Diagnosis of Intrahepatic Cholestasis of Pregnancy (ICP)
Diagnosis of intraheptic cholestastis of pregnancy

Summary

Diagnosis is based on symptoms and a Total bile acid test

  • Itching can occur weeks before bile acids become elevated. If symptoms continue, you should continue having your levels checked for diagnosis
  • 10 µmol/L is the agreed upon level for elevated bile acids

Diagnosis

Cholestasis of pregnancy is diagnosed based upon symptoms and elevated Total bile acids on blood work. Your doctor will rule out other causes of liver dysfunction, as in some patients there is an underlying cause to the elevated bile acids.

Cases that occur earlier in pregnancy or are more severe are more likely to have an underlying cause. Your physician will take a history of your symptoms, review your medical and family history and perform an examination for diagnosis. Blood work will then be sent for diagnosis.

Serum Bile Acids

Serum bile acid testing is the most accurate way to diagnose intrahepatic cholestasis of pregnancy.  This testing can be performed at any point in the day and, based on recent recommendations, does not require fasting.

There are a number of different bile acid tests, depending on the laboratory, and these all can be used for diagnosis. Bile acids over 10 µmol/L indicate ICP.  Prior studies have shown that levels of bile acids above 10 µmol/L are consistent with a diagnosis of ICP, even on tests which show this to be within normal range. Fractionated bile acid tests can be used to diagnose at a lower level, as these tests measure only select bile acids.

Bile acid results in the United States can take anywhere between 36 hours-10 days for results to return, as these are specialized tests that are only performed in a few laboratories in the country.

Normal bile acids do not rule out an eventual diagnosis of cholestasis.  Itching is often related to a chemical known as lysophosphatidic acid and not directly to the elevation of the bile acids. Studies have shown that itching can occur even a few weeks prior to an elevation in blood bile acid levels. If you continue to have itching, you should be retested as long as your symptoms persist.

Bile acid levels should also be followed in pregnancy even after diagnosis. Prior studies have shown a greater risk for pregnancy complications with higher bile acid levels. Mild cases of ICP have bile acids below 40 µmol/L. Severe cases of ICP have bile acids above 40 µmol/L. Complications such as preterm labor, respiratory issues after birth, and meconium staining of the amniotic fluid occur at greater rates with bile acids over 40.  A recent analysis of a large number of cholestasis pregnancies also found that most pregnancy complications occur with bile acids over 100, and bile acids over this level require a more aggressive management plan. There is no consensus for how often bile acids should be measured, but it is recommended that they be followed, especially near the end of pregnancy, so that delivery timing can be planned.

Please visit the Diagnostic Testing page for additional information on the different types of bile acid tests and their reference ranges.

Liver Function Tests (or Complete Metabolic Panel)

Approximately 60% of people with Intrahepatic Cholestasis of Pregnancy will have elevated liver functions during their pregnancies. A normal liver function panel does not rule out the disorder as bile acid testing still needs to be performed. However, liver function results return within hours instead of days, which can provide your doctor with information more promptly.

There are many components to liver function testing. The following are important to note regarding Intrahepatic Cholestasis of Pregnancy.

  • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST): These enzymes are released when liver cells are damaged and can be elevated in a pregnancy complicated by cholestasis. The ALT is the most sensitive in aiding in the diagnosis of Intrahepatic Cholestasis of Pregnancy, followed by AST. Elevation of either or both of these may indicate that you have ICP, but there are also some other disorders that can cause these enzymes to be elevated, and therefore bile acid levels are still needed for diagnosis.
  • Alkaline Phosphatase: Alkaline phosphatase is produced by the placenta and is normally elevated in pregnancy. Therefore, elevation of ALP/ALK (alkaline phosphatase) alone does not provide an indication of Intrahepatic Cholestasis of Pregnancy.
  • Bilirubin: Bilirubin is elevated in a small minority of cases (estimated to be less than 10%). Elevated bilirubin may also lead to jaundice. When bilirubin is elevated it is generally only mildly elevated.
  • Other tests included in a complete metabolic panel are not specific to ICP, but if they are abnormal discuss with your doctor what this may indicate.

Understand the Uncommon Nature of Intrahepatic Cholestasis of Pregnancy

Since Intrahepatic Cholestasis of Pregnancy is a rare disease, estimated to affect approximately 6,000 people in the United States annually, some doctors may not have a working knowledge of the disease. In practice, physicians will only rarely have patients with the condition and therefore may not know the most current guidelines for diagnosis and management.

You may need to provide information to your physician for proper diagnosis. ICP Care has a concise and comprehensive overview for providers  ***HERE. Recent guidelines from SMFM have also been developed that clarify many of the points in diagnosis and management and can be given to your physician. Your OB physician may also refer you to an OB who specialises in high risk pregnancies called an Maternal-Fetal Medicine Specialist (MFM).

Working to Spread Intrahepatic Cholestasis of Pregnancy Awareness

While it may be frustrating that your doctor may be unaware of many of the intricacies of management of a pregnancy complicated by ICP, many organizations are working to spread awareness and education. We honor each baby lost to ICP and support the mothers who have experienced this tragic loss.

We are passionate about empowering every person with ICP to have the resources needed to advocate for proper testing, medication and early delivery – to save every baby’s life.

Learn more about ICP Care’s efforts to spread awareness or donate to the cause.

References
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  2. Stieger B, et al: Drug- and Estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology 2000 Feb;118(2):422-30. http://www.ncbi.nlm.nih.gov/pubmed/10648470
  3. Abu-Hayyeh S, Ovadia C, Lieu T, et al: Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum. Hepatology, 2015;doi:10.1002/hep.28265. http://www.ncbi.nlm.nih.gov/pubmed/26426865
  4. Wongjarupong N, et al: Never Too Soon: An Unusual Case of Intrahepatic Cholestasis of Pregnancy at Five Weeks Gestation. Cureus. 2020 Sep; 12(9): e10540. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574978/
  5. Bacq Y, Sapey T, Brechot MC, et al: Intrahepatic cholestasis of pregnancy: a French prospective study. Hepatology 1997;26:358-364 http://www.ncbi.nlm.nih.gov/pubmed/9252146
  6. Pacella G, Salsi G, Archangeli T, et al: The impact of assisted reproductive technology and chorionicity in twin pregnancies complicated by obstetric cholestasis. J Matern Fetal Neonatal Med, 2015; doi:10.3109/14767058.2015.1051954 http://www.ncbi.nlm.nih.gov/pubmed/26043641
  7. Gonzalez MC, Reyes J, Arrese M, et al: Intrahepatic cholestasis of preganancy in twin pregnancies. J Hepatology 1989;9:84-90 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678574/
  8. Reyes H, Maez ME, Gonzalez MC, et al: Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile. J Hepatology 2000;32:542-549 http://www.ncbi.nlm.nih.gov/pubmed/10782901