Does pregnancy increase pruritus due to bile?

Does Pregnancy Increase Pruritus Due to Bile?

Yes, pregnancy directly causes intrahepatic cholestasis of pregnancy (ICP), a condition where elevated bile acids trigger generalized pruritus, typically in the second or third trimester, affecting 0.4%-10% of pregnancies. 1

Mechanism and Pathophysiology

Pregnancy creates a unique cholestatic state through multiple mechanisms:

• Hormonal factors including elevated estrogen and sulphated progesterone directly impair bile acid transport and excretion, leading to accumulation of bile acids in maternal serum 1
• Genetic predisposition plays a major role, with mutations in hepatobiliary transport proteins (ABCB4, ABCB11, ATP8B1) explaining familial clustering and ethnic variations 1
• In healthy pregnancy, a mild increase in total bile acids occurs but remains within normal range (<10 μmol/L), whereas ICP is defined by bile acids >10 μmol/L 1

Clinical Presentation

The hallmark symptom is generalized pruritus without accompanying rash, with specific characteristics:

• Location: Most severe in palms and soles 1, 2
• Timing: 80% of women present after 30 weeks of gestation, though first trimester onset has been reported 1
• Pattern: Worsens at night 2
• Only excoriations from scratching are visible on examination—no primary dermatologic lesions 2

Critical Diagnostic Approach

Measure serum bile acids and liver transaminases (ALT/AST) immediately in any pregnant woman with pruritus, particularly in the second or third trimester: 1, 2

• Bile acids >10 μmol/L confirm the diagnosis 1
• Random (non-fasting) samples are acceptable and more convenient 2
• If initial bile acids are normal but pruritus persists, repeat testing is mandatory as pruritus can precede laboratory abnormalities by weeks 1, 2
• Transaminases are typically elevated 2-30 fold but are not required for diagnosis 1

Fetal Risk Stratification by Bile Acid Levels

The risk of adverse fetal outcomes correlates directly with maternal bile acid concentrations:

• Bile acids <40 μmol/L: Similar fetal outcomes to women without ICP 1
• Bile acids 40-99 μmol/L: 0.3% risk of intrauterine fetal demise (IUFD) 1
• Bile acids ≥100 μmol/L: 3.4% risk of IUFD, with stillbirth risk increasing after 35 weeks 1

Additional fetal complications include preterm birth, meconium-stained amniotic fluid, neonatal respiratory depression, and fetal distress 1

Management Algorithm

First-line treatment: Ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in divided doses for all confirmed ICP cases: 1, 2

• UDCA improves maternal pruritus, reduces bile acid levels, and decreases adverse outcomes including preterm birth and stillbirth 1, 2
• For refractory pruritus, add rifampicin, cholestyramine, or antihistamines 1

Delivery timing based strictly on bile acid levels: 1, 2

• Bile acids ≥100 μmol/L: Deliver at 36 weeks or at diagnosis if after 36 weeks 1, 2
• Bile acids <100 μmol/L: Deliver between 36-39 weeks 1, 2
• Bile acids <40 μmol/L: Consider delivery at term (39 weeks) 1, 2

Critical Pitfalls to Avoid

Never deliver before 37 weeks based on clinical suspicion alone without laboratory confirmation of elevated bile acids 2

• Always exclude other causes of pruritus and elevated liver tests, particularly pre-eclampsia/HELLP syndrome and acute fatty liver of pregnancy, which carry significant maternal mortality risk 2
• Monitor bile acids at least weekly from 32 weeks in confirmed ICP to identify those with concentrations >40 μmol/L 1
• Cholestyramine at high doses can exacerbate vitamin K deficiency, increasing risk of fetal intracranial hemorrhage and postpartum hemorrhage 1

Postpartum Considerations

• Symptoms and laboratory abnormalities typically resolve within days to weeks postpartum 1
• If pruritus or abnormal liver tests persist beyond 6 weeks postpartum, refer to hepatology for evaluation of underlying chronic liver disease such as primary biliary cholangitis or genetic cholestatic syndromes 1, 2
• Recurrence risk in subsequent pregnancies is 40-92% 1
• Genetic testing should be considered in women with severe ICP (bile acids >100 μmol/L), recurrent ICP, or early-onset ICP 1