单核苷酸多态性微阵列技术联合核型分析在颈项透明层增厚胎儿产前诊断中的应用

Application of SNP microarray and karyotype analysis in prenatal diagnosis of fetuses with thickened nuchal translucency

目的探讨单核苷酸多态性微阵列(SNP array)技术联合核型分析在颈项透明层(NT)增厚胎儿产前诊断中的应用价值。方法收集2020年3月至2023年3月在安徽省妇幼保健院因NT增厚而行羊膜穿刺术的胎儿516例,分别运用核型分析技术和SNP array技术对胎儿羊水细胞进行检测,分析胎儿染色体异常情况;根据NT值分成4组:2.5~2.9 mm组183例、3.0~3.9 mm组261例、4.0~4.9 mm组46例和≥5 mm组26例;根据是否合并其他异常指征包括高龄、超声异常、血清学异常和不良妊娠史等,分为合并其他异常指征组156例和单纯NT增厚组360例。结果在516例NT增厚胎儿中SNP array技术检出致病性染色体异常70例(13.57%);核型分析组为10.66%(55/516),与SNP array组比较差异无统计学意义(χ^(2)=2.048,P=0.152)。2.5~2.9 mm组染色体异常7.10%、3.0~3.9 mm组13.79%、4.0~4.9 mm组23.91%、≥5 mm组38.46%,各组比较差异有统计学意义(χ^(2)=24.472,P=0.000)。合并其他异常指征组染色体异常25.64%,而单纯NT增厚组为8.33%,两组比较差异有统计学意义(χ^(2)=27.805,P=0.000)。结论当NT厚度增加或合并其他异常指征时,胎儿发生染色体异常的风险增加。采用SNP array技术联合核型分析的检测模式,可以提高异常染色体的检出率。推荐将3.5 mm和3.0 mm作为单纯NT增厚和NT增厚合并其他异常指征行侵入性产前诊断的截断值。

Objective To explore the application of single nucleotide polymorphism(SNP)microarray combined with karyotype analysis in the fetus with increased nuchal translucency(NT).Methods A total of 516 fetuses performed amniocentesis due to NT thickening in Anhui Maternal and Child Health Hospital from March 2020 to March 2023 were collected.The fetal amniotic fluid cells were detected by karyotype analysis and SNP array,respectively,and the fetal chromosome abnormalities were analyzed.According to the thickness of NT,the fetuses were divided into four groups:2.5 to 2.9 mm group(183 cases),3.0 to 3.9 mm group(261 cases),4.0 to 4.9 mm group(46 cases)and≥5 mm group(26 cases).Depending on whether other abnormal indications existed,such as advanced age,abnormal ultrasound,abnormal serology and adverse pregnancy history,they were divided into two groups:NT thickening combined with other indications group(156 cases),NT thickening alone group(360 cases).Results In the 516 fetuses with NT thickening,70 cases(13.57%)of pathogenic chromosome abnormalities were detected by SNP array,and 55 cases(10.66%)of pathogenic chromosome abnormalities were detected by karyotype analysis.The difference between two methods was not statistically significant(χ^(2)=2.048,P=0.152).The detection rates in 2.5 to 2.9 mm group,3.0 to 3.9 mm group,4.0 to 4.9 mm group and≥5 mm group were 7.10%,13.79%,23.91%and 38.46%,respectively.The difference among the four groups was statistically significant(χ^(2)=24.472,P=0.000).The detection rate was 25.64%in the group with other abnormal indications,and 8.33%in NT thickening alone group,the difference between two groups was statistically significant(χ^(2)=27.805,P=0.000).Conclusion The risk of fetal chromosomal abnormalities increased when NT thickness increased or other abnormal indications were present.The detection mode of SNP array combined with karyotype analysis could improve the detection rate of abnormal chromosomes.3.5 mm and 3.0 mm should be recommended as the cut-off values for NT thickening alone,and NT thickening combined with other abnormal indications may be the cut off value for invasive prenatal diagnosis.