R F Burrows1, O Clavisi, E Burrows. 1. Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, Australia, 3168. robert.burrows@med.monash.edu.au
Abstract
BACKGROUND: Cholestasis of pregnancy has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is unresolved, therapies have been empiric. OBJECTIVES: The objective of the review is to evaluate the effectiveness and safety of therapeutic interventions in women with a clinical diagnosis of cholestasis of pregnancy (CIP) SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE and PREMEDLINE, EMBASE, CINAHL and Current Contents. Date of last search: March 2001. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared an intervention to either a placebo or alternative treatment in women with a diagnosis of intrahepatic cholestasis of pregnancy. Trials published only as abstracts were excluded. DATA COLLECTION AND ANALYSIS: Reviewers assessed identified trials for 1) eligibility and 2) methodological quality. Attempts were made to contact authors for missing data. MAIN RESULTS: Nine RCTs involving 227 women were included but adequate data for appropriate comparisons in pruritus, bile acids or liver enzymes were not consistently reported. S-adenosylmethionine (SAMe) versus placebo (four trials, 82 women): only one trial showed significantly greater improvements in pruritus, bile salts and liver enzymes with SAMe. Ursodeoxycholic acid (UDCA) versus placebo (three trials, 56 women): in two trials a significant difference in pruritus relief was not detected. One trial observed greater reductions in bile salts and liver enzymes with UDCA. Preterm births were fewer with UDCA in one study while two studies reported no difference in fetal distress incidence. Guar gum versus placebo (one trial, 48 patients): no differences in pruritus, bile salts, or fetal/neonatal outcomes were observed. Activated charcoal versus no treatment (one trial, 20 patients): the reduction in bile salts was greater with charcoal, but no difference in pruritus relief: relative risk (RR) 9.0 95% confidence interval (CI) 0.6 - 148 or fetal/neonatal outcomes. UDCA versus SAMe (two trials, 36 patients): pruritus relief was better with UDCA in one study and with SAMe in the other. UDCA was better in reducing bile acids but not liver enzymes in one trial. UDCA + SAMe versus placebo, UDCA or SAMe (one study, eight patients/arm): UDCA + SAMe versus placebo or UDCA resulted in greater improvements in pruritus, bile salts and selected liver function assays; UDCA + SAMe versus SAMe resulted in greater improvements in bile salts and ALP only. No treatments were found to be unsafe. REVIEWER'S CONCLUSIONS: There is insufficient evidence to recommend guar gum, activated charcoal, SAMe and UDCA alone or in combination in treating women with CIP. Inconsistent and inadequate reporting of results precluded pooling the results of small studies.
BACKGROUND:Cholestasis of pregnancy has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is unresolved, therapies have been empiric. OBJECTIVES: The objective of the review is to evaluate the effectiveness and safety of therapeutic interventions in women with a clinical diagnosis of cholestasis of pregnancy (CIP) SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE and PREMEDLINE, EMBASE, CINAHL and Current Contents. Date of last search: March 2001. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared an intervention to either a placebo or alternative treatment in women with a diagnosis of intrahepatic cholestasis of pregnancy. Trials published only as abstracts were excluded. DATA COLLECTION AND ANALYSIS: Reviewers assessed identified trials for 1) eligibility and 2) methodological quality. Attempts were made to contact authors for missing data. MAIN RESULTS: Nine RCTs involving 227 women were included but adequate data for appropriate comparisons in pruritus, bile acids or liver enzymes were not consistently reported. S-adenosylmethionine (SAMe) versus placebo (four trials, 82 women): only one trial showed significantly greater improvements in pruritus, bile salts and liver enzymes with SAMe. Ursodeoxycholic acid (UDCA) versus placebo (three trials, 56 women): in two trials a significant difference in pruritus relief was not detected. One trial observed greater reductions in bile salts and liver enzymes with UDCA. Preterm births were fewer with UDCA in one study while two studies reported no difference in fetal distress incidence. Guar gum versus placebo (one trial, 48 patients): no differences in pruritus, bile salts, or fetal/neonatal outcomes were observed. Activated charcoal versus no treatment (one trial, 20 patients): the reduction in bile salts was greater with charcoal, but no difference in pruritus relief: relative risk (RR) 9.0 95% confidence interval (CI) 0.6 - 148 or fetal/neonatal outcomes. UDCA versus SAMe (two trials, 36 patients): pruritus relief was better with UDCA in one study and with SAMe in the other. UDCA was better in reducing bile acids but not liver enzymes in one trial. UDCA + SAMe versus placebo, UDCA or SAMe (one study, eight patients/arm): UDCA + SAMe versus placebo or UDCA resulted in greater improvements in pruritus, bile salts and selected liver function assays; UDCA + SAMe versus SAMe resulted in greater improvements in bile salts and ALP only. No treatments were found to be unsafe. REVIEWER'S CONCLUSIONS: There is insufficient evidence to recommend guar gum, activated charcoal, SAMe and UDCA alone or in combination in treating women with CIP. Inconsistent and inadequate reporting of results precluded pooling the results of small studies.