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

doi:10.3877/cma.j.issn.1673-5250.2014.04.015

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

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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