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Evidence summaries

Interventions for Treating Cholestasis in Pregnancy

Ursodeoxycholic acid (UDCA) may reduced adverse maternal and fetal outcomes and slightly improve pruritus for cholestasis in pregnancy compared with placebo. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 26 RCTs involving 2007 women. The trials were small and heterogeneous assessing 9 different interventions. Compared with placebo, ursodeoxycholic acid (UDCA) showed small improvement in pruritus on a 100 mm visual analogue scale (VAS) (mean difference [MD] 7.64 points, 95% CI 9.69 to 5.60 points; 2 trials, n=715). The evidence for fetal distress and stillbirth were uncertain.

A meta-analysis 3 included 12 RCTs involving a total of 662 patients. In pooled analyses that compared UDCA with all controls, UDCA was associated with resolution of pruritus (RR 1.68; 95% CI 1.12 to 2.52; P=0.01),decrease of serum levels of alanine aminotransferase (ALT) (standardized mean difference (SMD), -1.36; 95% CI -2.08 to -0.63; P<0.001), reduced serum levels of bile acid (SMD, -0.68; 95% CI -1.15 to -0.20; P<0.001), fewer premature births (RR 0.56; 95% CI 0.43 to 0.72; P<0.001),reduced fetal distress (RR 0.68; 95% CI 0.49 to 0.94; P=0.02), high Apgar scores at 5 minutes (RR 0.44; 95% CI 0.24 to 0.82; P=0.009), less frequent respiratory distress syndrome (RDS) (RR 0.33; 95% CI 0.13 to 0.86; P=0.02), and fewer neonates in the intensive care unit (NICU) (RR,0.55; 95% CI 0.35 to 0.87; P<0.05), increased gestational age (SMD 0.44; 95% CI 0.26 to 0.63; P<0.001), and birth weight (SMD 0.21; 95% CI 0.02 to 0.40; P=0.03). There were no differences in meconium staining and intrauterine growth retardation (IUGR) between the groups (P>0.05). No trials reported adverse effects on mothers and fetuses except nausea and emesis.

A double-blind, multicentre RCT 2 included 605 women who were randomly assigned 1:1 to ursodeoxycholic acid or placebo, given as two oral tablets a day at an equivalent dose of 500 mg twice a day. The primary outcome was a composite of perinatal death (in-utero fetal death after randomisation or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge). The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0.85, 95% CI 0.62 to 1.15). Two serious adverse events were reported in the ursodeoxycholic acid group and 6 serious adverse events were reported in the placebo group; no serious adverse events were regarded as being related to treatment.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, blinding, selective reporting in some trials) and imprecise results.

    References

    • Walker KF, Chappell LC, Hague WM et al. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev 2020;(7):CD000493.[PubMed]
    • Chappell LC, Bell JL, Smith A et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet 2019;394(10201):849-860. [PubMed]
    • Kong X, Kong Y, Zhang F et al. Evaluating the effectiveness and safety of ursodeoxycholic acid in treatment of intrahepatic cholestasis of pregnancy: A meta-analysis (a prisma-compliant study). Medicine (Baltimore) 2016;95(40):e4949. [PubMed]

Primary/Secondary Keywords