Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP, “obstetric cholestasis”) is a pruritus-with-raised-bile-acids condition of the second half of pregnancy. It matters because high maternal bile acids are associated with stillbirth, so it drives fetal surveillance and delivery timing — but note the modern, level-stratified understanding below, which is more nuanced than “cholestasis = deliver early”.

It is the most common liver disorder specific to pregnancy, with a global incidence around 2.9%. The cause is multifactorial — the cholestatic effect of reproductive hormones in a genetically predisposed woman. Familial clustering is real: first-degree female relatives are at higher risk.

Presentation

• Pruritus without a primary rash, classically the palms and soles, though it can appear anywhere. Usually late second or third trimester, and typically worse at night — enough to cause insomnia, low mood and depression. Only secondary excoriations are seen on the skin.
• Itch severity does not correlate with the bile acid level — a woman scratching all night may have modest bile acids and vice versa.
• Jaundice occurs in 17–75% of cases, usually 1–4 weeks after the itch starts, and unlike the pruritus does not worsen with advancing gestation.
• Uncommonly: dark urine, pale stools, mild RUQ discomfort, steatorrhoea.
• Usually resolves within days of birth (as placental oestrogen falls).
• More common in multiple pregnancy, with a personal/family history of ICP, and in those with gallstones, hepatitis C, or gestational diabetes.

Diagnosis

• Serum bile acids are the key test (a non-fasting sample is acceptable). A threshold above 10 µmol/L is commonly used. LFTs may be normal, so normal transaminases do not exclude ICP; when deranged, a modest rise in ALT/GGT is typical with a normal bilirubin.
• Bile-acid elevation can lag the itch by 1–2 weeks — so if pruritus persists with initially normal bloods, repeat bile acids and LFTs every 1–2 weeks.
• It is a diagnosis of exclusion — consider other causes of itch/abnormal LFTs (pre-eclampsia/HELLP, viral hepatitis, primary biliary cholangitis, gallstones, skin disease).

Severity by peak bile acid

• Mild: peak total bile acids 10–39 µmol/L (RCOG uses 19–39 as its mild band)
• Moderate: peak total bile acids of 40–99 µmol/L on any sample
• Severe: peak total bile acids of 100 µmol/L or above at any point

The peak bile-acid level is the prognostic marker. The stillbirth risk is meaningfully increased once bile acids reach ≥100 µmol/L at any point in the pregnancy — probably through fetal arrhythmia and placental vasoconstriction.. Below that, the risk approaches the background population risk, though levels above 40 µmol/L are associated with low birthweight, meconium-stained liquor and postpartum haemorrhage.

Preterm delivery — spontaneous and iatrogenic — occurs in about a third of ICP pregnancies.

Management

Get specialist/obstetric input — as a guide, bile acids ≥40 µmol/L or ALT >200 generally warrant specialist involvement and closer monitoring (severe disease often needs inpatient/day-assessment management), whereas milder disease can often be co-managed as an outpatient.

Ursodeoxycholic acid (UDCA), 10–15 mg/kg/day in two or three divided doses, is the usual first-line drug. Be honest about what it does and doesn’t do:

• The PITCHES trial (2019) randomised 605 women and found the composite perinatal outcome (perinatal death, preterm delivery, or neonatal-unit admission ≥4 h) occurred in 23% on UDCA versus 27% on placebo — no significant difference. Its authors concluded routine use should be reconsidered.
• Cochrane found UDCA clearly associated only with a partial reduction in pruritus, with a possible reduction in preterm birth on moderate-to-low quality evidence, and unclear effect on other adverse fetal outcomes.
• So treat it as symptomatic, not disease-modifying, and do not let it substitute for surveillance and delivery planning.

Other agents: rifampicin, cholestyramine and S-adenosyl-L-methionine are used where UDCA fails, and antihistamines for the itch. Cochrane found no evidence that S-adenosylmethionine, guar gum, activated charcoal, dexamethasone, cholestyramine or Chinese herbal medicines are effective. Topical emollients and menthol aqueous cream are untested in trials but harmless and often helpful.

Monitoring: serial bile acids/LFTs, frequency guided by severity, plus fetal surveillance per the obstetric team. Fetal ultrasound and cardiotocography do not predict or prevent stillbirth in ICP.

Vitamin K if there is steatorrhoea or a prolonged PT (fat-soluble-vitamin malabsorption).

Delivery timing (bile-acid stratified)

RCOG:

• Peak bile acids ≥100 µmol/L (severe): planned birth at 35–36 weeks.
• Peak bile acids 40–99 µmol/L (moderate): planned birth at 38–39 weeks.
• Peak bile acids 19–39 µmol/L (mild): planned birth by 40 weeks.

Other bodies stratify similarly. FIGO advises 37–39 weeks for bile acids of 10–39 µmol/L, 36–39 weeks (closer to 36) for 40–99, and 35–36 weeks once bile acids are 100 or above. ACOG advises delivery between 36 0/7 and 39 0/7 weeks where total bile acids are under 100 µmol/L, and at 36 0/7 weeks or at diagnosis at or above that level.

Timing is individualised with the obstetric team, weighing prematurity against the stillbirth risk that rises in the late third trimester.

Postnatal & future

• Itch and LFTs should resolve after birth — confirm resolution with LFTs (± bile acids) at ≥4 weeks postpartum. Persistent derangement needs hepatology work-up (underlying liver disease).
• Recurrence is around 60% in subsequent pregnancies; counsel accordingly.
• ICP is associated with a later increased risk of hepatobiliary disease (gallstones, hepatitis C) — worth noting for long-term care.
• Oestrogen-containing contraception can be resumed once LFTs normalise, with awareness it may occasionally provoke cholestatic itch.