1 安徽医科大学附属妇幼保健院危急重症产科，合肥 230000
目的：探讨核型分析联合染色体微阵列分析(chromosomal microarray analysis，CMA)在颈项透明层(nuchal translucency，NT)增厚胎儿中的应用。方法：回顾性分析2017年1月至2019年6月于安徽医科大学附属妇幼保健院孕11~13+6周行NT厚度检查的胎儿共32 100例，超声提示NT≥2.5 mm共546例(1.70%)，其中行核型分析联合CMA者235例。本研究将这235例孕妇纳入研究，根据NT厚度分为2.5~2.9 mm组(47例)、3.0~3.4 mm组(106例)、3.5~4.4 mm组(56例)、4.5~5.4 mm组(15例)和≥5.5 mm组(11例)，根据不同产前诊断指征分为单纯NT增厚组(A组，182例)、合并其他组(包括高龄、血清学筛查异常及不良孕产史；B组，53例)。结果：1)235例中44例染色体异常(18.72%)；2)核型分析、CMA对异常染色体的检出率各自组内相比，差异有统计学意义(P<0.05)，两种方法总体相比差异无统计学意义(P>0.05)，但随NT增厚染色体异常的发生率随之增加(Ptrend<0.001)；3)CMA异常染色体检出率为18.30%(43/235)，较核型分析异常染色体检出率高[14.04%(33/235)]，其中核型正常而CMA增加检出11例染色体拷贝数变异(copy number variants，CNVs)，而核型分析1例染色体易位CMA未见异常；4)A组、B组异常染色体检出率分别为14.29%(26/182)和33.96%(18/53)，差异有统计学意义(P<0.001)；5)A组、B组ROC曲线下面积(0.741、0.674)显示，行侵入性检查截断值分别为3.25和2.85时，敏感度为0.793和1.000，特异度为0.569和0.379，约登指数为0.362和0.179。结论：核型分析联合CMA可更有效提高异常染色体的检出，有益于产前诊断；单纯NT增厚及NT增厚合并其他，与临床实际相结合，建议分别取3.0 mm和2.5 mm为截断值行侵入性检查。
Application of thickening of nuchal translucency in prenatal diagnosis
CorrespondingAuthor: CHEN Xianxia
This work was supported by Hefei Municipal Health Commission’s 2019 Key Project of Applied Medicine Research, China (2019-16).
Objective: To explore the application of karyotype analysis combined with chromosomal microarray analysis (CMA) in the fetus with the thickening of nuchal translucency (NT). Methods: A retrospective analysis was performed on 32 100 fetuses who received NT thickness examination during 11–13+6 weeks of pregnancy in our hospital from January 2017 to June 2019. Ultrasound revealed 546 cases (1.70%) with NT ≥2.5 mm. Among them, 235 fetuses received karyotype analysis combined with CMA. In this study, these 235 pregnant women were included in the study. According to the thickness of NT, they were divided into 2.5–2.9 mm group (47 cases), 3.0–3.4 mm group (106 cases), 3.5–4.4 mm group (56 cases), 4.5–5.4 mm group (15 cases) and ≥5.5 mm group (11 cases). According to different prenatal diagnosis indications, they were divided into simple NT thickening group (group A, 182 cases), combined with other groups (including advanced age, abnormal serological screening and poor history of pregnancy and childbirth) (group B, 53 cases). Results: 1) Totally 44 out of 235 cases had chromosomal abnormalities (18.72%). 2) Karyotype analysis and CMA’s detection rate of abnormal chromosomes were statistically significant (P<0.05). The overall difference between the two methods was not statistically significant (P>0.05), but the incidence of chromosome abnormalities increased with NT thickening (Ptrend<0.001). 3) The detection rate of abnormal chromosomes in CMA was 18.30% (43/235), which was higher than that in karyotype analysis [14.04% (33/235)]. The karyotype was normal and CMA increased the detection of 11 cases of chromosome copy number variants (CNVs). Karyotype analysis showed 1 case with chromosomal translocation had no abnormality in CMA. 4) The detection rates of abnormal chromosomes in groups A and B were 14.29% (26/182) and 33.96% (18/53) respectively, and the difference was statistically significant (P<0.001). 5) The area under the ROC curve (0.741, 0.674) of groups A and B showed that when the cut-off value of invasive examination was 3.25 and 2.85, the sensitivity was 0.793 and 1.000, and the specificity was 0.569 and 0.379. The Youden index was 0.362 and 0.179. Conclusion: Karyotype analysis combined with CMA can more effectively improve the detection of abnormal chromosomes, which is beneficial for prenatal diagnosis. It is recommended to take 3.0mm and 2.5mm as the cut-off value for intrusive examination for NT thickening alone and NT thickening combined with other methods, respectively.
nuchal translucency; invasive examination; chromosome abnormality; cut-off value; pregnancy outcome