para>The most severe complication is fetal death.
Fetal mortality has been reported as high as 20% but averages 1.5-7% (3).
DIAGNOSIS
HISTORY
Intense pruritus beginning in the 2nd or 3rd trimester of pregnancy accompanied by elevated serum bile acid levels
- Pruritus may localize to the palms and soles or may be generalized (7).
- Skin excoriations may result from the itching, but the condition is not typically heralded by a rash.
- Symptoms and lab abnormalities resolve within 3 weeks of delivery.
PHYSICAL EXAM
- Primary skin lesions are absent.
- Skin excoriations are possible (1).
- 20% of patients develop jaundice (1).
DIFFERENTIAL DIAGNOSIS
- Scabies
- Atopic dermatitis
- Allergic reaction
- Pruritic urticarial papules and plaques of pregnancy
- Prurigo of pregnancy
- Pemphigoid gestationis
- Impetigo herpetiformis
- Pruritic folliculitis of pregnancy
- HELLP syndrome
- Preeclampsia
- Primary biliary cirrhosis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Serum bile acid levels ≥10 μmol/L is the most sensitive test for ICP (2,7)[B].
- A significant increase in fetal death occurs for every 10 μmol/L increase in maternal serum bile acid levels (2)[B].
- Adverse fetal outcomes are statistically significant at serum bile acid levels ≥40 μmol/L (8)[B].
- Serum AST, ALT, and bilirubin levels may be elevated (7).
- Hepatitis C antibody testing should be performed to screen for concurrent infection (7).
Follow-Up Tests & Special Considerations
- Rapid diagnosis with serum bile acid testing can be challenging due to the turnaround time of the test.
- Do not delay delivery in a term patient with presumed ICP (classic symptoms and abnormal liver function testing) while awaiting the serum bile acids (3)[C].
- Prior to 36 weeks' gestation, follow serial serum bile acid levels. Expectant management is appropriate with bile acid levels <40 μmol/L (7)[B].
- Antenatal fetal surveillance with nonstress testing is routinely recommended if managing expectantly (6)[C].
- The optimal testing modality and frequency have not been determined.
- Fetal demises have been reported within hours of reactive nonstress testing (7).
- No accurate predictors of sudden fetal death past 36 weeks' gestation have been determined from antenatal fetal surveillance with ultrasound, biophysical profile, nonstress testing, or kick counts (3,7).
Diagnostic Procedures/Other
Amniocentesis to detect fetal lung maturity should be offered to patients who require delivery before 37 weeks' gestation.
TREATMENT
GENERAL MEASURES
Medications to normalize serum bile acid levels are for symptomatic control only.
MEDICATION
First Line
Ursodeoxycholic acid (UDCA, ursodiol, Actigall) is a bile acid that occurs naturally in humans. It promotes decreased secretion of other, more toxic bile acids in the hepatobiliary tract. It also protects cholangiocytes and hepatocytes from the effects of toxic bile acids.
- Dosage: 10 to 15 mg/kg/day. Starting dose: 300 mg 3 times daily, up titrating to 15 mg/kg/day as needed for itching
- UDCA effectively improves pruritus, serum bile acid levels, and transaminase levels when compared to controls (9)[A].
- Treatment with UDCA and subsequent normalization of bile acid levels have not been shown to negate the fetal risks of ICP; however, larger studies are needed (10).
- UDCA has been shown to be better tolerated, and it safely controls pruritus more effectively than S-adenosyl-L-methionine (SAMe), cholestyramine, dexamethasone, guar gum, and activated charcoal (10)[A].
Second Line
- Cholestyramine 6 to 16 g/day has been used although less effective and not tolerated as well as UDCA.
- Sedating antihistamines have not been shown to improve pregnancy outcomes, but they are commonly used to treat insomnia due to pruritus (7).
- Diphenhydramine 25 to 50 mg PO QHS
- Hydroxyzine 25 to 50 mg PO QHS
ISSUES FOR REFERRAL
- Upon diagnosis, consultation with a maternal-fetal medicine specialist is warranted, depending on local standards of care.
- If laboratory abnormalities do not normalize within 6 to 8 weeks of delivery, refer to a gastroenterologist for further workup (7).
ADDITIONAL THERAPIES
- Topical emollients are commonly used to protect from skin breakdown.
- Preparations with 2% menthol or calamine lotion may have the added benefit of relieving pruritus (7,10).
SURGERY/OTHER PROCEDURES
- Induction of labor is a reasonable option in patients who require immediate delivery if fetal compromise is not suspected.
- Local practice standards vary regarding induction of labor versus repeat cesarean delivery in the setting of a patient with previous cesarean delivery.
COMPLEMENTARY & ALTERNATIVE MEDICINE
- There is insufficient evidence to support the use of herbal and dietary supplements in the treatment of ICP (10).
- Salvia, Yin Chen Hao decoction, Danxioling, and Yiganling have been studied. They are not superior to UDCA in relieving pruritus or decreasing fetal risks of ICP (10).
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Evidence and expert opinion regarding the optimal timing of delivery are conflicting due to lack of large randomized studies.
- The risk of fetal mortality with advancing gestational age may outweigh the risk of elective late preterm delivery.
- Delivery at 37 weeks' gestation is ideal (7)[C].
- Some experts advocate delivery at 36 weeks, especially if serum bile acids ≥40 μmol/L, but it is not proven that the benefit outweighs the risks of late preterm delivery. Physicians should discuss the risks and benefits of elective preterm delivery in light of the increased fetal mortality with advancing gestational age (2,3)[C].
- Delivery between 34 and 37 weeks' gestation if serum bile acid levels ≥100 μmol/L may be justified (2)[B].
- Immediate delivery in women diagnosed after 37 weeks may be considered (3)[B].
- Delivery must occur before 39 to 40 weeks, regardless of serum bile acid levels due to increased risk of fetal death with advancing gestational age (2,8)[B].
Nursing
- Patients with ICP require continuous fetal monitoring during labor.
- An experienced neonatal resuscitation team should be available if fetal compromise is suspected.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Repeat serum bile acid levels and liver function tests 6 to 8 weeks after delivery (7).
- Persistent lab abnormalities necessitate gastroenterology referral to evaluate for primary biliary cirrhosis.
DIET
- No restrictions
- Women with ICP may safely breastfeed their infants.
PATIENT EDUCATION
American College of Obstetricians and Gynecologists: http://www.acog.org/
PROGNOSIS
- Pruritus typically improves and laboratory abnormalities resolve shortly after delivery.
- ICP commonly recurs in subsequent pregnancies (60-90% recurrence rate) (1,7).
- There is an increased lifetime incidence of hepatobiliary disease in women with ICP (7).
COMPLICATIONS
- Vitamin K deficiency and coagulopathy may occur in severe disease (1).
- The most severe complication is fetal death.
REFERENCES
11 Kroumpouzos G, Cohen LM. Specific dermatoses of pregnancy: an evidence-based systematic review. Am J Obstet Gynecol. 2003;188(4):1083-1092.22 Brouwers L, Koster MP, Page-Christiaens GC, et al. Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels. Am J Obstet Gynecol. 2015;212(1):100.e1-100.e7.33 Puljic A, Kim E, Page J, et al. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol. 2015;212(5):667.e1-667.e5.44 Lee RH, Goodwin TM, Greenspoon J, et al. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol. 2006;26(9):527-532.55 van der Woerd WL, van Mil SW, Stapelbroek JM, et al. Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. Best Pract Res Clin Gastroenterol. 2010;24(5): 541-553.66 Tunzi M, Gray GR. Common skin conditions during pregnancy. Am Fam Physician. 2007;75(2):211-218.77 Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2014;124(1):120-133.88 Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40(2):467-474.99 Di Martirio V, Sentilhes L, Reyes HM, et al. Ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP): a systematic review and meta-analyses with specific assessment of fetal outcome. J Hepatol. 2011;54(Suppl 1):S355.1010 Gurung V, Middleton P, Milan SJ, et al. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013;(6):CD000493.
ADDITIONAL READING
Pathak B, Sheibani L, Lee RH. Cholestasis of pregnancy. Obstet Gynecol Clin North Am. 2010;37(2):269-282.
CODES
ICD10
- K83.1 Obstruction of bile duct
- O26.619 Liver and biliary tract disord in pregnancy, unsp trimester
- O26.611 Liver and biliary tract disord in pregnancy, first trimester
- O26.612 Liver and biliary tract disord in preg, second trimester
- O26.613 Liver and biliary tract disord in pregnancy, third trimester
ICD9
- 576.8 Other specified disorders of biliary tract
- 646.70 Liver and biliary tract disorders in pregnancy, unspecified as to episode of care or not applicable
- 646.73 Liver and biliary tract disorders in pregnancy, antepartum condition or complication
SNOMED
cholestasis of pregnancy (disorder)
CLINICAL PEARLS
- Consider ICP in pregnant women with diffuse itching in the absence of rash.
- Serum bile acids are the most sensitive laboratory test for ICP, but liver function tests may also be abnormal.
- UDCA is an effective treatment for pruritus in ICP.
- Fetal death is a known complication.
- Patients should be monitored closely with serum bile acid levels and antepartum fetal surveillance until the risk of fetal demise outweighs the risk of preterm delivery.