Fetal complications due to intrahepatic cholestasis of pregnancy

2015 ◽  
Vol 43 (2) ◽  
Author(s):  
Patrik Šimják ◽  
Antonín Pařízek ◽  
Libor Vítek ◽  
Andrej Černý ◽  
Karolína Adamcová ◽  
...  

AbstractIntrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.

Author(s):  
Marco Arrese ◽  
Rocio I.R. Macias ◽  
Oscar Briz ◽  
Maria J. Perez ◽  
Jose J.G. Marin

Intrahepatic cholestasis of pregnancy (ICP) occurs mainly in the third trimester and is characterised by pruritus and elevated serum bile acid levels. ICP is associated with an increased perinatal risk and higher rates of foetal morbidity and mortality. Although the pathogenesis of this disease is unknown, a genetic hypersensitivity to female hormones (oestrogen and/or progesterone) or their metabolites is thought to impair bile secretory function. Recent data suggest that mutations or polymorphisms of genes expressing hepatobiliary transport proteins or their nuclear regulators may contribute to the development and/or severity of ICP. Unidentified environmental factors may also influence pathogenesis of the disease. This review summarises current knowledge on the potential mechanisms involved in ICP at the molecular level.


Author(s):  
Rebecca Roediger ◽  
Jaquelyn Fleckenstein

AbstractIntrahepatic cholestasis of pregnancy (ICP) is a common disorder in the second half of pregnancy characterized by pruritus and elevated serum bile acids (BAs) with spontaneous resolution after delivery. ICP carries a risk of adverse effects on the fetus which correlates with the degree of BA elevation. ICP occurs in genetically susceptible women as the reproductive hormones increase during pregnancy. Ursodeoxycholic acid is still considered the first-line treatment for ICP though it is of unproven benefit in preventing adverse effects on the fetus. Fetal complications, such as stillbirth, increase with gestational age, so preterm delivery is generally performed in cases of severe ICP, defined as BA levels above 40 μmol/L. ICP may recur in future pregnancies and is associated with an increased risk for future hepatobiliary, immune mediated, and cardiovascular diseases. Children born of mothers with ICP have normal development but may have a risk for subsequent metabolic disease.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Olawumi Adaramodu ◽  
Anthony Kodzo-Grey Venyo

Obstetric cholestasis (OC) is a liver disorder that occurs in the late second and early third trimester of pregnancy characterized by pruritus with increased serum bile acids and other liver function tests. The pathophysiology of OC is still not completely understood. The symptoms and biochemical abnormality rapidly resolve after delivery. OC is associated with an increased risk of adverse obstetrical outcomes. The aetiology of obstetric cholestasis of pregnancy is poorly understood and is thought to be complicated and multifactorial.  OC typically occurs in the late second trimester when the oestrogen levels are the highest in pregnancy. The most common complaint is generalized intense pruritus, which usually starts after the 30th week of pregnancy. Pruritus can be more common in the palms and soles and is typically worse at night. Other symptoms of cholestasis, such as nausea, anorexia, fatigue, right upper quadrant pain, dark urine, and pale stool, can be present. Clinical jaundice is rare but may present in 14% to 25% of patients after 1 to 4 weeks of the onset of pruritus. Some patients also complain of insomnia as a result of pruritus. Generally, physical examination is unremarkable except for scratch marks on the skin from pruritus. Pruritus is a cardinal symptom of intra-hepatic cholestasis of pregnancy (ICP) and may precede biochemical abnormalities. The diagnosis of intrahepatic cholestasis of pregnancy is via the presence of clinical symptoms pruritus in the third trimester with elevated maternal total serum bile acids and excluding other diagnoses, which can cause similar symptoms and lab abnormalities. Fasting blood samples should be used to check for the total bile salt acid level as it can become elevated in the postprandial state. Once the diagnosis of OC of pregnancy is confirmed, immediate treatment is necessary, and the primary goal of therapy is to decrease the risk of perinatal morbidity and mortality and to alleviate maternal symptoms. Maternal pruritus can be alleviated with use of moisturisers and oral antihistamines. Ursodeoxycholic acid (UDCA) is the drug of choice for the treatment of ICP. Many authors have advocated elective early delivery of women with intrahepatic cholestasis of pregnancy to reduce the risk of sudden foetal death. The Royal College of Obstetricians and Gynaecologists recommends induction of labour after 37+0 weeks of gestation. Obstetric cholestasis of pregnancy is not an indication for Caesarean delivery. Postpartum pruritus typically disappears in the first 2 to 3 days following delivery, and serum bile acid concentrations will normalize eventually. ICP is not a contraindication to breastfeeding, and mothers with a history of ICP in pregnancy can breastfeed their infants. Postpartum monitoring and follow up of bile acids and liver function tests should be done in 4-6 weeks to ensure resolution. Women with the persistent abnormality of liver function test after 6 to 8 weeks require investigation for other aetiologies.


2016 ◽  
Vol 5 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Sita Pokhrel Ghimire ◽  
Ashima Ghimire ◽  
Gauri Shankar Jha ◽  
Manisha Chhetry ◽  
Mahanand Kumar

Background Intrahepatic cholestasis of pregnancy has poor feto-maternal outcomes. To date there has been sparse publications regarding impact of intrahepatic cholestasis in feto-maternal outcomes in our setting. Therefore, we aimed to study the feto-maternal outcome in patients with intrahepatic cholestasis of pregnancy.Material and Methods A hospital based prospective cross-sectional study carried out in department of Obstetrics and Gynecology of Nobel Medical College, Biratnagar, Nepal from 1st January 2014 to 30th December 2015 in women who presented with pruritus in third trimester of pregnancy and having deranged liver function tests. All the cases were followed from admission to discharge. Socio-demographic, clinico-laboratory profile and feto-maternal outcomes were recorded in a preformed structured proforma. Descriptive statistics was used to present the data.Results Among 6,780 women admitted for delivery, 80 had cholestasis of pregnancy with incidence of 1.15%. 83% were of 18-35 years and 65% were primigravida. Most distressing symptom was generalized pruritus (75.0 %). The cesarean delivery rate was 46.25% and labor induction rate was (47.5%). Fetal complications were seen in majority of cases that included meconium aspiration syndrome 26 (32.5%), intrapartum fetal distress 21 (26.25%) and requirement of: intensive care 38 (48.75%). There were 7 perinatal and 3 neonatal deaths.Conclusion Intrahepatic cholestasis of pregnancy seems fairly common among pregnant women. It may be responsible for a large number of perinatal and neonatal deaths especially after 36 weeks of gestation. A large prospective study is needed to address the problems in time.Journal of Nobel Medical College Volume 5, Number 1, Issue 8, January-July 2016, 20-25


2019 ◽  
Vol 88 (4) ◽  
pp. 209-217
Author(s):  
Milena Gruszczyńska-Losy ◽  
Adrianna Mostowska ◽  
Łukasz Adamczak ◽  
Paweł Jagodziński ◽  
Ewa Wender-Ożegowska ◽  
...  

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during gestation. The exact pathogenesis of ICP is multifactorial and still unclear. Therefore, our study aimed to check whether the selected ABCB4and ABCB11nucleotide variants are associated with an increased risk of ICP. Methods:ICP was diagnosed based on clinical symptoms characteristic of this disease and confirmed by increase in serum bile acids and transaminases, spontaneous resolution of clinical symptoms and normalization of laboratory tests after delivery. The total of 86 pregnant women meeting the criteria were included into the study. Healthy pregnant women with uncomplicated pregnancy served as control group (n=310). Sixcommon nucleotide variants in theABCB11and ABCB4genes were genotypedwith the use of high-resolution melting curve analysis. Conclusion:Our study did not show any significant association of analysed ABCB4and ABCB11nucleotide variants with the increased risk of intrahepatic cholestasis of pregnancy.


2016 ◽  
Vol 94 (4) ◽  
pp. 402-407 ◽  
Author(s):  
Zhong Chen ◽  
Lingqing Hu ◽  
Mudan Lu ◽  
Zongji Shen

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disorder occurring specifically in pregnancy, and matrix metalloproteinase (MMP)-2 and MMP-9 were found to be elevated in ICP patients. Using ethinylestradiol-induced ICP rats as the model, we examined the effect of resveratrol on ICP symptoms such as bile flow rate, serum enzymatic activities, and TBA concentration, as well as MMP levels, and compared with the known ICP drug ursodeoxycholic acid. Both MMP-2 and MMP-9 were upregulated in ICP rats, and resveratrol treatment could inhibit the elevation of both MMPs, whereas ursodeoxycholic acid did not exhibit any effect. Although ursodeoxycholic acid alleviated ICP symptoms, resveratrol treatment in general exhibited better outcome in restoring bile flow rate, serum enzymatic activities, and TBA concentration. Our results for the first instance strongly supported the potential of RE as a new therapeutic agent in treating ICP, possibly through inhibiting MMP-2 and MMP-9.


2018 ◽  
pp. S499-S510
Author(s):  
P. ŠIMJÁK ◽  
M. HILL ◽  
A. PAŘÍZEK ◽  
L. VÍTEK ◽  
M. VELÍKOVÁ ◽  
...  

Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, within-subject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5α/β-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy.


Author(s):  
Samettin Çelik ◽  
Huri Guve ◽  
Canan Çalışkan ◽  
Sebahattin Çelik

Abstract Introduction Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disease that usually emerges during the third trimester of pregnancy. It is characterized by itching and elevated serum total bile acid levels, and it may lead to severe fetal complications. This study aimed to investigate the role of interleukin-8, a pro-inflammatory cytokine; interleukin-10, an anti-inflammatory cytokine; and melatonin in intrahepatic cholestasis of pregnancy. Materials and Methods This prospective, case-controlled study was conducted with 51 women with intrahepatic cholestasis of pregnancy (40 mild and 11 severe cases) and 43 healthy pregnant women. Serum interleukin-8, interleukin-10, and melatonin levels were evaluated. Results Melatonin and interleukin -10 were significantly lower in subjects with intrahepatic cholestasis of pregnancy (p=0.001; p=0.001, respectively p<0.05). Interleukin-8 levels were found to be significantly higher in the cholestasis group than control group (p=0.001, p<0.05). Conclusions Because interleukin-8, interleukin-10, and melatonin were found to be significantly correlated with intrahepatic cholestasis of pregnancy, we believe this finding could shed light on the etiology of the disease.


2018 ◽  
Vol 12 (2) ◽  
pp. 76-78 ◽  
Author(s):  
Adam Morton ◽  
Josephine Laurie

Background Bile acid levels and liver function tests may be normal at presentation in women with intrahepatic cholestasis of pregnancy. The biochemical results of patients presenting with pruritus typical for intrahepatic cholestasis of pregnancy were reviewed. Methods A retrospective audit of women coded as having intrahepatic cholestasis of pregnancy over a three-year period. Results One hundred and ninety-three women (1.1% of the obstetric population) presented with pruritus typical of intrahepatic cholestasis of pregnancy. Forty (21%) of these women had normal biochemistry at presentation, half subsequently developing abnormal results. Women with a history of allergic reactions were more likely to develop intrahepatic cholestasis of pregnancy. Conclusions Normal biochemistry should not preclude a trial of ursodeoxycholic acid in women with distressing pruritus typical for intrahepatic cholestasis of pregnancy. Biochemical tests which are more sensitive and specific in the diagnosis of intrahepatic cholestasis of pregnancy would be valuable. Investigation of other populations with intrahepatic cholestasis of pregnancy regarding a possible association with atopy/allergy would be interesting.


2016 ◽  
Vol 22 (1) ◽  
Author(s):  
Cem Yaşar Sanhal ◽  
Korkut Dağlar ◽  
Özgür Kara ◽  
Ayşe Kırbaş ◽  
Dilek Uygur ◽  
...  

<p>Objective: To evaluate the presence of any seasonal variation in the frequency of intrahepatic cholestasis of pregnancy (ICP).<br />Study Design: A total of 126 cases with ICP were compared with a cohort of 37614 pregnant women who delivered. The diagnosis ICP was performed on the basis of severe itching and the absence of dermal rash and any other hepatic disease, with the co-existence of elevated serum aminotransferase levels and/or serum bile acid concentration. For each month and season, observed and expected ICP rates were analysed and compared by using chi-square statistics. Multivariate logistic regression was performed to investigate certain parameters on cumulative risk. <br />Results: A significantly lower frequency of ICP in winter (6/126 (4.8%), p=0.001) and a significantly higher frequency in spring (44/126 (34.9%), p=0.034) were detected. A 2.1 and 3.8-fold higher risk were found for the nulliparity and the twin pregnancy, respectively. Logistic regression analysis confirmed the significant (10-fold) decrease in the frequency of ICP in winter. The significance of spring did not persist after the adjustment.<br />Conclusion: Main outcome of the study points at seasonality in ICP frequency. Future studies in different populations may reveal data about factors that interact with seasonality and playing roles in ICP. <br /><br /></p>


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