Definition

Intrahepatic cholestasis of pregnancy is a liver condition that occurs in pregnant women. Cholestasis refers to a disruption in the bile secretion produced by the liver. This condition can lead to the accumulation of bile in the liver, affecting its function. Because this condition occurs within the liver, it is termed intrahepatic cholestasis.

Intrahepatic cholestasis of pregnancy typically occurs during the second trimester or around the beginning of the third trimester. The flow of accumulated bile usually returns to normal after childbirth, and the symptoms experienced by the mother typically resolve. However, symptoms may recur in subsequent pregnancies.

The incidence of new cases of intrahepatic cholestasis of pregnancy is reported to be between 0.2% to 2% of pregnancies, with higher prevalence in South America and North Europe. In the United States, the incidence is approximately 0.2-0.3% of all pregnancies.

Causes

The exact cause of intrahepatic cholestasis of pregnancy is currently unknown. It is believed to be a result of a combination of factors, including genetic, hormonal, and environmental factors.

The incidence of intrahepatic cholestasis of pregnancy is thought to be linked to pregnancy hormones. During pregnancy, estrogen levels increase, peaking towards the end of the second trimester. In women genetically predisposed to intrahepatic cholestasis, the elevated estrogen levels may slow down the flow of bile from the liver to the gallbladder. Disruption in this flow can lead to the accumulation of bile in the liver. Some of this bile may enter the bloodstream, causing symptoms such as changes in urine color, yellowing of the skin, and itching.

Environmental factors are also considered to play a role in intrahepatic cholestasis of pregnancy. The condition is more common in women with low selenium mineral and vitamin D levels.

Risk factor

Doctors will assess whether you have risk factors that may contribute to intrahepatic cholestasis of pregnancy. Some of the identified risk factors include:

• Family History: If there is a history of intrahepatic cholestasis of pregnancy among close family members.
• Previous History: If you have experienced intrahepatic cholestasis of pregnancy in a previous pregnancy.
• Liver Organ Damage: A history of liver organ damage.
• Chronic Hepatitis C Infection: Having a chronic infection with hepatitis C.
• In Vitro Fertilization (IVF): A history of undergoing in vitro fertilization.
• Multiple Pregnancies: Carrying two or more babies at once during a pregnancy.
• Winter Season Residence: Living in a region with a winter season.
• Low Selenium and Vitamin D Levels

Symptoms

Intrahepatic cholestasis of pregnancy (ICP) typically manifests its symptoms during the third trimester of pregnancy or even earlier. The most prominent and distressing symptom is severe itchiness, which can occur before visible skin changes. It often begins on the palms and soles and may later spread to other areas of the skin.

Other symptoms of ICP can include:

• Jaundice: Yellowing of the skin or eyes.
• Gallbladder Stones: Studies suggest an increased risk of gallbladder stones in women with ICP.
• Dark Urine: Changes in urine color.
• Fatigue: Feeling unusually tired or weak.
• Loss of Appetite: Decreased desire for food.
• Pale Stool: Light-colored stool.
• Pain in the Upper Right Abdomen: Discomfort or pain in the upper right side of the abdomen.
• Nausea and Vomiting: Feeling nauseous and vomiting.

It's important to note that not all women with ICP will experience the same symptoms, and the severity of symptoms can vary. Additionally, ICP has been associated with adverse effects on the baby, including an increased risk of premature birth, stillbirth, slow heartbeat, and lack of oxygen during birth. 

Diagnosis

The diagnosis of intrahepatic cholestasis of pregnancy is established through a medical interview, physical examination, and diagnostic tests, if available and necessary.

Medical Interview

During the medical interview for suspected intrahepatic cholestasis of pregnancy (ICP), the doctor will inquire about the symptoms experienced. It's crucial to provide detailed information about the symptoms and when they started. This information is vital for establishing a specific medical diagnosis. The doctor may ask about your medical history, family history, and any history of prior treatments.

If ICP is suspected following the medical interview, the doctor will proceed with a physical examination and may recommend diagnostic tests to confirm the diagnosis and assess the severity of the condition. 

Physical Examination

During the physical examination for intrahepatic cholestasis of pregnancy, doctors will assess clinical signs based on the reported symptoms. Palpation may reveal tenderness or pain in the upper right area of the abdomen. Additionally, jaundice, characterized by yellowing of the skin or eyes, can be observed during the examination.

Diagnostic test

The diagnosis of intrahepatic cholestasis of pregnancy (ICP) involves various diagnostic tests, including laboratory tests to assess liver function and bile metabolism. Some of the specific laboratory tests that can help establish the diagnosis of ICP include:

• Total Serum Bile Acids: Elevated levels of bile acids in the blood are a characteristic finding in ICP.
• Liver Function Tests (e.g., SGOT and SGPT) measure the levels of enzymes released by the liver into the bloodstream. Elevated levels may indicate liver dysfunction.
• Alkaline Phosphatase
• Blood Bilirubin: Elevated bilirubin levels may suggest impaired liver function or bile flow.
• Prothrombin Time: This test assesses blood clotting function, and abnormalities may be seen in liver diseases.
• Vitamin K Levels: Vitamin K deficiency can occur.

Management

Intrahepatic cholestasis of pregnancy (ICP) management involves a combination of home-based strategies and medical interventions. Individuals can alleviate symptoms at home by applying cold compresses to itchy skin areas and opting for loose, soft clothing. However, seeking prompt medical attention is crucial for accurate diagnosis and proper care. If ICP is confirmed, healthcare providers may prescribe Ursodeoxycholic Acid (UDCA) to reduce bile acid levels and alleviate symptoms, ensuring the safety of both mother and baby. Early delivery before 37 weeks may be advised depending on the severity and gestational age.

Complications

Intrahepatic cholestasis of pregnancy (ICP) can lead to complications for both the mother and the baby. The mother may experience severe itchiness, which, if persistent, can increase the risk of skin infections. On the baby's side, there is an elevated risk of stillbirth, premature birth, and the potential need for hospitalization in the neonatal intensive care unit (NICU). These complications arise because bile, affected by ICP, may flow from the mother to the baby through the placenta. Additionally, bile accumulation in the amniotic fluid can contribute to further complications.

Prevention

There are currently no specific and guaranteed preventive measures to avoid intrahepatic cholestasis of pregnancy (ICP). However, certain lifestyle practices may contribute to reducing the risk of developing ICP:

• Consuming a balanced nutritious die
• Avoiding smoking
• Avoiding alcohol consumption.
• Exercising regularly
• Adequate rest

When to see a doctor?

Suppose you notice a deterioration in your current symptoms, such as worsening itchiness, increased fatigue, or difficulty eating due to vomiting and nausea. In that case, it is advisable to seek consultation with an internal medicine doctor. The doctor will conduct a thorough medical interview and physical examination and may suggest additional diagnostic tests to identify the underlying condition or disease, providing you with the appropriate and necessary treatment. 

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