Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18 Daoshan Road, Fuzhou City, 350001, Fujian Province, China.
Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.
Sci Rep. 2024 Apr 22;14(1):9220. doi: 10.1038/s41598-024-59422-8.
This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.
本研究旨在评估因胎儿生长受限（FGR）伴结构畸形而接受侵袭性产前诊断的胎儿的病因学和妊娠结局。本研究收集了 2011 年 7 月至 2023 年 7 月期间因 FGR 伴结构畸形而接受产前诊断的 130 例妊娠病例。对所有患者均进行了传统的核型分析。核型分析共检出 37 例（28.5%）染色体异常，包括 30 例数目异常和 7 例非平衡性结构异常。三体 18 是最常见的异常，占 51.4%，显著高于其他任何染色体异常。本队列主要为早发型 FGR（88.5%），晚发型 FGR（11.5%）较少。这两组的染色体异常发生率分别为 29.6%（34/115）和 20.0%（3/15），差异无统计学意义（p>0.05）。大多数（74.6%，97/130）患者存在单一系统畸形，其中 19.6%（19/97）的病例存在染色体异常。在结构畸形涉及两个或多个系统的妊娠中，频率分别为 56.5%（13/23）和 50.0%（5/10）。对 65 例患者同时进行了单核苷酸多态性微阵列（SNP 微阵列）分析，结果显示与核型分析相比，拷贝数变异（CNVs）的检出率增加了 7.7%。对 92 例患者进行了巨细胞病毒（CMV）DNA 的聚合酶链反应（PCR）检测。所有 FGR 伴两个或多个系统畸形的胎儿均被终止妊娠或死胎，无论染色体是否异常。相反，71.8%的单一系统畸形且遗传检测正常的妊娠患者均分娩存活新生儿。此外，有 2 例（2.2%）CMV DNA 检测阳性，导致 1 例终止妊娠，1 例出生后出现严重发育障碍。本研究表明，FGR 相关的结构畸形更可能影响单一器官系统。当涉及多个系统时，染色体异常的发生率和终止率显著升高。我们建议在 FGR 患者行侵袭性产前诊断时进行 CMA 和 CMV DNA 检查，这些检查可以为病因学探索和妊娠管理提供有价值的信息。
