Prediction of intrahepatic cholestasis of pregnancy in the first 20 weeks of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a significant risk of fetal complications including pre-term delivery and fetal death. Typically, it was diagnosed in the third trimester of pregnancy. This study utilized characteristics from routine maternal examinations in the first 20 weeks’ gestation to predict ICP in pregnant women. This is a retrospective case-control study. 13,329 medical records were collected on pregnant women presenting to the West China Second University Hospital between December 2017 and December 2018. After screening according to strict criteria, a total of 487 patients, 250 intrahepatic cholestasis of pregnancy cases, and 237 controls were selected for this study. We collected seven maternal characteristics indices for analysis and forty-three routine blood examination indices were obtained from routine hepatic, renal, and coagulation function examinations. The least absolute shrinkage and selection operator regression was applied for variable selection. Classification and regression trees, logistic regression, random forests, and light gradient boosting machines were fit for predictive modeling. We randomly divided 25% of the original data as testing set to conduct internal validation of the performance of the prediction model. The area under the receiver operating characteristic curves (AUC) was used to compare methods. Eight variables were selected out as potentially significant predictors that could reliably predict ICP. The sensitivity, specificity, accuracy, and AUC of the final prediction model obtained by light gradient boosting machines were 72.41, 79.69, 76.23, and 79.77%, respectively. Significantly higher platelet large cell ratio, alanine aminotransferase, glutamyl transpeptidase, and fibrinogen levels were found in cases as compared to healthy controls, while activated partial thromboplastin time and mean corpuscular hemoglobin concentration levels were significantly lower (<i>p</i> &lt; .001). The combination of alanine aminotransferase, glutamyl transpeptidase, fibrinogen, platelet large cell ratio, activated partial thromboplastin time, lactate dehydrogenase, creatinine, and mean corpuscular hemoglobin concentration levels can effectively predict ICP in the first 20 weeks of gestation. These could help provide direction for earlier detection and prevention of ICP.

妊娠期肝内胆汁淤积症（Intrahepatic cholestasis of pregnancy, ICP）是一种妊娠特异性肝病，与早产、胎儿死亡等严重胎儿不良并发症风险显著相关。该病通常于妊娠晚期确诊。本研究利用妊娠前20周的常规产检特征指标，对孕妇罹患妊娠期肝内胆汁淤积症的风险进行预测。本研究为回顾性病例对照研究，收集了2017年12月至2018年12月期间于四川大学华西第二医院就诊的13329名孕妇的病历资料。经严格纳入排除标准筛选后，最终纳入487例研究对象，其中妊娠期肝内胆汁淤积症病例250例，健康对照237例。本研究收集了7项孕妇基础特征指标，并从常规肝肾功能、凝血功能检测中提取了43项血液检测指标。采用最小绝对收缩和选择算子（Least Absolute Shrinkage and Selection Operator, LASSO）回归进行变量筛选，分别采用分类与回归树、logistic回归、随机森林以及轻量梯度提升机（Light Gradient Boosting Machines, LightGBM）构建预测模型。本研究将原始数据按75%:25%的比例随机划分为训练集与测试集，以对预测模型的性能进行内部验证，并采用受试者工作特征曲线下面积（Area Under the Receiver Operating Characteristic Curve, AUC）对各模型的预测性能进行比较。最终筛选出8项具有显著预测价值的变量，可实现妊娠期肝内胆汁淤积症的可靠预测。轻量梯度提升机构建的最终预测模型的灵敏度、特异度、准确率及受试者工作特征曲线下面积分别为72.41%、79.69%、76.23%及79.77%。与健康对照相比，病例组的血小板大细胞比率、丙氨酸氨基转移酶、谷氨酰转肽酶及纤维蛋白原水平显著升高，而活化部分凝血活酶时间与平均红细胞血红蛋白浓度水平则显著降低（p<0.001）。联合检测丙氨酸氨基转移酶、谷氨酰转肽酶、纤维蛋白原、血小板大细胞比率、活化部分凝血活酶时间、乳酸脱氢酶、肌酐及平均红细胞血红蛋白浓度这8项指标，可在妊娠前20周有效预测妊娠期肝内胆汁淤积症的发生风险。该研究结果可为妊娠期肝内胆汁淤积症的早期筛查与预防提供参考方向。