PAPP-A, INH-A, β-hCG and uterine artery pulsatility index for the prediction of preeclampsia at the early second trimester
-
摘要:
目的 探索中孕早期孕妇血清中的PAPP-A、β-hCG、INH-A及子宫动脉搏动指数(PI)与子痫前期的相关性,及其联合预测子痫前期的可行性。 方法 采用前瞻性巢式病例对照研究,选取于本院产科门诊就诊的单胎孕妇(孕周为11~12+6)416例作系统研究,采血测定孕β-HCG、INH-A、PAPP-A,检测PI值。随访后,确诊为子痫前期的孕妇纳入子痫前期组,其余为对照组。 结果 416例孕妇在随访观察中,有23例发生子痫前期,纳入病例组;对照组393例,孕期血压正常。子痫前期的发病率5.52%。PAPP-A、β-hCG、INH-A、PI及入组年龄在子痫前期组与对照组间差异有统计学意义(P<0.05)。Logistic回归分析显示,年龄及PI值对疾病预测不产生显著性影响(P>0.05)。在子痫前期发病的相关因素中,PAPP-A和INH-A与子痫前期的发生呈负相关,而β-HCG与子痫前期的发生呈正相关。上述单变量的预测效力PAPP-A>β-hCG>INH-A,而PAPP-A、INH-A、β-hCG变量的联合预测效力明显优于上述变量单独预测,联合预测的曲线下面积可达0.867。 结论 在中孕早期,PAPP-A、INH-A、β-hCG对子痫前期有一定预测价值,PAPP-A、INH-A、β-hCG联合预测子痫前期有相对较高的敏感度和特异性,其预测价值高于单独预测。 Abstract:Objective To evaluate the predictive value of PAPP-A, INH-A, β-hCG and uterine artery pulsatility (PI) for preeclampsia at the early stage of second trimester. Methods The prospective nested case-control study was carried out. Serum samples of 416 pregnant women were obtained at 11~12+6 weeks of the gestation. PAPP-A, INH-A and β-hCG concentrations were measured by chemiluminescence method or enzyme-linked immunosorbent assay (ELISA), while uterine artery pulsatility index (PI) was measured by Doppler velocimetry at the same time. Results 23 pregnant women who were found to have developed preeclampsia were used as the preeclampsia group (PE group), and the other 393 cases whose blood pressure remained normal were chosen as the control group. The incidence of PE was 5.52%. The MOM values of PAPP-A, β-hCG, INH-A and PI in PE group were significantly different from the control group(P< 0.05).The logistic regression showed that age and PI have no significant effect on the prediction of PE. Among the relative factors, PAPP-A and INH-A are two factors that are negatively correlated with the occurrence of PE, while β-HCG is a positive factor. Comparing these predictive factors individually, the ranking in terms of predictive ability is following: PAPP-A>β-hCG>INH-A. The predictive ability for PE was significantly improved when PAPP-A, INH-A and β-hCG were combinedly used, and the area under the ROC curve can reach to 0.867. Conclusion Combining the screening of different biomarkers, such as serum PAPP-A, INH-A and β-hCG, could increase the predictive value of PE at the early stage of second-trimester. -
Key words:
- preeclampsia /
- combined prediction /
- early stage of second-trimester
-
表 1 子痫前期组与对照组入组时一般临床资料的比较(Mean±SD)
组别 n 年龄(岁) 采血日孕周 体质量(kg) 体质量指数 Control组 393 29.77±3.69 12.6±1.19 55.15±6.96 21.85±2.71 PE组 23 32.44±4.17 12.5±1.03 55.23±6.23 22.52±2.36 P 0.001 0.420 0.967 0.510 表 2 子痫前期与对照组PAPP-A、INH-A、β-hCG、PI MOM值比较(Mean±SD)
组别 PAPP-A MOM β-hCG MOM INH-A MOM PI MOM Control组 0.99±0.50 1.04±.64 1.03±0.47 1.06±0.14 PE组 0.68±0.52 1.84±1.51 0.74±0.36 1.15±0.10 P 0.031 0.000 0.027 0.02 表 3 子痫前期预测因子的Logistic回归分析
自变量 β S.E. Wals P OR (INT) 3.350 1.742 3.697 0.055 28.495 PAPP-A(x1) –0.001 0.000 14.994 0.000 0.999 INH-A(x2) –0.019 0.006 11.992 0.001 0.981 β-HCG(x3) 0.022 0.008 7.146 0.008 0.980 表 4 PAPP-A、INH-A、β-hCG预测子痫前期的曲线下面积及假阳性率的敏感度
检验变量 曲线下面积 标准误 P 95%可信区间 敏感度 下限 上限 假阳性率10% 假阳性率20% PAPP-A 0.687 0.087 0.024 0.516 0.857 80.3 84.6 INH-A 0.654 0.081 0.062 0.479 0.812 82.6 83.5 β-HCG 0.677 0.095 0.033 0.491 0.863 80.2 83.1 PAPP-A、INH-A、β-hCG、 0.867 0.057 0.000 0.756 0.981 86.7 92.3 -
[1] Abalos E, Cuesta C, Grosso AL, et al. Global and regional estimates of preeclampsia and eclampsia: a systematic review[J]. Eur J Obstet Gynecol Reprod Biol, 2013, 170(1): 1-7. doi: 10.1016/j.ejogrb.2013.05.005 [2] 中国妊高征科研协作组. 全国妊高征的流行病学调查[J]. 中华妇产科杂志, 1991, 26(2): 67-70. [3] 李跃萍, 闫庆峰, 胡春霞. 子痫前期发病机制及其预测的研究进展[J]. 基层医学论坛, 2017, 21(16): 2126-9. [4] 徐亚玲, 常 颖, 陈 叙. 子痫前期预测指标的临床应用研究进展[J]. 国际妇产科学杂志, 2016, 43(01): 11-4. [5] 李之朋, 杨春艳, 陈 敏. 唐氏综合征的早期筛查[J]. 中国实用妇科与产科杂志, 2008, 24(2): 87-90. [6] 齐一鸣, 王东梅, 曾玉坤, 等. 辅助生育与自然妊娠孕妇早期唐氏筛查结果的对照研究[J]. 中外医疗, 2014, 33(31): 44-5, 48. doi: 10.3969/j.issn.1674-0742.2014.31.022 [7] Goetzinger KR, Zhong Y, Cahill AG, et al. The efficiency of first-trimester uterine artery Doppler,Adam12,PAPP-A andmaternal characteristics in the prediction of pre-eclampsia[J]. J Ultrasound Med, 2013, 32(6): 1593-600. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929514 [8] Yu H, Shen YT, Li HL, et al. The relationship between maternal serum prenatal screening combined with epidemiological study and early onset preeclampsia[J]. Arch Gynecol Obstet, 2014, 289(4): 749-53. doi: 10.1007/s00404-013-3039-x [9] Jin HK, Antonio F. Ji HP down syndrome biochemical markers and screening for preeclampsia at first and second trimester:correlation with the week of onset and the severity[J]. Prenat Diagn, 2008, 28(7): 704–9. [10] Allen RE, Rogozinska E, Cleverly K, et al. Abnormal blood biomarkers in early pregnancy are associated with preeclampsia: a meta-analysis[J]. Eur J Obstet Gynecol Reprod Biol, 2014, 182(12): 194-201. https://www.sciencedirect.com/science/article/pii/S0301211514005041 [11] 谢 幸, 苟文丽. 妇产科学[M]8版. 北京: 人民卫生出版社, 2013: 64-7. [12] 梅志雄, 邓 妮, 侯红瑛. PIGF、sVEGFR-1、NO联合PI对高危孕妇发生子痫前期的预测[J]. 中山大学学报:医学科学版, 2015, 36(6): 889-93, 911. https://www.wenkuxiazai.com/doc/247f26e63169a4517723a3e8-3.html [13] 张 悦, 杨 青, 李 蕊, 等. 20~24孕周PLGF水平在子痫前期预测中的临床价值[J]. 河北医药, 2017, 39(20): 3144-6. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhfck201401007 [14] Roberge S, Villa P, Nicolaides K, et al. Early administration of Low-Dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and Meta-Analysis[J]. Fetal Diagn Ther, 2012, 31(3): 141-6. doi: 10.1159/000336662 [15] Spencer K, Yu CK, Cowans NJ, et al. Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free bhCG and with second-trimester uterine artery Doppler[J]. Prenat Diagn, 2005, 25(6): 949-53. [16] Orabona R, Gerosa V, Gregorini ME, et al. The prognostic role of various indices and ratios of Doppler velocimetry in patients with preeclampsia[J]. Clin Exp Hypertens, 2015, 37(1): 57-62. doi: 10.3109/10641963.2014.897723 [17] Herraiz I, Escribano D, Gomez-Arriaga P, et al. Predictive value of sequential models of uterine artery Doppler in pregnancies at high risk for pre-eclampsia[J]. Ultrasound Obstet Gynecol, 2012, 40(1): 68-74. doi: 10.1002/uog.10147 [18] Gómez O, Figueras F, Fernández S, et al. Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation[J]. Ultrasound Obstet Gynecol, 2008, 32(2): 128-32. doi: 10.1002/uog.v32:2 [19] Alves JA, Silva BY, de Sousa PC, et al. Reference range of uterine artery Doppler parameters between the 11th and 14th pregnancy weeks in a population sample from Northeast Brazil[J]. Rev Bras Ginecol Obstet, 2013, 35(8): 357-62. doi: 10.1590/S0100-72032013000800004 [20] Yasmin C, Barbara V, Nicolaou E. Uterine artery Doppler screening as a predictor of pre-eclampsia[J]. Health Gesondheid, 2016, 21(1): 391-6. https://www.sciencedirect.com/science/article/pii/S1025984816300187 [21] Melchiorre K, Wormald B, Leslie K, et al. First-trimester uterine artery Doppler indices in term and preterm pre-eclampsia[J]. Ultrasound Obstet Gynecol, 2008,32(4):133-7. [22] Napolitano R, Rajakulasingam R, Memmo A, et al. Uterine artery Doppler screening for preeclampsia:comparison of the lower,mean and higher first trimester pulsatility indices[J].Ultrasound Obstet Gynecol, 2011,37(8):534-7. [23] 李丽洁, 王梁萍, 郑艳鹛. 抑制素A、激活素A与子宫动脉搏动指数联合预测子痫前期的效果分析[J]. 预防医学, 2017, 29(03): 251-4, 259. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgcqzdzz201103003