Intrahepatic Cholestasis of Pregnancy

What is intrahepatic cholestasis of pregnancy (ICP)?

Some women suffer from an itchy skin during pregnancy. This is usually harmless but it may be a sign of a more serious liver condition called obstetric cholestasis (also known as intrahepatic cholestasis of pregnancy or ICP). This type of liver damage may occur during the second or third trimester of pregnancy.

The risks associated with ICP include an increased risk of premature birth and, before the advent of modern obstetric and new born care, a risk of still births.

ICP also raises the risk of bleeding from the womb in the first few days after the birth. This is called postpartum haemorrhage.

These risks make it important to distinguish between a harmless mild itch and a more serious obstetric cholestasis. 1-5

Symptoms of intrahepatic cholestasis of pregnancy (ICP)

ICP commonly shows up with symptoms of itching. Normally around 1 in 5 women complain of itching during pregnancy, especially in the later and more advanced stages of pregnancy.

The cause in most of these cases remains unexplored. It is thought that the itching is caused in normal pregnancies due to the effect on the liver of high levels of hormones or even the stretching of the skin over the abdomen as the pregnancy progresses.

Usually a lotion (e.g. calamine lotion) with soothing elements is prescribed for this itching and no pills or other drug treatments are needed.

Mild itching is common in pregnancy because of the increased blood supply to the skin. However, when a person has obstetric cholestasis there may be other more serious symptoms like:

  • intense itching especially bad at night on the arms, legs, palms and soles

  • tiredness

  • difficulty sleeping

  • loss of appetite

  • nausea even at later stages of pregnancy

  • and importantly, jaundice

Jaundice is detected clinically when there is yellowing of whites of eyes and skin. These symptoms may go unnoticed in many women.

Causes of intrahepatic cholestasis of pregnancy (ICP)

ICP is caused when there is a rise of the pigment called bilirubin in blood. Bilirubin is made by the liver and is formed when old red blood cells die and their iron containing pigment haemoglobin is converted to bilirubin.

Normally bilirubin passes into the bile (a yellow liquid released from the gall bladder into the digestive tract) and helps in digestion.

Genetic and hormonal changes play a role in causing obstetric cholestasis. The excess bilirubin in blood is carried around to various organs and tissues and leads to deposition and irritation under the skin causing itching.

Excess bile in the mother’s blood may also put the baby at risk. If uncared for as many as 60 per cent of cases lead to a premature birth of the baby and the fetus is jeopardized with fetal distress in up to 33 per cent.

Still birth may be seen in 2% cases. Obstetric cholestasis doesn't usually cause long-term damage to the liver.

Frequency of intrahepatic cholestasis of pregnancy (ICP)

In Europe, obstetric cholestasis occurs in about 0.1 to 1.5 per cent of pregnancies. In England, about one in 160 women (or less than 1%) are affected with obstetric cholestasis. It is more common among twin and triplet pregnancies.

This condition is more common in some South American countries, such as Bolivia and Chile. There it may affect as many as one in six pregnancies. In fact, among the native Araucanian population in Chile, as many as 28% of all pregnancies, are affected.

Obstetric cholestasis is also slightly more common among women of Indian-Asian or Pakistani origin with three in 200 (1.5%) of women affected. These facts support a genetic cause.

Chances of recurrence of the condition in subsequent pregnancies vary from 40 to 90 per cent. All women who have had one episode of ICP during as pregnancy should be monitored carefully on their subsequent pregnancies.

These women are also advised against using contraceptive pills as they raise the risk of liver damage.

Causes of intrahepatic cholestasis of pregnancy (ICP)

Intrahepatic cholestasis or pregnancy (ICP also known as obstetric cholestasis) is usually seen as itching during later stages of pregnancy. In mild cases it is not harmful but severe cases may lead to fetal complications like premature birth, fetal distress (vital signs of the baby may be jeopardized) at birth and also the risk of still birth. 1-6

Bilirubin, bile and intrahepatic cholestasis of pregnancy (ICP)

The exact cause of ICP is not clear. Bile is a yellow-green fluid that is produced in the liver. It contains a green pigment bilirubin.

Bilirubin is the breakdown product of old red blood cells and contains a modified form of the haemoglobin present in the dead RBCs.

Bile also contains chemicals to aid digestion and helps in excretion of the waste products via faeces. Bile helps in digestion of fats and this is one of its most important roles in the body.

The bile acts as a detergent and breaks the fat into very small droplets so that it can be absorbed from food from the gut.

Certain vitamins like vitamin A, D, E and K are absorbed only via fat. Bile helps in absorption of these vitamins as well.

Why do bilirubin levels rise in intrahepatic cholestasis of pregnancy (ICP)?

In ICP the levels of bilirubin rises in blood. The exact cause is unknown but it is speculated that hormones might play a role.

During pregnancy the levels of hormones (estrogen and progesterone) rises in blood. The liver is probably unable to cope with these levels during pregnancy. This causes the levels of bile salts to rise in blood.

The bile salts get deposited under the skin and lead to itching and the yellow pigment leads to jaundice in some women with ICP. The transfer of bile salts across the placenta can affect the baby as well.

Genetic theories regarding intrahepatic cholestasis of pregnancy (ICP)

Some theories suggest the ICP may have a genetic cause. The functions and structures of the body are determined by the blue prints within the cells called the genes. These are inherited from parents. When there is an abnormality in the gene called a “mutation”.

Although the exact mutations that lead to ICP are as yet unknown, ICP is still seen to be running in families. It is speculated the these faulty genes may interfere with the removal of the breakdown products of the female hormones estrogen and progesterone and as the levels of these hormones rise in blood during pregnancy the risk of ICP rises.

Frequency of intrahepatic cholestasis of pregnancy (ICP)

In Europe, obstetric cholestasis occurs in about 0.1 to 1.5 per cent of pregnancies. The risk is greater in twin and triplet pregnancies, following in vitro fertilisation and in pregnant women over 35 years of age.

The number affected among South Asian women is slightly increased (1.5%) and much higher still in South American countries and in Chile and Scandinavia (over 2%).

Among the native Araucanian population in Chile, nearly 28 per cent of pregnancies are affected.

This could mean that there may be a genetic cause along with the environment that raises the risk of ICP. Further the risk of recurrence in subsequent pregnancies varies from 40 to 90 per cent.

Environmental factors and intrahepatic cholestasis of pregnancy (ICP)

Environmental factors such as diet and seasonal variations are also implicated in causation of ICP. Presence of gall bladder stones and Hepatitis C also raises the risk of ICP. However, these causes are usually accompanied by a genetic predisposition in most cases.

Symptoms of intrahepatic cholestasis of pregnancy (ICP)

Intrahepatic cholestasis (ICP, also known as obstetric cholestasis) is a condition of pregnancy that commonly manifests as itching and in rare cases jaundice.

It is important to evaluate the cases with symptoms of itching especially at later stages of pregnancy for ICP since this condition may be harmful for the unborn baby.

The symptoms of the condition intrahepatic cholestasis of pregnancy include itching, jaundice and so forth. 1-7

Itching in pregnancy and Intrahepatic cholestasis of pregnancy (ICP)

Some amount of itching is common during pregnancy. This is due to the increased blood supply to the skin layers in normal pregnancies.

In addition, the stretching of the skin over the abdomen as the baby grows also leads to itching of the skin. This is usually mild and can be treated using soothing lotions like Calamine lotion etc. Itching is seen in 1 in 5 pregnancies normally.

Itching seen in obstetric cholestasis is more intense. It usually begins after 25 to 28 weeks of pregnancy. There may be severe itching which is especially worse at nights and affects the arms, legs, soles and palms. It may also affect face, back, chest and breasts.

The patient may present with damage and scratch marks over the skin. These are called excoriations and may be complicated with bacterial infections as well.

The itching sites may sometimes bleed due to excessive scratching. Due to chronic itching the nails of the patient may also appear shiny and smooth.

The itching is generally worse at night and interferes with sleep.

The itching is present for days or weeks before the blood tests reveal abnormalities in the liver function tests.

The itching often resolves after giving birth and there are no long term health problems.

Jaundice and Intrahepatic cholestasis of pregnancy (ICP)

The increased build-up of bilirubin leads to jaundice, dark colored urine and pale white clay colored stool. This may be seen in very few severe cases of ICP.

At least 1 in five women with ICP may go on to develop mild jaundice. This is manifested as yellowish discoloration of skin, nail beds and whites of the eyes.

Other symptoms of Intrahepatic cholestasis of pregnancy (ICP)

In addition to itching and jaundice, other symptoms include:

  • general weakness, feeling of unwell and tiredness and easy fatigability
  • there may be loss of appetite - some women complain of nausea and vomiting as well

Risks to the baby

The risks to the baby include birth before due dates (premature birth), risk of derangement of vital signs (fetal distress) during labor and a small risk of still birth.

Long-term risks of Intrahepatic cholestasis of pregnancy (ICP)

Risks of long term liver problems after birth of the baby is low.

Diagnosis of intrahepatic cholestasis of pregnancy (ICP)

Women who develop obstetric cholestasis (also known as intrahepatic cholestasis of pregnancy) manifest with symptoms of intense itching.

Since itching is a normal feature especially towards the end of the pregnancy, ICP may often be missed. However, it is important to diagnose the condition since ICP may lead to harmful effects in the baby. This includes fetal distress at labor (derangements of fetal vital parameters increasing risk of new born complications and death), premature birth (birth before the due date leading to a decreased chances of survival) and even still birth and fetal death.

Diagnosis and initial assessment includes asking questions about previous history of ICP, ruling out other conditions and so forth. 1-5

Previous history of intrahepatic cholestasis of pregnancy (ICP)

All women who have had a previous history of obstetric cholestasis in a previous pregnancy need to be evaluated for ICP carefully in subsequent pregnancies.

Patients who have a family member with a similar condition (commonly a first degree relative like a mother, grandmother or a sister) need careful evaluation.

Some ethnic groups like those of Asian or South American, Scandinavian, Bolivian or from Chile need to be evaluated for itching during pregnancies. These ethnic groups and races are at a higher risk of this condition.

All these high-risk individuals need to be managed by a consultant-led team and should deliver at a hospital.

Ruling out alternative diagnoses

Causes of liver dysfunction apart from ICP including gallstones, hepatitis, viral infections with Epstein Barr virus, cytomegalovirus, hepatitis A, B, C or E, side effects of medications, preeclampsia (high blood pressure and complications of pregnancy) and fatty liver disease of pregnancy need to be rule out before diagnosing ICP.

The skin is also inspected for other skin conditions like eczema or parasitic infestations like scabies that may also lead to itching.

Blood tests for intrahepatic cholestasis of pregnancy (ICP)

An initial test is a routine blood test. This also includes the liver function test. Liver function tests (LFT) looks at levels of bilirubin and enzymes that show the liver health. These include Alkaline phoshphatase, ALT (Alanine transaminase) and AST (aspartate Transaminase), gamma-glutamyltransferase (gamma-GT) etc.

The LFT should be monitored weekly in suspected cases of ICP. In ICP the levels of bilirubin may be infrequently raised but the levels of liver enzymes may be raised. It should be kept in mind that the upper limit of normal levels of liver parameters is 20% lower than non-pregnant levels, throughout pregnancy.

Interpretation of the results should be made accordingly. LFTs may be conducted weekly if normal, or bi-weekly if abnormal. They may be conducted bi-weekly if serum bile acids are increasing, or are ≥40μmol/L.

Coagulation studies for intrahepatic cholestasis of pregnancy (ICP)

Coagulation studies may be prescribed if abnormal LFTs are seen. Prolonged prothrombin times may reflect Vitamin K deficiency. Since Vitamin K is a fat soluble vitamin that requires normal bile functions for absorption there may be vitamin K deficiency.

Ultrasound scan of the liver

An ultrasound scan of the liver may be prescribed. This is the safest diagnostic method that can be prescribed during pregnancies as X rays and CT scans etc. cause a raised risk of radiation exposure to the fetus.

An ultrasound scan helps to look at liver abnormalities and presence of gall bladder stones.

Fetal surveillance and intrahepatic cholestasis of pregnancy (ICP)

Fetal surveillance is performed to check for the fetal wellbeing. This includes a baseline ultrasound scan to detect fetal growth. Cardiotocograph monitoring (CTG) looks at the heart health of the fetus.

Monitoring suspected cases of intrahepatic cholestasis of pregnancy (ICP)

Visits to the doctor or antenatal visits are schedules every second week in suspected cases.