Cholestasis of Pregnancy

Cholestasis of pregnancy is a multifactorial condition of pregnancy characterized by itching in the absence of a skin rash with abnormal liver function tests (LFTs), both of which resolve after birth. It usually occurs in the last trimester of pregnancy. It can, however, occur earlier in gestations. It is one of the main common causes of jaundice in pregnancy after viral hepatitis. Genetics and environmental factors play an important role in the occurrence of the condition.

Genetic mutation of the various genes such as hepatocellular transport protein ABCB4 and genetic changes in the bile salt export molecules and selenium deficiency is known to contribute to the development of the condition. Family history, multiple pregnancies, suffering from hepatitis, and the presence of gallstones increase the risk of its development

The pregnant woman affected with cholestasis of pregnancy mainly presents with itching and jaundice. The condition should be diagnosed and treated early as it can be life-threatening if left untreated. It can lead to the death of the mother as well as the baby. The presence of jaundice, severe itching, and raised liver function tests confirm the diagnosis.

Cholestasis of Pregnancy: Causes

Several factors are known to play the role in the development of the condition. The important causes of the cholestasis of the pregnancy include −

• Genetic mutation of the hepatocellular transport protein ABCB4 which controls the secretion of phosphatidylcholine into the bile.

• Genetic changes in the bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump ABCB11, and high levels of sulfated progesterone metabolites to inhibit the ABCB4 phospholipid transporter.

• Some of the studies have shown the role of selenium deficiency in the development of the condition as it acts as a co-factor of several enzymes in the oxidative metabolism in the liver.

Winter month is also not associated with the development of the condition.

Cholestasis of Pregnancy: Symptoms

The main symptoms of the cholestasis of the pregnancy include −

• Pruritis − It is the most common symptom seen in these patients, which increases in the night, is not associated with rashes, mainly presents on palms and soles, and increases as the pregnancy advance. It mainly occurs because of the increased bile acid and increased autotoxin.

• Jaundice − Yellowish discoloration of the body and eyes.

• Pale or clay-colored stool and dark urine.

• Some women may present with pain in the right upper quadrant if there is a presence of the gallstones.

Cholestasis of Pregnancy: Risk Factors

Several factors are known to increase the risk of the development of cholestasis during pregnancy. Important factors include −

• Woman with a family history of the same condition

• Woman with multiple pregnancies is known to have a risk.

• Advanced maternal age: women with little increased age during the pregnancy increase the risk.

• Woman with a history of hepatitis infection

• Women with a history of the same condition in the past

Cholestasis of Pregnancy: Diagnosis

The diagnosis of cholestasis is mainly done based on the history, clinical examination, and liver function tests.

• History of pruritis in pregnancy with no rash, usually presenting in the third trimester.

• Increase in the levels of fasting bile acid which becomes normal after the delivery.

• No tests suggesting other liver diseases.

• Liver function tests: ALT is more sensitive, usually more than 200.

• Serum bilirubin is found to be raised.

• Transaminase enzyme is found to be 20% lower than in non-pregnant women

• Coagulation tests are also observed in some of the patients.

Cholestasis of Pregnancy: Treatment

The treatment of the cholestasis of the pregnancy is very important, as it can lead to the death of the child as well as the baby. There is no specific treatment for the cure of the condition. Some of the treatment measures to reduce the symptoms and prevent the complications are given; which include −

• Ursodeoxycholic acid (UDCA): this medicine is safe to give during pregnancy. it is a naturally occurring hydrophilic bile acid that improves pruritis and liver function. It enhances bile acid clearance across the placenta, this may protect the hepatocyte membrane from the damaging toxicity of bile salts.

• Topical therapies: Creams and lotions containing menthol or other cooling agents can be applied to the skin to alleviate itching. Soothing baths with oatmeal can also provide relief.

• Topical emollients − Topical emollients like calamine lotion and aqueous cream with menthol are used to relieve itching but the efficacy is not more

• Systemic treatments − Cholestyramine and antihistamines such as chlorphenamine are tried in some patients but do not significantly impact pruritus.

• S-adenosyl methionine − this also known to help in some women.

• Dexamethasone − 10 mg orally for 7 days and then stopping over 3, the results are conflicting, with some improvement in symptoms and biochemistry in some women.

• Role of vitamin K − 5- 10 mg given daily orally, which helps to improve maternal and neonatal levels, reducing postpartum hemorrhage and fetal or neonatal bleeding. The use of water-soluble vitamin K (menadiol sodium phosphate) is indicated. Postnatal vitamin K must be offered to the babies in the usual way.

• Use of Rifampicin − recent studies have shown the efficacy of combined ursodeoxycholic acid (UDCA) and rifampicin. It increases the bile acid detoxification as well as bilirubin concentration and increases the excretion of bilirubin glucuronides by increasing MRP2 expression. Phenobarbitone increases the excretion of bile salt.

• Monitoring of fetal health: Women with cholestasis of pregnancy may require frequent monitoring of their baby's health, using techniques such as fetal heart rate monitoring, non-stress tests, or ultrasound.

• Early delivery − In some cases, early delivery may be recommended to prevent complications. This may be done through induction of labor or cesarean section, depending on the circumstances.

• Management of complications − If complications such as preterm labor or fetal distress occur, prompt treatment may be necessary to prevent further harm to the mother or baby.

Cholestasis of Pregnancy: Prevention

There are no preventive measures to reduce the occurrence of the condition. Some of the measures can reduce the overall risk of cholestasis and helps to reduce the severity of the condition, which include −

• Avoiding oral contraceptives or hormone replacement therapy can reduce the risk to some extent.

• Maintain a healthy balanced diet: a diet high in fiber and low in saturated fats can help support liver health and reduce the risk.

• Drinking plenty of water can help support liver function and prevent dehydration which is known to exacerbate symptoms of cholestasis during pregnancy.

• Regular exercise can help improve overall health and can also support liver function.

Conclusion

Cholestasis of the pregnancy is a condition occurring in pregnant women most commonly in the 3rd trimester, which is characterized by itching without a rash and abnormal liver function test. The condition occurs because of increased bile acid accumulation.

Some women may present with jaundice and pain in the abdomen. Early diagnosis and treatment are important as they can cause severe complications such as preterm labor, fetal distress, and stillbirth.

It is important to inform the mother about the complications she can face related to childbirth, as there is no specific treatment for the condition. Ursodeoxycholic acid, topical creams for a soothing effect, and vitamin k are known to have some influence to reduce the complications of the condition. There are no specific measures to prevent the occurrence of the condition.