What is Intrahepatic Cholestasis of Pregnancy (ICP)?
ICP is a group of liver disorders specific to pregnancy which interfere with the flow of bile. Bile is a substance produced by the cells of the liver to aid in digestion of fats. During normal liver function, the bile which is produced is transported out of the cells and into the bile duct by special pumps. During Intrahepatic Cholestasis of Pregnancy, the cells are unable to transport the bile out of the cells normally, which leads to bile acids building up in the blood. Elevated bile acids in the blood are associated with increased risk to the unborn baby. It is important to note that Intrahepatic Cholestasis of Pregnancy is not a single disorder, but a heterogeneous group of many different disorders which all lead to elevated bile acids. This means that the disorder presents very differently in different affected women. About 80% of cases are diagnosed in the third trimester, about 10% in the second trimester, and about 10% in the first trimester, with documented cases as early as 8 weeks pregnant.
What are the symptoms of Intrahepatic Cholestasis of Pregnancy (ICP)?
- Itching The most commonly noticed symptom of obstetric cholestasis of pregnancy is itching which can be moderate to severe. Itching due to Intrahepatic Cholestasis of Pregnancy does not typically respond to antihistamines. The itching is usually not associated with a rash, but a rash can, in some cases, develop as a result of scratching. The severity and location of itching can vary greatly. The most common location of itching is hands and feet, but some women experience itching on the arms and legs, the scalp, or all-over itching. Some women with the disorder itch everywhere except the hands and feet. In the majority of cases, itching is the only symptom reported. Other important symptoms of cholestasis to be aware of include:
- Dark urine
- Pale Stool
- Right upper quadrant pain
- Mild depression
- Pre-term labor
- Nausea/lack of appetite
- Rarely jaundice
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What causes Intrahepatic Cholestasis of Pregnancy (ICP)?
Intrahepatic Cholestasis of Pregnancy is caused by a combination of factors including:
- Genetics – Research has identified several genetic mutations which are associated with ICP. Not all genes have been identified. Many of these mutations cause defects in the bile salt export protein (BSEP), which is responsible for moving bile out of liver cells. Intrahepatic Cholestasis of Pregnancy can be considered a genetic disorder, even when there is no family history of the disorder. Mothers, sisters, and daughters of women affected by Intrahepatic Cholestasis of Pregnancy are at higher risk of developing the disorder, though it is not guaranteed.
- Hormones – The initiation of ICP during pregnancy is influenced by the high levels of the pregnancy hormones estrogen and progesterone, which are responsible for maintaining the pregnancy. The high levels of hormones further interfere with the liver’s ability to transport bile acids.
- Environmental Factor– Intrahepatic Cholestasis of Pregnancy recurs in future pregnancies in 70% of cases (severe cases may be as high as 90%), which indicates that environmental factors also play a role. It is not entirely understood why ICP sometimes does not recur, but research has found evidence that seasonal influences as well as improved nutrition may play a role. More women are diagnosed with Intrahepatic Cholestasis of Pregnancy in winter months, and selenium deficiency has been linked to the disorder, though it is not known if this is a cause or effect of ICP.
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What is the treatment for Intrahepatic Cholestasis of Pregnancy (ICP)?
- Early Delivery – Active management of Intrahepatic Cholestasis of Pregnancy reduces the risks associated with the disorder to that of an uncomplicated pregnancy, but there is no cure for ICP except delivery. Active management includes, most importantly, the medicine Ursodeoxycholic Acid (also known as UDCA, Actigall, Ursodiol, or Ursofalk), and early delivery. In most cases, delivery will occur at 36 0/7-37 0/7 weeks gestation as recommended by the American College of Obstetrics and Gynecology (ACOG) in their committee opinion published in February 2019. However, newer guidelines from the Society for Maternal Fetal Medicine (SMFM) allow for a slightly larger delivery window of 36 0/7 to 39 0/7 for mild cases. Severe cases with bile acids reaching 40 should also be delivered in the earliest portions of this window. Very severe cases with total bile acids over 100 are recommended to deliver at 36 and 0/7 exactly, or earlier with other complicating factors.
- Medication – Ursodeoxycholic Acid is considered the frontline treatment for the disorder. It has been proven safe in meta-analysis for both mother and baby, and research has identified many ways in which it potentially can provide a safer environment and protect the baby against harmful effects of bile acids until delivery can occur. It is a naturally occurring substance in the body, and has been proven to reduce the total bile acids in the bloodstream of women affected by Intrahepatic Cholestasis of Pregnancy. Sometimes other treatments will be used in conjunction with Ursodeoxycholic Acid with the aim of reducing maternal symptoms.
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What are the risks associated with Intrahepatic Cholestasis of Pregnancy (ICP)?
Intrahepatic Cholestasis of Pregnancy puts affected pregnancies at higher risk for several complications. With active management it is believed that the risk of stillbirth is similar to that of an uncomplicated pregnancy (less than 1%).
- Pre-term labor/delivery
- Fetal Distress
- Meconium Passage
- Respiratory distress syndrome (RDS)
- Failure to establish breathing (sometimes called fetal asphyxia)
- Maternal hemorrhage
- Stillbirth (Intrauterine Fetal Demise/IUFD)
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What happens after the birth?
Bile levels can return to normal after 6 to 12 weeks, but should be monitored. For some women, ICP can lead to a higher risk for liver disease. It is important to have a follow up plan for postpartum monitoring. Studies have shown, Intrahepatic Cholestasis of Pregnancy recurs in future pregnancies in up to 70% (severe cases may be as high as 90%) of women who have had ICP. Pregnant women having their second child should be monitored closely within the first trimester of pregnancy.