妊娠早中期孕妇血清中β-hCG、PAPP-A、AFP及uE3水平检测在联合预测子痫前期中的价值

The value of maternal first and second trimester serum data of β-hCG, PAPP-A, AFP and uE3 in the prediction of preeclampsia

目的探讨孕早中期孕妇血清中β-hCG、妊娠相关血浆蛋白A（PAPP-A）、甲胎蛋白（AFP）及游离雌三醇（uE3）水平检测在联合预测子痫前期中的价值。方法前瞻性随机选取2012年4月至2013年6月上海交通大学医学院附属国际和平妇幼保健院产科行产前检查并分娩的1805例孕妇，根据随访结果将其分为正常对照组及子痫前期组（包括轻度及重度子痫前期）。孕10～14周时检测孕妇血清中PAPP-A、β-hCG的水平；孕15～20周时检测其血清中AFP、β-hCG及uE3的水平。对血清指标与部分妊娠结局的相关性进行分析，应用受试者工作曲线（ROC曲线）及约登指数评判各血清指标预测子痫前期的价值，并确定相应的预测界值。结果（1）1805例孕妇中未发生妊娠期高血压疾病1739例（正常对照组）,发生子痫前期66例（子痫前期组）,子痫前期发生率为3.66%（66/1805）,其中轻度子痫前期43例、重度子痫前期23例。（2）孕10～14周时正常对照组孕妇血清PAPP-A水平平均为（3972±2311）mU/L，子痫前期组孕妇平均为（2837±1849）mU/L，两组比较，差异有统计学意义（P〈0.01）；正常对照组孕妇血清β-hCG水平为55（37~83）U/L，子痫前期组孕妇平均为（57±35）U/L，两组比较，差异无统计学意义（P〉0.05）。子痫前期组轻度孕妇血清PAPP-A、β-hCG及AFP水平分别为（3249±1877）mU/L、（61±38）U/L及（35±11）μg/L，重度孕妇分别为（1758±1297）mU/L、（47±23） U/L及（47±22）μg/L，两者PAPP-A水平比较，差异有统计学意义（P〈0.05）。（3）孕15～20周时子痫前期组孕妇血清β-hCG、AFP及uE3水平分别为（47909±31396）U/L、（38±15）μg/L及（0.98±0.31）μg/L,正常对照组分别为（39267±25054）U/L、（47±18）μg/L及（1.17±0.39）μg/L,子痫前期组孕妇血清中AFP及uE3水平均明显低于正常对照组，分别比较，差异均有统计学意义（P〈0.05）。子痫前期组轻度孕妇血清β-hCG及uE3水平分别与重度孕妇比较，差异均无统计学意义（P〉0.05）。（4）孕10～14周时，孕妇血清PAPP-A水平与新生儿出生体质量（r=0.068,P=0.011）及分娩孕周（r=0.057,P=0.048）呈正相关；孕15～20周时，孕妇血清AFP水平与新生儿出生体质量（r=0.149,P=0.000）呈正相关；血清β-hCG水平与新生儿1分钟Apgar评分（r=-0.085,P=0.024）呈负相关；血清uE3水平与分娩孕周（r=0.086,P=0.036）呈正相关。（5）将血清PAPP-A、AFP及uE3水平作为检验变量得出预测子痫前期的界值，分别为PAPP-A 1831 mU/L、AFP 41μg/L及uE31.04μg/L，预测子痫前期的特异度分别为97.82%、98.54%及98.80%。（6）以PAPP-A、AFP及uE3的联合预测因子作为检验变量绘制ROC曲线并计算约登指数，联合预测因子为0.032时约登指数最大（为0.41），其预测子痫前期的价值最大。故以0.032作为PAPP-A、AFP及uE3联合预测因子的预测界值，其预测子痫前期的特异度为98.93%，敏感度为70.59%，相对风险度为2.37。结论无论是PAPP-A、AFP及uE3各单项血清指标还是联合预测因子，对子痫前期发病均有预测价值，但联合预测因子的预测价值要优于任一单项血清指标。

Objective To discover the value of combined maternal first and second-trimester serumβ-hCG, pregnancy associated plasma protein A （PAPP-A）, alpha-fetoprotein（AFP）and unconjugated estriol （uE3） in the prediction of preeclampsia.Methods A total of 1 805 pregnant women who had antenatal care at International Peace Maternal and Child Health Hospital Affiliated to Shanghai Jiaotong University between April 2012 and June 2013 were selected prospectively by random method. According to the outcome, they were defined as the control group and the preeclampsia group （including mild and severe cases）. PAPP-A and β-hCG level were measured at 10-14 gestational weeks. AFP, β-hCG and uE3 were measured at 15-20 gestational weeks. The relevance between the serological indicators and outcomes was analyzed. The value of the indicators was judged by receiver operating characteristic（ROC）and Youden index, and the relevant predictive boundary values were identified.Results （1） Among the 1 805 cases, 1 739 women did not have hypertension（the control group）, while 66 women had preeclampsia（the preeclampsia group）. The incidence of preeclampsia was 3.66% （66/1 805）, including 43 mild cases and 23 severe cases. （2） At 10-14 gestational weeks, the mean value of PAPP-A in the control group was（3 972± 2 311） mU/L, while in the preeclampsia group it was（2 837 ± 1 849）mU/L. The difference between the two groups had statistical significance（P〈0.01）. The mean value ofβ-hCG of the control group was 55（37~83） U/L, while in the preeclampsia group it was （57 ± 35） U/L. There was no statistical significance （P〉0.05）. PAPP-A,β-hCG and AFP of mild preeclampsia cases were（3 249 ± 1 877）mU/L,（61 ± 38）U/L and（35 ± 11）μg/L respectively, and in severe cases they were（1 758±1 297）mU/L,（47±23）U/L and（47±22）μg/L, respectively. There was statistically significant difference in PAPP-A（P〈0.05）. （3） At 15-20 gestational weeks,β-hCG, AFP and uE3 in the preeclampsia group were（47 909±31 396）U/L,（38±15）μg/L and（0.98± 0.31）μg/L respectively, and in the control group they were（39 267 ± 25 054）U/L,（47 ± 18）μg/L and （1.17±0.39）μg/L,respectively. AFP and uE3 of the preeclampsia group were lower than those in the control group and the difference was statistically significant （P〈0.05）. However, β-hCG and uE3 of the mild preeclampsia cases and the severe cases had no statistical difference （P〉0.05）. （4）At 10-14 gestational weeks, PAPP-A demonstrated positive relevance to the newborn weight（r=0.068, P=0.011）and gestational weeks at delivery（r=0.057,P=0.048）. At 15-20 weeks, positive relevance was found between AFP and the newborn weight （r=0.149,P=0.000）, while negative relevance was found between β-hCG and Apgar scores （r=-0.085,P=0.024）, and positive relevance was found between uE3 and gestational weeks at delivery（r=0.086,P=0.036）.（5） PAPP-A, AFP and uE3 data were used as testing parameters to obtain the boundary values of preeclampsia prediction as follows： PAPP-A 1 831 mU/L, AFP 41 μg/L and uE3 1.04 μg/L. The specificity was 97.82%,98.54% and 98.80%, respectively. （6） ROC was drawn and Youden index was calculated based on the joint predicative factor of PAPP-A, AFP and uE3. Youden index reached its peak （0.41） when the joint predictive factor was 0.032, meaning that the factor had the highest prediction value. The prediction value of the PAPP-A, AFP and uE3 was 0.032, with the specificity and sensitivity of 98.93%and 70.59%, respectively. The odds ratio was 2.37. Conclusion Both the individual parameter （PAPP-A, AFP and uE3） and the combined data have prediction value for preeclampsia, but the latter is more effective than any of the single parameter.