70例孤立性胎儿颈项透明层增厚的临床咨询及妊娠结局分析

Clinical consultation and pregnancy outcomes in 70 cases of isolated fetal nuchal translucency thickening

摘要

目的 总结孤立性颈项透明层（NT）增厚胎儿的遗传学病因及预后，为产前咨询与诊断提供指导。方法 回顾性纳入2024年1月至2025年4月于遵义医科大学附属医院产前诊断中心因胎儿孤立性 NT增厚而接受产前诊断的单胎妊娠孕妇（ｎ=70）的临床资料。根据 NT增厚程度分为 4组（组 1：≥95百分位 ～＜3.0mm；组 2：≥3.0～＜3.5mm；组 3：≥3.5～＜4.0mm；组 4：≥4.0mm），分析遗传学结果与妊娠结局。结果 胎儿染色体非整倍体异常检出率为 11.43％，致病性拷贝数变异（CNVs）为 5.71％。在 62例核型分析正常病例中，CNV-seq检出 CNV异常 4例，诊断效能增加 6.45％。对 34例核型及 CNV未见异常的胎儿进行家系全外显子测序（trio-WES）分析中共发现 5个基因出现致病性变异，诊断效能增加14.71％。NT＜3.0mm组的染色体检出率为 4.17％，NT≥3.0mm组染色体异常检出率为 23.91％，差异具有统计学意义（P<0.05）。孤立性 NT增厚且35岁及以上染色体异常检出率为25.00％，35岁以下检出率为16.13％，差异不具有统计学意义（P=0.62）。结论 对于染色体阴性或孕周较大有时限性的孕妇，染色体数目异常检出率与 NT值呈正相关，建议同步沟通行 trio-WES检测，对于孤立性 NT增厚患者无论是否合并高龄，均建议行介入性产前诊断。

Abstract

Objective To investigate the genetic etiologies and prognoses of fetuses with isolated increased nuchal transluceney (NT), and to provide evidence for prenatal diagnosis and genetic counseling. Methods This retrospective study enrolled 70 singleton pregnant women who underwent invasive prenatal diagnosis for isolated increased fetal NT at the Prenatal Diagnosis Center, the Affliated Hospital of Zuny Medical University from January 2024 to April 2025. All cases were divided into four groups based on NT thickness: group I(≥95th percentile to＜3. 0 mm)， group 2(≥3.0 to＜3.5 mm)， group 3(≥3.5 to＜4.0 mm), and group 4(≥4.0 mm). Genetic findings and pregnaney outcomes were analyzed. Results The detection rate of fetal chromosomal aneuploidy was 11. 43%(8/70), and the rate of pathogenic copy number variations (CNVs) was 5. 71%(4/70). CNV sequencing (CNV-seq) identified 4 CNV abnormalities in 62 cases with normal karyotype, yielding an additional diagnostic yield of 6.45%. Trio-based whole-exome sequencing(trio-WES) was performed in 34 fetuses with normal karyotype and CNV-seq results, and 5 pathogenic gene variants were detected, providing an additional diagnostic yield of 14.71%. The chromosomal abnormality rate was 4.17%(1/24) in the NT＜3.0 mm group and 23.91%(11/46) in the NT ≥3.0 mm group,with a statistically significant difference(P＜0.05). The chromosomal abnormality rate was 25. 00%(2/8) in women with advanced matermal age(≥35 years) and 16.13%(10/62) in women＜35 years, with no statistically significant difference (P =0.62). Conclusion For pregnant women who are chromosome negative or have a time limited pregnancey, the detection rate of chromo some number abnormalities is positively correlated with NT values. It is recommended to use Trio WES testing simultaneously. For patients with isolated NT thickening, regardless of whether they are elderly or not, interventional prenatal diagnosis is recommended.

关键词

颈项透明层 / 妊娠结局 / 产前诊断 / 遗传咨询

Key words

nuchal translucency / pregnancy outcome / prenatal diagnosis / genetic counseling

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基金资助

遵义市科技计划项目(遵市科合HZ字(2024)238)