Correlations of serum pregnancy-associated plasma protein-A2 and insulin-like growth factor binding protein 5 levels with preeclampsia in pregnant women in high altitude area
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摘要:目的 探讨高海拔地区孕妇血清妊娠相关血浆蛋白-A2(PAPP-A2)、胰岛素样生长因子结合蛋白5(IGFBP5)水平与子痫前期的相关性。方法 选取2017年6月-2019年6月收治的子痫前期孕妇76例及正常妊娠孕妇70例为研究对象。比较2组孕妇一般资料; 检测2组孕妇妊娠12~15周、32~35周时血清PAPP-A2、IGFBP5水平; 采用受试者工作特征(ROC)曲线评价孕早期孕妇血清PAPP-A2、IGFBP5水平对子痫前期的诊断价值; 采用多因素Logistic模型分析影响子痫前期发生的危险因素。结果 子痫前期组孕妇孕周、新生儿体质量低于正常妊娠组，孕32~35周时孕妇收缩压、舒张压及24 h尿蛋白定量水平均高于正常妊娠组，差异均有统计学意义(P<0.05)。孕12~15周、孕32~35周时，子痫前期组孕妇血清PAPP-A2、IGFBP5水平高于正常妊娠组，差异有统计学意义(P<0.05)。孕12~15周时，血清PAPP-A2联合IGFBP5诊断子痫前期的曲线下面积(AUC)为0.916, 灵敏度和特异度分别为88.16%、84.29%。多因素Logistic分析显示，孕12~15周时血清PAPP-A2(OR=1.528, 95%CI为1.141~2.046)、IGFBP5(OR=1.892, 95%CI为1.246~2.872)是子痫前期的影响因素(P<0.05)。结论 高海拔地区子痫前期孕妇血清PAPP-A2、IGFBP5水平呈高表达。孕早期检测血清PAPP-A2、IGFBP5水平对诊断子痫前期有一定的价值，或可作为预测子痫前期的早期生物标志物。
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关键词:
- 高海拔地区 /
- 妊娠相关血浆蛋白-A2 /
- 胰岛素样生长因子结合蛋白5 /
- 子痫前期 /
- 诊断
Abstract:Objective To explore the correlations of serum pregnancy-associated plasma protein-A2 (PAPP-A2) and insulin-like growth factor binding protein 5 (IGFBP5) levels with preeclampsia in pregnant women in high altitude area.Methods A total of 76 pregnant women with preeclampsia and 70 normal pregnant women from June 2017 to June 2019 were selected as research objects. General materials of the two groups were compared; the levels of serum PAPP-A2 and IGFBP5 were detected at 12 to 15 weeks and 32 to 35 weeks of gestation in both groups; the receiver operating characteristic (ROC) curve was used to evaluate the value of serum PAPP-A2 and IGFBP5 in diagnosing preeclampsia in early pregnancy; the multivariate Logistic model was used to analyze the risk factors affecting preeclampsia.Results The gestational weeks and neonatal body mass of pregnant women in the preeclampsia group were significantly lower than those in the normal pregnancy group, while the systolic blood pressure, diastolic blood pressure and quantitative level of 24 h proteinuria in pregnant women at 32 to 35 weeks of pregnancy were significantly higher than those in the normal pregnancy group (P<0.05). At 12 to 15 weeks and 32 to 35 weeks of gestation, the levels of serum PAPP-A2 and IGFBP5 in the preeclampsia group were significantly higher than those in the normal pregnancy group (P<0.05). At 12 to 15 weeks of gestation, the area under the curve (AUC) of serum PAPP-A2 combined with IGFBP5 in the diagnosis of preeclampsia was 0.916, and the sensitivity and specificity were 88.16% and 84.29% respectively. Multivariate Logistic analysis showed that serum PAPP-A2 (OR=1.528, 95%CI, 1.141 to 2.046) and IGFBP5 (OR=1.892, 95%CI, 1.246 to 2.872) were the influencing factors of preeclampsia (P<0.05).Conclusion The levels of serum PAPP-A2 and IGFBP5 in pregnant women with preeclampsia at high altitude are highly expressed. The detection of serum PAPP-A2 and IGFBP5 in early pregnancy has a certain value in the diagnosis of preeclampsia, which might be used as biomarkers for early prediction of preeclampsia. -
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表 1 2组孕妇一般资料比较(x±s)[n(%)]
一般资料 子痫前期组(n=76) 正常妊娠组(n=70) 年龄/岁 26.94±4.16 27.35±3.92 体质量指数/(kg/m2) 23.57±1.26 23.48±1.09 孕周/周 35.17±1.02* 39.31±1.14 初次分娩 42(55.26) 46(65.71) 新生儿体质量/kg 2.47±0.82* 3.25±0.64 居住地海拔高度 < 3 500 m 35(46.05) 33(47.14) ≥3 500 m 41(53.95) 37(52.86) 收缩压/mmHg 孕12~15周 126.29±8.64 124.67±6.53 孕32~35周 146.27±13.72* 134.20±10.15 舒张压/mmHg 孕12~15周 78.61±6.38 76.84±5.92 孕32~35周 87.64±10.36* 82.49±7.26 24 h尿蛋白定量/g 孕12~15周 0.17±0.06 0.16±0.04 孕32~35周 1.63±0.54* 0.19±0.07 与正常妊娠组比较, * P<0.05。 
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表 2 2组孕妇不同孕期血清PAPP-A2、IGFBP5水平比较(x±s)
ng/mL 组别 孕12~15周 孕32~35周 PAPP-A2 IGFBP5 PAPP-A2 IGFBP5 子痫前期组(n=76) 5.62±1.27* 8.67±1.48* 79.34±9.75* 57.49±8.46* 正常妊娠组(n=70) 4.79±1.02 6.51±1.19 42.16±5.32 31.82±3.95 PAPP-A2: 妊娠相关血浆蛋白-A2; IGFBP5: 胰岛素样生长因子结合蛋白5。与正常妊娠组比较, * P<0.05。
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表 3 孕早期孕妇血清PAPP-A2、IGFBP5水平对子痫前期的诊断效能
指标 截断值/(ng/mL) AUC 灵敏度/% 特异度/% 95%CI Z PAPP-A2 5.04 0.749 76.32 71.43 0.670~0.817 6.020 IGFBP5 7.56 0.873 77.63 85.71 0.808~0.922 12.711 二者联合 - 0.916 88.16 84.29 0.858~0.955 17.289 PAPP-A2: 妊娠相关血浆蛋白-A2; IGFBP5: 胰岛素样生长因子结合蛋白5; AUC: 曲线下面积。
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表 4 影响子痫前期发生的多因素Logistic分析
变量 β SE Wald χ2 P OR 95%CI 24 h蛋白尿定量 0.385 0.221 3.039 0.081 1.470 0.953~2.267 PAPP-A2 0.424 0.149 8.096 0.004 1.528 1.141~2.046 IGFBP5 0.638 0.213 8.961 0.003 1.892 1.246~2.872 PAPP-A2: 妊娠相关血浆蛋白-A2; IGFBP5: 胰岛素样生长因子结合蛋白5。
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