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中华妇幼临床医学杂志(电子版) ›› 2014, Vol. 10 ›› Issue (04) : 473 -476. doi: 10.3877/cma.j.issn.1673-5250.2014.04.015

所属专题： 文献；

论著

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
林晓娟1, 孙庆梅1,*,*(), 刘婷婷1, 吕玲1, 郝胜菊1, 吴菊1, 李静1, 宋筱玉1, 代维斯1, 赵媛1   
  1. 1. 730050　兰州，甘肃省妇幼保健院产前诊断中心
  • 收稿日期:2014-02-15 修回日期:2014-05-23 出版日期:2014-08-01
  • 通信作者: 孙庆梅

Preliminary Study on the Application of Pregnancy-Sociated Plasma Protein-A, Disintegrin-Metalloproteinase 12 in Prenatal Screening During First Trimester

Xiaojuan Lin1, Qingmei Sun1(), Tingting Liu1, Ling Lyu1, Shengju Hao1, Ju Wu1, Jing Li1, Xiaoyu Song1, Weisi Dai1, Yuan Zhao1   

  1. 1. Gansu Provincial Maternity and Child-Care Hospital, Lanzhou 730050, Gansu Province, China
  • Received:2014-02-15 Revised:2014-05-23 Published:2014-08-01
  • Corresponding author: Qingmei Sun
  • About author:
    (Corresponding author: Sun Qingmei, Email: )
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引用本文：

林晓娟, 孙庆梅, 刘婷婷, 吕玲, 郝胜菊, 吴菊, 李静, 宋筱玉, 代维斯, 赵媛. 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[J/OL]. 中华妇幼临床医学杂志(电子版), 2014, 10(04): 473-476.

Xiaojuan Lin, Qingmei Sun, Tingting Liu, Ling Lyu, Shengju Hao, Ju Wu, Jing Li, Xiaoyu Song, Weisi Dai, Yuan Zhao. Preliminary Study on the Application of Pregnancy-Sociated Plasma Protein-A, Disintegrin-Metalloproteinase 12 in Prenatal Screening During First Trimester[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2014, 10(04): 473-476.

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1 609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1 609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=0.955 2，0.993 3，0.996 5;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= 0.949 0,P<0.05;血清游离β-hCG vs.血清ADAM12，r=0.944 0，P<0.05；血清ADAM12 vs.血清PAPP-A,r= 0.977 0,P<0.05) 。此外，1 609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。

关键词: 血清解整合素-金属蛋白酶12, 妊娠初期, 产前诊断
Objective

To discuss the application of pregnancy-sociated plasma protein (PAPP)-A, disintegrin-metalloproteinase (ADAM) 12 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, free β-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 ADAM12 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 free β-hCG, PAPP-A and ADAM12 showed strong positive correlation (free β-hCG vs. PAPP-A, r=0.949 0,P<0.05;free β-hCG vs. ADAM12, r=0.944 0, P<0.05; ADAM12 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

Serum PAPP-A and ADAM12 could be used as indicators of prenatal screening for chromosomal abnormalities during the first trimester.

Key words: Serum disintegrin-metalloproteinase 12, First trimester, Prenatal diagnosis
表1 各孕周孕妇的一般资料比较(±s)
Table 1 Comparison of general clinical data among pregnant women with different gestational weeks (±s)
孕龄(周） n 年龄(岁） 体质量(kg)
9～10 80 30.12±3.93 56.53±9.39
>10～11 198 29.23±4.09 56.68±8.12
>11～12 323 28.79±3.83 57.62±9.20
>12～13 521 28.95±3.36 55.26±7.18
>13～13+6 487 39.28±3.64 57.43±8.00
t 　 1.32 1.21
P 　 >0.01 >0.01
表2 不同孕周孕妇血清PAPP-A、游离β-hCG和ADAM12水平比较(MoM)
Table 2 Comparison of Serum PAPP-A, free β-hCG, ADAM12 levels in pregnant women with different gestational weeks
孕龄(周） n 游离β-hCG(ng/mL) PAPP-A( mIU/mL) ADAM12(ng/mL)
9～10 80 34.40 995 303.12
>10～11 198 40.30 1 560 355.20
>11～12 323 44.35 2 980 451.39
>12～13 521 47.40 3 790 512.80
>13～13+6 487 47.85 4 710 598.12
表3 羊水穿刺染色体核型分析结果异常孕妇血清PAPP-A、游离β-hCG及ADAM12水平(MoM)
Table 3 Comparison of serum PAPP-A,free β-hCG and ADAM12 levels among three cases with DS and one case with 18-trisomy syndrome (MoM)
患者(No.) 染色体结果 年龄(岁） 孕龄(周） ADAM12 PAPP-A 游离β-hCG
1 47，XX，+21 30 13+3 1.485 1.017 1.485
2 47，XX,+21 36 11+6 0.374 0.190 0.374
3 47，XY，+21 32 11+1 0.227 0.400 1.631
4 47，XY,+ 18 35 13+4 1.196 0.240 2.196
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