Establishment of a nomogram model for predicting risk of intrahepatic cholestasis in pregnant women during pregnancy
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摘要:目的 建立孕妇发生妊娠期肝内胆汁淤积症(ICP)的风险列线图模型并验证其评估效果。方法 将575例孕妇依据简单随机化方式分为建模组(n=460)与验证组(n=115), 采用Logistic回归分析确定ICP发生的危险因素，应用R软件获得列线图风险预测模型，并评估风险预测模型预测效能。结果 乙肝病毒感染、妊娠期高血压、低硒摄入量、ICP家族史、孕激素保胎治疗、高尿酸血症为孕妇ICP发生的危险因素(P < 0.05); 列线图预测ICP发生风险的曲线下面积(AUC)与C指数均为0.840(95%CI: 0.764~0.916)。Calibration校准曲线表明，列线图预测ICP的发生风险与实际诊断发生风险一致性优异; 验证组中，列线图预测ICP发生风险的AUC与C指数均为0.801(95%CI: 0.711~0.892)。Calibration校准曲线表明，预测ICP发生风险与实际诊断发生风险一致性优异。结论 构建列线图可以个性化预测ICP的发生风险，有助于鉴别ICP的高风险人群，并制订合适干预措施。Abstract:Objective To establish a nomogram model for predicting the risk of intrahepatic cholestasis of pregnancy (ICP), and verify its efficiency.Methods A total of 575 pregnant women were enrolled and were divided into modeling group (n=460) and verification group (n=115) according to simple randomization method. Logistic regression analysis was performed to determine the risk factors for ICP. A nomogram model was established using R software, and its predictive performance was evaluated.Results Hepatitis B virus infection, gestational hypertension, low selenium intake, family history of ICP, fetal protection treatment with progesterone and hyperuricemia were risk factors of ICP (P < 0.05). The area under the curve (AUC) value and C index of the nomogram for predicting the risk of ICP were both 0.840 (95%CI, 0.764 to 0.916). The calibration curve showed that predictive results of the nomogram were highly consistent with the results of actual diagnosis. In the verification group, the AUC value and C index of the nomogram for predicting the risk of ICP both were 0.801(95%CI, 0.711 to 0.892). The calibration curve showed that predictive results of the nomogram were highly consistent with the results of actual diagnosis.Conclusion Establishing anomogram can help to predict the risk of ICP, which is conducive to screening high-risk groups of ICP and formulating appropriate intervention measures.
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表 1 建模组与验证组孕妇一般资料比较(x±s)
一般资料 n 建模组(n=460) 验证组(n=115) 年龄/岁 28.05±4.20 28.45±3.64 不良妊娠史 有 111 87(18.91) 24(20.87) 无 464 373(81.09) 91(79.13) 饮食 正常 419 339(73.70) 80(69.57) 挑食 100 79(17.17) 21(18.26) 偏食 56 42(9.13) 14(12.17) 乙肝病毒感染 有 75 59(12.83) 16(13.91) 无 500 401(87.17) 99(86.09) 低锌摄入量 有 86 68(14.78) 18(15.65) 无 489 392(85.22) 97(84.35) 孕前BMI/(kg/m2) 24.32±3.08 24.46±2.92 受精方式 人工受精 39 30(6.52) 9(7.83) 自然受精 536 430(93.48) 106(92.17) 妊娠期高血压 有 149 117(25.43) 32(27.83) 无 426 343(74.57) 83(72.17) 低硒摄入量 有 111 85(18.48) 26(22.61) 无 464 375(81.52) 89(77.39) 分娩孕周/周 37.89±1.93 38.10±1.93 ICP家族史 有 51 41(8.91) 10(8.70) 无 524 419(91.09) 105(91.30) 激素保胎治疗 有 179 146(31.74) 33(29.70) 无 396 314(68.26) 82(71.30) 妊娠期糖尿病 有 162 133(28.91) 29(25.22) 无 413 327(71.09) 86(74.78) 高雄激素血症 有 69 53(11.52) 16(13.91) 无 506 407(88.48) 99(86.09) 高尿酸血症 有 60 46(10.00) 14(12.17) 无 515 414(90.00) 101(87.83) 发生ICP 37 29(6.30) 8(6.96) BMI: 体质量指数; ICP: 妊娠期肝内胆汁淤积症。 
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表 2 建模组ICP与非ICP孕妇各项资料比较(x±s)[n(%)]
因素 n ICP组(n=29) 非ICP组(n=431) t/χ2 P 年龄/岁 28.38±4.13 28.02±4.20 0.442 0.659 不良妊娠史 有 87 10(34.48) 77(17.87) 4.892 0.027 无 373 19(65.52) 354(82.13) 饮食 正常 339 20(68.97) 319(74.01) 0.367 0.832 挑食 79 6(20.69) 73(16.94) 偏食 42 3(10.34) 39(9.05) 乙肝病毒感染 有 59 10(34.48) 49(11.37) 12.983 < 0.001 无 401 19(65.52) 382(88.63) 低锌摄入量 有 68 6(20.69) 62(14.39) 0.857 0.354 无 392 23(79.31) 369(85.61) 孕前BMI/(kg/m2) 24.14±3.41 24.33±3.06 -0.332 0.740 受精方式 人工受精 30 3(10.34) 27(6.26) 0.742 0.389 自然受精 430 26(89.66) 404(93.74) 妊娠期高血压 有 117 13(44.83) 104(24.13) 6.138 0.013 无 343 16(55.17) 327(75.87) 低硒摄入量 有 85 12(41.38) 73(16.94) 10.776 0.001 无 375 17(58.62) 358(83.06) 分娩孕周/周 37.59±1.97 37.91±1.93 -0.880 0.379 ICP家族史 有 41 8(27.59) 33(7.66) 13.293 < 0.001 无 419 21(72.41) 398(92.34) 孕激素保胎治疗 有 146 16(55.17) 130(30.16) 7.845 0.005 无 314 13(44.83) 301(69.84) 妊娠期糖尿病 有 133 8(27.59) 125(29.00) 0.027 0.871 无 327 21(72.41) 306(71.00) 高雄激素血症 有 53 4(13.79) 49(11.37) 0.157 0.692 无 407 25(86.21) 382(88.63) 高尿酸血症 有 46 7(24.14) 39(9.05) 6.874 0.009 无 414 22(75.86) 392(90.95) BMI: 体质量指数; ICP: 妊娠期肝内胆汁淤积症。
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表 3 孕妇发生ICP的危险因素分析
因素 单因素 多因素 OR 95%CI P OR 95%CI P 年龄 0.994 0.899~1.098 0.900 - - - 不良妊娠史 0.491 0.193~1.248 0.135 - - - 挑食 0.721 0.242~2.150 0.558 - - - 偏食 1.105 0.237~5.154 0.899 - - - 乙肝病毒感染 0.281 0.107~0.742 0.010 0.268 0.107~0.676 0.005 低锌摄入量 0.662 0.226~1.938 0.452 - - - 孕前BMI 1.047 0.909~1.205 0.525 - - - 受精方式 2.254 0.601~8.458 0.229 - - - 妊娠期高血压 0.281 0.114~0.695 0.006 0.316 0.132~0.755 0.010 低硒摄入量 0.236 0.094~0.590 0.002 0.225 0.093~0.541 0.001 分娩孕周 1.113 0.556~2.227 0.763 - - - ICP家族史 0.219 0.081~0.593 0.003 0.237 0.088~0.641 0.005 孕激素保胎治疗 0.335 0.139~0.810 0.015 0.323 0.140~0.743 0.008 妊娠期糖尿病 0.957 0.382~2.397 0.926 - - - 高雄激素血症 1.033 0.296~3.600 0.959 - - - 高尿酸血症 0.245 0.080~0.749 0.014 0.227 0.079~0.651 0.006 BMI: 体质量指数; ICP: 妊娠期肝内胆汁淤积症。
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