Spencer Kevin, Cowans Nicholas J
Prenatal Screening Unit, Clinical Biochemistry Department, Harold Wood Hospital, Romford, UK.
J Matern Fetal Neonatal Med. 2007 Sep;20(9):645-50. doi: 10.1080/14767050701483389.
ADAM12 (a disintegrin and metalloprotease 12) is a placentally derived glycoprotein that appears to be involved in growth and differentiation. The maternal serum concentration of ADAM12 appears to be a very good marker of trisomy 21 in the early first trimester when levels are reduced, and in the second trimester around 16-18 weeks levels are elevated. One small preliminary study of first trimester pregnancies with trisomy 18 found reduced levels in the maternal serum, and we examine herein the potential of ADAM12 as a marker of trisomy 18 in both the first and second trimester of pregnancy.
The concentration of ADAM12 was determined by a time-resolved immunofluorometric assay in 132 first and 12 second trimester cases of trisomy 18, and 389 first and 341 second trimester gestational age-matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and used to determine the population distribution parameters for the trisomy 18 and control groups. Correlation with previously established pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) multiples of the median (MoMs) and nuchal translucency thickness (NT) MoM were determined and used to model the performance of first trimester screening with ADAM12 in combination with other first trimester markers.
The maternal serum concentration of ADAM12 in the first trimester was significantly reduced with a median MoM of 0.829 (p < 0.001) and a mean log10 MoM SD of 0.2663 compared to 0.3353 in the controls. In the second trimester small series ADAM12 was significantly increased with a median MoM of 2.09 (p = 0.001) and a mean log10 MoM SD of 0.2607 compared to 0.4318 in controls. There was a significant correlation of ADAM12 MoM with gestational age (r = 0.510) in trisomy 18 cases, and the median MoM increased from 0.51 at 10 weeks to 1.28 at 13 weeks and 2.09 across the 14-18 week window. ADAM12 was correlated with PAPP-A (r = 0.1918) in the first trimester of cases with trisomy 18 but less so with NT (r = 0.1594) and free beta-hCG (r = 0.0938). Modeled detection rates incorporating ADAM12, free beta-hCG, and NT were 92% at 1% false positive rate (88% at 0.5%) A combination of all four markers had a detection rate of 96.5% at a false positive rate of 1% (95% at 0.5%).
ADAM12 may be a useful addition to early screening for trisomy 18 alongside other chromosomal anomalies, particularly if biochemical screening can occur before 10 weeks.
ADAM12（解整合素金属蛋白酶12）是一种胎盘来源的糖蛋白，似乎参与生长和分化过程。在孕早期，当21三体水平降低时，母体血清中ADAM12的浓度似乎是21三体的一个很好的标志物；而在孕中期约16 - 18周时，其水平会升高。一项关于孕早期18三体妊娠的小型初步研究发现母体血清中ADAM12水平降低，在此我们研究ADAM12作为孕早期和孕中期18三体标志物的潜力。
采用时间分辨免疫荧光分析法测定132例孕早期和12例孕中期18三体病例以及389例孕早期和341例孕中期孕周匹配的对照妊娠中ADAM12的浓度。通过多项式回归确定正常妊娠的中位数，并用于确定18三体组和对照组的总体分布参数。确定ADAM12与先前确立的妊娠相关血浆蛋白A（PAPP - A）、游离β - 人绒毛膜促性腺激素（β - hCG）中位数倍数（MoMs）以及颈项透明层厚度（NT）MoM的相关性，并用于模拟将ADAM12与其他孕早期标志物联合进行孕早期筛查的性能。
与对照组相比，孕早期18三体病例中母体血清ADAM12浓度显著降低，中位数MoM为0.829（p < 0.001），平均log10 MoM标准差为0.2663，而对照组为0.3353。在孕中期小样本中，与对照组相比，ADAM12显著升高，中位数MoM为2.09（p = 0.001），平均log10 MoM标准差为0.2607，而对照组为0.4318。在18三体病例中，ADAM12 MoM与孕周显著相关（r = 0.510），中位数MoM从10周时的0.51增加到13周时的1.28，在14 - 18周期间为2.09。在孕早期，18三体病例中ADAM12与PAPP - A相关（r = 0.1918），但与NT（r = 0.1594）和游离β - hCG（r = 0.0938）相关性较低。纳入ADAM12、游离β - hCG和NT的模拟检测率在假阳性率为1%时为92%（在0.5%时为88%）。四种标志物联合使用时，在假阳性率为1%时检测率为96.5%（在0.5%时为95%）。
ADAM12可能是孕早期筛查18三体以及其他染色体异常的有用补充，特别是如果生化筛查能在10周前进行。
