Laboratory Studies

Jaundice may occur in 17-75% of cases of intrahepatic cholestasis of pregnancy (ICP) but typically develops 1-4 weeks after the onset of pruritus.^{[24, 45, 46, 47]}Multiple laboratory abnormalities can be seen in ICP. The most specific and sensitive marker of ICP is total serum bile acid (BA) levels greater than 10 micromol/L.^[48]In addition to the elevation in serum BA levels, the cholic acid level is significantly increased and the chenodeoxycholic acid level is mildly increased, leading to elevation in the cholic/chenodeoxycholic acid level ratio.^{[49, 50]}The elevation of aminotransferases associated with ICP varies from a mild increase to a 10- to 25-fold increase.^[48]

Total bilirubin levels are also increased but usually the values are less than 5 mg/dL. Alkaline phosphatase (AP) is elevated in ICP up to 4-fold, but this is not helpful for diagnosis of the disorder since AP is elevated in pregnancy due to production by the placenta. Mild elevation of gamma glutamyltransferase (GGT) is seen with ICP but occurs in fewer than 30% of cases.^[16]If GGT is elevated in cases of ICP, the patient is more likely to have a genetic component of the liver disease.^[15]

BA levels have been suggested to be used for diagnosis and management of ICP but there is no uniform agreement on the criteria for diagnosing ICP. Most laboratories have a turnover time of 3-4 days for BA level results, making management decisions based solely on BA levels difficult. Davis et al asserted that alanine aminotransferase (ALT) is the most sensitive of the conventional liver tests for diagnosis of ICP in the presence of pruritus without a rash.^[51]Palma et al also used ALT and aspartate aminotransferase (AST) values greater than 40 IU/L as partial criteria for the diagnosis of ICP.^[48]

Recommended laboratory studies for the diagnosis of ICP include total serum bile acid levels, cholic acid, chenodeoxycholic acid (to evaluate the cholic/chenodeoxycholic acid ratio), total bilirubin, transaminases, GGT, PT, PTT, and INR. These laboratory studies are used in conjunction with physical examination and symptoms to make a diagnosis of ICP. Once a diagnosis of ICP has been made, total bile acid levels can be followed every 2-3 weeks to guide therapy and timing of delivery. In addition, coagulation studies and transaminase levels should be monitored to measure progression of the disease.

Diagnosis of ICP may thus be made in the presence of pruritus without a rash in the absence of other liver disease in a gravid patient beyond 25 weeks’ gestation with the elevation of serum BA and/or aminotransferases levels.

Procedures

Liver biopsy is not required to make the diagnosis of ICP. However, if liver biopsy is performed, it is common to demonstrate bile plugs without evidence of inflammation and bile pigment in hepatocytes.^[44]

Other Tests

A study by Kremer et al reported that increased serum autotaxin activity represents a highly sensitive, specific and robust diagnostic marker of ICP and can distinguish ICP from other pruritic disorders of pregnancy and pregnancy-related liver diseases.^[52]

Treatment & Management

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Author

Fidelma B Rigby, MD Associate Professor, Department of Obstetrics and Gynecology, Section of Maternal-Fetal Medicine, Virginia Commonwealth University Medical Center

Fidelma B Rigby, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Stacey Ehrenberg-Buchner, MD Fellow in Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan Health System

Stacey Ehrenberg-Buchner, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Suzanne R Trupin, MD, FACOG Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center

Suzanne R Trupin, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, International Society for Clinical Densitometry, AAGL, North American Menopause Society, American Medical Association, Association of Reproductive Health Professionals

Disclosure: Nothing to disclose.

Acknowledgements

George A VanBuren, MD Assistant Professor, Department of Reproductive Biology, Case Western Reserve University School of Medicine

George A VanBuren, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists

Disclosure: Nothing to disclose.