Prevalence and clinical significance of proteinuria in intrahepatic cholestasis of pregnancy: A retrospective cohort study

Intrahepatic cholestasis of pregnancy (IHCP) is the most common pregnancy-specific liver disease. This study aimed to determine the prevalence of proteinuria in patients with IHCP and to evaluate its association with adverse pregnancy outcomes. This retrospective cohort study included pregnant patients with gestational age > 24 weeks who were diagnosed with IHCP and completed 24-hour urine protein collection at Haseki Training and Research Hospital (January 2018-December 2024). Proteinuria was defined as ≥300 mg/24-h urine collection. Patients were categorized into 3 groups: non-proteinuric, isolated proteinuria (proteinuria ≥ 300 mg/24 h in the absence of hypertension), and preeclampsia (defined according to the American College of Obstetricians and Gynecologists [ACOG] criteria). The primary outcome was a composite adverse pregnancy outcome, including preterm delivery at <34 weeks, umbilical artery pH < 7.1, and emergency cesarean delivery due to fetal distress. Group comparisons were performed using the Kruskal-Wallis test for continuous variables and the chi-square or Fisher exact test for categorical variables. Multivariate logistic regression was performed adjusting for maternal age, twin gestation, and in vitro fertilization conception. Among 341 patients, 207 (60.7%) had no proteinuria, 105 (30.8%) had isolated proteinuria, and 29 (8.5%) had preeclampsia. Overall, 39.3% of IHCP patients demonstrated proteinuria. The distribution of IHCP severity, as classified by maximum total bile acid (TBA) concentration, was comparable among the 3 groups (P = .976). The demographic parameters were comparable between the groups. The preeclampsia group exhibited significantly higher composite adverse outcome rates (P < .001). Multivariate logistic regression demonstrated that preeclampsia was independently associated with composite adverse outcomes (adjusted odds ratio: 6.96, 95% confidence interval: 2.69-18.01; P < .001), whereas isolated proteinuria showed no significant association (adjusted odds ratio: 1.54, 95% confidence interval: 0.95-2.50; P = .079). Approximately 39% of IHCP patients exhibited proteinuria. Isolated proteinuria without hypertension was not an independent predictor of adverse pregnancy outcomes. In the absence of hypertension or other features of preeclampsia, the presence of proteinuria alone may not warrant escalation of care or accelerated delivery decisions in IHCP. However, prospective validation of these findings is needed before definitive clinical recommendations can be established.