-
产前筛查是我国预防出生缺陷的措施之一,唐氏筛查临床上主要应用血清学四联筛查,但其检出率低,假阳性率高,仍需产前侵入性检查,染色体核型分析是产前诊断胎儿染色体异常的金标准,因其属于有创操作,可能引起孕妇流产,临床应用受限[1-2]。无创产前检测(non-invasive prenatal testing,NIPT)具有无创、简便、容易接受等特点,有研究[3-5]表明,NIPT用于胎儿染色体异常检查假阴性低,检测敏感性可达91.7%~100.0%;然而由于其费用偏高,应用于胎儿染色体筛查尚未完全普及。本研究筛查11 796例孕妇血清甲胎蛋白(alpha fetoprotein,AFP)、游离绒毛膜促性腺激素(chorionic gonadotropin,β-hCG)、结合雌三醇(unconjugated estriol,uE3)和抑制素A血清学四联筛查后,联合NIPT产筛模式,以染色体核型分析结果为金标准,探讨产前血清学四联筛查后联合NIPT产筛模式在胎儿染色体筛查中的应用价值。
-
唐氏筛查筛选出高风险孕妇721例,临界风险孕妇1 455例。高风险的721例孕妇中,NIPT检测高风险19例,即需要行侵入性产前诊断占2.64%;临界风险的1 455例孕妇中,NIPT检测高风险5例,即需要行侵入性产前诊断占0.34%(见表 1)。
分组 n 21-三体综合征 18-三体综合征 13-三体综合征 性染色体数目异常 其他 阳性率/% 高风险组 721 12 4 1 1 1 2.64 临界风险组 1 455 2 2 1 0 0 0.34 合计 2 176 14 6 2 1 1 1.10 表 1 NIPT检测结果(n)
-
染色体核型分析显示共有20例孕妇显示染色体异常,唐氏筛查高风险孕妇确诊19例,其中包括21-三体综合征13例,18-三体综合征4例,13-三综合征1例,其他染色体异常1例; 临界风险孕妇确诊1例,为21-三体综合征;NIPT显示高风险的24例孕妇中20例与核型分析结果一致,其中包括21-三体综合征12例,18-三体综合征5例,13-三综合征1例,性染色体数目异常1例,其他染色体异常1例。NIPT筛查与染色体核型诊断一致率为83.33%,二者检查结果差异无统计学意义(Fisher′s确切概率法,P>0.05)(见表 2)。
染色体异常 NIPT异常 羊水/脐静脉血核型一致 羊水/脐静脉血核型不一致 47,XN,+21 14 12 2 47,XN,+18 6 5 1 47,XN,+13 2 1 1 性染色体数目异常 1 1 0 其他染色体非整倍数 1 1 0 合计 24 20 4 表 2 NIPT阳性检测结果与染色体核型分析结果比较(n)
-
经产前诊断中心核实,结合妊娠结局,唐氏筛查高风险率为6.11%,联合NIPT筛查后染色体假阳性率3.29%,染色体异常检出率为83.33%。
-
对所有NIPT筛查孕妇均进行随访,随访至产后42 d,随访率100%,NIPT筛查提示有4例假阳性,经随访未发现异常;18例孕妇经核型分析确诊后引产,1例因胎儿畸形引产,1例胎死宫内引产,引产孕妇均做核型分析。
产前血清学四联筛查后联合NIPT产筛模式在胎儿染色体筛查中的应用
Application of combination of prenatal serological quadruple screening and NIPT birth screening mode in fetal chromosome screening
-
摘要:
目的探讨产前血清学四联筛查后联合无创产前检测(NIPT)产筛模式在胎儿染色体筛查中的应用价值。 方法选择进行产检的孕妇11 796例为观察对象,按照产前血清学四联筛查将孕妇分为高风险组和临界风险组,对高风险组和临界风险组孕妇进行NIPT检测,同时对NIPT结果为高危的孕妇,行常规染色体核型分析和/或高通量测序检测,对所有孕妇进行随访。 结果唐氏筛查筛选出高风险孕妇721例,临界风险孕妇1 455例。高风险的721例孕妇中,NIPT检测高风险19例,即需要行侵入性产前诊断者为2.64%;显示临界风险的1 455例孕妇中,NIPT检测高风险5例,即需要行侵入性产前诊断者为0.34%;NIPT显示高风险的24例孕妇全部进行染色体核型分析,结果显示共有20例孕妇显示染色体异常。唐氏筛查高风险孕妇确诊19例,其中包括21-三体综合征13例,18-三体综合征4例,13-三综合征1例,其他染色体异常1例;临界风险孕妇确诊1例,为21-三体综合征;24例孕妇中20例与核型分析结果一致经产前诊断中心核实,结合妊娠结局,唐氏筛查高风险率为6.11%,联合NIPT筛查后染色体假阳性率3.29%,检出率为83.33%。 结论产前血清学四联筛查后联合NIPT产筛模式可减少高风险孕妇有创检查的比例,对21-三体综合征、18-三体综合征的筛查具有一定临床意义。 Abstract:ObjectiveTo explore the application value of combination of prenatal serological quadruple screening and non-invasive prenatal testing (NIPT) birth screening mode in fetal chromosome screening. MethodsA total of 11 796 pregnant women undergoing maternity check-ups were selected as the observation subjects.According to the prenatal serological quadruple screening, the pregnant women were divided into high-risk group and borderline-risk group.The pregnant women in the high-risk group and borderline-risk group were tested for NIPT, meanwhile the pregnant women with a high-risk NIPT result were subjected to routine karyotyping and/or high-throughput sequencing tests, and all pregnant women were followed up. ResultsDown's screening screened out 721 high-risk pregnant women and 1 455 borderline-risk pregnant women.Among the 721 high-risk pregnant women, 19 were high-risk by NIPT, that was 2.64% of those who required invasive prenatal diagnosis.Among the 1 455 pregnant women who showed a borderline-risk in Down's screening, 5 cases were high-risk by NIPT, that was 0.34% of those who needed invasive prenatal diagnosis.The 24 pregnant women with high-risk NIPT were all subjected to karyotype analysis, which showed that 20 pregnant women showed chromosomal abnormalities.The high-risk pregnant women in Down's screening confirmed 19 cases, including 13 cases of 21-trisomy syndrome, 4 case of 18-trisomy syndrome, 1 case of 13-trisomy syndrome, and 1 case of other chromosomal abnormalities.A borderline-risk pregnant woman was diagnosed as 21-trisomy syndrome.A total of 20 cases of 24 pregnant women were consistent with the results of the karyotype analysis.Combined with the pregnancy outcome, the high-risk rate of Down's screening was 6.11%, the false positive rate of chromosome after combined NIPT screening was 3.29%, and the detection rate was 83.33%. ConclusionsCombination of prenatal serological quadruple screening and NIPT birth screening mode can reduce the proportion of invasive examinations in high-risk pregnant women, it has certain clinical significance for the screening of 21-trisomy syndrome and 18-trisomy syndrome. -
表 1 NIPT检测结果(n)
分组 n 21-三体综合征 18-三体综合征 13-三体综合征 性染色体数目异常 其他 阳性率/% 高风险组 721 12 4 1 1 1 2.64 临界风险组 1 455 2 2 1 0 0 0.34 合计 2 176 14 6 2 1 1 1.10 表 2 NIPT阳性检测结果与染色体核型分析结果比较(n)
染色体异常 NIPT异常 羊水/脐静脉血核型一致 羊水/脐静脉血核型不一致 47,XN,+21 14 12 2 47,XN,+18 6 5 1 47,XN,+13 2 1 1 性染色体数目异常 1 1 0 其他染色体非整倍数 1 1 0 合计 24 20 4 -
[1] 唐凯, 成艳, 张娟玲, 等. 1 240例羊水产前诊断胎儿染色体核型分析[J]. 中国优生与遗传杂志, 2018, 26(4): 21. [2] JUMMAAT F, AHMAD S, MOHAMED ISMAIL NA. 5-Year review on amniocentesis and its maternal fetal complications[J]. Horm Mol Biol Clin Investig, 2019, 40(2): 1. [3] 赵咏梅, 张传英, 席海林. 孕中期高危孕妇外周血中胎儿游离DNA与高危产前诊断指征相关性分析[J]. 中国实验诊断学, 2021, 25(2): 229. [4] 李书平, 胥红斌, 韩慧, 等. 孕中期血清学筛查、超声、NIPT联合在胎儿染色体异常筛查中的价值[J]. 中国超声医学杂志, 2020, 36(2): 166. doi: 10.3969/j.issn.1002-0101.2020.02.021 [5] 尹虹, 李扬, 罗颖, 等. 超声联合无创产前基因检测在早孕期胎儿染色体异常筛查中的价值[J]. 山东医药, 2018, 58(30): 83. [6] KOUMBARIS G, KYPRI E, TSANGARAS K, et al. Cell-free DNA analysis of targeted genomic regions in maternal plasma for non-invasive prenatal testing of trisomy 21, trisomy 18, trisomy 13, and fetal sex[J]. Clin Chem, 2016, 62(6): 848. doi: 10.1373/clinchem.2015.252502 [7] 郭芳芳, 杨洁霞, 齐一鸣, 等. 无创产前基因检测在产前筛查异常指标中的应用[J]. 中华检验医学杂志, 2018, 41(7): 509. [8] KIM MS, MOON MJ, KANG S, et al. Obstetrical outcomes of amniocentesis or chorionic villus sampling in dichorionic twin pregnancies[J]. J Korean Med Sci, 2019, 34(18): 1. [9] 王素侠, 陈琼琼, 程莉. 淮北地区2932例孕妇无创DNA产前筛查的调查分析[J]. 蚌埠医学院学报, 2021, 46(9): 1261. [10] 王芳芳, 王超, 刘羽, 等. 225例产前诊断指征及胎儿异常染色体核型分析[J]. 中国优生与遗传杂志, 2018, 26(2): 38. [11] MOURGUES C, EYMARD-PIERRE E, LAURICHESSE-DELMAS H, et al. Analysis of the cost effectiveness of different strategies for the antenatal diagnosis of chromosomal aberrations in cases of ultrasound-identified fetal abnormalities[J]. Ann Biol Clin (Paris), 2020, 78(5): 483. [12] 段秀群, 刘思嘉, 黄艳. 产前血清学筛查与无创产前基因检测在胎儿染色体异常筛查中的联合应用[J]. 中国优生与遗传杂志, 2019, 27(5): 545. [13] CERNAT A, DE FREITAS C, MAJID U, et al. Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women's experiences[J]. BMC Pregnancy Childbirth, 2019, 19(1): 27. doi: 10.1186/s12884-018-2168-4 [14] 周颖, 王振宇, 毛倩倩, 等. 无创产前检测技术在胎儿染色体非整倍体筛查中的应用价值[J]. 中华医学遗传学杂志, 2019, 36(11): 1094. [15] HEALTH QUALITY ONTARIO. Noninvasive prenatal testing for trisomies 21, 18, and 13, sex chromosome aneuploidies, and microdeletions: a health technology assessment[J]. Ont Health Technol Assess Ser, 2019, 19(4): 1. [16] 吴丽萍, 胡亮, 皮回春, 等. 唐氏筛查高风险孕妇590例胎儿染色体及NIPT结果[J]. 广东医学, 2020, 41(20): 2137. [17] 姚静怡, 崔岚, 岳胜, 等. 酌情联合无创基因检测的产前筛查模式探讨[J]. 医学理论与实践, 2018, 31(22): 3330.