无创基因检测(NIPT)对胎儿染色体异常筛查的临床应用

Application of Noninvasive Prenatal Testing in the Screening of Chromosome Abnormality

目的探讨无创产前基因检测(NIPT)在预测胎儿染色体异常中的临床应用价值。方法选取2016年4月～2018年4月在福建省宁德市闽东医院行NIPT的单活胎孕妇6 357例,按孕周分为早、中、晚孕期组,按孕龄分为高、低龄组,低龄组又按申请理由分唐氏筛查高风险组、临界风险组、单项指标或中位数倍数(MOM值)异常组,B超软指标异常组和直接选择NIPT组,对于结果异常者签署知情同意书行羊膜腔穿刺术。结果 (1)6 357例孕妇共检出染色体异常76例,早、中、晚孕期组阳性率分别为2.17%,1.23%和0.70%,三者之间差异无统计学意义(χ~2=2.265～6.052,均P>0.05);(2)6 357例孕妇按孕龄和申请理由分组,各组阳性率分别为1.45%,1.07%,0.97%,0.60%,1.29%和1.15%,各组之间差异无统计学意义(χ~2=0.017～1.809,均P>0.05);(3)76例NIPT结果异常孕妇有64例接受了羊膜腔穿刺羊水细胞染色体检查,其中21,18和13-三体的诊断率分别为90%,100%和100%,符合率分别为88.9%,88.9%和50%;性染色体的诊断率为83.9%,符合率61.5%;其它染色体异常诊断率为58.3%,符合率为0。结论 (1)不同孕期NIPT的阳性率之间无差异,孕妇可以尽早行NIPT,为后续介入性诊断争取时间;(2)不同申请理由NIPT的阳性率之间无差异,高龄和错过唐筛时间的孕妇可将NIPT作为筛查胎儿染色体异常的首选,而唐筛高风险、临界风险、单项指标或MOM值异常的孕妇可将NIPT作为二线筛查,从而避免不必要的羊膜腔穿刺;(3)NIPT不仅对21和18-三体具有较高的特异度和敏感度,对13-三体、性染色体也有一定的预示作用,可作为产前检测胎儿染色体异常的辅助手段。

Objective To explore the clinical application value of noninvasive prenatal testing（NIPT） in the screening of chromosome abnormality. Methods From April 2016 to April 2018,a total of 6 357 cases of single pregnant women undergoing NIPT in Mindong Hospital were selected. They were divided into early-pregnancy group, mid-pregnancy group and laterpregnancy group by gestational age. They also were divided into advanced maternal age group and non-advanced maternal age group. The non-advanced maternal age group was secondly divided into high risk group, critical risk group, single index or MOM anomaly group about Down＇ s syndrome screening, soft indexes anomaly group about ultrasonic diagnosis and preferred alternative group by reasons for application of NIPT. The pregnant women with high-risk NIPT results were suggested amniotic fluid puncture for karyotype analysis. Results ①76 pregnant women were found with high-risk NIPT results. The positive rate was 2.17% in early-pregnancy group, 1.23% in mid-pregnancy group and 0.70% in later-pregnancy group. They didn＇t have statistic significance （χ^2=2. 265%6. 052, P〉0.05）. ②A total of 6 537 cases were divided by age and reason for application of NIPT. The positive rate were 1.45 %, 0.97 %, 0.60 %, 1.29 % and 1.15 % respectively. They didn＇t have statistic significance （χ^2=0. 017-1. 809, P〉0.05）. ③Among 76 pregnant women with high-risk NIPT results, 64 cases underwent amniotic fluid puncture for karyotype analysis. The diagnosis rate of T21, T18 and T13 were 90 %,100 % and 100 % respectively. The positive predictive values of T21, T18 and T13 were 88.9 %, 88.9 % and 50 %, respectively. The diagnosis rate of sex chromosome abnormality was 83.9%, the coincidence rate was 61.5%, the diagnosis rate of other chromosome abnormality was 58.3%,the coincidence rate was 0o Conclusion ①The positive rates didn＇t have significant difference among different pregnancy duration, so pregnant woman after 12 weeks can do NIPT as early as possiblefor striving more time for subsequent interventional diagnosis.② The positive rates didn＇t have significant difference among different groups divided by reasons for application of NIPT,so pregnant women with advanced age or missing Down＇s syndrome screening can do NIPT as the first chioce for screening fetal chromosomal abnormality. The pregnant women with high risk, critical risk and single in dex or MOM anomaly in Down＇s syndrowe screening select NIPT as second-line screening to avoiding unnecessary puncture. ③NIPT not only have high specificity and sensitivity in screening of T21 and T18 ,but also have certain indicative for T13 and sex chromosome abnormality. NIPT can be a powerful and reliable supplementary.