Safety of Ursodeoxycholic Acid in Pregnancy
Ursodeoxycholic acid is safe to use during pregnancy and breastfeeding, and should be continued or initiated when clinically indicated for cholestatic liver conditions. 1
Safety Profile in Pregnancy
UDCA is regarded as safe during pregnancy based on extensive clinical experience and guideline consensus. 1 The 2023 EASL guidelines provide a strong recommendation with strong consensus that UDCA should be continued during pregnancy in primary biliary cholangitis and primary sclerosing cholangitis, explicitly stating it is safe in pregnancy and breastfeeding. 1
Evidence Supporting Safety
No adverse maternal or fetal effects have been observed in multiple studies and case series documenting UDCA use during pregnancy. 1, 2, 3
The FDA drug label notes that inadvertent exposure of 4 women to therapeutic doses in the first trimester led to no evidence of effects on the fetus or newborn baby, though it conservatively states the drug is not recommended for pregnancy due to lack of adequate controlled studies. 4
Medium-dose UDCA (15-20 mg/kg/day) is specifically regarded as safe during pregnancy and is recommended for use in pregnant women with primary biliary cholangitis and primary sclerosing cholangitis. 1
All newborns in early studies were thriving normally during follow-up periods lasting 5 months after delivery, with no adverse reactions detected in mothers or babies. 2
Clinical Indications During Pregnancy
Intrahepatic Cholestasis of Pregnancy (ICP)
UDCA should be offered to women with ICP and serum bile acids >40 μmol/L to reduce the risk of spontaneous preterm birth and potentially protect against stillbirth. 1 This represents a Level 2 evidence strong recommendation from the 2023 EASL guidelines. 1
UDCA should be considered for treatment of maternal pruritus in ICP, though it has a relatively small effect on symptoms (Level 2 evidence, strong recommendation). 1
Do not start UDCA empirically before obtaining laboratory confirmation of elevated bile acids, as this may prevent detection of biochemical abnormalities and make definitive diagnosis impossible. 5
UDCA can be considered for severe pruritus only after initial testing is complete and while awaiting repeat results, with the understanding this may complicate subsequent diagnosis. 5
Pre-existing Cholestatic Liver Diseases
UDCA should be continued during pregnancy in women with primary biliary cholangitis and primary sclerosing cholangitis who were already on treatment, as discontinuation is not warranted. 1
Approximately 50% of women with pre-existing cholestatic diseases will have worsening or de novo pruritus during pregnancy, but most maintain stable hepatic function. 1
Up to 70% experience postnatal deterioration of serum liver tests, requiring continued monitoring postpartum. 1
Dosing Considerations
Standard dosing is 15-20 mg/kg/day, typically administered as 500 mg twice daily with the option to adjust from one to four tablets daily based on clinical response. 1, 4
Low doses (300-450 mg/day or 4-6 mg/kg/day) have shown efficacy in improving biochemical markers and clinical symptoms in almost 90% of ICP patients. 6
Anion exchange resins (cholestyramine, colestipol) should be given at least 4 hours after UDCA to avoid interference with absorption. 1
Efficacy Considerations
Important Caveat on Perinatal Outcomes
The largest and highest quality randomized controlled trial (PITCHES, 2019) found that UDCA does not reduce adverse perinatal outcomes in ICP. 7 This double-blind, multicenter trial of 605 women showed no significant reduction in the composite outcome of perinatal death, preterm delivery, or neonatal unit admission (adjusted risk ratio 0.85,95% CI 0.62-1.15). 7
However, current guidelines continue to recommend UDCA based on:
- Its demonstrated safety profile 1
- Reduction in spontaneous preterm birth rates 1
- Potential protective effect against stillbirth 1
- Improvement in maternal symptoms and biochemical parameters 6, 8
UDCA is superior to cholestyramine for both symptom relief (66.6% vs 19.0% reduction in pruritus) and biochemical improvement, with babies delivered significantly closer to term (38.7 vs 37.4 weeks). 8
Breastfeeding Safety
UDCA is considered safe during breastfeeding. 1 The 2023 EASL guidelines explicitly state this with strong consensus. 1
The FDA label notes it is not known whether UDCA is excreted in human milk, recommending caution as with all drugs during lactation. 4
Significant amounts of UDCA cannot be found in milk during lactation, supporting its safety profile. 1
Monitoring During Treatment
Serum bile acids should be monitored after UDCA treatment is commenced to evaluate risk of adverse pregnancy outcomes, though clinicians should be aware that UDCA itself is measured by enzymatic total serum bile acid assays. 1
Weekly bile acid measurements from 32 weeks' gestation are recommended to identify concentrations >40 μmol/L associated with increased risk. 1
Liver enzymes (AST/ALT) should be measured at initiation of therapy and thereafter as clinically indicated, though abnormalities have not been associated with UDCA therapy. 4
Key Clinical Pitfalls
Never diagnose ICP or make delivery decisions based on pruritus alone without laboratory confirmation of elevated bile acids, as this leads to unnecessary preterm deliveries with associated neonatal morbidity. 5, 9
Do not assume normal initial labs permanently rule out ICP—pruritus can precede bile acid elevation by several weeks, requiring repeat testing if symptoms persist. 5, 9
Avoid obeticholic acid during pregnancy and lactation due to lack of safety data, unlike UDCA which has established safety. 1