妊娠中期鼻骨发育异常胎儿的染色体检测结果及相关因素分析

背景　胎儿鼻骨发育情况评估作为常规产前超声检查项目，是胎儿染色体检查的重要指标，近几年染色体微阵列分析技术（CMA）的应用使得产前胎儿染色体疾病的检查范围更广、准确度更高，在此基础上有必要对鼻骨发育异常和染色体异常之间的相关性重新进行总结，为临床提供参考。目的　探讨胎儿鼻骨发育异常或与其他产前筛查高危因素结合在预测胎儿染色体异常中的价值，以及CMA在胎儿鼻骨发育异常遗传学检测中的应用价值。方法　选取2016年12月-2020年1月于内蒙古自治区妇幼保健院进行产前超声检查并提示胎儿鼻骨缺失或发育不良的92例孕妇及胎儿为研究对象。收集其产检信息、遗传学检测结果及妊娠结局。遗传学检测方法包括染色体核型分析和CMA。结果　染色体核型分析检出染色体异常19例（20.7%），均为21-三体；CMA检出染色体异常25例（27.2%），包括21-三体19例，染色体微缺失微重复6例。孤立性与非孤立性鼻骨发育异常胎儿染色体异常发生率比较，差异无统计学意义（P>0.05）。与单纯孤立性鼻骨发育异常胎儿相比，孤立性鼻骨发育异常+颈项透明层（NT）增厚、孤立性鼻骨发育异常+血清学筛查（MSS）高风险、孤立性鼻骨发育异常+无创产前筛查（NIPT）高风险、孤立性鼻骨发育异常+2种及以上产前筛查高危因素胎儿染色体异常发生率均升高（P<0.05）。结论　鼻骨缺失或发育不良的胎儿染色体异常发生率较高，且与基因组变异有关；染色体核型分析、CMA结合其他产前筛查高危因素将有效提高染色体异常的检出率。CMA的应用为产前诊断提供了更多的染色体变异信息，建议所有类型的胎儿鼻骨缺失或发育不良进行染色体核型分析与CMA结合的遗传学检测。

Chromosome Detection Results and Related Factors in Second-trimester Fetuses with Nasal Bone Abnormalities

Background　Fetal nasal bone development，an item assessed by routine prenatal ultrasound，is often used as a key ultrasound marker for assessing fetal chromosomal anomalies.With recent application of chromosomal microarray analysis（CMA），prenatal fetal chromosomal diseases have been detected in a wider range and with higher accuracy.So it is necessary to re-summarize the correlation between nasal bone abnormalities and chromosomal abnormalities，to provide evidence for clinical practice.Objective　To investigate the predictive value of fetal nasal bone abnormalities or its combination with other prenatal risk factors for chromosomal abnormalities，and to evaluate the application value of CMA in the genetic examination of fetal nasal bone abnormalities.Methods　92 pregnant women with fetuses with prenatal ultrasound-suggested nasal bone abnormalities were recruited from Inner Mongolia Maternal and Child Care Hospital from December 2016 to January 2020.Prenatal examination information，prenatal genetic test results（including karyotype analysis and CMA） and pregnancy outcomes were collected.Results　Karyotype analysis detected chromosome abnormalities in 19 cases （20.7%），all of which were trisomy 21.CMA detected chromosomal abnormalities in 25 cases （27.2%），including 19 cases of trisomy 21 and 6 cases of chromosomal microdeletions and microduplications.There was no statistical difference in the rate of chromosome abnormalities between fetuses with isolated and non-isolated nasal bone abnormalities （P>0.05）.Compared with fetuses with isolated nasal bone abnormalities，the incidence of chromosomal abnormalities in those with isolated nasal bone abnormalities with increased nuchal translucency thickness，isolated nasal bone abnormalities with high risk for chromosomal abnormalities suggested by maternal serum screening，isolated nasal bone abnormalities with high risk for chromosomal abnormalities suggested by non-invasive prenatal testing，or isolated nasal bone abnormalities with 2 or more high-risk factors for chromosomal abnormalities was increased（P<0.05）.Conclusion　The incidence of chromosomal abnormalities in fetuses with nasal bone absence or hypoplasia was higher，which was related to copy number variations.Karyotype analysis and CMA in combination with other prenatal examinations may effectively improve the detection rate of chromosomal abnormalities.The application of CMA technology provides more information on chromosome variation for prenatal diagnosis，and it is recommended that all fetuses with nasal bone absence or hypoplasia should be tested by karyotype analysis and CMA.