Clinical features and genetic analysis of 471 cases of fetal congenital heart disease: A systematic review

Abstract

Abstract Background Congenital heart disease (CHD) is a heterogeneous collection of structural abnormalities of the heart or great vessels that are present at birth. These birth defects are one of the leading causes of infant mortality and morbidity worldwide. The etiology and pathogenesis of CHD are unclear and largely considered to be multifactorial in nature. Since the chromosomal profile of CHD has not been analyzed in a large sample size, we aimed to summarize the clinical features, cytogenetics findings, and pregnancy outcomes of CHD to provide a clinical reference for prenatal diagnosis. Methods Among 21152 pregnant women, 471 showed fetal CHD on cordocentesis or amniocentesis. The number of cases showing simple CHD, simple CHD plus extracardiac abnormality, complex CHD, and complex CHD plus extracardiac abnormality was 128, 124, 89, and 130, respectively. For prenatal genetic diagnosis, rapid karyotyping was performed with single-nucleotide polymorphism (SNP) arrays, fluorescence in situ hybridization, and copy number variation (CNV) and BACs-on-Beads™ analyses. We also recorded the results of ultrasonography examinations and genetic analysis and the pregnancy outcomes. Results Ventricular septal defects were observed in 245 cases of fetal CHDs. Among the 471 cases of CHDs, 258 showed other ultrasound abnormalities. The most common ultrasound abnormalities were abnormalities of the central nervous system. The 471 cases included 93 cases with chromosomal abnormalities, and the incidence of these abnormalities increased with advanced maternal age or the presence of other ultrasound abnormalities. In eight cases, karyotype analysis showed normal results, while SNP-array or CNV-seq results were abnormal. Among the 453 cases that were followed-up, 166 involved pregnancy termination, 273 involved live births, seven involved fetus death in utero, and seven involved neonatal death after birth. Conclusions Fetuses with CHD showed higher rates of chromosomal abnormalities. In cases diagnosed with fetal CHD during fetal ultrasonic examination, the mothers should undergo a careful and comprehensive fetal ultrasound scan as well as prenatal genetic testing, including karyotype analysis and SNP-array or CNV-sequencing. The prognosis for simple fetal CHD is good, while the prognosis for complex fetal CHD and extracardiac anomalies is poor.