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目的 探讨无创产前检测(NIPT)在辅助生殖技术(ART)和自然妊娠胎儿染色体疾病筛查中的应用效能和前景。方法 选取2020年1月至2023年12月在马鞍山市妇幼保健院接受NIPT筛查的13 067例孕妇为研究对象，收集产前诊断及妊娠结局。根据受孕方式不同分为两组：ART组(n=1 329)和自然妊娠组(n=11 738),分析NIPT在两组孕妇胎儿目标疾病(21-三体、18-三体和13-三体)、性染色体非整倍体(SCA)及其他常染色体异常中的检出效能，并分析孕妇妊娠年龄、NIPT检测孕周、受孕方式及胎儿游离DNA浓度与染色体异常的关系。结果 NIPT筛查孕妇妊娠年龄、检测孕周及胎儿类型在ART组与自然妊娠组中的分布均有显著性差异(P<0.05),两组胎儿游离DNA浓度比较无显著性差异(P>0.05),NIPT高风险率只在孕妇妊娠年龄中具有显著性差异(P<0.05)。NIPT共筛查出149例高风险孕妇，阳性率为1.14%(149/13 067),其中有125例孕妇接受了介入性产前诊断，目标疾病产前诊断率为92.31%(36/39),SCA及其他常染色体异常的产前诊断率为80.91%(89/110)。ART组中有14例(1.05%,14/1 329)高风险病例，其中目标疾病高风险病例4例，21-三体、18-三体、13-三体的阳性预测值分别为100.00%(1/1)、0.00%和0.00%,三者复合阳性预测值为25.00%(1/4);SCA高风险病例8例，阳性预测值为50.00%(3/6);其他常染色体高风险病例2例，经产前诊断结果均为假阳性。自然妊娠组共有135例(1.15%,135/11 738)NIPT高风险孕妇，目标疾病高风险孕妇35例，21-三体、18-三体、13-三体的阳性预测值分别为95.45%(21/22)、57.14%(4/7)和0.00%,三者复合阳性预测值为78.13%(25/32);SCA高风险和其他常染色体异常高风险分别检出54例和46例，阳性预测值分别为31.82%(14/44)和8.11%(3/37)。两组中目标疾病检测的敏感度和特异性均高于99.85%,对所有病例随访中发现自然妊娠组中有1例常染色体异常假阴性病例。结论 NIPT在ART和自然妊娠胎儿21-三体、18-三体和13-三体筛查中具有良好的筛查效能，对SCA具有一定的筛查作用，对常染色体异常筛查效能较低，可作为ART和自然妊娠人群中较理想的产前筛查方法。
Abstract：Objectives:To explore the efficacy and application prospect of non-invasive prenatal testing(NIPT) for screening chromosomal diseases in fetuses with assisted reproductive technology(ART) and natural pregnancies.Methods:A total of 13 067 pregnant women who received NIPT in Maanshan Maternal and Child Health Care Hospital from January 2020 to December 2023 were selected. Prenatal diagnostic results and pregnancy outcomes were collected. Participants were divided into two groups based on the conception method: the ART group(n=1 329) and the natural conception group(n=11 738). The screening performance of NIPT for target diseases in terms of trisomies(21 trisomy, 18 trisomy, and 13 trisomy),sex chromosome aneuploidies(SCA),and other autosomal abnormalities was analyzed. Additionally, correlations of maternal age, gestational age at the time of NIPT,conception mode, fetal free DNA concentration with chromosomal abnormalities were evaluated.Results:There were significant differences in maternal age, gestational age, and fetal type between the ART group and the natural conception group for NIPT screening of pregnant women(P<0.05). There was no significant difference in the concentration of free DNA between the two groups of fetuses(P>0.05). The high-risk rate of NIPT only showed significant differences in the age of pregnant women(P<0.05). NIPT identified 149 high-risk cases with a positive rate of 1.14%(149/13 067). Among these cases, 125 cases underwent invasive prenatal diagnosis. The diagnostic confirmation rates were 92.31%(36/39) for target trisomies and 80.91%(89/110) for SCA and other autosomal abnormalities. In the ART group, 14 high-risk cases(1.05%,14/1 329) were identified, in whom 4 cases of the target trisomies were found with positive predictive value of 100.00%(1/1) for 21 trisomy, 0.00% for 18 trisomy and 0.00% for 13 trisomy, and a composite positive predictive value for three abnormalities was 25.00%(1/4). Eight SCA cases with a positive predictive value of 50.00%(3/6),and 2 other autosomal abnormalities(both false positives) were found. In the natural conception group, 135 high-risk cases(1.15%,135/11 738) were identified, in whom 35 cases of the target trisomies were found with positive predictive value of 95.45%(21/22) for 21 trisomy, 57.14%(4/7) for 18 trisomy, 0.00% for 13 trisomy, and the composite positive predictive value for three abnormalities was 78.13%(25/32). A total of 54 SCA abnormalities with positive predictive value of 31.82%(14/44) and 46 other autosomal ones with positive predictive value of 8.11%(3/37) were detected. The sensitivity and specificity for the detection of target trisomies exceeded 99.85% in both groups. One false-negative autosomal abnormality was identified during follow-up in the natural conception group.Conclusions:NIPT exhibits good screening efficacy for 21 trisomy, 18 trisomy, and 13 trisomy in fetuses from both ART and natural pregnancies, exerts a certain screening effect for SCA,and has relatively low screening efficacy for autosomal abnormalities, making it an ideal prenatal screening method in the population of both ART and natural pregnancies.
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基本信息:
中图分类号:R714.5
引用信息:
[1]黄保月,魏澄,赵巍松.无创产前检测在辅助生殖和自然妊娠胎儿染色体疾病筛查中的应用分析[J].生殖医学杂志,2025,34(11):1493-1501.
基金信息:
马鞍山市医疗卫生领域科技计划项目(YL-2023-15)