Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population‐based case‐control study

Geenes, Victoria; Chappell, Lucy C; Seed, Paul; Steer, Philip; Knight, Marian; Williamson, Catherine

doi:10.1002/hep.26617

Cited by 376 publications

(372 citation statements)

References 37 publications

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“…Maternal outcomes are excellent, however, there is a risk of fetal distress, preterm labor, prematurity, and intrauterine death (41)(42)(43)(44)(45). Early delivery at 37 weeks is encouraged, because intrauterine death is more common in the last month of pregnancy and few deaths occur before 37 weeks ( 46 ).…”

Section: Second and Third Trimestermentioning

confidence: 99%

ACG Clinical Guideline: Liver Disease and Pregnancy

Tran

Ahn

Reau

2016

American Journal of Gastroenterology

223

240

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Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both the expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver disease in pregnant women. Am J Gastroenterol 2016; 111:176-194; doi: 10.1038/ajg.2015 Initial evaluation of pregnant patientA pregnant patient presenting with abnormal liver tests should undergo standard workup as with any non-pregnant individual (strong recommendation, very low level of evidence). Imaging in pregnancyUltrasound is safe and the preferred imaging modality used in assessment of abnormal liver tests suggestive of biliary tract disease (strong recommendation, low level of evidence).Magnetic resonance imaging without gadolinium can be used in the second and third trimester (conditional recommendation, low level of evidence).Computed tomography scans carry a risk of teratogenesis and childhood hematologic malignancies but may be used judiciously with minimized radiation protocols (2-5 rads; conditional recommendation, very low level of evidence). Endoscopy in pregnancyEndoscopy is safe in pregnancy but should be deferred until the second trimester if possible (strong recommendation, low level of evidence).Meperidine and propofol can be used for endoscopic sedation (strong recommendation, moderate level of evidence). Management of biliary disease in pregnancyERCP can be performed when indicated for pregnant women presenting with biliary disease that strongly necessitates intervention such as biliary pancreatitis, symptomatic choledocholithiasis, and/or cholangitis. Minimizing fetal exposure to fl uoroscopy is imperative (strong recommendation, low level of evidence).Symptomatic cholecystitis should be managed with early surgical intervention with laparoscopic cholecystectomy (strong recommendation, low level of evidence). Liver masses in pregnancyAsymptomatic hemangioma and focal nodular hyperplasia do not need routine imaging or surveillance during pregnancy (strong recommendation, very low level evidence).Hepatic adenomas should be monitored with ultrasound during pregnancy for growth. Patients with large adenomas (>5 cm) should be referred for resection prior to pregnancy (strong recommendation, low level of evidence). Hepatitis B in pregnancyActive-passive immunoprophylaxis with hepatitis B immunoglobulin and the HBV vaccination series should be administered to all infants born to HBV-infected mothers to prevent perinatal transmission (strong recommendation, low level of evidence).Women chronically infected with HBV and high viral load (>10 6 log copies/ml (200,000 IU/ml) and higher) should be offered antiviral medication with tenofovir or telbivudine in the third trimester to reduce perinatal transmission of HBV (strong recommendation, low level of evidence).C-section should not be performed electively in HBV-pos...

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Section: Second and Third Trimestermentioning

confidence: 99%

ACG Clinical Guideline: Liver Disease and Pregnancy

Tran

Ahn

Reau

2016

American Journal of Gastroenterology

223

240

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“…As UDCA is currently in use for clinical treatment of both ICP and other cardiac diseases (Geenes and Williamson, 2009;Geenes et al, 2014Geenes et al, , 2013Rainer et al, 2013;Von Haehling et al, 2012), the short term and long term effects of UDCA on neonatal cardiomyocytes and fibroblasts were investigated. Optical recording of calcium transients was carried out with control (HBSS) solution, followed by UDCA treatment (10 nM, 100 nM, 1 μM or 100 μM).…”

Section: The Effect Of Udca On the Heartmentioning

confidence: 99%

The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts

Schultz

Hasan

Alvarez-Laviada

et al. 2016

Progress in Biophysics and Molecular Biology

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“…The present study (1) identified three sulfated progesterone metabolites, 5a-pregnan-3a,-20a-diol-3,20-disulfate, 5b-pregnan-3a-20a-diol-3-sulfate, and 5b-pregnan-3a-20a-diol-3,20-disulfate, that were present in ICP patients in serum samples obtained even at [9][10][11][12][13][14][15] Abbreviations: ICP, intrahepatic cholestasis of pregnancy; PG, pruritus gravidarum.…”

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confidence: 58%

“…Patients with these characteristics have been identified in several studies, being usually labeled as having pruritus gravidarum (PG), an enigmatic entity that does not carry the fetal risks of a genuine ICP. (5,(9)(10)(11) Table 1 summarizes clinical and biochemical data previously reported in patients with ICP and in normal pregnancies, (7) comparing them with a concurrent unreported cohort of patients with PG in whom pruritus appeared at the same gestational age but was slightly less severe than in patients with ICP. In three of these patients with PG, pruritus diminished spontaneously 1 week prior to delivery; and in another patient, pruritus disappeared in the final week of pregnancy, a phenomenon that was not observed in patients with a genuine ICP.…”

mentioning

confidence: 99%

Sulfated progesterone metabolites in the pathogenesis of intrahepatic cholestasis of pregnancy: Another loop in the ascending spiral of medical knowledge

Reyes

2016

Hepatology

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P rogress in medical knowledge can be represented by an ascending spiral in which every loop stands over previous data, adds new findings that deepen our understanding of a disease, and helps to design further research and therapeutic strategies. New loops are frequently inspired by novel approaches to accepted hypotheses and usually supported by the use of more advanced technologies, as seems to be the case in the article by Abu-Hayyeh et al. (1) Intrahepatic cholestasis of pregnancy (ICP), a frequent liver disorder of pregnancy, implies an unpredictable risk of fetal distress, with premature deliveries and stillbirths. Its pathogenesis has been linked to effects of sex hormones during pregnancy, and in recent decades successive reports have revealed a role for progesterone derivatives.In this regard, the spiral started in 1970 when Sj€ ovall and Sj€ ovall reported increased sulfated metabolites of progesterone in serum and urine of Swedish patients with ICP, in contrast to normal pregnancies.(2) Furthermore, this biochemical peculiarity was identified in two patients during an early stage of pregnancy, before the onset of pruritus and abnormalities in serum liver tests, suggesting that it could have predicted the development of ICP.In 1979, Giusti et al. reported that an increase in sulfated progesterone metabolites in plasma from Italian patients with ICP did not occur in patients with viral hepatitis in pregnancy, giving further support to its specificity in ICP. In the 1990s, a series of reports centered in Sj€ ovall's laboratory, in Stockholm, Sweden, using now more sophisticated and precise techniques applied to serum and urine from Chilean patients with ICP and their controls, clarified that a distinctive biochemical feature in ICP was the switch of progesterone metabolism toward a four-fold to 10-fold increase in serum and urine concentration of sulfated metabolites, with an increased ratio of 3a-hydroxysteroid sulfates to 3b-hydroxysteroid sulfates, changes that were reversed after treatment with ursodeoxycholic acid. (4) Among other important steps in this research line, Glantz et al., in Sweden, reported similar changes in the pattern of progesterone metabolites in urine of ICP patients, with a reversal after ursodeoxycholic acid administration, correlating with an improvement in maternal pruritus (5) ; and Abu-Hayyeh et al. also reported increased levels of progesterone sulfates in ICP patients studied in the United Kingdom. (6) Therefore, this metabolic pattern has been detected in ICP patients from different geographic locations and ethnic origins.The present study (1) identified three sulfated progesterone metabolites, 5a-pregnan-3a,-20a-diol-3,20-disulfate, 5b-pregnan-3a-20a-diol-3-sulfate, and 5b-pregnan-3a-20a-diol-3,20-disulfate, that were present in ICP patients in serum samples obtained even at 9-15 Abbreviations: ICP, intrahepatic cholestasis of pregnancy; PG, pruritus gravidarum.

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Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population‐based case‐control study

Cited by 376 publications

References 37 publications

ACG Clinical Guideline: Liver Disease and Pregnancy

ACG Clinical Guideline: Liver Disease and Pregnancy

The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts

Sulfated progesterone metabolites in the pathogenesis of intrahepatic cholestasis of pregnancy: Another loop in the ascending spiral of medical knowledge

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