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

doi:10.12280/gjfckx.20250061

Abstract

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

LIANG Yi-xuan, ZHOU Ran, MENG Lu-lu, LIU Ting-ting, HUO Hai-qin, ZHANG Qin-xin, HU Ping, XU Zheng-feng, WANG Yan. Application of Chromosomal Microarray Analysis in Prenatal Diagnosis of Fetuses with Increased Nuhal Translucency[J]. Journal of International Obstetrics and Gynecology, 2025, 52(3): 302-308.

Figures/Tables 6

References 30

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病例号	年龄（岁）	NT （mm）	合并其他超声软指标	CMA结果（hg19）	大小（kb）	致病性	外显率（%）	遗传来源
1	32	3.4	无	15q26.1q26.3(93,666,490_102,429,040)×1	8 763	P	-	-
2	26	3.8	无	15q11.2(22,770,421_23,282,798)×1	512	P	8.0~10.4	母亲
3	35	3.5	无	Xq23q24(114,368,811_117,162,958)×0	2 794	LP	-	-
4	31	3.4	无	15q11.2(22,770,421_23,290,788)×1	520	P	8.0~10.4	新发
5	26	4.8	无	16p13.11p12.3(15,171,146_18,242,713)×1	3 072	P	13.1	-
6	32	3.0	无	Yq11.222q11.23(20,252,055_26,202,092)×0	5 950	P	-	-
7	26	5.5	无	Yq11.223q11.23(24,820,715_28,420,380)×0	3 600	P	-	-
8	38	3.2	无	22q11.21(18,648,855_21,800,471)×3	3 152	P	21.9	新发
9	31	3.2	无	17q11.2q12(27,327,677_35,603,747)×1	8 276	P	-	-
10	34	3.4	鼻骨缺失	15q11.2(22,770,421_23,276,605)×1	506	P	8.0~10.4	-
11	26	3.9	无	15q11.2(22,770,421_23,282,798)×1	512	P	8.0~10.4	-
12	26	3.1	无	22q11.21(18,631,364_21,800,471)×1	3 169	P	-	-
13	28	3.2	无	15q11.2(22,770,421_23,214,655)×1	444	P	8.0~10.4	新发
14	33	4.0	无	16p11.2(29,428,531_30,350,748)×1	922	P	46.8	新发
15	25	3.0	鼻骨发育不良	15q11.2q13.1(22,770,421_28,915,864)×1	6 145	P	-	-
16	20	5.4	无	16p11.2(29,591,326_30,190,029)×3	599	P	27.2	-
17	29	3.4	鼻骨发育不良	22q11.21(18,916,960_21,800,471)×1	2 884	P	-	-
18	23	3.0	无	15q11.2(22,770,421_23,082,237)×1	312	P	8.0~10.4	-
19	31	3.3	无	6q21(108,127,595_108,249,946)×1	122	P	-	-
20	31	3.6	无	22q11.21(18,649,189_21,804,597)×3	3155	P	21.9	新发
21	26	3.3	无	15q11.2(22,770,422_23,282,798)×1	512	P	8.0~10.4	新发
22	35	4.4	颈项褶皱增厚	15q11.2(22,770,421_23,282,798)×1	512	P	8.0~10.4	-
23	25	3.0	无	15q11.2(22,770,421_23,276,605)×1	506	P	8.0~10.4	母亲
24	29	3.0	无	15q11.2(22,770,421_23,082,237)×1	312	P	8.0~10.4	母亲
25	25	5.0	无	1q21.2(149,801,419_149,942,900)×1	141	P	-	-
26	35	5.3	无	5q11.2q12.3(54,803,019_63,748,705)×1	8 946	P	-	-
27	26	5.0	无	1q21.2(149,801,419_149,942,900)×1	141	P	-	-
28	26	4.2	无	15q11.2(22,770,421_23,277,436)×1	507	P	8.0~10.4	-
29	33	3.0	鼻骨缺失	15q11.2(22,770,422_23,277,436)×1	507	P	8.0~10.4	母亲
30	31	4.1	无	22q11.21(18,648,856_21,800,471)×3	3 152	P	21.9	新发
31	34	3.0	无	16p13.12p12.3(14,769,089_16,858,332)×1	2 089	LP	13.1	新发
32	31	3.1	无	15q11.2(22,770,421_23,277,436)×1	507	P	8.0~10.4	新发
33	27	3.1	无	Xp22.33 or Yp11.32(363,237_1,358,801 or 313,237_1,308,801)×1	996	P	-	-
34	35	4.3	无	15q11.2(22,770,421_23,082,237)×1	312	P	8.0~10.4	母亲
35	31	5.7	无	15q11.2(22,770,422_23,277,436)×1	507	P	8.0~10.4	母亲
36	21	3.7	无	22q11.21(18,631,364_21,800,471)×1	3 169	P	-	-
37	27	3.6	无	15q11.2(22,770,422_23,282,798)×1	512	P	8.0~10.4	新发
38	33	3.2	无	22q11.21(18,636,749_21,800,471)×1	3164	P	-	-

病例号	年龄（岁）	NT （mm）	合并其他超声软指标	CMA结果（hg19）	大小（kb）	致病性	外显率（%）	遗传来源
1	32	3.4	无	15q26.1q26.3(93,666,490_102,429,040)×1	8 763	P	-	-
2	26	3.8	无	15q11.2(22,770,421_23,282,798)×1	512	P	8.0~10.4	母亲
3	35	3.5	无	Xq23q24(114,368,811_117,162,958)×0	2 794	LP	-	-
4	31	3.4	无	15q11.2(22,770,421_23,290,788)×1	520	P	8.0~10.4	新发
5	26	4.8	无	16p13.11p12.3(15,171,146_18,242,713)×1	3 072	P	13.1	-
6	32	3.0	无	Yq11.222q11.23(20,252,055_26,202,092)×0	5 950	P	-	-
7	26	5.5	无	Yq11.223q11.23(24,820,715_28,420,380)×0	3 600	P	-	-
8	38	3.2	无	22q11.21(18,648,855_21,800,471)×3	3 152	P	21.9	新发
9	31	3.2	无	17q11.2q12(27,327,677_35,603,747)×1	8 276	P	-	-
10	34	3.4	鼻骨缺失	15q11.2(22,770,421_23,276,605)×1	506	P	8.0~10.4	-
11	26	3.9	无	15q11.2(22,770,421_23,282,798)×1	512	P	8.0~10.4	-
12	26	3.1	无	22q11.21(18,631,364_21,800,471)×1	3 169	P	-	-
13	28	3.2	无	15q11.2(22,770,421_23,214,655)×1	444	P	8.0~10.4	新发
14	33	4.0	无	16p11.2(29,428,531_30,350,748)×1	922	P	46.8	新发
15	25	3.0	鼻骨发育不良	15q11.2q13.1(22,770,421_28,915,864)×1	6 145	P	-	-
16	20	5.4	无	16p11.2(29,591,326_30,190,029)×3	599	P	27.2	-
17	29	3.4	鼻骨发育不良	22q11.21(18,916,960_21,800,471)×1	2 884	P	-	-
18	23	3.0	无	15q11.2(22,770,421_23,082,237)×1	312	P	8.0~10.4	-
19	31	3.3	无	6q21(108,127,595_108,249,946)×1	122	P	-	-
20	31	3.6	无	22q11.21(18,649,189_21,804,597)×3	3155	P	21.9	新发
21	26	3.3	无	15q11.2(22,770,422_23,282,798)×1	512	P	8.0~10.4	新发
22	35	4.4	颈项褶皱增厚	15q11.2(22,770,421_23,282,798)×1	512	P	8.0~10.4	-
23	25	3.0	无	15q11.2(22,770,421_23,276,605)×1	506	P	8.0~10.4	母亲
24	29	3.0	无	15q11.2(22,770,421_23,082,237)×1	312	P	8.0~10.4	母亲
25	25	5.0	无	1q21.2(149,801,419_149,942,900)×1	141	P	-	-
26	35	5.3	无	5q11.2q12.3(54,803,019_63,748,705)×1	8 946	P	-	-
27	26	5.0	无	1q21.2(149,801,419_149,942,900)×1	141	P	-	-
28	26	4.2	无	15q11.2(22,770,421_23,277,436)×1	507	P	8.0~10.4	-
29	33	3.0	鼻骨缺失	15q11.2(22,770,422_23,277,436)×1	507	P	8.0~10.4	母亲
30	31	4.1	无	22q11.21(18,648,856_21,800,471)×3	3 152	P	21.9	新发
31	34	3.0	无	16p13.12p12.3(14,769,089_16,858,332)×1	2 089	LP	13.1	新发
32	31	3.1	无	15q11.2(22,770,421_23,277,436)×1	507	P	8.0~10.4	新发
33	27	3.1	无	Xp22.33 or Yp11.32(363,237_1,358,801 or 313,237_1,308,801)×1	996	P	-	-
34	35	4.3	无	15q11.2(22,770,421_23,082,237)×1	312	P	8.0~10.4	母亲
35	31	5.7	无	15q11.2(22,770,422_23,277,436)×1	507	P	8.0~10.4	母亲
36	21	3.7	无	22q11.21(18,631,364_21,800,471)×1	3 169	P	-	-
37	27	3.6	无	15q11.2(22,770,422_23,282,798)×1	512	P	8.0~10.4	新发
38	33	3.2	无	22q11.21(18,636,749_21,800,471)×1	3164	P	-	-

超声情况	n	非整倍体	CNV≥10 Mb	CNV<10 Mb	合计
单纯NT增厚	918	82（8.9）	10（1.1）	33（3.6）	125（13.6）
NT增厚合并其他超声软指标	115	40（34.8）	-	5（4.3）	45（39.1）
χ²		65.568	-	-	48.388
P		<0.001	0.613*	0.603*	<0.001

超声情况	n	非整倍体	CNV≥10 Mb	CNV<10 Mb	合计
单纯NT增厚	918	82（8.9）	10（1.1）	33（3.6）	125（13.6）
NT增厚合并其他超声软指标	115	40（34.8）	-	5（4.3）	45（39.1）
χ²		65.568	-	-	48.388
P		<0.001	0.613*	0.603*	<0.001

合并其他超声软指标	n	非整倍体	CNV	合计
颈项褶皱增厚	13	-	1（7.7）	1（7.7）
鼻骨缺失或发育不良	60	26（43.3）	4（6.7）	30（50.0）
轻度侧脑增宽	1	-	-	-
肠管回声增强	2	1（50.0）	-	1（50.0）
肱骨/股骨偏短	1	-	-	-
脉络丛囊肿	18	1（5.6）	-	1（5.6）
单脐动脉	15	9（60.0）	-	9（60.0）
肾盂扩张	2	-	-	-
颈项褶皱增厚+鼻骨缺失或发育不良	1	1（100.0）	-	1（100.0）
鼻骨缺失或发育不良+单脐动脉	1	1（100.0）	-	1（100.0）
鼻骨缺失或发育不良+脉络丛囊肿	1	1（100.0）	-	1（100.0）