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.
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