases (48.1%,78/162). (2) Genetic examination results: there were 39 cases (24.1%, 39/162) of pathogenic genetic abnormalities, including 35 cases (21.6%, 35/162) of pathogenic chromosome karyotype abnormality, 3 cases (1.9%, 3/162) of pathogenic copy number variant (CNV), and 1 case (0.6%, 1/162) of pathogenic gene variation. The detection rates of pathogenic genetic abnormalities were 16.3% (14/86) in fetuses with isolated cardiac abnormalities and 32.9% (25/76) in fetuses with cardiac abnormalities and extra-cardiac abnormalities, and the difference was statistically significant (χ²=6.094, P=0.014). The detection rate of genetic abnormalities was 28.6% (24/84) in the single cardiac abnormalities, among which ventricular septal defect was 36.7% (11/30), atrioventricular septal defect was 8/13, tetralogy of Fallot was 3/17, persistent trancus arteriosus was 1/1, cardiac tumor was 1/1; no genetic abnormality was detected in the other single cardiac abnormality types (22 cases in total). The main types of pathogenic genetic abnormalities were trisomy 21 (41.7%, 10/24) and trisomy 18 (41.7%, 10/24). (3) Pregnancy outcome and fetal prognosis: among 72 fetuses with isolated heart abnormalities without pathogenic genetic abnormalities, there were 4 cases of grade Ⅰ, all of which continued pregnancy; 39 cases of grade Ⅱ, with 21 cases induced labor, 18 cases continued pregnancy; 26 cases of grade Ⅲ, with 23 cases induced labor, 3 cases continued pregnancy; 3 cases of grade Ⅳ, all of which induced labor. Totally, there were 47 cases induced labor and 25 cases continued pregnancy, 24 cases (96.0%, 24/25) of which were alive. Conclusions: When fetal cardiac abnormalities are detected by prenatal ultrasound, comprehensive cardiac and extra-cardiac ultrasound assessment and further genetic testing are recommended. Fetuses excluded pathogenic genetic abnormalities and extra-cardiac abnormalities should perform clinical prognostic score evaluation through multidisciplinary collaboration, to improve maternal and fetal outcomes.