Intrahepatic cholestasis of pregnancy: risk factors for severe disease

Abstract

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated hepatic disorder characterized by pruritus in the setting of elevated serum bile acids (BA). Risk factors for the disease include preexisting hepatobiliary disease, personal or family history of ICP, and advanced maternal age. Recent data suggests that patients with severe ICP (BA ≥100 μmol/L) have a higher risk of adverse pregnancy outcomes including stillbirth.

Material and methods: This was a retrospective cohort study of patients diagnosed with ICP between 2012 and 2019 at a tertiary referral center. ICP was defined as symptomatic pruritus combined with serum BA >10 μmol/L. Maternal characteristics and outcomes were abstracted from electronic medical records. Baseline characteristics were compared between patients with mild (BA <40 μmol/L), moderate (BA 40-99 μmol/L) and severe (BA ≥100 μmol/L) ICP. Obstetrics and neonatal outcomes for patients in each category were then analyzed. Shapiro-Wilk test was used to test for normality for continuous variables, and ANOVA, Kruskal-Wallis, Chi-squared or Fisher's exact tests were used as appropriate. A p-value <.05 was considered statistically significant.

Results: 438 patients were included in the analysis. Individuals with pregestational diabetes (p < .01), history of ICP (p < .01), prior cholecystectomy (p < .01), and tobacco use (p < .05) were more likely to have severe disease. When compared to individuals with moderate and mild disease, individuals with severe disease were more likely to be diagnosed earlier (29w1d vs 34w1d vs 34w1d, p < .05), have gestational diabetes (50% vs 6% vs 13%, p < .01), hypertensive disorders of pregnancy (42% vs 10% vs 15%, p = .02), and abnormal aspartate aminotransferase (91% vs 65% vs 27%, p < .01) and alanine aminotransferase levels (91% vs 60% vs 26%, p < .01). There were no differences in preterm labor, meconium-stained amniotic fluid, or neonatal respiratory distress syndrome and no stillbirths in this cohort.

Conclusions: In patients with ICP, those with pregestational diabetes, history of ICP, prior cholecystectomy, and tobacco use are more likely to develop severe disease. Given the adverse outcomes associated with severe disease, serial BA measurements to monitor for development of severe disease may be warranted in this population.

Keywords: Cholestasis; intrahepatic; liver; pregnancy; risk.