Obstetric Cholestasis

Obstetric cholestasis (intrahepatic cholestasis of pregnancy, ICP) is a liver disorder of the second and third trimester characterised by pruritus and raised serum bile acids, resolving after delivery. Prevalence is about 0.5 to 1% in Europe (higher in South Asia and Chile, 5 to 15%).

Risk factors:

• Previous ICP, family history, multiple pregnancy, IVF
• Hepatitis C, gallstones
• ABCB4, ABCB11 and ATP8B1 variants

Fetal risks relate to bile acid levels (risk rises with levels above 40 micromol/L):

• Spontaneous and iatrogenic preterm birth, meconium stained liquor, neonatal respiratory distress, NICU admission
• Stillbirth: about 1 to 2% with levels at or above 100 micromol/L. Risk is not significantly raised below 100 micromol/L.

Maternal risks: vitamin K deficiency with postpartum haemorrhage (rare), sleep disturbance, and recurrence (about 90%) in later pregnancies.

• Intense pruritus without rash, worse at night, typically palms and soles, but generalised; excoriations from scratching
• Mild jaundice (10 to 15%), dark urine, pale stools, steatorrhoea
• Onset after 28 weeks in most (can be earlier)
• Fatigue and anorexia; right upper quadrant discomfort is unusual

• Pruritus with raised fasting serum bile acids (above 10 micromol/L; mild 10 to 39, moderate 40 to 99, severe 100 or above); a non-fasting sample is acceptable if fasting is not possible
• Liver function tests: raised ALT and AST (often markedly elevated, 2 to 10 times normal), GGT normal or mildly raised, bilirubin usually under 100 micromol/L, alkaline phosphatase (physiologically raised in pregnancy, not useful)
• Exclude other causes: viral hepatitis serology (A, B, C, E, EBV, CMV), autoimmune markers (ANA, anti-smooth muscle, anti-mitochondrial antibodies), liver ultrasound for gallstones and biliary obstruction, pre-eclampsia and HELLP, acute fatty liver, dermatological conditions (pemphigoid gestationis, atopic eruption of pregnancy)
• Coagulation screen (prothrombin time) when jaundiced or steatorrhoea
• Resolution after delivery (bile acids and LFTs normalise in 2 to 8 weeks; if persistent, investigate chronic liver disease)

• Ursodeoxycholic acid (UDCA) 10 to 15 mg/kg/day orally (typically 500 mg twice daily; up to 21 mg/kg/day in divided doses, maximum 2 g/day) until delivery: improves itching and liver tests in many; large trials show reduction in composite adverse perinatal outcome only in some analyses (not a proven reduction in stillbirth); it is safe.
• Symptomatic relief: emollients, calamine lotion, cool environment, chlorphenamine 4 mg at night (sedating; for sleep), and rifampicin 150 to 300 mg twice daily for refractory pruritus (second line).
• Vitamin K 10 mg orally daily if prolonged prothrombin time or cholestatic malabsorption.
• Surveillance: weekly or twice weekly bile acids and LFTs; fetal monitoring (cardiotocography is not predictive of stillbirth; use in line with local protocols); growth ultrasound.
• Timing of delivery: plan delivery based on peak bile acid level.
  • 100 micromol/L or above: 35 to 36 weeks.
  • 40 to 99 micromol/L: 36 to 38 weeks.
  • 10 to 39 micromol/L: 38 to 39 weeks (39 weeks 6 days at the latest).
  • Deliver earlier with deranged coagulation, jaundice, pre-eclampsia, or fetal compromise.
• Betamethasone 12 mg IM two doses 24 hours apart before 34 to 36 weeks if delivery is considered.
• Postpartum: stop UDCA; repeat LFTs at 10 days and 6 weeks; avoid oestrogen containing contraceptives if there was severe cholestasis with persistent abnormal tests (progestogen only or non-hormonal methods).
• Counsel about recurrence and the possibility of oestrogen related cholestasis.