BACKGROUND AND PURPOSE:

• PITCHES RCT: Ursodeoxycholic acid (UDCA) was not associated with a significant benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission)
• Ovadia et al. (The Lancet Gastroenterology & Hepatology, 2021) evaluated whether UDCA affects specific adverse perinatal outcomes

METHODS:

• Systematic review and individual participant data meta-analysis
• Study inclusion criteria
  • ≥30 study participants
  • ≥1 individual with intrahepatic cholestasis of pregnancy (ICP) and bile acid concentrations of ≥40 μmol/L 
• Study design
  • Individual participant data were collected from the authors
    • Subgroup analyses: Limited to RCTs, singletons or 2 arm studies
  • Mixed-effects meta-analysis used for calculations
  • Adjustments made for bile acid concentration, parity, and multifetal pregnancy
• Primary outcome
  • The prevalence of stillbirth
• Secondary outcomes
  • Main secondary outcome (authors anticipate lack of power to assess stillbirth): Composite of stillbirth and preterm birth
  • Other secondary outcomes: Pregnancy complications | Mode of delivery | Onset of labor  

RESULTS:

• 34 studies
  • Individual participant data: 32 published studies
  • 2 unpublished cohort studies
• 6974 women
  • UDCA users: 67.8%
• There was no significant difference in stillbirth between women with ICP who took UDCA and non-users
  • UDCA: 0.7% (35 of 5097 fetuses)
  • Non-users: 0.6% (12 of 2038 fetuses)
  • Adjusted odds ratio (aOR) 1.04 (95% CI, 0.35 to 3.07; P = 0.95)
• UDCA had no effect on the prevalence of stillbirth when only RCTs were examined
  • aOR 0.29 (95% CI, 0.04 to 2.42; P = 0.25)
• UDCA had no effect on the composite outcome in all studies
  • aOR 1.28 (95% CI, 0.86 to 1.91; P = 0.22)
• Based on individual participant data and following adjustments for covariates, UDCA was associated with
  • Reduced composite outcome: aOR 0.68 (95% CI, 0.48 to 0.97)
  • Reduced spontaneous preterm birth (<37 weeks): aOR 0.54 (95% CI, 0.31 to 0.94)  
• Reduction in composite outcome and preterm birth was also seen in RCTs that only included singleton pregnancies
• Limiting analyses to RCTs only
  • UDCA significantly reduced the composite outcome with number needed to treat of 15 (95% CI, 9 to 54)

CONCLUSION:

• For women with ICP, taking UDCA had no effect on the incidence of stillbirth but result likely underpowered
• Limiting analysis to RCTs, UDCA was associated with a reduction in a composite of stillbirth and preterm birth
• The authors conclude

In summary, this meta-analysis suggests that ursodeoxycholic acid treatment in women with intrahepatic cholestasis of pregnancy reduces the risk of preterm birth

Previous work has shown that there is an increased risk of preterm birth in women with peak bile acid concentrations of 40 μmol/L or more …

…ursodeoxycholic acid treatment should therefore be considered for these women with disease onset before 37 weeks’ gestation

Learn More – Primary Sources:

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis

Related ObG Topics:

PITCHES RCT: Ursodeoxycholic Acid and Intrahepatic Cholestasis of Pregnancy

More from the PITCHES Trial: Subgroup Analysis of Participants with Intrahepatic Cholestasis of Pregnancy and UDCA Treatment

Risk of Stillbirth with Intrahepatic Cholestasis of Pregnancy: What do Bile Acid Concentrations Tell Us?