Clinical Review

Managing intrahepatic cholestasis of pregnancy

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For the pregnant patient experiencing intense itching, a diagnosis of ICP signals an increased risk of stillbirth, but serum bile acid measurements can help guide management, including timing of delivery



CASE Pregnant woman with intense itching

A 28-year-old woman (G1P0) is seen for a routine prenatal visit at 32 3/7 weeks’ gestation. She reports having generalized intense itching, including on her palms and soles, that is most intense at night and has been present for approximately 1 week. Her pregnancy is otherwise uncomplicated to date. Physical exam is within normal limits, with no evidence of a skin rash. Cholestasis of pregnancy is suspected, and laboratory tests are ordered, including bile acids and liver transaminases. Test results show that her aspartate transaminase (AST) and alanine transaminase (ALT) levels are mildly elevated at 55 IU/L and 41 IU/L, respectively, and several days later her bile acid level result is 21 µmol/L.

How should this patient be managed?

Intrahepatic cholestasis of pregnancy (ICP) affects 0.5% to 0.7% of pregnant individuals and results in maternal pruritus and elevated serum bile acid levels.1-3 Pruritus in ICP typically is generalized, including occurrence on the palms of the hands and soles of the feet, and it often is reported to be worse at night.4 Up to 25% of pregnant women will develop pruritus during pregnancy but the majority will not have ICP.2,5 Patients with ICP have no associated rash, but clinicians may note excoriations on exam. ICP typically presents in the third trimester of pregnancy but has been reported to occur earlier in gestation.6

Making a diagnosis of ICP

The presence of maternal pruritus in the absence of a skin condition along with elevated levels of serum bile acids are required for the diagnosis of ICP.7 Thus, a thorough history and physical exam is recommended to rule out another skin condition that could potentially explain the patient’s pruritus.

Some controversy exists regarding the bile acid level cutoff that should be used to make a diagnosis of ICP.8 It has been noted that nonfasting serum bile acid levels in pregnancy are considerably higher than those in in the nonpregnant state, and an upper limit of 18 µmol/L has been proposed as a cutoff in pregnancy.9 However, nonfasting total serum bile acids also have been shown to vary considerably by race, with levels 25.8% higher in Black women compared with those in White women and 24.3% higher in Black women compared with those in south Asian women.9 This raises the question of whether we should be using race-specific bile acid values to make a diagnosis of ICP.

Bile acid levels also vary based on whether a patient is in a fasting or postprandial state.10 Despite this variation, most guidelines do not recommend testing fasting bile acid levels as the postprandial state effect overall is small.7,9,11 The Society for Maternal-Fetal Medicine (SMFM) recommends that if a pregnancy-specific bile acid range is available from the laboratory, then the upper limit of normal for pregnancy should be used when making a diagnosis of ICP.7 The SMFM guidelines also acknowledge, however, that pregnancy-specific values rarely are available, and in this case, levels above the upper limit of normal—often 10 µmol/L should be considered diagnostic for ICP until further evidence regarding optimal bile acid cutoff levels in pregnancy becomes available.7

For patients with suspected ICP, liver transaminase levels should be measured in addition to nonfasting serum bile acid levels.7 A thorough history should include assessment for additional symptoms of liver disease, such as changes in weight, appetite, jaundice, excessive fatigue, malaise, and abdominal pain.7 Elevated transaminases levels may be associated with ICP, but they are not necessary for diagnosis. In the absence of additional clinical symptoms that suggest underlying liver disease or severe early onset ICP, additional evaluation beyond nonfasting serum bile acids and liver transaminase levels, such as liver ultrasonography or evaluation for viral or autoimmune hepatitis, is not recommended.7 Obstetric care clinicians should be aware that there is an increased incidence of preeclampsia among patients with ICP, although no specific guidance regarding further recommendations for screening is provided.7


Continue to: Risks associated with ICP...


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