Early intrahepatic cholestasis of pregnancy linked to adverse outcomes

Early intrahepatic cholestasis of pregnancy linked to adverse outcomes | Image Credit: © WavebreakMediaMicro – © WavebreakMediaMicro – stock.adobe.com.

There is a link between early diagnosis of intrahepatic cholestasis of pregnancy (ICP) and adverse outcomes that is not fully driven by peak total bile acid (TBA) levels, according to a recent study published in Pregnancy.¹

ICP is often reported in the third trimester and has been linked to increased TBAs. While rare, certain maternal complication have been linked to fat-soluble vitamin deficiency caused by the condition. Adverse fetal outcomes have also been reported, such as stillbirth and preterm birth.² Peak TBA level is often used to guide management.¹

“Consequently, there are no current guidelines surrounding whether TBA levels should be repeated, and if so, when this should occur,” wrote investigators. “Given the lack of a management paradigm, diagnosis of ICP prior to late third trimester has limited evidence-based approaches.”

Comparing early vs late ICP diagnosis

The retrospective cohort study was conducted to assess the impact of early ICP diagnosis on adverse outcomes. Singleton, live gestations complicated by ICP between 2005 and 2019 with prenatal care given were included in the analysis.

At the study center, ICP screening was performed during prenatal visits, and a ursodeoxycholic acid regimen of 300 mg twice per day was provided to patients following ICP diagnosis. Doctors also trended TBA levels every 3 to 4 weeks medically until medically indicated delivery.

Adverse outcomes in pregnancies with an early ICP diagnosis, defined as under 32-weeks’ gestation, were compared to those with a late diagnosis, defined as 32-weeks’ gestation or later. Exclusion criteria included being aged under 18 years and having underlying hepatobiliary pathology.

Severe ICP and outcomes

Comparisons were also made between women diagnosed early or late with severe cholestasis, defined as peak TBAs of 40 µmol/L or greater. The spontaneous preterm birth rate was defined as the primary outcome of the analysis.

Secondary outcomes included iatrogenic preterm birth rates, meconium-stained amniotic fluid, cesarean deliver (CD) for non-reassuring fetal heart tracing (NRFHT), umbilical artery pH under 2.70, and neonatal intensive care unit (NICU) admission.

There were 1247 singleton, live gestations complicated by ICP included in the final analysis. Of these, 19.3% had an early diagnosis and 80.7% had a late diagnosis. Higher peak TBA levels were reported in early ICP diagnosis vs late diagnosis, which was linked to greater ICP severity, prior cholestasis rates, prior preterm birth rates, and delivery at an earlier gestational age.

Key findings on adverse outcomes

Rates of spontaneous preterm birth, iatrogenic preterm birth, and NICU admission were higher in patients with early ICP diagnosis, at 14.5%, 32%, and 50.7%, respectively. In comparison, these rates were 6%, 14.8%, and 37%, respectively, in those with late diagnosis.

After adjustments, patients with early ICP diagnoses had odds ratios (ORs) of 1.81, 1.59, and 1.43, respectively, for these adverse outcomes. No significant associations were reported for umbilical artery pH, meconium-stained amniotic fluid, or CD for NRFHT.

Severe ICP was reported in 36.5% of ICP cases, with 23.7% of these diagnosed early and 76.3% diagnosed late. Greater rates of prior cholestasis, prior preterm birth, and ursodeoxycholic acid treatment were identified in these cases, alongside delivery at an earlier gestational age.

Associations with severe ICP were also reported for spontaneous preterm birth, iatrogenic preterm birth, and NICU admission, with rates of 22.2%, 38%, and 57.6%, respectively. These associations remained when adjusting for peak TBA levels and preterm birth history.

Implications

Overall, the data indicated an increased risk of adverse outcomes in cases of ICP diagnosed before 32-weeks’ gestation. As these outcomes were consistent even when analyzing early severe ICP, investigators concluded outcomes are also dependent on the duration of time exposed to elevated bile acids.

“While this study better describes the outcomes associated with cholestasis, further studies are needed to determine the mechanism for early ICP associated spontaneous preterm birth and whether trending TBA after early diagnosis can improve outcomes,” wrote investigators.

References

1. Sarker MR, Canfield D, Ferrara L, Debolt CA. Earlier diagnosis of intrahepatic cholestasis of pregnancy and adverse pregnancy outcomes. Pregnancy. 2025. doi:10.1002/pmf2.70073
2. Brouwers L, Koster MP, Page-Christiaens GC, et al. Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels. Am J Obstet Gynecol. 2015;212(1):100.e1-7. doi:10.1016/j.ajog.2014.07.026