Pitch: Ursodeoxycholic acid versus placebo, and early delivery versus expectant management in the management of intrahepatic cholestasis of pregnancy: Two randomised controlled trials.

Objectives: Intrahepatic cholestasis of pregnancy (ICP) causes maternal pruritus and is associated with adverse fetal outcomes. There is considerable uncertainty as to whether ursodeoxycholic acid (UDCA) alleviates itching or improves fetal/neonatal outcomes in women with ICP and whether the benefits of early term delivery are outweighed by the risks when compared to expectant management. The aim of the trial was to test the hypothesis that UDCA reduces maternal itching in women with ICP, and that early term delivery does not increase rate of Caesarean section. Materials: 125 women with ICP took part in the trial. The trial was conducted in nine consultant-led maternity units in the United Kingdom. Methods: We conducted two semi-factorial double blind randomised controlled trials 1) UDCA vs. placebo and (2) early term delivery vs. expectant management. For the drug comparison, the primary endpoint was maternal itching. For the timing of delivery comparison, Caesarean section was the primary endpoint. Secondary endpoints included improvement in biochemical parameters and fetal/neonatal outcomes. Results: Of the 111 women randomised to the drug comparison, women treated with UDCA had a 16mm (95% CI 6 to 27) reduction in itching on a 100mm visual analogue scale, which was statistically significant (p = 0.003). However, the pre-specified clinically meaningful reduction of pruritus defined as 30mm reduction by obstetricians and women was not reached. Women in the UDCA group also had a significant reduction in ALT, GGT and bilirubin levels, but the improvement in bile acid and AST levels were not significant. There were no stillbirths or neonatal deaths. Gestational age at delivery, preterm delivery, mode of delivery and birth weight did not differ between the two groups. However, pregnancies treated with UDCA had lower rates of passage of meconium stained liquor. 63 women were randomised to the timing of delivery comparison. 7/30 (23%) in the immediate delivery group had a Caesarean section compared to 11/33 (33%) (Risk ratio 0.70 (0.31 to 1.57)). There was no difference in other major neonatal outcomes. Conclusions: UDCA significantly reduces maternal pruritus in women with ICP. However, this improvement in pruritus is less than the level pre-specified as clinically valuable by clinicians and women. Planned early term delivery does not increase incidence of Caesarean section.