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Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"

Intrahepatic cholestasis of pregnancy is a complex disorder. It is believed to be caused by a combination of genetic, hormonal, and environmental factors. Risk factors for developing intrahepatic cholestasis of pregnancy include underlying liver disease and a form of diabetes called gestational diabetes that occurs during pregnancy. Being pregnant with more than one baby or having a history of intrahepatic cholestasis of pregnancy also increases the risk of developing this condition. Sometimes, more than one person in a family has this condition.

Variants in several different genes are believed to increase the risk of developing intrahepatic cholestasis of pregnancy. Many of these genes provide instructions for making proteins that help with the production (synthesis) or transportation of bile acids. In most cases, the variants that increase the risk of developing intrahepatic cholestasis of pregnancy are present in only one of the two copies of the gene,

The largest genetic contributor is the ABCB4 gene; variants in this gene have been found in up to 25 percent of women with intrahepatic cholestasis of pregnancy. The ABCB4 gene provides instructions for making a protein that helps move certain fats called phospholipids across cell membranes before releasing them into bile. Phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Many of the variants in the ABCB4 gene that have been found in women with intrahepatic cholestasis of pregnancy cause one protein building block (amino acid) to be substituted for another. A few ABCB4 gene variants cause the cell to produce an abnormally short protein. Variants in other genes have been found to have a more limited contribution to the risk of developing intrahepatic cholestasis of pregnancy.

Even with these variants, enough protein is still available in most cases to move an adequate amount of phospholipids out of liver cells to bind to bile acids. The added stress on the liver during pregnancy, however, contributes to the buildup of bile acids. Toxic levels of bile acids can impair liver function, including the regulation of bile flow.

MedlinePlus Genetics: Causes

","key":"forms","title":"What causes Intrahepatic cholestasis of pregnancy?"},{"bodyHtml":"

Severe itchiness (pruritus) is typically one of the first symptoms of intrahepatic cholestasis of pregnancy. The itchiness usually begins on the palms of the hands and the soles of the feet before spreading to other parts of the body. Women with intrahepatic cholestasis of pregnancy have a buildup of bile acids in the blood. Bile acids are a component of bile and are produced when the liver processes cholesterol. Bile acid levels in the blood are normally low, but they can increase in people with liver disease.

Occasionally, women with intrahepatic cholestasis of pregnancy have yellowing of the skin and whites of the eyes (jaundice). Women with intrahepatic cholestasis of pregnancy typically do not continue to have signs and symptoms of the condition after having the baby, though they may have an increased risk of developing disorders of the gallbladder, liver, or heart later in life.

Intrahepatic cholestasis of pregnancy can cause problems for the baby. This condition is associated with an increased risk of premature delivery and breathing problems in the newborn (meconium aspiration). Some infants born to women with intrahepatic cholestasis of pregnancy experience a slow heart rate and a lack of oxygen during delivery (fetal distress). Women with higher levels of bile acids in their blood also have an increased risk of stillbirth.

Source: MedlinePlus Genetics

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