12 085例无创产前基因检测在胎儿染色体异常筛查中的临床应用

Application of non-invasive prenatal testing for the screening of fetal chromosomal abnormalities in 12085 cases

目的探讨无创产前基因检测(non-invasive prenatal testing,NIPT)在胎儿染色体异常筛查中的临床应用价值。方法选择2017年11月1日至2019年5月31日于嘉兴市妇幼保健院产前诊断中心行NIPT的12085名孕妇的检测结果与介入性产前诊断确诊结果进行比较分析。结果12085例样本中,检测成功12067例,共检出染色体异常179例,筛查阳性率1.48%,灵敏度98.39%,特异度99.02%。检测失败的18例中有3例行产前诊断,核型分析未见异常;分娩结果除1例双胎剖宫产一正常女性胎儿及一未知性别死胎外,其余新生儿均无异常。各检测指征中,超声提示异常组NIPT筛查阳性率高于其他组,差异有统计学意义(P<0.01)。NIPT筛查阳性结果中122例行介入性产前诊断,确诊21三体25例、18三体7例、13三体3例、其他常染色体非整倍体异常4例、性染色体非整倍体异常13例、微缺失/微重复9例,阳性预测值分别为86.21%、50.00%、23.08%、21.05%、46.43%、47.36%。结论NIPT具有较高的灵敏度、特异度和阳性预测值,是一种高效的筛查手段。除对21、18、13号染色体外,NIPT对其他常染色体非整倍体异常、性染色体非整倍体异常、微缺失/微重复的提示结果具有一定参考价值,能够为后续的核型分析和基因芯片验证提供参考依据。

Objective To assess the value of non-invasive prenatal testing(NIPT)for the screening of fetal chromosomal abnormalities.Methods For 12085 pregnant women,the results of NIPT and invasive prenatal diagnosis were compared.Results The test was successful in 12067 cases and has detected 179 chromosomal abnormalities,with a positive rate of 1.48%,sensitivity of 98.39%and specificity of 99.02%.Invasive prenatal diagnosis was performed for 3 of 18 patients who had failed NIPT but has detected no karyotypic abnormality.Except for one case of twin Cesarean section which delivered a normal female fetus and a stillbirth of unknown sex,the remainder of the 18 cases all had a normal delivery.The positive rate of NIPT screening for the abnormal ultrasound group was significant higher than that other groups(P<0.01).Among those with positive results of NIPT,122 underwent invasive prenatal diagnosis,and 25 trisomy 21,7 trisomy 18,3 trisomy 13,4 aneuploidies of other autosomes,13 sex chromosomal aneuploidies and 9 microdeletion/microduplications were confirmed,which yielded a positive predictive rate of 86.21%,50.00%,23.08%,21.05%,46.43%,and 47.36%,respectively.Conclusion NIPT has high sensitivity,specificity and positive predictive value,and is an effective method for prenatal screening.In addition to chromosomes 21,18 and 13,NIPT has certain predictive value for other autosomal aneuploidies,sex chromosomal aneuploidies,microdeletion/microduplications,and can provide a reference for karyotype analysis and chromosomal microarray verification.