血清妊娠相关蛋白-A与解整合素-金属蛋白酶12在早孕期产前筛查中运用的初步探讨

目的：探讨孕妇血清妊娠相关蛋白（PAPP）-A 与解整合素-金属蛋白酶（ADAM）12在早孕期产前筛查中的运用。方法收集2010年5月至2012年7月于甘肃省妇幼保健院产前诊断中心门诊就诊并自愿接受早孕期产前筛查孕妇的静脉血血清标本1609份为研究对象,其年龄为19~45岁,孕龄为9~13＋6孕周（本研究遵循的程序符合甘肃省妇幼保健院人体试验委员会制定的伦理学标准,得到该委员会批准,并征得受试对象的知情同意）。各孕周孕妇的年龄和体质量比较,差异无统计学意义（P＞0.05）。采用 Auto-DELFIA 全自动时间分辨荧光免疫分析仪、ADAM12、PAPP-A 和游离β-人绒毛膜促性腺激素（hCG）试剂盒,检测早孕期孕妇血清 ADAM12、PAPP-A 和游离β-hCG的水平,并采用 Lifecycle 3.0产前筛查软件评估 ADAM12、PAPP-A 和游离β-hCG 水平及其与唐氏综合征（DS）、开放性神经管缺陷（ONTD）、18-三体综合征等不良妊娠结局的关系。结果本组1609例孕妇的血清游离β-hCG、PAPP-A和ADAM12水平随孕周延长而升高,相关系数呈显著相关,且差异均有统计学意义（r=0.9552,0.9933,0.9965；P＜0.05）。将血清PAPP-A、游离β-hCG和ADAM12分别进行直线回归分析结果显示,早孕期血清游离β-hCG、PAPP-A和 ADAM12水平具有较强的正相关关系（血清游离β-hCG vs.血清 PAPP-A,r=0.9490,P＜0.05；血清游离β-hCG vs.血清 ADAM12,r=0.9440,P＜0.05；血清 ADAM12 vs.血清PAPP-A,r=0.9770,P＜0.05）。此外,1609例孕妇中,染色体核型异常为11例（0.68%）,其中45,XO 为4例（0.25%）、DS为3例（0.19%）、神经管畸形为2例（0.12%）、18-三体综合征为1例（0.06%）、13-三体综合征为1例（0.06%）。DS高风险孕妇血清 PAPP-A 和 ADAM12中位数倍数（MoM）均低于正常孕妇。结论血清PAPP-A和 ADAM12可作为早孕期产前筛查染色体异常的指标之一。

Preliminary Study on the Application of Pregnancy-Sociated Plasma Protein-A,Disintegrin-Metalloproteinase 1 2 in Prenatal Screening During First Trimester

Objective To discuss the application of pregnancy-sociated plasma protein （PAPP）-A, disintegrin-metalloproteinase （ADAM）1 2 in prenatal screening during first trimester.Methods A total of 1 609 samples which were collected from pregnant women receiving prenatal screening in the first trimester in Gansu Provincial Maternity and Child-Care Hospital from May 2010 to July 2012 were included into this study.Their age ranged from 18 to 45 years old,and gestational age ranged from 9 to 13＋6 gestational weeks.Auto-DELFLA were used to test the levels of serum ADAM 12,PAPP-A and free β-human chorionic gonadotrophin（hCG）,then the results were analyzed by LifeCycle 3.0 risk assessment software. Furthermore,the relationship between fetal risks [Down syndrome （DS ）, open neural tube defect （ONTD）,trisomy 18 syndrome]and levels of ADAM12,PAPP-A,freeβ-hCG were detected.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Gansu Provincial Maternity and Child-Care Hospital.Informed consent was obtained from each participants′ parents. Results Among the 1 609 samples,the levels of free β-hCG,PAPP-A and ADAM12 increased with gestational age. The related indexes of serum free β-hCG, PAPP-A and ADAM1 2 showed positive correlations with gestational weeks （r=0.955 2,0.993 3,0.996 5;P〈0.05 ）.The results of linear regression analysis among serum freeβ-hCG,PAPP-A and ADAM1 2 showed strong positive correlation （freeβ-hCG vs.PAPP-A,r=0.949 0,P〈0.05;freeβ-hCG vs.ADAM12,r=0.944 0,P〈0.05;ADAM12＆amp;nbsp;vs.PAPP-A,r=0.977 0,P〈0.05 ）.In addition,of the 1 609 samples,eleven cases （0.68%）had chromosome abnormalities,including four cases of 45,XO （0.25%）,three cases of DS （0.19%）,two cases of neural tube defects （0.12%）,one case of 18-trisomy syndrome （0.06%）,one case of 13-trisomy syndrome （0.06%）.The multiples of median （MoM）levels of serum PAPP-A and ADAM12 were lower than those of normal chromosome pregnant women.Conclusions Ser