国际妇产科学杂志 ›› 2025, Vol. 52 ›› Issue (3): 302-308.doi: 10.12280/gjfckx.20250061

• 产科生理及产科疾病: 论著 • 上一篇    下一篇

染色体微阵列分析技术在NT增厚胎儿产前诊断中的应用

梁逸萱, 周冉, 孟露露, 刘婷婷, 霍海芹, 张沁欣, 胡平, 许争峰, 王艳()   

  1. 210004 南京医科大学附属妇产医院(南京市妇幼保健院)产前诊断中心
  • 收稿日期:2025-01-17 出版日期:2025-06-15 发布日期:2025-06-19
  • 通讯作者: 王艳 E-mail:wangyan@njmu.edu.cn
  • 基金资助:
    国家自然科学基金(81801445)

Application of Chromosomal Microarray Analysis in Prenatal Diagnosis of Fetuses with Increased Nuhal Translucency

LIANG Yi-xuan, ZHOU Ran, MENG Lu-lu, LIU Ting-ting, HUO Hai-qin, ZHANG Qin-xin, HU Ping, XU Zheng-feng, WANG Yan()   

  1. Center of Prenatal Diagnosis, Women′s Hospital of Nanjing Medical University, Nanjing Women and Children′s Healthcare Hospital, Nanjing 210004, China
  • Received:2025-01-17 Published:2025-06-15 Online:2025-06-19
  • Contact: WANG Yan E-mail:wangyan@njmu.edu.cn

摘要:

目的:探讨染色体微阵列分析(chromosomal microarray analysis,CMA)在颈后透明层厚度(nuchal translucency,NT)增厚胎儿产前诊断中的应用价值。方法:选取2017年6月—2024年6月于南京医科大学附属妇产医院超声提示NT增厚(≥3.0 mm)并接受CMA检测的孕妇1 033例。根据是否合并其他超声软指标分为单纯NT增厚组(918例)和NT增厚合并其他超声软指标组(115例)。单纯NT增厚组根据孕妇年龄分为高龄组(≥35岁,135例)和非高龄组(<35岁,783例);根据NT厚度分为3.0~3.4 mm组(506例)、3.5~4.4 mm组(288例)、4.5~5.4 mm组(80例)以及≥5.5 mm组(44例)。结果:1 033例NT增厚胎儿共检出染色体异常170例(16.5%),其中染色体非整倍体122例(11.8%),大片段结构异常[拷贝数变异(copy number variation,CNV)≥10 Mb]10例(1.0%)和致病性微缺失微重复(CNV<10 Mb)38例(3.7%)。NT增厚合并其他超声软指标组的染色体异常检出率高于单纯NT增厚组,差异有统计学意义(39.1% vs. 13.6%,χ2=48.388,P<0.001)。单纯NT增厚的孕妇中,高龄组的染色体异常检出率高于非高龄组,差异有统计学意义(25.9% vs. 11.5%,χ2=20.389,P<0.001);无论高龄组或非高龄组,染色体异常检出率随NT厚度的增加呈上升趋势(均P<0.05);NT在3.5~4.4 mm和4.5~5.4 mm时,高龄组的染色体异常检出率高于非高龄组,差异有统计学意义(45.0% vs. 10.9%,P<0.001;42.9% vs. 16.7%,P=0.040)。结论:除非整倍体外,染色体微缺失微重复与NT增厚也密切相关,CMA可有效提高NT增厚胎儿染色体异常的检出率。染色体异常检出率随NT厚度的增加呈上升趋势,NT增厚合并孕妇高龄或合并其他超声软指标将提高胎儿染色体异常的风险。

关键词: 颈部透明带检查, 染色体畸变, DNA拷贝数变异, 微阵列分析, 序列缺失, 染色体微阵列分析

Abstract:

Objective: To investigate the application value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with increased nuchal translucency (NT). Methods: A total of 1 033 pregnant women with increased NT (≥3.0 mm) detected by ultrasound and who underwent CMA testing at the Women′s Hospital of Nanjing Medical University from June 2017 to June 2024 were selected. According to the presence of other ultrasonographic soft markers, they were divided into a simple increased NT group (918 cases) and increased NT combined with other ultrasonographic soft markers group (115 cases). The simple increased NT group was further divided into an advanced-age group (≥35 years old, 135 cases) and a non-advanced-age group (<35 years old, 783 cases) according to the pregnant women′s age; and divided into a 3.0-3.4 mm group (506 cases), a 3.5-4.4 mm group (288 cases), a 4.5-5.4 mm group (80 cases) and a ≥5.5 mm group (44 cases) according to the NT thickness. Results: Among the 1 033 fetuses with increased NT, 170 cases (16.5%) of chromosomal abnormalities were detected, including 122 cases (11.8%) of chromosomal aneuploidy, 10 cases (1.0%) of large-scale structural abnormalities [(copy number variations,CNV) ≥10 Mb] and 38 cases (3.7%) of pathogenic microdeletion and microduplication (CNV<10 Mb). The detection rate of chromosomal abnormalities in the increased NT combined with other ultrasonographic soft markers group was significantly higher than in the simple increased NT group (39.1% vs. 13.6%, χ2=48.388, P<0.001). In the simple increased NT group, the detection rate of chromosomal abnormalities in the advanced-age group was significantly higher than that in the non-advanced-age group (25.9% vs. 11.5%, χ2=20.389, P<0.001). In both the advanced-age and non-advanced-age group, the detection rate of chromosomal abnormalities significantly increased with the increased NT thickness(all P<0.05). When NT values were between 3.5-4.4 mm and 4.5-5.4 mm, the detection rate of chromosomal abnormalities in the advanced-age group was significantly higher than that in the non-advanced-age group (45.0% vs. 10.9%, P<0.001; 42.9% vs. 16.7%, P=0.040). Conclusions: In addition to aneuploidy, chromosomal microdeletion and microduplication are closely related to increased NT. CMA can effectively improve the detection rate of chromosomal abnormalities in fetuses with increased NT. The detection rate of chromosomal abnormalities shows an upward trend with the increase of NT thickness. Increased NT combined with advanced maternal age or other ultrasonographic soft markers will increase the risk of fetal chromosomal abnormalities.

Key words: Nuchal translucency measurement, Chromosome aberrations, DNA copy number variations, Microarray analysis, Sequence deletion, Chromosomal microarray analysis