解整合素金属蛋白酶12分泌型在中孕期唐氏综合征胎儿筛查中的应用研究

摘要

[Objective]To investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome,DS),and to develop an appropriate prenatal DS screening protocol.[Methods] Serum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus.ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA).Curve fitting by weighted regression and other statistical methods were conducted,and the model was optimized for prenatal trisomy 21 screening program in second trimester.ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR).[Results] By comparison,the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P＜0.01).When FPR=5％,the DR of ADAM12-S was 28.3％,and the positive and negative likelihood ratios were 5.66 and 0.75,respectively.The DR of three-combination test of ADAM12-S,alpha fetoprotein(AFP) and free betasubunit of human chorionic gonadotropin (β-HCG) has increased to 52.80％ from 39.62％ of the conventional two-combination test (AFP and free β-HCG).For women with a risk between 1/300 and 1/ 1000 by two-combination test for DS,the DR has increased from 39.62％ to 47.12％,but FPR only increased by 0.8％ after adding ADAM12-S as a maternal serum marker.[Conclusion] Considering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester,ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-hCG,The cost-effectiveness ratio is reasonable.%目的 探讨解整合素金属蛋白酶12分泌型(a disintegfin and metalloprotease 12 secreting-form,ADAM12-S)在中孕期筛查唐氏综合征(Down syndrome,DS)胎儿的应用价值和适宜的筛查方案.方法 应用时间分辨荧光免疫法检测参与中孕期筛查的53名DS胎儿和621名孕龄和体重匹配的正常新生儿孕母血清样本的ADAM12-S水平,通过加权回归曲线拟合等统计学处理,选择最佳筛查模型,建立ADAM12-S筛查DS胎儿的方法,并分析ADAM12-S单独或联合中孕期二联筛查方案的检出率及假阳性率.结果 DS妊娠组的ADAM12-S中位数倍数(multiple of the median,MoM)的中位数水平要高于正常妊娠对照组(P＜0.01).在5％的筛查假阳性率时,ADAM1 2-S筛查的检出率为28.3％,其阳性似然比为5.66,阴性似然比为0.75.采用三联筛查方案(ADAM12-S+血清甲胎蛋白+游离伊绒毛膜促性腺激素)可将检出率从二联筛查方案(血清甲胎蛋白+游离β-绒毛膜促性腺激素)的39.62％提高到52.80％;对于在二联筛查风险率在1/300～1/1000的孕妇,进一步用ADAM12-S进行酌情筛查可将检出率从39.62％提高到47.12％,而假阳性率仅从5％增加到5.8％.结论 ADAM12-S是中孕期筛查DS妊娠的一个有效标记物.对中孕期二联筛查风险率在1/300～1/1000的孕妇采用ADAM12-S进行酌情筛查有更高的费效比.