胎儿颈项透明层厚度与染色体异常的相关性研究

Relationship between the thickness of fetal nuchal translucency and fetal chromosomal abnormalities

目的通过分析超声测量颈项透明层(NT)厚度(NT≥2.5mm)胎儿与染色体异常的情况,探讨合理的NT截断值和NT临界厚度,以及低覆盖度大规模平行测序技术(CNV-seq)对NT≥2.5mm胎儿产前诊断的应用价值。方法对2013年1月至2016年12月在首都医科大学附属北京妇产医院就诊的孕11~13+6周NT≥2.5mm且行产前诊断的病例进行回顾性研究,分析其超声结果及胎儿染色体情况。结果 453例孕妇和457例胎儿符合入组标准,胎儿染色体异常率为22.1%(101/457)。超声报告合并其他结构异常55例,染色体异常26例(47.3%),合并结构异常与不合并结构异常比较,胎儿染色体异常的差异有显著性(χ~2=23.012,P<0.001)。按NT厚度2.5~2.9mm、3.0~3.9mm、4.0~5.9mm及6.0mm分为四组,每组例数及胎儿染色体异常例数分别为87例,3例(3.5%);190例,35例(18.9%);111例,32例(28.8%);69例,31例(44.9%);分析四组间差异有显著性(χ~2=42.878,P<0.001),两两比较第一组和其他各组比较差异均有显著性(χ~2分别为11.303、21.590、38.843,均P<0.01),NT厚度2.5~2.9mm的87例中,胎儿染色体异常3例,1例超声提示鼻骨缺失,2例穿刺术前NIPT高风险。CNV-seq结合STR检测224例,发现CNVs 50例,致病性9例(4.0%)。结论随着NT厚度增加,胎儿染色体异常率显著增加,NT截断值定3.0mm,NT2.5~2.9mm时定为临界厚度较为合理。NT增厚时即使胎儿染色体无异常建议增加胎儿超声心动图及孕期超声监测,对NT增厚的胎儿使用CNV-seq结合STR检测可使致病性染色体畸变检测率提高。

Objective To investigate the reasonable nuchal translucency（NT）cutoff value and NT critical thickness and the application value of low-coverage massively parallel CNV Sequencing（CNV-seq）for prenatal diagnosis of fetus with NT≥2.5 mm by analyzing the fetal NT thickness（NT2.5 mm）measured ultrasonography and fetal chromosomal abnormalities.Methods The pregnant women with 11-13＋6 gestational weeks and NT≥2.5 mm who accepted prenatal diagnosis were studied retrospectively to analyze the results of ultrasonography and the situation of fetal chromosome.Results There were 453 pregnant women and 457 fetuses meeting the inclusion criteria.The rate of fetus abnormal chromosome was 22.1%（101/457）.A total of 55 cases were found with other structural abnormalities according to ultrasonography report and 26 cases presented chromosomal abnormalities（47.3%）.Compared the fetal chromosomal abnormalities between the cases with other structural abnormalities and the cases without other structure abnormalities,the difference was significant（χ~2=23.012,P0.001）.The cases were divided into four groups by NT thickness.The cases whose NT thickness was 2.5 mm-2.9 mm were divided into the first group,the cases whose NT thickness was 3.0 mm-3.9 mm were divided into the second group,the cases whose NT thickness was 4.0 mm-5.9 mm were divided into the third group,while the cases whose NT thickness was 6.0 mm were divided into the fourth group.The number of cases and the number of cases presenting fetal chromosomal abnormalities in each group were 87,3（3.5%）;190,35（18.9%）;111,32（28.8%）;69,31（44.9%）.The differences among four group were significant（χ~2=42.878,P0.001）.According to the pairwise comparison,the differences between the first group and other groups were significant（χ~2 value was 11.303,21.590 and38.843,respectively,P 0.01）.In 87 cases with 2.5 mm-2.9 mm NT thickness,there were 3 cases of fetal chromosomal abnormalities,1 case of nasal bone loss by ultrasonography and 2 cases of high risk of NIPT before puncture.In 224 cases detected by CNV-seq combined with STR detection,50 cases were found presenting CNVs,and 9 cases were of pathogenicity（4.0%）.Conclusion With the increase of NT thickness,fetal chromosomal abnormalities increases significantly.It is reasonable when the NT cutoff value is 3.0 mm and the NT critical thickness is 2.5 mm-2.9 mm.If the fetus presents an incrassated NT,it is recommended to perform additional fetal echocardiography and prenatal ultrasound monitoring even if the fetal chromosome is normal.For the fetus with an incrassated NT,the detection rate of pathogenetic chromosome aberration can be improved by using CNV-seq combined with STR detection.