Raised bile salts in pregnancy

Intrahepatic cholestasis of pregnancy (ICP: also known as obstetric cholestasis) is a pregnancy-specific liver condition appearing most often in the third trimester

• is a relatively benign but often very distressing condition for the woman, but it may adversely affect fetal outcome, as seen by associations with preterm labour, fetal distress and stillbirth, particularly in severe cases (1)
  
  
• in England,obstetric cholestasis (also referred to as intrahepatic cholestasis of pregnancy) affects 0.7% of pregnancies in multiethnic populations and 1.2–1.5% of women of Indian–Asian or Pakistani–Asian origin
  
  
• clinical pruritus may precede the development of abnormal biochemistry
  • following birth, there is usually spontaneous relief of signs and symptoms within the first few days, although occasionally resolution may take several weeks
  • ongoing clinical symptoms and abnormal liver biochemical values for longer than six weeks after birth may not be consistent with a primary diagnosis of intrahepatic cholestasis of pregnancy, and other causes should be considered
    
    
• diagnosed when otherwise unexplained pruritus occurs in pregnancy and abnormal liver function tests (LFTs) and/or raised bile acids occur in the pregnant woman and both resolve after delivery. Pruritus that involves the palms and soles of the feet is particularly suggestive (2). Other causes of itching and of liver dysfunction should be excluded
  • diagnosis of ICP is based on a combination of pruritus (itching), which classically affects palms and soles but may become generalised, but without a rash apart from excoriations, together with increased concentrations of serum bile acids (values usually at least 10 micromol/ L, or above the upper limit of the normal range for the local
    laboratory)
    • increased concentrations of serum transaminases (e.g. alanine aminotransferase (ALT)) greater than 50 U/L are often seen
    • there is now movement towards an international consensus that the diagnosis should only be made if serum bile acids are increased, irrespective of whether serum transaminases are increased, either alone or in combination (1)
  • women with persistent pruritus and normal biochemistry should have LFTs repeated every 1–2 weeks
  • pregnancy-specific reference ranges for LFTs should be used
  • postnatal resolution of pruritus and abnormal LFTs should be confirmed
  • once obstetric cholestasis is diagnosed, it is reasonable to measure LFTs weekly until delivery
  • postnatally, LFTs should be deferred for at least 10 days
    
    

Fetal effects:

• implication of excess circulating maternal serum bile acids for the fetus is not completely understood
• increased rates of fetal complications, perinatal mortality rates, stillbirths, low birthweight, preterm labour and birth, and fetal distress in labour have been linked with the condition
• evidence to suggest an increased incidence of meconium-stained amniotic fluid in women with intrahepatic cholestasis of pregnancy, and it is more common in those with serum bile acid concentrations greater than 40 micromol/L (1)

Management:

• seek specialist advice
• topical emollients are safe but their efficacy is unknown
• ursodeoxycholic acid (UDCA) improves pruritus and liver function in women with obstetric cholestasis - women should be informed of the lack of robust data concerning protection against stillbirth and safety to the fetus or neonate

Following pregnancy (2):

• as a minimum,healthcare practitioners must ensure that LFTs return to normal,pruritus resolves,all investigations carried out during the pregnancy have been reviewed and the mother has fully understood the implications of obstetric cholestasis
  • the latter will include reassurance about the lack of long-term sequelae for mother and baby and discussion of the high recurrence rate (45–90%), contraceptive choices (usually avoiding estrogen-containing methods) and the increased incidence of obstetric cholestasis in family members
  • LFTs at 6 weeks after delivery and an appointment at 8 weeks is a suggested model
  • appropriate follow-up should be arranged by a medical practitioner with appropriate skills

Notes (2):

• although a wide variety of cut-off points have been used for defining abnormal LFTs and bile salts, pregnancy-specific ranges should be applied
  • for transaminases, gamma glutamyl transferase and bilirubin, the upper limit of normal throughout pregnancy is 20% lower than the nonpregnant range; many laboratories will use pregnancy-specific ranges for bile salts but this should not be assumed
• a substantial number of women will have pruritus for days or weeks prior to the development of abnormal liver function: if the pruritus persists, LFTs should be measured every 1-2 weeks

Reference:

1. Walker KF et al. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD000493. DOI: 10.1002/14651858.CD000493.pub3.
2. Royal College of Obstetricians and Gynaecologists (April 2011). Guideline No. 43 - Obstetric cholestasis.