Guideline sources The following summarized guidelines for the evaluation and management of intrahepatic cholestasis of pregnancy (ICP) are prepared by our editorial team based on guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG 2022), the American Association for the Study of Liver Diseases (AASLD 2021), the Society for Maternal-Fetal Medicine (SMFM 2021), the American College of Gastroenterology (ACG 2016), and the Italian Association for the Study of the Liver (AISF 2016). 1 2 3 4 5 Guidelines 1. Screening and diagnosis Diagnosis: As per RCOG 2022 guidelines, suspect ICP in pregnant patients presenting with itching of normal-appearing skin and raised peak random total bile acid concentration of 19 mcmol/L. B Show 2 more As per AASLD 2021 guidelines, diagnose ICP in pregnant patients with pruritus presenting in the second or third trimester in combination with total bile acid levels > 10 mcmol/L, in the absence https://web.pathway.md/diseases/recsn0j0p9Vd6dZtn 1/6 6/24/23, 2:34 PM Intrahepatic cholestasis of pregnancy Pathway of other causes of pruritus. Do not obtain AST and ALT measurements for the diagnosis, although elevation is frequent. E Differential diagnosis: As per RCOG 2022 guidelines, recognize that the diagnosis of ICP is unlikely to be correct if the resolution of itching is associated with the normalization of bile acids and LFTs during pregnancy. B As per AASLD 2021 guidelines, evaluate patients with persistent symptoms or elevated liver tests or total bile acids postpartum for other causes of chronic liver diseases, including genetic variants associated with cholestasis. E 2. Diagnostic investigations History and physical examination: elicit a structured history and perform a physical examination to exclude other causes of itching and liver dysfunction in patients with suspected ICP. B Liver function tests, baseline: As per RCOG 2022 guidelines, consider obtaining additional laboratory tests on an individual basis. Consider obtaining antenatal testing only if there are atypical clinical symptoms, relevant comorbidities, or early onset severe ICP. C As per SMFM 2021 guidelines, obtain liver transaminase and serum bile acid measurements in patients with suspected ICP. B Liver function tests, monitoring: As per RCOG 2022 guidelines: Obtain repeat LFTs and bile acid measurement (depending on gestation and clinical context) in patients with persisting itching and normal blood results, if no other cause is apparent. Consider repeating LFTs and bile acids after 1 week, and then at frequencies determined on an individual basis, in patients with ICP. B Consider obtaining postnatal evaluation if the resolution of abnormal LFTs is delayed or does not occur. C As per AISF 2016 guidelines, monitor serum bile acids in patients with ICP, although there is no general consensus on a correlation between severe complications and high serum bile acid levels. B Diagnostic imaging: As per RCOG 2022 guidelines, consider obtaining imaging evaluation on an individual basis. Consider obtaining antenatal evaluation only if there are atypical clinical symptoms, relevant comorbidities, or early onset severe ICP. C As per ACG 2016 guidelines: Obtain ultrasound as the preferred imaging modality for the assessment of abnormal liver tests suggestive of biliary tract disease. B Consider obtaining MRI without gadolinium in the second and third trimesters. B https://web.pathway.md/diseases/recsn0j0p9Vd6dZtn 2/6 6/24/23, 2:34 PM Intrahepatic cholestasis of pregnancy Pathway Recognize that CT carries a risk of teratogenesis and childhood hematologic malignancies, but consider obtaining judiciously with minimized radiation protocols (2-5 cGy). B Screening for HCV infection: obtain testing for HCV infection in patients with ICP, if not previously obtained. E 3. Medical management General principles: As per RCOG 2022 guidelines: Consider discussing the care of patients with severe, very early, or atypical presentation of ICP with a hepatologist. C Review patients with ICP within a consultant-led maternity unit. B As per AISF 2016 guidelines, manage patients with ICP by a dedicated team. B Ursodeoxycholic acid: As per RCOG 2022 guidelines, do not offer routine UDCA for the purpose of reducing adverse perinatal outcomes in patients with ICP. D As per AASLD 2021 guidelines, offer UDCA 10-15 mg/kg as first-line therapy for pruritus management. E As per SMFM 2021 guidelines, offer UDCA as first-line therapy for maternal symptoms of ICP. A As per ACG 2016 guidelines, offer UDCA 10-15 mg/kg for symptomatic improvement in patients with ICP. B As per AISF 2016 guidelines, offer UDCA 15 mg/kg of body weight for the management of symptoms of ICP. B Antihistamines: As per RCOG 2022 guidelines, consider offering antihistamines such as chlorphenamine, particularly at night, in patients with ICP. C As per AASLD 2021 guidelines, consider offering antihistamines for the management of refractory pruritus. E Vitamin K: As per RCOG 2022 guidelines, consider administering maternal vitamin K only if there appears to be reduced absorption of dietary fats (such as steatorrhea) and/or evidence of abnormal proTT if coagulation tests are obtained. C As per AASLD 2021 guidelines, administer vitamin K when proTT is prolonged. Consider obtaining more frequent monitoring of proTT in patients on cholestyramine. E Other agents: consider offering cholestyramine, rifampin, and S-adenosyl-L-methionine for the management of refractory symptoms. E https://web.pathway.md/diseases/recsn0j0p9Vd6dZtn 3/6 6/24/23, 2:34 PM Intrahepatic cholestasis of pregnancy Pathway 4. Nonpharmacologic interventions Topical emollients: consider offering topical emollients such as aqueous cream (with or without menthol added) to ameliorate skin symptoms. C 5. Patient education General counseling (management of symptoms): Counsel patients with ICP that the predominant symptom is itching and it can be severe, may fluctuate, and may markedly affect sleep. B Counsel patients that there are no treatments improving pregnancy outcome (or raised bile acid concentrations) and treatments to improve maternal itching are of limited benefit. B General counseling (risk of preterm birth): counsel patients with moderate or severe ICP about the higher risks of spontaneous and iatrogenic preterm birth. B General counseling (risk of stillbirth): Counsel patients with isolated ICP and a singleton pregnancy that the risk of stillbirth only increases above the population rate once the serum bile acid concentration is 100 mcmol/L: the risk of stillbirth is similar to the background risk in patients with peak bile acid concentration of 19-39 mcmol/L, in the absence of other risk factors the risk of stillbirth is similar to the background risk until 38-39 weeks of gestation in patients with peak bile acid concentration of 40-99 mcmol/L, in the absence of other risk factors the risk of stillbirth is higher than the background risk in patients with peak bile acid concentration of 100 mcmol/L. B Show 2 more General counseling (risk of meconium-stained amniotic fluid): Counsel patients with moderate or severe ICP about the increased chance of meconium-stained amniotic fluid during labor and delivery. B Counsel patients that meconium-stained liquor is more common in moderate and severe ICP and it will influence decision-making around continuous electronic fetal monitoring. General counseling (risk of postpartum hemorrhage): counsel patients with uncomplicated ICP that there is no evidence of an increased risk of postpartum hemorrhage. B General counseling (fetal monitoring): advise patients to monitor fetal movements and present for immediate assessment at their local maternity unit if they have any concerns. B General counseling (neonatal care): counsel patients with moderate or severe ICP about the increased risk that their newborn will need neonatal care. B General counseling (mode of birth): Counsel patients that ICP in itself does not impact their choice around the mode of delivery and that these decisions should be based on usual obstetric practice for that woman. B https://web.pathway.md/diseases/recsn0j0p9Vd6dZtn 4/6 6/24/23, 2:34 PM Intrahepatic cholestasis of pregnancy Pathway Counsel patients that the presence of risk factors (such as gestational diabetes, preeclampsia, or multifetal pregnancy) appear to increase the risk of adverse perinatal outcomes and that these conditions themselves may necessitate monitoring during delivery or in conjunction with ICP may influence decision-making around monitoring in labor. 6. Follow-up and surveillance Surveillance for preeclampsia and diabetes: obtain BP and urine monitoring and testing for gestational diabetes according to national guidance since patients with ICP have a higher risk of developing preeclampsia and gestational diabetes. B Fetal monitoring: As per RCOG 2022 guidelines: Obtain continuous electronic fetal monitoring in patients with peak bile acid levels 100 mcmol/L. B Insufficient evidence to recommend for or against continuous electronic fetal monitoring in patients with peak bile acid levels < 100 mcmol/L. Recognize that fetal U/S and/or cardiotocography do not predict or prevent stillbirth in ICP. B As per SMFM 2021 guidelines, consider obtaining antenatal fetal surveillance starting at a gestational age when delivery would be performed in response to abnormal fetal testing results or at the time of diagnosis if the diagnosis is made later in gestation in patients with ICP. C Delivery: As per RCOG 2022 guidelines, consider offering options of planned birth by 40 weeks of gestation or ongoing antenatal care according to national guidance in patients with mild ICP (peak bile acids 19-39 mcmol/L) and no other risk factors. B Show 3 more As per SMFM 2021 guidelines, offer delivery at 36 0/7 weeks of gestation in patients with total bile acid levels of 100 mcmol/L, given that the risk of stillbirth increases substantially around this gestational age. B Show 3 more As per ACG 2016 guidelines, offer early delivery at 37 weeks of gestation because of the increased risk of fetal complications with ICP. B Confirmation of resolution: follow-up patients with uncomplicated ICP at least 4 weeks after birth to confirm resolution of ICP. B Subsequent contraception and hormone therapy: counsel patients that ICP itself does not influence their choice of contraception or HRT. B Show 2 more https://web.pathway.md/diseases/recsn0j0p9Vd6dZtn 5/6 6/24/23, 2:34 PM Intrahepatic cholestasis of pregnancy Pathway Evaluation in future pregnancies: Advise patients with a history of ICP that they have an increased chance of recurrence of ICP in subsequent pregnancies. B Obtain a baseline liver function test and bile acid concentration at booking blood tests in subsequent pregnancies. B References 1. Joanna Girling, Caroline L Knight, Lucy Chappell et al. Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022 Green-top Guideline No. 43 June 2022. BJOG. 2022 Aug 9. Open 2. Tram T Tran, Joseph Ahn, Nancy S Reau. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenterol. 2016 Feb;111 2 176 94; quiz 196. Open 3. Monika Sarkar, Carla W Brady, Jaquelyn Fleckenstein et al. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Jan;73 1 318 365. Open 4. Italian Association for the Study of the Liver AISF , Italian Association for the Study of the Liver AISF. AISF position paper on liver disease and pregnancy. Dig Liver Dis. 2016 Feb;48 2 120 37. Open 5. Society for Maternal-Fetal Medicine SMFM , Richard H Lee, Mara Greenberg et al. Society for Maternal- Fetal Medicine Consult Series #53 Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. Am J Obstet Gynecol. 2021 Feb;224 2 B2 B9. Open https://web.pathway.md/diseases/recsn0j0p9Vd6dZtn 6/6