What is intrahepatic cholestasis of pregnancy?
Intrahepatic cholestasis of pregnancy (ICP), previously called obstetric cholestasis, is the most common liver disease specific to pregnancy (StatPearls). It presents with new-onset pruritus and raised serum bile acids, usually in the late second or third trimester, and it resolves after delivery.
For the mother it is uncomfortable but benign. The concern is the baby: ICP is linked to preterm birth, meconium-stained liquor, neonatal unit admission and stillbirth — and the stillbirth risk tracks the peak bile acid level.
Why does ICP happen and who gets it?
The cause is multifactorial — hormonal, genetic and environmental. StatPearls notes that oestrogen and progesterone are thought to impair bile acid flow in the liver; because both hormones peak in the late second and third trimesters, that is when ICP appears. Bile acids then build up in maternal blood and cross to the fetus.
| Feature | What the sources say |
|---|---|
| Overall incidence | Reported 0.3% to 15% worldwide; most estimates 0.3–0.5% (StatPearls) |
| UK | About 7 in 1000 pregnancies (RCOG) |
| South Asian women | Up to 15 in 1000 in women of Indian-Asian or Pakistani-Asian origin (RCOG) |
| Ethnic variation | 5.6% in a Hispanic population in California vs 0.32% in Connecticut (StatPearls) |
| Recurrence | 60–70% in later pregnancies (StatPearls) |
What are the clinical features of ICP?
- Pruritus without a rash — can be anywhere but classically palms and soles (StatPearls).
- Worse at night — sleep disturbance is a common complaint.
- Timing: usually late second to early third trimester; RCOG says it usually begins after 28 weeks. Onset in the first trimester should prompt a search for underlying liver disease.
- Skin: excoriations from scratching only — there is no primary skin lesion.
- Resolution: itching settles within days of birth; liver tests normalise over a few weeks.
What bile acid levels diagnose ICP and grade its severity?
The key test is serum total bile acids (TBA). Fasting is not needed (StatPearls). Liver transaminases are often raised too, but bile acids can be abnormal even when liver function tests are normal (RCOG).
| Source | Diagnostic cut-off | Severity bands |
|---|---|---|
| StatPearls (US practice) | TBA greater than 10 µmol/L | ≥ 40 µmol/L → specialist referral; ≥ 100 µmol/L → highest stillbirth risk |
| RCOG Green-top 43 (2022) | Itching with peak bile acids 19 µmol/L or more | Mild 19–39, moderate 40–99, severe ≥ 100 µmol/L |
Other conditions that cause itching without a rash and raised bile acids or transaminases must be considered (StatPearls): viral hepatitis and other infections, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, biliary duct obstruction and drug-induced cholestasis. Itch without a rash also occurs with thyroid disease, chronic renal failure, polycythaemia vera, lymphoma and medication reactions.
What are the fetal risks and how do they relate to bile acids?
The largest data set is the Ovadia et al. individual-patient meta-analysis (Lancet 2019; 5269 ICP cases with individual data). In singleton pregnancies, stillbirth was associated with the peak total bile acid level but not with ALT.
| Peak total bile acids | Stillbirth prevalence | Interpretation |
|---|---|---|
| < 40 µmol/L | 3 of 2310 (0.13%) | Similar to background risk |
| 40–99 µmol/L | 4 of 1412 (0.28%) | Not significantly raised (HR 2.35) |
| ≥ 100 µmol/L | 18 of 524 (3.44%) | Sharply raised (HR about 30) |
- Other fetal and neonatal risks: spontaneous and iatrogenic preterm birth, meconium-stained amniotic fluid, birth asphyxia, respiratory distress and neonatal unit admission (StatPearls).
- Mechanism: unclear. Bile acids may accumulate in fetal cardiac muscle and cause arrhythmia and sudden death, or act on the placenta (StatPearls).
- ICP is not typically associated with fetal growth restriction, which is why standard fetal tests may not predict the sudden death.
Does ursodeoxycholic acid help? What did PITCHES show?
Ursodeoxycholic acid (UDCA) is an oral bile acid that has long been the standard drug for ICP. It reduces maternal ALT and may modestly ease the itch, but its effect on the baby was untested until PITCHES.
| Item | Detail |
|---|---|
| Design | Double-blind, placebo-controlled RCT at 33 UK maternity units |
| Participants | 605 women with ICP, 20 to 40+6 weeks, singleton or twin |
| Intervention | UDCA 500 mg twice daily (adjustable) vs placebo, until birth |
| Primary outcome | Composite of perinatal death, preterm birth < 37 weeks, or neonatal unit admission ≥ 4 h |
| Result | 23% vs 27% (adjusted RR 0.85, 95% CI 0.62–1.15) — no significant reduction |
| Conclusion | UDCA does not reduce adverse perinatal outcomes; routine use should be reconsidered |
- RCOG 2022 (patient information): UDCA 'may slightly reduce itching in a small number of women', does not prevent stillbirth, and no treatment improves bile acids for the baby. It may reduce the chance of preterm birth.
- StatPearls dosing (US practice): 10–15 mg/kg/day, typically starting at 300 mg daily and titrating up to 300 mg three times daily; still described as first-line for maternal symptoms.
- Vitamin K: RCOG says a daily dose may be advised for a small number of women, because ICP can rarely affect clotting.
When should a woman with ICP be delivered?
Delivery timing is chosen by the peak bile acid level and by any additional risk factors — multiple pregnancy, gestational diabetes or pre-eclampsia. These are the options RCOG presents to women:
| Severity | Peak bile acids | Planned birth |
|---|---|---|
| Mild | 19–39 µmol/L | Consider birth by 40 weeks, or await spontaneous labour |
| Moderate | 40–99 µmol/L | Planned birth at 38–39 weeks |
| Severe | ≥ 100 µmol/L | Planned birth at 35–36 weeks |
- Monitoring: RCOG advises continuous CTG in labour for bile acids above 100 µmol/L or other risk factors; bloods are usually repeated after a week.
- US practice (StatPearls): antenatal testing once or twice weekly from diagnosis (non-stress test and amniotic fluid assessment); if bile acids are below 40 µmol/L, repeat around 34–36 weeks to plan delivery; consider antenatal corticosteroids if delivery is before 37 weeks.
| Total bile acids | Delivery timing |
|---|---|
| 11–99 µmol/L | 36 0/7 to 39 0/7 weeks |
| ≥ 100 µmol/L | 36 0/7 weeks |
| ≥ 100 µmol/L plus unrelenting itch despite ursodiol, prior ICP stillbirth before 36 weeks, or worsening liver disease | 34 0/7 to 36 0/7 weeks |
What happens after delivery and in later pregnancies?
- Itch settles within days of birth; bile acids and liver tests usually normalise within a few weeks.
- Postnatal check: RCOG recommends confirming at the 6-week check that itching has gone and repeating liver tests and bile acids; persistent abnormalities need hepatology review.
- Recurrence: 60–70% in future pregnancies (StatPearls); RCOG advises checking liver tests and bile acids early in any future pregnancy.
- Long term: cohort studies show more hepatobiliary disease later — gallstones, hepatitis C, fibrosis/cirrhosis, cholangitis (StatPearls).
- Contraception: RCOG says ICP does not limit the choice once liver tests have returned to normal.
How is ICP asked in NEET PG and INI-CET?
- Vignette diagnosis: third-trimester itching of palms and soles, worse at night, no rash → ICP.
- Best investigation: serum total bile acids.
- Most feared complication: sudden intrauterine fetal death, linked to bile acids ≥ 100 µmol/L.
- Drug: ursodeoxycholic acid — relieves the mother, does not prevent stillbirth (PITCHES 2019).
- Timing: earlier planned birth as bile acids rise; recurrence 60–70%.
- Differentials: biliary obstruction, viral and autoimmune hepatitis, primary biliary cholangitis and drug-induced cholestasis — ICP is the pregnancy-specific cause of itch with raised bile acids.