妊娠期肝内胆汁淤积症的诊疗监测和不良妊娠结局预测

Diagnosis and Monitoring of Intrahepatic Cholestasis of Pregnancy and Prediction of Adverse Pregnancy Outcomes

摘要: 目的：探讨妊娠期肝内胆汁淤积症(ICP)的临床特征及其对妊娠结局的影响，分析影响不良妊娠结局(APO)的危险因素，评估血清总胆汁酸(TBA)在预测APO中的价值。方法：采用回顾性研究，收集354例ICP首诊孕妇、440例接受熊去氧胆酸(UDCA)治疗的ICP孕妇及295例正常孕妇的临床资料，比较了各组间一般临床资料、肝功能指标及妊娠结局。根据是否发生APO将UDCA治疗组进一步分为APO组(n = 164)与Non-APO组(n = 276)，采用受试者工作特征(ROC)曲线评估TBA的预测不良妊娠结局的效能。结果：与对照组相比，ICP首诊组的肝功能指标(TBA、ALT、AST等)及剖宫产、早产、羊水粪染、低出生体重儿和NICU入住率均显著升高(P < 0.05)，新生儿生长参数显著降低(P < 0.05)。APO组相较于Non-APO组，其首诊孕周和分娩孕周更早，辅助生殖、多胎妊娠率及TBA、ALT、AST等肝功能指标更高，而血清Alb、PA水平更低(P < 0.05)。ROC曲线分析显示，单独使用TBA预测APO的曲线下面积(AUC)仅为0.632 (临界值20.8 μmol/L)，灵敏度为53.2%，特异度为69.8%。值得注意的是，75.32%的APO患者TBA水平处于10~40 μmol/L的范围内。结论：ICP显著增加不良妊娠结局风险。APO的发生与ICP发病早、辅助生殖率、多胎率及肝细胞损伤、功能减退综合相关。使用TBA (>40 μmol/L)预测APO易导致漏诊，临床应结合肝酶、肝脏合成功能、发病孕周及妊娠背景进行综合评估。

Abstract: Objective: This study aimed to investigate the clinical features of intrahepatic cholestasis of pregnancy (ICP), evaluate its impact on pregnancy outcomes, identify risk factors for adverse pregnancy outcomes (APO), and assess the predictive value of serum total bile acid (TBA) levels for APO. Methods: A retrospective analysis was performed on 354 patients with initial ICP diagnosis, 440 ICP patients treated with ursodeoxycholic acid (UDCA), and 295 healthy pregnant controls. Clinical data, liver function parameters, and pregnancy outcomes were compared across groups. UDCA-treated patients were stratified into APO (n = 164) and non-APO (n = 276) groups based on adverse outcome occurrence. The predictive performance of TBA for APO was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Compared with controls, the ICP group demonstrated significantly elevated liver function parameters (TBA, ALT, AST, etc.) and higher incidence of cesarean delivery, preterm birth, meconium-stained amniotic fluid, low birth weight, and NICU admission (P < 0.05), along with significantly reduced neonatal growth parameters (P < 0.05). Relative to the non-APO group, the APO group exhibited earlier gestational age at diagnosis and delivery, increased rates of assisted reproduction and multiple gestation, elevated liver function markers (TBA, ALT, AST, etc.), and decreased serum Alb and PA levels (P < 0.05). ROC analysis revealed limited predictive utility of TBA alone for APO, with an area under the curve of 0.632 at a cut-off value of 20.8 μmol/L, yielding 53.2% sensitivity and 69.8% specificity. Notably, 75.32% of APO cases presented with TBA levels within the 10-40 μmol/L range. Conclusion: ICP significantly increases APO risk. APO is associated with earlier disease onset, higher prevalence of assisted reproduction and multiple gestation, and combined hepatocellular injury and dysfunction. Sole reliance on TBA, particularly using the >40 μmol/L threshold, may result in APO underdetection. Comprehensive clinical assessment should integrate liver enzymes, synthetic function, gestational age at onset, and obstetric history.