Pihl Kasper, Larsen Torben, Krebs Lone, Christiansen Michael
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
Prenat Diagn. 2008 Dec;28(12):1131-5. doi: 10.1002/pd.2141.
To examine the ability of predicting fetuses being small-for-gestational-age (SGA) at delivery with the maternal serum markers pregnancy-associated plasma protein A (PAPP-A), beta-human chorionic gonadotrophin (beta-hCG) and A disintegrin and metalloprotease 12 (ADAM12) in first trimester.
In all,36 cases being SGA (birth weight < 5th centile) and 108 controls being non-SGA were matched on ethnicity (only Caucasians), smoking status (only nonsmokers), body mass index (BMI), age and parity. Stored blood samples from PAPP-A and beta-hCG testing obtained at gestational age (GA) of 8 weeks to 13 weeks and 6 days were analyzed for ADAM12. Median MoM values were compared using Mann-Whitney test. Monte Carlo estimation and receiver-operator-characteristics curves were used to asses screening performance.
Median MoM values of PAPP-A (0.64 vs 1.02, p < 0.001), beta-hCG (0.74 vs 1.04, p = 0.007) and ADAM12 (0.74 vs 0.97, p = 0.004) were significantly reduced in cases compared to controls. The combination of PAPP-A MoM and beta-hCG MoM yielded a detection rate (DR) for SGA of 26% for a 5% false-positive rate (FPR). Addition of ADAM12 only improved (28% DR for a 5% FPR) screening performance modestly.
Early prediction of fetuses being SGA is feasible with the combination of first trimester PAPP-A, beta-hCG and ADAM12. Screening performance is approaching clinical relevance. The inclusion of further markers is an attractive option.
研究孕早期母体血清标志物妊娠相关血浆蛋白A（PAPP-A）、β-人绒毛膜促性腺激素（β-hCG）和去整合素金属蛋白酶12（ADAM12）预测分娩时小于胎龄儿（SGA）的能力。
总共纳入36例SGA（出生体重<第5百分位数）病例和108例非SGA对照，根据种族（仅白种人）、吸烟状况（仅非吸烟者）、体重指数（BMI）、年龄和产次进行匹配。分析孕8周零天至13周零6天期间进行PAPP-A和β-hCG检测时采集的储存血样中的ADAM12。使用曼-惠特尼检验比较中位数MoM值。采用蒙特卡洛估计和受试者工作特征曲线评估筛查性能。
与对照组相比，病例组中PAPP-A（0.64对1.02，p<0.001）、β-hCG（0.74对1.04，p = 0.007）和ADAM12（0.74对0.97，p = 0.004）的中位数MoM值显著降低。PAPP-A MoM和β-hCG MoM联合使用时，对于5%的假阳性率（FPR），SGA的检测率（DR）为26%。仅添加ADAM12仅适度提高了筛查性能（对于5%的FPR，DR为28%）。
孕早期PAPP-A、β-hCG和ADAM12联合使用可对SGA胎儿进行早期预测。筛查性能正接近临床应用价值。纳入更多标志物是一个有吸引力的选择。
