Obstetric Cholestasis
Summary
Obstetric cholestasis (intrahepatic cholestasis of pregnancy, ICP) is a pregnancy-specific liver disorder characterised by intense pruritus (itching) and elevated serum bile acids. It typically presents in the third trimester and resolves rapidly after delivery. The main concern is the risk of stillbirth, which is unpredictable and increases when bile acids are >40 μmol/L, with highest risk at >100 μmol/L. Treatment involves ursodeoxycholic acid (UDCA) to reduce bile acids and relieve itching, and planned delivery at 37-38 weeks (earlier if severe) to reduce stillbirth risk.
Key Facts
- Symptoms: Intense pruritus (palms and soles, worse at night) without primary rash
- Biochemistry: Raised bile acids (>10 μmol/L), raised ALT
- Key Risk: Stillbirth (sudden, unpredictable; higher if bile acids >100)
- Treatment: Ursodeoxycholic acid (UDCA)
- Delivery: Planned at 37-38 weeks (earlier if severe)
- Prognosis: Resolves after delivery; may recur in future pregnancies
Clinical Pearls
"Itch Without Rash": The pruritus in ICP has no primary rash. Excoriations and scratch marks are secondary. Always check bile acids.
"Palms and Soles, Worse at Night": The classic distribution. Patients often describe unbearable itching that disrupts sleep.
"Bile Acids >100 = High Risk": Stillbirth risk increases significantly with bile acids >100 μmol/L. Consider earlier delivery.
"Resolves Post-Delivery": Symptoms and biochemistry resolve within days to weeks of delivery. If persistent, investigate other causes.
Incidence
- 0.5-1.5% of pregnancies in UK
- Higher in South Asian and South American populations
Risk Factors
| Factor | Notes |
|---|---|
| Previous ICP | 45-70% recurrence |
| Family history | Genetic predisposition |
| Multiple pregnancy | Higher incidence |
| IVF pregnancy | Possibly higher risk |
| Hepatitis C | Associated |
Mechanism
- Impaired bile acid transport in hepatocytes
- Exacerbated by high oestrogen levels in pregnancy
- Genetic variants in bile salt transporters (ABCB4, ABCB11)
Why Stillbirth?
- High bile acids cross placenta
- Cause fetal cardiac arrhythmias
- Vasoconstriction of placental vessels
- Usually sudden and unpredictable
Symptoms
| Feature | Description |
|---|---|
| Pruritus | Intense, generalised; worst on palms and soles |
| Timing | Worse at night; disrupts sleep |
| Rash | No primary rash; excoriations from scratching |
| Onset | Usually 3rd trimester (can be earlier) |
| Other | Dark urine, pale stools, mild jaundice (rare) |
Symptoms Resolve
General
- Excoriations and scratch marks (secondary)
- No primary rash
- Rarely: Mild jaundice
Abdominal
- Uterus size appropriate for dates
- Normal fetal movements initially
First-Line
| Test | Finding |
|---|---|
| Serum bile acids | Elevated (>0 μmol/L diagnostic) |
| LFTs | Raised ALT (often 2-10x normal); may precede bile acid rise |
| Bilirubin | Usually normal or mildly elevated |
Risk Stratification by Bile Acids
| Bile Acids | Risk Category |
|---|---|
| 10-39 μmol/L | Mild |
| 40-99 μmol/L | Moderate |
| ≥100 μmol/L | Severe (highest stillbirth risk) |
Exclude Other Causes
- Hepatitis serology (A, B, C, E)
- Liver ultrasound (for biliary obstruction)
- Autoimmune screen if needed
Management Approach
┌──────────────────────────────────────────────────────────┐
│ OBSTETRIC CHOLESTASIS MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ SYMPTOMATIC RELIEF: │
│ • Emollients (aqueous cream, menthol cream) │
│ • Chlorphenamine (antihistamine - temporary relief) │
│ • Cool baths │
│ │
│ URSODEOXYCHOLIC ACID (UDCA): │
│ • 10-15 mg/kg/day in 2 divided doses │
│ • Reduces bile acids and pruritus │
│ • Evidence for fetal benefit uncertain (PITCHES trial) │
│ │
│ MONITORING: │
│ • Weekly bile acids and LFTs │
│ • Fetal movements (advise woman to report changes) │
│ • CTG (limited predictive value for stillbirth) │
│ │
│ DELIVERY TIMING: │
│ • Bile acids <40: 38-39 weeks │
│ • Bile acids 40-99: 37-38 weeks │
│ • Bile acids ≥100: Consider earlier (from 36 weeks) │
│ • Balance stillbirth risk vs prematurity │
│ │
│ VITAMIN K: │
│ • Consider oral vitamin K if prolonged cholestasis │
│ (impaired fat-soluble vitamin absorption) │
│ │
│ POSTNATAL: │
│ • Symptoms resolve within days to weeks │
│ • Repeat LFTs at 6-8 weeks to confirm resolution │
│ • Counsel about recurrence (45-70%) │
│ • Avoid oestrogen-containing contraception │
│ │
└──────────────────────────────────────────────────────────┘
Fetal
- Stillbirth (main concern; sudden and unpredictable)
- Preterm birth (spontaneous or iatrogenic)
- Meconium-stained liquor
- Fetal distress
Maternal
- Severe pruritus (psychological impact)
- Vitamin K deficiency (rare)
- PPH (if vitamin K deficiency)
Stillbirth Risk
| Bile Acids | Approximate Risk |
|---|---|
| <40 μmol/L | ~0.1% (background) |
| 40-99 μmol/L | ~1% |
| ≥100 μmol/L | ~3-5% |
After Pregnancy
- Rapid resolution of symptoms and biochemistry
- May recur in future pregnancies (45-70%)
- May recur with COC use
Key Guidelines
- RCOG Green-top Guideline No. 43: Obstetric Cholestasis
- UpToDate: Intrahepatic Cholestasis of Pregnancy
Key Evidence
PITCHES Trial (2019)
- UDCA did not significantly improve perinatal outcomes
- But may still help symptom relief
Stillbirth Risk
- Meta-analyses confirm risk increases with bile acid level
What is Obstetric Cholestasis?
Obstetric cholestasis (ICP) is a liver condition that happens in pregnancy. It causes intense itching, especially on the palms and soles, and is diagnosed by a blood test showing raised bile acids.
Why Does it Matter?
The main concern is a slightly increased risk of stillbirth. This risk is higher when bile acid levels are very high. That's why your doctors will monitor you closely and may recommend having your baby a bit earlier than your due date.
What Are the Symptoms?
- Severe itching (especially palms and soles, worse at night)
- No rash (just scratch marks)
- Sometimes dark urine or pale stools
How is it Treated?
- Creams to soothe itching
- Ursodeoxycholic acid (UDCA) tablets to lower bile acids
- Earlier delivery (usually around 37-38 weeks) to reduce the stillbirth risk
- Monitoring with regular blood tests
What Happens After Birth?
The itching and abnormal blood tests go away within a few weeks of delivery. If you get pregnant again, there's a chance (about 50-70%) it could happen again.
Primary Guidelines
- Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 43: Obstetric Cholestasis. 2011. rcog.org.uk
Key Studies
- Chappell LC, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394(10201):849-860. PMID: 31378395