Obstetric cholestasis, also known as intrahepatic cholestasis of pregnancy, refers to stasis of bile acids within the liver during pregnancy. It affects about 1% of pregnancies and usually occurs after 24 weeks of gestation. The definitive cure for obstetric cholestasis is ultimately delivery of the baby.
Pathophysiology
The mechanism is not fully understood. It seems to be due to be a combination of genetic factors, hormonal factors and environmental factors:
Hormonal factors
The disease usually has an onset in the third trimester. During this period the circulating hormones, such as oestrogen and progesterone, are at their highest level. These hormones seem to impair hepatocyte uptake of bile acids → cholestasis.
Women using the combined oral contraceptive pill may develop cholestasis and pruritus, thus indicating that hormonal interplay is almost certain.
Genetic factors
Strong family histories of obstetric cholestasis as well as increased prevalence in women of South Asian heritage all point to a genetic component of the disease. Mutations in bile secretory pathways have been identified.
Environmental factors
There is some evidence that shows that the disease is more prevalent in times of vitamin D deficiency, for example in the winter months. Selenium (found in Brazil nuts, seafood and also meat) deficient patients also seem to have increased prevalence of obstetric cholestasis.
⚠️ Risk factors
- Family history
- History in previous pregnancy
- History of hepatitis infection
- Multiple pregnancy
- South Asian ethnicity
😷 Presentation
- Pruritus - it is often worse on the palms, soles and abdomen of the mother. The itching may lead to excoriation of the skin without any papules, pustules, urticaria that could be causing the itching.
- Jaundice - clinically visible jaundice may be present in 20% of patients. Pale stools, dark urine may be reported while the conjunctiva may appear yellow.
- Fatigue
- Steatorrhoea
🔍 Investigations
LFTs and bile acid levels are the important investigations to ask for. Bilirubin is raised in the overwhelming majority of cases.
Other investigations that one can consider are:
- Coagulatory profile (prothrombin time) - as bile acids help with absorption of fat-soluble vitamins (vitamins A, D, E, K), we may see derangements in the prothrombin time as vitamin K is involved in activation of many of the clotting factors. This is also important to assess as we may need to manage it accordingly as well.
🧰 Management
If a diagnosis of obstetric cholestasis is made, the mother should be under consultant-led care.
- Ursodeoxycholic acid - helps regulate the bile acid levels as well as improve symptoms. However, it doesn’t reduce the likelihood of complications.
- Emollients - such as calamine lotion can help with itching.
- Chlorphenamine - a sedating antihistamine. Its purpose is not to improve itching as the itching does not derive from histamine release. It is solely used to improve sleep as it is sedating.
- Vitamin K (phytomenadione) - used to treat vitamin K deficiency that may occur with bile acid malabsorption.
Delivery dates:
Date for delivery of the baby may depend on the bile acid levels in the mother. This is to reduce the chance of a stillbirth. These guidelines are provided by the RCOG.
- 19-39 umol/L - 40 weeks.
- 40-99 umol/L - 38-39 weeks.
- >100umol/L - 35-36 weeks. A CTG will be needed to monitor the baby’s heart rate throughout labour.
🚨 Complications
- Premature labour
- Meconium aspiration - as bile acids have a prokinetic effect on the GI tract.
- Pre-eclampsia
- Gestational diabetes
- Stillbirth - dependent on the level. Only if the bile acid levels are >100umol/L then there is a 3% chance of stillbirth, most of which occur after 36 weeks. This is why we opt for early delivery in severe cases of obstetric cholestasis.