妊娠早期孕妇血清瘦素、β-hCG及融合素α(ADAM12)水平与自然流产发生的相关性研究

Relationship between Maternal Serum Leptin,β-hCG, Meltrin-α (ADAM12) Levels during First Trimester Pregnancy and Spontaneous Abortion

目的:探讨妊娠早期妇女血清瘦素、人绒毛膜促性腺激素β(β-hCG)及融合素-α(ADAM12)的浓度变化及这些指标对自然流产发生的预测价值。方法:分别测定172例妊娠妇女(其中自然流产者20例)及非妊娠健康妇女48例,妊娠组在孕10～12周时分别测血清瘦素、β-hCG、ADAM12的浓度。瘦素、β-hCG采用ELISA法测定,ADAM12采用时间分辨荧光免疫分析方法测定,预测界限值根据ROC曲线确定。结果:①在妊娠早期自然流产患者血清β-hCG、瘦素、ADAM12水平低于正常妊娠者,差异显著(P<0.001);自然流产组、正常妊娠组β-hCG、瘦素水平均高于非妊娠组,差异显著(P<0.05)。②妊娠早期以血清瘦素≤11 ng/ml、血清β-hCG≤22 IU/ml及血清ADAM12≤335 ng/ml为预测界值,其预测自然流产发生的曲线下面积、灵敏度、特异度、阳性预测值(PPV)及阴性预测值(NPV)分别为:79.60%、90.00%、71.71%、29.51%和98.20%;91.00%、85.00%、87.50%、47.22%和97.79%;78.40%、80.00%、78.75%、48.48%和94.03%。③根据ROC曲线图确定临界值:以血瘦素≤11 ng/ml、血β-hCG≤22 IU/ml为预测界值,两者联合灵敏度75%,特异度96.05%,阳性预测值71.43%,阴性预测值96.69%,两者联合预测阳性率显著高于单项血清β-hCG及瘦素预测率(P<0.05)。④根据ROC曲线图确定临界值:以血β-hCG≤22 IU/ml、血ADAM12≤335 ng/ml为预测界值,两者联合灵敏度75%、特异度95%,阳性预测值78.95%,阴性预测值93.83%,两者联合预测阳性率显著高于单项血清β-hCG及ADAM12预测率(P<0.05)。结论:妊娠早期,检测孕妇血瘦素、β-hCG及ADAM12,可作为自然流产发生的有效预测指标;联合多项指标可进一步提高对自然流产发生的阳性预测率及准确率。

Objective：To investigate the changes of maternal serum concentrations of leptin,beta-human chorionic gonadotropin（β-hCG） and ADAM12 during first trimester of pregnancy,and its relationship with spontaneous abortion.Methods： Samples from 48 nonpregnant healthy women and 172 pregnant women were included in this prospective study,of those pregnant women 20 were subsequently developed spontaneous abortion and 152 were normal pregnant women.The maternal serum was conducted between the 10th and 12th week of pregnancy.Leptin and β-hCG levels were ascertained by enzyme-linked immunosorbent assay（ELISA）.The level of ADAM12 was measured by time-resolved fluoroimmunoassay.The cutoff point was determined using a receiver operating characteristic curve（ROC）.Results： 1） The first trimester levels of serum β-hCG,Leptin and ADAM12 in pregnancies that subsequently developed spontaneous abortion were significantly lower than those in normal pregnant women（P〈0.05）.The levels of serum β-hCG and Leptin in both groups of pregnant women were higher than those in the nonpregnant group（P〈0.05）.2） The cutoff concentration of β-hCG was 22 IU/ml,leptin was 11 ng/ml and ADAM12 was 335 ng/ml in first trimester of pregnancy,the area below the curve was 91%,79.60% and 78.40%,sensitivity was 85%,90% and 80%;specificity was 87.50%,71.71% and 78.75%;positive predictive value was 47.22%,29.51% and 48.48%;negative predictive value was 97.79%,98.20% and 94.03%.3） Combining the values of β-hCG and leptin to form a screening test would detect an estimated 71.43% of affected pregnancies.4） Combining the first trimester levels of serum β-hCG and ADAM12 to form a screening test would detect an estimated 78.95% of affected pregnancies.Conclusion： The measuring levels of β-hCG,leptin and ADAM12 during the first trimester of pregnancy are useful in clinical practice to identify pregnant women who will suffer spontaneous abortion.