孕早中期唐氏综合征筛查及297例介入产前诊断数据分析

Analysis of serum screening for Down's Syndrome in early and middle period of pregnancy and antenatal diagnosis of 297 patients

目的:探索一种有效的产前筛查唐氏综合征和其他严重出生缺陷儿的方法及各血清标志物筛查的截断界值。方法:应用时间分辨荧光免疫分析技术,对4762例孕妇进行血清标志物(PAPP-A/freeβ-hCG或者AFP/freeβ-hCG/μE3)联合筛查,使用Multical软件筛查高风险对象,通过羊水或脐带血细胞培养获得染色体核型给予诊断。结果:①筛查随访的2602例孕妇中,筛查出唐氏综合征及18三体高风险140例,NTD高风险17例,单项指标异常574例。共发现唐氏综合征10例、18三体4例、13三体2例、45,X3例、臂间倒位2例、缺失3例、遗传多态5例;重型地贫2例、无脑畸形1例、先天性肾病综合征1例。②血清标志物联合筛查的灵敏度、特异度、假阳性率、假阴性率分别为56.52%、94.41%、5.59%、43.48%;仅用PAPP-A作为独立指标筛查的灵敏度、特异度、假阳性率、假阴性率分别为100.00%、95.81%、4.19%、0;仅用AFP作为独立指标筛查的灵敏度、特异度、假阳性率、假阴性率分别为37.50%、90.84%、9.16%、62.50%;仅用freeβ-hCG作为独立指标筛查的灵敏度、特异度、假阳性率、假阴性率分别为33.33%、87.16%、12.84%、66.67%。③μE3的诊断界点为≤0.733MoM时可筛查出50%的唐氏综合征,假阳性率为9.36%;AFP的诊断界点为<0.6MoM时可筛查出40%的唐氏综合征,假阳性率为8.40%;若AFP的诊断界点为≤0.7MoM时可筛查出70%的唐氏综合征,假阳性率为19.40%;freeβ-hCG的诊断界点为<0.4MoM可筛查出75%的18三体病例,假阳性率为4.00%;freeβ-hCG的诊断界点为≥1.8MoM可筛查出40%的21三体病例,假阳性率为18.60%;freeβ-hCG的诊断界点为≥1.7MoM可筛查出50%的21三体病例,假阳性率为21.90%。以假阳性率5.00%为标准,freeβ-hCG的诊断界点为≥3.0MoM可筛查出10.00%的21三体病例。结论:血清标志物联合筛查的效率高于单项指标,但对血清标志物单项筛查阳性者也要建议产前诊断。唐氏综合征筛查是预测不良妊娠结局的有效指标,结合产前诊断对防止先天缺陷有实用价值。

Objective：To explore an effective methods of screening the Down＇s syndrome and severe birth defects through large sample of Down＇s syndrome screening in the early and middle period of pregnancy.Methods：The technology of time-distinguished fluorescence immunoassay was used to detect the serum AFP,freeβ-HCG and μE3 levels of 4762 pregnant women.The high risk pregnant women were calculated with Multical software.These high risk pregnant women were advised to receive amniocentesis or cordocentesis to know the fetal karyotype.Results：①2 602 pregnant women underwent antenatal screening,140 of them were in high risk of Down＇s syndrome and trisomy 18,17 of them were in high risk of NTD and 547 of them were unusual in single index.There were 10 cases of Down＇s syndrome,4 cases of trisomy 18,2 cases of trisomy 13,3 cases of monosomy,2 cases of pericentric inversion,3 cases of chromosome missing,5 cases of genetic polymorphism,2 cases of thalassemia,1 case of anencephaly,1 case of inborn dropsical nephritis.②The sensitivity and specificity and false positive rate and false negative rate of the allied screening of serum marker were 56.52%,94.41%,5.59%,43.48%;The sensitivity and specificity and false positive rate and false negative rate of PAPP-A as the single index were 100%,95.81%,4.19%,0;The sensitivity and specificity and false positive rate and false negative rate of AFP as the single index were 37.5%,90.84%,9.16%,62.5%;The sensitivity and specificity and false positive rate and false negative rate of freeβ-hCG as the single index were 33.33%,87.16%,12.84%,66.67%.③If theμE3 diagnostic point was lower than 0.733MoM,50% of Down＇s Syndrome cauld be found,the false positive rate was 9.36%;The AFP diagnostic point was lower than 0.6MoM,40% of Down＇s Syndrome cauld be found,the false positive rate was 8.4%;If the AFP diagnostic point was lower than 0.7MoM,70% of Down＇s Syndrome cauld be found,the false positive rate was 19.4%;The free β-hCG diagnostic point was lower than 0.4MoM,75% of trisomy 18 cauld be found,the false positive rate was 4%;The free β-hCG diagnostic point was higher than 1.8MoM,40% of trisomy 21 cauld be found,the false positive rate was 18.6%;If the free β-hCG diagnostic point was higher than 1.7MoM,50% of trisomy 21 cauld be found,the false positive rate was 21.9%;If the false positive rate was 5%,the free β-hCG diagnostic point was higher than 3.0MoM,10% of trisomy 21 cauld be found.Conclusion：The serum AFP,freeβ-HCG and μE3 levels of pregnant women are more effective in screening trisomy fetus than single index.The women whose single index are positive are advised to receive amniocentesis or cordocentesis.Combined with antenatal diagnosis it would be a practical method of preventing the congenital defect of fetus.