Objective: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that have assessed the effect and safety of ursodeoxycholic acid (UDCA), S-adenosylmethionine (SAMe) and UDCA-SAMe combination therapies for intrahepatic cholestasis of pregnancy (ICP).
Methods: Using searching protocols and assessment methods recommended by the Cochrane Collaboration to reduce bias in systematic reviews, the databases of Medline, EMBASE, Cochrane Central Register of Controlled Trials (CCRT), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature (CBM) and Wanfang China Online Journals were searched to identify relevant RCTs published from database inception to December 2011.
Results: Ten RCTs (of 727 pregnant women) were included in the study and represented a low risk for bias. Compared to the patients who received UDCA monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of Cesarean section (odds ratio (OR) =0.45, 95% confidence interval (CI):0.24-0.86), preterm birth (OR=0.36, 95% CI:0.20-0.63), and fetal asphyxia (OR=0.27, 95% CI:0.13-0.56) (all P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of amniotic fluid pollution (OR=0.38, 95% CI:0.14-1.01) or better new bom weight (mean difference (MD) =397.36, 95% CI:-96.17-890.89). Compared to the patients who received SAMe monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of preterm birth (OR=0.39, 95% CI:0.21-0.73), fetal asphyxia (OR=0.23, 95% CI:0.07-0.75), and amniotic fluid pollution (OR=0.41, 95% CI:0.20-0.85) (all, P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of Cesarean section (OR =0.62, 95% CI:0.27-1.44) or better new bom weight (MD =445.95, 95% CI:-143.51-1035.42). Comparison of the two monotherapies (UCDA vs.SAMe) showed no statistical differences in rates of Cesarean section (OR=0.91, 95% CI:0.47-1.78), preterm birth (OR =0.79, 95% CI:0.49-1.38), fetal asphyxia (OR=0.90, 95% CI:0.38-2.12), and amniotic fluid pollution (OR=1.14, 95% CI:0.61-2.13), as well as of new born weight (MD =-62.86, 95% CI:-157.81-32.09). Six studies reported no side effects.None of the included studies reported use of allocation concealment or blinding.
Conclusion: UDCA-SAMe combination therapy is better than either UDCA or SAMe monotherapy for improving the outcome of ICP without adverse effects. Large-scale trials with adequate sample sizes and higher quality study design are needed to further confirm the efficiency and safety of UDCA and SAMe for treating ICP.