Interventions for treating cholestasis in pregnancy

Department of Obstetrics and Gynaecology, University of Nottingham, Nottingham City Hospital NHS Trust, Hucknall Road, Nottingham, Nottinghamshire, UK, NG5 1PB.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 06/2013; 6(6):CD000493. DOI: 10.1002/14651858.CD000493.pub2
Source: PubMed


Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update.
To evaluate the effectiveness and safety of therapeutic and delivery interventions in women with cholestasis of pregnancy.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 February 2013) and reference lists of identified studies.
Randomised controlled trials that compared two intervention strategies for women with a clinical diagnosis of obstetric cholestasis.
The review authors independently assessed trials for eligibility and risk of bias. We independently extracted data and checked these for accuracy.
We included 21 trials with a total of 1197 women. They were mostly at moderate to high risk of bias. They assessed 11 different interventions resulting in 15 different comparisons.Compared with placebo, ursodeoxycholic acid (UDCA) showed improvement in pruritus in five (228 women) out of seven trials. There were no significant differences in instances of fetal distress in the UDCA groups compared with placebo (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.22 to 2.02; five trials, 304 women; random-effects analysis: T² = 0.74; I² = 48%). There were significantly fewer total preterm births with UDCA (RR 0.46; 95% CI 0.28 to 0.73; two trials, 179 women). The difference for spontaneous preterm births was not significant (RR 0.99; 95% CI 0.41 to 2.36, two trials, 109 women).Two trials (48 women) reported lower (better) pruritus scores for S-adenosylmethionine (SAMe) compared with placebo, while two other trials of 34 women reported no significant differences between groups.UDCA was more effective in improving pruritus than either SAMe (four trials; 133 women) or cholestyramine (one trial; 84 women), as was combined UDCA+SAMe when compared with placebo (one trial; 16 women) and SAMe alone (two trials; 68 women). However, combined UDCA+SAMe was no more effective than UDCA alone in regard to pruritus improvement (one trial; 53 women) and two trials (80 women) reported data were insufficient to draw any conclusions from. In one trial comparing UDCA and dexamethasone (83 women), a significant improvement with UDCA was seen only in a subgroup of women with severe obstetric cholestasis (23 women).Danxiaoling significantly improved pruritus in comparison to Yiganling. No significant differences were seen in pruritus improvement with other interventions.Eight trials reported fetal or neonatal deaths, with two deaths reported overall (both in the placebo groups).Women receiving UDCA and cholestyramine experienced nausea, vomiting and diarrhoea. Guar gum caused mild abdominal distress, diarrhoea and flatulence during the first days of treatment. Women found charcoal suspension unpleasant to swallow. Dexamethasone caused nausea, dizziness and stomach pain in one woman.One trial (62 women) looked at the timing of delivery intervention. There were no stillbirths or neonatal deaths in 'early delivery' or the 'await spontaneous labour' group. There were no significant differences in the rates of caesarean section, meconium passage or admission to neonatal intensive care unit between the two groups.
Different approaches to assessing and reporting pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on pruritus, but examination of individual trials suggests that UDCA significantly improves pruritus, albeit by a small amount. Fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.A single trial was too small to rule in or out a clinically important effect of early term delivery on caesarean section.There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy.

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Available from: Philippa Middleton, Jan 04, 2016
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    • "It has been shown that UDCA causes a significant reduction in liver function tests in ICP [13] [14]. Gurung et al. (2013) concluded in the Cochrane collaboration that UDCA significantly improves pruritus and fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant [15]. Bacq et al. [16] found UDCA have a several benefits for mothers, fetuses as well as for newborns. "
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    ABSTRACT: To exam the biochemical, obstetric management and pregnancy outcome in women with intrahepatic cholestasis of pregnancy (ICP) and treatment with ursodeoxycholic acid (UDCA). Pregnancy outcome in patients with ICP (N = 307) was studied and patients treated with UDCA (N = 208) vs. no UDCA were compared. The data of the antenatal visits, deliveries and neonatal outcome of 307 pregnancies with ICP was collected from the hospital computerized delivery room log book. UDCA was used in 208 pregnancies. The diagnosis was made by maternal pruritus and elevation of total fasting bile acid (BA) (>6 μmol/l) and elevation of serum alanine aminotransferases (ALT) (>45 U/l). Maternal and neonatal data was analysed and data of the patients who used UDCA during pregnancy was analysed separately and compared with the data from patients without medication. UDCA was well tolerated. Mothers receiving UDCA had ICP diagnosed five weeks earlier than mothers without medication. At the diagnosis, levels of total BA and ALT were higher in the group using UDCA compared to the group without medication. Most deliveries were induced and perinatal outcome was good. Apgar scores at 5 min were significantly lower in UDCA group (p < 0.05), but fetal umbilical artery pH values were similar in both groups (p > 0.05). There were 30 patients with total BA > 40 μmol/l at diagnosis, 24 with UDCA and 6 without medication and those deliveries were induced soon after diagnosis. The preterm labour was also more common in these patents (p < 0.05). Women with preterm babies had significantly early onset pruritus and ICP was diagnosed earlier. Serum ALT and total BA levels were significantly higher in those pregnancies at diagnosis and also at first control. Preterm labour was associated in severe ICP (total BA > 40 μmol/l), ALT levels were also significantly higher and ICP was diagnosed earlier (p < 0.05). Apgar scores were lower in preterm babies (p < 0.05), but umbilical artery pHvalues were not significantly lower. UDCA was well tolerated by pregnant women. With low-dose UDCA treatment the obstetric outcome was good. We still recommend careful obstetrical follow-up.
    Full-text · Article · Dec 2015 · BMC Gastroenterology
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    • "It also reduces serum activities of ALT and gamma-glutamyl transferase, as well as concentrations of bilirubin and TBA, and significantly improves fetal outcomes [4] [9] . It is associated with decreases in total prematurity, fetal distress, and RDS [4] [16] . The incidence of MSAF is significantly lower in patients treated with UDCA when compared to placebo [9] , and UDCA shows a good safety profile for both mother and fetus [4] . "
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    ABSTRACT: Abstract Intrahepatic 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.
    Full-text · Article · Aug 2014 · Journal of Perinatal Medicine
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    ABSTRACT: Intrahepatic cholestasis of pregnancy (ICP) is an uncommon obstetric condition characterised by intense maternal pruritis and biochemical abnormality. There is a degree of contention regarding the diagnosis and management of ICP, and currently, there are no nationally accepted guidelines. To conduct a survey of Fellows and Members of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) regarding their diagnosis and management ICP. An online survey of currently practising RANZCOG Fellows and Members, utilising Survey Monkey. Thirty percent of those sent the survey responded, comprising approximately 40% of practising obstetricians. Fasting bile acid and serum transaminase elevation in association with the characteristic itch define the disease process for the majority of respondents and also inform management decisions. There was no critical level of bile acid elevation that mandated treatment for the majority of respondents. Nearly 90% of respondents induce women with ICP at 37-38 completed weeks of pregnancy, due to concerns regarding possible fetal demise. About one-third of respondents refer to the Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guideline to advise their decision-making process, and a similar proportion use local or hospital-based guidelines. Elevated fasting bile acids and abnormal liver function tests define the diagnosis and inform management of ICP by Australian obstetricians. Routine induction of labour for patients with ICP at 37-38 completed weeks of pregnancy is widely practised in Australia. An evidence-based guideline would assist clinicians who manage such cases in Australia.
    Full-text · Article · Feb 2014 · Australian and New Zealand Journal of Obstetrics and Gynaecology
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