Ursodeoxycholic Acid in Pregnancy
Ursodeoxycholic acid (UDCA) is safe to use during pregnancy and breastfeeding, and should be continued or initiated when clinically indicated for cholestatic liver diseases. 1, 2
Safety Profile
UDCA has an established safety record in pregnancy with strong guideline support:
The European Association for the Study of Liver (EASL) provides a strong recommendation (100% consensus) that UDCA is safe during pregnancy and breastfeeding at therapeutic doses of 15-20 mg/kg/day. 1, 2
The FDA label notes that 4 women inadvertently exposed to therapeutic doses of UDCA in the first trimester showed no evidence of fetal harm or effects on newborns, though it conservatively states the drug is "not recommended" during pregnancy due to limited data. 3
Animal studies at 20- to 100-fold human doses in rats and 5-fold doses in rabbits revealed no evidence of impaired fertility or fetal harm. 3
UDCA is minimally secreted into breast milk—when analyzed by high-pressure liquid chromatography, only trace amounts of endogenous bile acids (cholic, deoxycholic, lithocholic acid) were detected, but UDCA itself was not found. 4
Clinical Indications in Pregnancy
Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC)
UDCA should be continued throughout pregnancy in women with PBC or PSC who were on treatment pre-conception (100% consensus). 1
Approximately 50% of women with pre-existing cholestatic diseases will experience worsening or de novo pruritus during pregnancy, but most maintain stable hepatic function. 1
Up to 70% experience postnatal deterioration of liver tests, making continued treatment important. 1
Case reports demonstrate that withdrawing UDCA in pregnant PBC patients leads to rapid development of severe pruritus within 9 days and worsening liver enzymes, which resolve upon restarting therapy. 4
Intrahepatic Cholestasis of Pregnancy (ICP)
UDCA should be offered to women with ICP and serum bile acid concentrations >40 μmol/L to reduce spontaneous preterm birth risk and potentially protect against stillbirth (strong recommendation, consensus). 1, 2
UDCA should be considered for maternal pruritus relief in ICP, though the effect on symptoms is relatively modest. 1
The risk of stillbirth rises markedly from 35 weeks' gestation in women with total serum bile acids >100 μmol/L, making treatment particularly important in severe cases. 1
UDCA protects against cholic acid-induced arrhythmia in fetal cardiac myocytes and prevents abnormal fetal heart rate variability. 1, 2
Dosing Strategies
Standard Dosing
For ICP: Start at 10 mg/kg/day and gradually increase to 20 mg/kg/day as tolerated. 2
Evidence for Low-Dose Efficacy
Very low doses (300-450 mg/day; 4-6 mg/kg/day) showed efficacy in 89.1% of ICP patients, with significant improvements in total bile acids, bilirubin, aminotransferases, and pruritus severity. 5
However, a 2024 study suggests gradual dose escalation may improve composite neonatal outcomes compared to full-dose initiation, with lower rates of unfavorable outcomes (30% vs 53%) and greater gestational age at delivery (37 vs 36 weeks). 6
Comparative Efficacy
UDCA is superior to cholestyramine for ICP: 66.6% of patients had >50% pruritus reduction with UDCA versus only 19.0% with cholestyramine. 7
UDCA reduced serum ALT/AST by 78.5%/73.8% versus only 21.4% with cholestyramine. 7
Babies were delivered significantly closer to term with UDCA (38.7 weeks) versus cholestyramine (37.4 weeks). 7
Monitoring During Treatment
Monitor liver function tests (ALT/AST, bilirubin) at initiation and as clinically indicated. 2, 3
Check coagulation tests (INR) and vitamin K status, especially when combined with anion exchange resins or in women with steatorrhea, as cholestasis increases vitamin K deficiency risk. 1, 2
In ICP, measure total serum bile acids at least weekly, as levels may continue rising with advancing gestation despite treatment. 1
Drug Interactions and Timing
Separate UDCA and cholestyramine administration by at least 4 hours, as bile acid sequestering agents reduce UDCA absorption. 1, 2, 3
Aluminum-based antacids may similarly interfere with UDCA absorption. 3
Stop UDCA at the time of delivery and reduce gradually over 2-4 weeks postpartum if symptoms persist. 1
Important Caveats
Obeticholic acid must be discontinued immediately upon pregnancy confirmation due to lack of safety data and should not be used during lactation. 1, 2
Fibrates may be considered after the first trimester only if benefits clearly outweigh risks (85% consensus). 1
Ensure total serum bile acids, ALT/AST, and bilirubin return to normal within 3 months of delivery; if not, investigate for underlying liver disease. 1
Consider genetic screening if there is family history of hepatobiliary disease, early onset, or severe disease. 1