Medical Genetic Center, Jiangxi Maternal and Child Health Hospital, No. 318, Bayi Avenue, Nanchang, China.
Jiangxi Key Laboratory of Birth Defect Prevention and Control, No. 318, Bayi Avenue, Nanchang, China.
Orphanet J Rare Dis. 2024 Aug 22;19(1):307. doi: 10.1186/s13023-024-03317-4.
Congenital heart defect (CHD) is one of the most common birth defects. The aim of this cohort study was to evaluate the prevalence of chromosomal abnormalities and the clinical utility of chromosomal microarray analysis (CMA) in fetuses with different types of CHD, aiming to assist genetic counseling and clinical decision-making.
In this study, 642 fetuses with CHD were enrolled from a single center over a six-year period (2017-2022). Both conventional karyotyping and CMA were performed simultaneously on these fetuses.
The diagnostic yield of CMA in fetuses with CHD in our study was 15.3% (98/642). Our findings revealed a significant increase in the diagnostic yield of CMA compared to karyotyping in fetuses with CHD. Among CHD subgroups, the diagnostic yields were high in complex CHD (34.9%), conotruncal defects (28.6%), right ventricular outflow tract obstructive defects (RVOTO) (25.9%), atrioventricular septal defects (AVSD) (25.0%) and left ventricular outflow tract obstructive defects (LVOTO) (24.1%), while those in other CHD (10.6%) and septal defects (10.9%) were relatively low. The overall detection rate of clinically significant chromosomal abnormalities was significantly higher in the non-isolated CHD group compared to the isolated CHD group (33.1% vs. 9.9%, P < 0.0001). Interestingly, numerical chromosomal abnormalities were more likely to occur in the non-isolated CHD group than in the isolated CHD group (20.3% vs. 2.0%, P < 0.0001). The rate of termination of pregnancy (TOP)/Still birth in the non-isolated CHD group was significantly higher than that in the isolated CHD group (40.5% vs. 20.6%, P < 0.0001). Compared to the isolated CHD group, the detection rate of clinically significant chromosomal abnormalities was significantly higher in the group of CHD with soft markers (35.6% vs. 9.9%, P < 0.0001) and in the group of CHD with additional structural anomalies (36.1% vs. 9.9%, P < 0.0001).
CMA is a reliable and high-resolution technique that should be recommended as the front-line test for prenatal diagnosis of fetuses with CHD. The prevalence of chromosomal abnormalities varies greatly among different subgroups of CHD, and special attention should be given to prenatal non-isolated cases of CHD, especially those accompanied by additional structural anomalies or soft markers.
先天性心脏病（CHD）是最常见的出生缺陷之一。本队列研究旨在评估不同类型 CHD 胎儿中染色体异常的发生率，以及染色体微阵列分析（CMA）的临床应用价值，旨在为遗传咨询和临床决策提供辅助。
本研究纳入了 642 例来自单一中心的 CHD 胎儿，研究时间为 2017 年至 2022 年。对这些胎儿同时进行常规核型分析和 CMA。
在本研究中，CMA 在 CHD 胎儿中的诊断率为 15.3%（98/642）。我们的研究结果显示，与核型分析相比，CMA 在 CHD 胎儿中的诊断率显著提高。在 CHD 亚组中，复杂 CHD（34.9%）、圆锥动脉干畸形（28.6%）、右心室流出道梗阻性病变（RVOTO）（25.9%）、房室间隔缺损（AVSD）（25.0%）和左心室流出道梗阻性病变（LVOTO）（24.1%）的诊断率较高，而其他 CHD（10.6%）和间隔缺损（10.9%）的诊断率较低。非孤立性 CHD 组的临床意义染色体异常总检出率明显高于孤立性 CHD 组（33.1% vs. 9.9%，P<0.0001）。有趣的是，非孤立性 CHD 组中数值性染色体异常的发生率高于孤立性 CHD 组（20.3% vs. 2.0%，P<0.0001）。非孤立性 CHD 组的终止妊娠（TOP）/死胎率明显高于孤立性 CHD 组（40.5% vs. 20.6%，P<0.0001）。与孤立性 CHD 组相比，伴有软标记物的 CHD 组（35.6% vs. 9.9%，P<0.0001）和伴有其他结构异常的 CHD 组（36.1% vs. 9.9%，P<0.0001）的临床意义染色体异常检出率显著升高。
CMA 是一种可靠且高分辨率的技术，应推荐作为 CHD 胎儿产前诊断的一线检测方法。染色体异常的发生率在不同类型的 CHD 亚组中差异很大，应特别关注产前非孤立性 CHD 病例，尤其是伴有其他结构异常或软标记物的病例。
