ABC | Volume 111, Nº4, Octuber 2018

Original Article Genetic Testing and Pregnancy Outcome Analysis of 362 Fetuses with Congenital Heart Disease Identified by Prenatal Ultrasound Shiyu Luo, Dahua Meng, Qifei Li, Xuehua Hu, Yuhua Chen, Chun He, Bobo Xie, Shangyang She, Yingfeng Li, Chunyun Fu Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 1 Guangxi - China Mailing Address: Chunyun Fu • N°.59 Xiangzhu Road, Nanning, Guangxi – China E-mail: fuchunyun2008@sina.com , 948178849@qq.com Manuscript received July 16, 2017, revised manuscript April 11, 2018, accepted April 11, 2018 DOI: 10.5935/abc.20180144 Abstract Background: Congenital heart defects (CHD), as the most common congenital anomaly, have been reported to be associated with chromosomal abnormalities. Currently, patients with CHD are routinely offered karyotyping and chromosomal microarray (CMA) testing, but the genotype‑phenotype relationship has not yet been fully established. Objective: To determine the type and frequency of chromosomal abnormalities in fetuses with CHD and to analyze pregnancy outcomes of fetuses with heart abnormalities caused by different genetic factors. Methods: A total of 362 cases of CHDwere enrolled from 2009 to 2016. Detailed ultrasound and laboratory examinations, including karyotyping and CMA, were performed. Outcome was obtained from discharge summaries. Results: Of the 362 fetuses, 220 were found with an isolated CHD, and 142 had CHD with extracardiac anomaly. Among these 362 fetuses, 140 were identified with a genetic cause, including 111 cases with aneuploidy, 10 cases with abnormality of chromosomal structure by karyotyping and 19 cases with pathogenic or likely pathogenic copy‑number variations (CNVs) by CMA. The detection rate is close to 38.7%. Only one (identified as trisomy 18 syndrome) in 140 positive cases resulted in perinatal death, with the others being induced. The remaining 222 cases had negative results for both genetic testing and of these cases, 56 resulted in induced labor, and 77 had natural childbirth or caesarean births. The pregnancy outcome of the remaining 89 cases was uncertain. Conclusions: Karyotyping and CMA are effective and accurate prenatal genetic techniques for identifying fetal chromosomal abnormalities associated with cardiac defects, and this can assist clinical doctors to perform appropriate genetic counselling with regard to the etiology and outcome of CHD. (Arq Bras Cardiol. 2018; 111(4):571-577) Keywords: Heart Defects, Congenital; Chromosome Disorders; Spectral Karyotyping; Pregnancy; Fetus; Ultrasonography. Introduction Congenital heart disease (CHD), one of the most common birth defects, affecting approximately 1 in 100 live births. 1-3 With the availability of advanced surgical techniques, normal or near normal cardiac function can be restored after surgical treatment of most types of CHDs ranging from simple ventricular septal defects (VSD) tomore complex cardiovascular abnormalities. However, the long-term prognosis of a small, but significant number of CHD fetuses is usually complicated by severe extracardiac abnormalities, such as developmental delay and mental retardation. There is increasing evidence that genetic factors influence the development of most types of CHD, 4-6 but the precise genetic basis of most CHD cases remains not fully understood. Current ultrasound technologies are able to detect most of CHD. However, it is difficult for physicians to make a comprehensive assessment of fetuses with CHDmerely based on the evidence of prenatal ultrasound, as well as to manage the course of established pregnancy. 7 Therefore, genetic testing is now highly recommended for fetuses with CHD. Karyotyping has been the mainstream diagnostic method for detecting chromosomal abnormalities associated with CHD. 8 For CHD cases in prenatal diagnosis, chromosomal anomalies are estimated to be as high as 22. 9,10 Now, chromosomal microarray (CMA) has become the first tier technique in fetal structural anomalies detected by ultrasonography. 11,12 TheadventofCMAtechnologyhasallowedgenome-widesearches of submicroscopic chromosomal deletions or duplications in the genome, known as copy-number variations (CNVs). CNV is a form of structural variation in the genome: specifically, it is a type of duplication or deletion that has an influence in the base pairs, 13 and CNVs play an important role in generating necessary variation in the population and disease phenotypes. 14 Recent studies have shown that a substantial proportion of CHD patients were detected with pathogenic CNVs, 15, 16 and the syndromic or isolated CHD patients were found with multiple recurrent CNV loci, such as 22q11.2 (the DiGeorge syndrome region), 7q11.23, 8p23.1, 9q34.3, and 1q21.1. 17-19 571