Adverse Outcomes Associated with Progressive Intrahepatic Cholestasis of Pregnancy.

Objective:  This study aimed to assess the association between increasing bile acid levels in pregnancies with cholestasis and adverse outcomes.

Study design:  This is a retrospective cohort study of singleton, non-anomalous gestations complicated by cholestasis delivered at a single academic medical center from 2005 to 2019. We compared rates of adverse outcomes in pregnancies complicated by mild cholestasis (initial total bile acid [TBA] <40 μmol/L and peak TBA <40 μmol/L), progressive cholestasis (initial TBA <40 μmol/L and peak TBA ≥40 μmol/L), and severe cholestasis (initial TBA ≥40 μmol/L). Our primary outcome was a composite adverse outcome including spontaneous preterm labor and delivery, umbilical artery pH <7.20, 5-minute Apgar <7, cesarean delivery for nonreassuring fetal heart rate tracing, meconium-stained amniotic fluid, and neonatal intensive care unit (NICU) admission. Analyses were performed using mild cholestasis as the base comparator and a second analysis using severe cholestasis as the base comparator.

Results:  Of the 1,182 pregnancies complicated by cholestasis, 732 (61.9%) had mild cholestasis, 78 (6.6%) had progressive cholestasis, and 372 (31.5%) had severe cholestasis. After adjusting for confounders including gestational age at diagnosis and using mild cholestasis as the base comparator, both progressive and severe cholestasis were associated with the composite adverse outcome (progressive intrahepatic cholestasis of pregnancy [ICP] OR 1.70; 95% CI 1.04-2.78 and severe ICP OR 1.60; 95% CI 1.24-2.06). When using progressive cholestasis as the base comparator, there were no statistically significant differences in the primary or secondary outcomes between progressive cholestasis and severe cholestasis.

Conclusion:  This study highlights the significance of monitoring peak bile acid levels and that some cases of cholestasis may progress in pregnancy and the adverse associations are better reflected by the peak TBA level and not the cholestasis severity at initial diagnosis.

Key points: · Outcomes with worsening cholestasis severity (progressive) are unknown.. · Retrospective study comparing mild to progressive to severe cholestasis.. · Progressive cholestasis outcomes are more similar to severe cholestasis.. · Clinical utility of trending bile acids warrants further study..