{"title":"胎儿心脏畸形的未知变异：分布及其对产前决策的影响。","authors":"Qingsong Wang, Jun Yin, Xiaomeng Zhang, Huimin Ou, Fuyan Li, Yundong Zhang, Caiyu Guo, Weiyi Wan, Yongyu Cao, Tongyong Luo, Xianmin Wang","doi":"10.3389/fped.2025.1605899","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the distribution patterns of variants of unknown significance (VUS) in fetuses with heart malformations (CHD) combined with extracardiac abnormalities and their impact on prenatal decision-making.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the chromosomal microarray analysis (CMA) data of 697 cases of fetal heart malformations (including simple, complex, and combined with extracardiac abnormalities) and 2,689 controls from Sichuan Provincial Maternal and Child Health Care Hospital between January 2020 and August 2022. Copy number variants (CNVs) were classified according to the ACMG guidelines (pathogenic, VUS, benign), and the differences in VUS detection rates and their impact on pregnancy outcomes were compared among groups.</p><p><strong>Results: </strong>Among 697 fetuses with prenatally diagnosed cardiac malformations, 602 (86.37%) had simple, 69 (9.90%) complex, 18 (2.58%) combined with structural extracardiac anomalies, and 8 (1.15%) with soft markers. Karyotype abnormalities occurred in 4.74% (26/549), 16.36% (9/55), 27.78% (5/18), and 12.50% (1/8) of these groups, respectively, all exceeding controls (4.71%, <i>P</i> < 0.05). Pathogenic CNVs were detected in 4.88% (27/553), 7.69% (5/65), 8.33% (2/24), and 0% (0/2), respectively; the first three rates were significantly higher than controls (1.38%, <i>P</i> < 0.05, <i>P</i> = 0.002, <i>P</i> = 0.033). VUS rates rose progressively: 0.54% (3/553), 1.54% (1/65), 12.50% (3/24), and 100% (2/2). Among nine VUS-positive pregnancies, six resulted in live-born infants without abnormalities; three were terminated due to additional malformations or parental anxiety.</p><p><strong>Conclusion: </strong>Fetuses with cardiac malformations accompanied by structural extracardiac anomalies carry the highest genetic risk; karyotyping combined with CMA should therefore be performed routinely. Complex cardiac malformations also warrant concurrent testing, whereas simple malformations and those with soft markers can be evaluated individually.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":"13 ","pages":"1605899"},"PeriodicalIF":2.0000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504073/pdf/","citationCount":"0","resultStr":"{\"title\":\"Variants of unknown significance in fetal heart malformations: distribution and impact on prenatal decision-making.\",\"authors\":\"Qingsong Wang, Jun Yin, Xiaomeng Zhang, Huimin Ou, Fuyan Li, Yundong Zhang, Caiyu Guo, Weiyi Wan, Yongyu Cao, Tongyong Luo, Xianmin Wang\",\"doi\":\"10.3389/fped.2025.1605899\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate the distribution patterns of variants of unknown significance (VUS) in fetuses with heart malformations (CHD) combined with extracardiac abnormalities and their impact on prenatal decision-making.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the chromosomal microarray analysis (CMA) data of 697 cases of fetal heart malformations (including simple, complex, and combined with extracardiac abnormalities) and 2,689 controls from Sichuan Provincial Maternal and Child Health Care Hospital between January 2020 and August 2022. Copy number variants (CNVs) were classified according to the ACMG guidelines (pathogenic, VUS, benign), and the differences in VUS detection rates and their impact on pregnancy outcomes were compared among groups.</p><p><strong>Results: </strong>Among 697 fetuses with prenatally diagnosed cardiac malformations, 602 (86.37%) had simple, 69 (9.90%) complex, 18 (2.58%) combined with structural extracardiac anomalies, and 8 (1.15%) with soft markers. Karyotype abnormalities occurred in 4.74% (26/549), 16.36% (9/55), 27.78% (5/18), and 12.50% (1/8) of these groups, respectively, all exceeding controls (4.71%, <i>P</i> < 0.05). Pathogenic CNVs were detected in 4.88% (27/553), 7.69% (5/65), 8.33% (2/24), and 0% (0/2), respectively; the first three rates were significantly higher than controls (1.38%, <i>P</i> < 0.05, <i>P</i> = 0.002, <i>P</i> = 0.033). VUS rates rose progressively: 0.54% (3/553), 1.54% (1/65), 12.50% (3/24), and 100% (2/2). Among nine VUS-positive pregnancies, six resulted in live-born infants without abnormalities; three were terminated due to additional malformations or parental anxiety.</p><p><strong>Conclusion: </strong>Fetuses with cardiac malformations accompanied by structural extracardiac anomalies carry the highest genetic risk; karyotyping combined with CMA should therefore be performed routinely. Complex cardiac malformations also warrant concurrent testing, whereas simple malformations and those with soft markers can be evaluated individually.</p>\",\"PeriodicalId\":12637,\"journal\":{\"name\":\"Frontiers in Pediatrics\",\"volume\":\"13 \",\"pages\":\"1605899\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504073/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Pediatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fped.2025.1605899\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fped.2025.1605899","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
摘要
目的：探讨心脏畸形（CHD）合并心外异常胎儿中未知意义变异（VUS）的分布规律及其对产前决策的影响。方法：回顾性分析2020年1月至2022年8月四川省妇幼保健院697例胎儿心脏畸形（包括单纯性、复杂性及合并心外异常）和2689例对照组的染色体微阵列分析（CMA）数据。根据ACMG指南对拷贝数变异（CNVs）进行分类（致病性、VUS、良性），比较各组间VUS检出率的差异及其对妊娠结局的影响。结果：697例产前诊断心脏畸形胎儿中，单纯性602例（86.37%），复合性69例（9.90%），合并结构性心外异常18例（2.58%），软标记物8例（1.15%）。各组核型异常发生率分别为4.74%（26/549）、16.36%（9/55）、27.78%（5/18）和12.50%(1/8)，均超过对照组（4.71%,P P = 0.002, P = 0.033）。VUS率依次上升，分别为0.54%（3/553）、1.54%（1/65）、12.50%（3/24）和100%（2/2）。在9例vus阳性妊娠中，6例无异常活产婴儿；其中三人因额外的畸形或父母的焦虑而终止。结论：心脏畸形合并结构性心外异常的胎儿遗传风险最高；因此，核型联合CMA应常规进行。复杂的心脏畸形也需要同时检测，而简单的畸形和那些有软标记的可以单独评估。
Variants of unknown significance in fetal heart malformations: distribution and impact on prenatal decision-making.
Objective: To investigate the distribution patterns of variants of unknown significance (VUS) in fetuses with heart malformations (CHD) combined with extracardiac abnormalities and their impact on prenatal decision-making.
Methods: A retrospective analysis was conducted on the chromosomal microarray analysis (CMA) data of 697 cases of fetal heart malformations (including simple, complex, and combined with extracardiac abnormalities) and 2,689 controls from Sichuan Provincial Maternal and Child Health Care Hospital between January 2020 and August 2022. Copy number variants (CNVs) were classified according to the ACMG guidelines (pathogenic, VUS, benign), and the differences in VUS detection rates and their impact on pregnancy outcomes were compared among groups.
Results: Among 697 fetuses with prenatally diagnosed cardiac malformations, 602 (86.37%) had simple, 69 (9.90%) complex, 18 (2.58%) combined with structural extracardiac anomalies, and 8 (1.15%) with soft markers. Karyotype abnormalities occurred in 4.74% (26/549), 16.36% (9/55), 27.78% (5/18), and 12.50% (1/8) of these groups, respectively, all exceeding controls (4.71%, P < 0.05). Pathogenic CNVs were detected in 4.88% (27/553), 7.69% (5/65), 8.33% (2/24), and 0% (0/2), respectively; the first three rates were significantly higher than controls (1.38%, P < 0.05, P = 0.002, P = 0.033). VUS rates rose progressively: 0.54% (3/553), 1.54% (1/65), 12.50% (3/24), and 100% (2/2). Among nine VUS-positive pregnancies, six resulted in live-born infants without abnormalities; three were terminated due to additional malformations or parental anxiety.
Conclusion: Fetuses with cardiac malformations accompanied by structural extracardiac anomalies carry the highest genetic risk; karyotyping combined with CMA should therefore be performed routinely. Complex cardiac malformations also warrant concurrent testing, whereas simple malformations and those with soft markers can be evaluated individually.
期刊介绍：
Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.
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