无创产前检测适用人群的探讨及其临床应用评价

Clinical application of NIPT and expansion of its scope

背景无创产前检测(noninvasive prenatal test,NIPT)是目前筛查胎儿常见非整倍体最准确的方法。不同产前诊断指征的孕妇,其胎儿染色体异常的风险也不相同。在接受侵入性产前诊断的孕妇中,选择胎儿染色体异常风险相对较低的人群行NIPT筛查,可以在减轻产前诊断负担的同时,尽可能地降低NIPT的漏检风险。目的探讨在接受侵入性产前诊断的孕妇中NIPT筛查的适用人群及临床应用评价。方法选取2018年1月16日-2020年6月30日在解放军总医院第一医学中心行侵入性产前诊断的孕妇。所有孕妇均行NIPT。通过多因素logistic回归分析比较不同产前诊断指征与胎儿染色体异常的相关性,分析不同高危因素的孕妇应用NIPT后产前诊断的需求量及阳性率。结果纳入分析的1261例孕妇,平均年龄(34.65±5.02)岁,侵入性产前诊断的阳性率为6.90%。与侵入性产前诊断相比,NIPT整体的特异性为97.61%(1146/1174),阴性预测值为97.20%(1146/1179),诊断符合率95.16%(1200/1261)。多因素logistic全模回归分析显示:在这一人群中,高龄(OR=0.470,P=0.010)和超声异常(OR=2.939,P<0.001)与胎儿染色体异常的相关性有统计学意义,而血清学筛查异常(OR=0.075)和不良孕产史及家族史(OR=0.492)无统计学意义。单纯高龄孕妇应用NIPT可以使产前诊断的需求量下降达42.19%,产前诊断的阳性率升至11.11%。结论在接受侵入性产前诊断的孕妇中,单纯高龄孕妇的胎儿染色体异常风险低于这一人群的平均风险。高龄孕妇应用NIPT可显著减少侵入性产前诊断需求量,并提高产前诊断的效率。

Background Noninvasive prenatal test(NIPT)based on fetal cell-free DNA(cf-DNA)is currently the most accurate prenatal screening for fetal common chromosomal aneuploidies.Pregnant women with different indications for prenatal diagnosis vary in risk of fetal chromosomal abnormalities.It can reduce prenatal diagnostic procedures if we select pregnant women with relatively low risk of fetal chromosomal abnormalities for NIPT,and avoid false negative results of NIPT.Objective To explore candidates suitable for NIPT in pregnant women undergoing invasive prenatal diagnosis and evaluate its clinical application.Methods Totally 1261 pregnant women who had undergone prenatal diagnostic procedure in the First Medical Center of Chinese PLA General Hospital from January 16,2018 to June 31,2020 were selected in our study.All participants had undergone NIPT.Related risk characteristic of fetal chromosomal abnormalities was analyzed by multiple logistic regression analysis.Positive rate and demand for prenatal diagnosis were calculated separately when NIPT was applied in pregnant women with different risk factors.Results A total of 1261 pregnant women with an average age of(34.65±5.02)years were included in the analysis.The positive rate of invasive prenatal diagnosis was 6.90%.The overall specificity of NIPT was 97.61%(1146/1174),negative predictive value was97.20%(1146/1179),and diagnostic accuracy was 95.16%(1200/1261).Multivariate logistic regression analysis showed that in this population,there was statistically significant correlation between advanced age(OR=0.470,P=0.010),abnormal ultrasound(OR=2.939,P<0.001)with fetal chromosomal abnormalities,while there was no statistically significant correlation between abnormal serological screening(OR=0.075),adverse maternal history with family history(OR=0.492).NIPT could reduce the demand for prenatal diagnosis by 42.19%and increase the positive rate of prenatal diagnosis to 11.11%.Conclusion Among pregnant women undergoing invasive prenatal diagnosis,the risk of fetal chromosomal abnormalities in pregnant women with advanced maternal age is lower than the average risk in this population.Remarkable decline and higher proportion of fetal chromosomal anomalies in invasive procedure can be achieved when NIPT is applied in pregnant women with advanced maternal age.