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.

Further Reading

Last Updated: May 31, 2019

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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