Description¹

Also known as intrahepatic cholestasis of pregnancy (ICP), obstetric cholestasis is a multifactorial condition affecting 0.7% of pregnancies (1.2-1.5% of women of Indian-Asian or Pakistani descent). It is characterised by intense pruritus in the absence of a skin rash and abnormal liver function tests (particularly aspartate transaminase (AST) and alanine aminotransferase (ALT) elevation) in the absence of other causes and which resolve following delivery.¹

The underlying cause is not known but is likely to consist of a combination of both genetic and environmental factors.

The importance relates to the risks associated with this condition:

• There is an increased risk of fetal distress (partly due to increased likelihood of meconium passage) and intrauterine death.²
• There is an increased risk of premature birth (spontaneous and iatrogenic).³
• Maternal morbidity due to intense itching and lack of sleep.¹
• There is no current evidence supporting the claims of increased risk of Caesarean section or postpartum haemorrhage.

Risk factors¹

• Past history of obstetric cholestasis.
• Family history of obstetric cholestasis, e.g. mother.
• Multiple pregnancy.
• Presence of gallstones.
• Hepatitis C.

Presentation

• Intense pruritus ± excoriation, affecting any part of the body but particularly the palms of the hands and soles of the feet. Pruritus is common in pregnancy and only a minority will have obstetric cholestasis.¹
• It is often worse at night and may interfere with sleep.
• Some women develop other signs associated with cholestasis, e.g. pale stool, dark urine, jaundice.
• There may be generalised malaise and fatigue.
• The itching may precede the LFT abnormalities by days or weeks.

Diagnosis

Women with obstetric cholestasis (present or past history) should be managed by a consultant-led team and should deliver in hospital.

Other causes of liver dysfunction and itching need to be excluded. Think of gallstones, hepatitis, Epstein-Barr virus, cytomegalovirus, medications, an autoimmune process (anti-smooth muscle and antimitochondrial antibodies) and organise a liver ultrasound scan. Other conditions to rule out are pre-eclampsia and fatty liver of pregnancy.¹ Monitor LFTs weekly over this period of investigation.

If no other cause is found for the symptoms and LFT abnormalities, a diagnosis can be made on the basis of symptoms and LFTs: transaminases, gamma-glutamyltransferase (gamma-GT) - both raised - and bilirubin - infrequently raised.
More recently, the total bile acid level has been proposed as an alternative diagnostic marker, and is used in many centres.³

Management

• Monitoring - LFTs should be monitored weekly. If they return to normal or soar (into the 100s), the diagnosis needs to be revised. Following the delivery, wait at least 10 days before re-checking to avoid the confounding factor of the normal fluctuations in LFTs during this time following normal pregnancies.¹ There are no current guidelines regarding specific fetal monitoring that might reduce the risks described above.
• Treatment - topical emollients are safe for both mother and baby but their efficacy is unproven.¹ Ursodeoxycholic acid (UDCA) is the mainstay of medical management, with noted positive effects on both maternal and fetal outcome as well as on pruritus.² Vitamin K can be offered (daily supplement of water-soluble preparation), particularly if there is steatorrhoea or a prolongation of the prothrombin time. Dexamethasone has been studied in small clinical trials but is not recommended due to adverse neurological effects in the fetus/neonate.¹
• Delivery - there are no current data supporting the blanket recommendation of the popular practice of inducing an early labour and delivery (aimed at reducing a late stillbirth). The biochemical results are not helpful in predicting outcome, but continuous fetal monitoring during labour should be offered. However, perinatal and maternal morbidity increases from 37 weeks of gestation onwards, and induction of labour should be considered from this point onwards.¹ This is probably more so in those with more severe disease and more severe transaminases and bile acids.

Outcome

This is a condition that should settle spontaneously following delivery. Follow-up should be long enough to ensure a normalisation of LFTs, and it is reasonable to check the LFTs at six weeks.¹ If, after six months, there is no improvement, further specialist input will be required. Women will have to be advised that there is a significant risk of recurrence (reports vary between 60% and 90%).

Document references

1. Obstetric Cholestasis, Royal College of Obstetricians and Gynaecologists (RCOG), April 2011
2. Kondrackiene J, Kupcinskas L; Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems. World J Gastroenterol. 2008 Oct 14;14(38):5781-8. [abstract]
3. Wong LF, Shallow H, O'Connell MP; Comparative study on the outcome of obstetric cholestasis. J Matern Fetal Neonatal Med. 2008 May;21(5):327-30. [abstract]