URSODEOXYCHOLIC ACID IN THE TREATMENT OF CHOLESTASIS OF PREGNANCY - ARANDOMIZED, DOUBLE-BLIND-STUDY CONTROLLED WITH PLACEBO

Background/Aims: Intense pruritus and the risk of stillbirths and prem ature deliveries justify the search for an effective pharmacologic tre atment of intrahepatic cholestasis of pregnancy This study was designe d to test the efficacy of ursodeoxycholic acid in maternal pruritus, t he biochemical abnormalities and the outcome of pregnancy in patients with intrahepatic cholestasis of pregnancy of early onset. Methods: Pr egnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotran sferases, detected before week 33 of pregnancy were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally or an identical pl acebo, until delivery in a double-blind study A 3-week trial period wa s chosen to compare drug and placebo effects, The follow-up was extend ed for 3 months after delivery. Results: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dr opped out, The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo, No adverse effects were detec ted in the mothers or in their babies, After 3 weeks of treatment, pat ients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body we ight) had a significant improvement in pruritus (p<0.02), in serum bil irubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.38 in patients r eceiving placebo, p<0.01), in aspartate aminotransferase (52+/-32 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 mu mol/l vs 55.0/-44.8, p N.S.), Deliveries occurred at or near term in all mothers wh o received ursodeoxycholic acid (mean week of pregnancy: 38), while th ey occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth, All babies born alive had birth, we ights adequate for gestational age and they were thriving normally 3 m onths after delivery. Conclusions: Ursodeoxycholic acid is effective a nd safe in patients with intrahepatic cholestasis of pregnancy of earl y onset, attenuating pruritus and correcting some biochemical abnormal ities in the mothers, Relevant aspects of fetal outcome were also impr oved in patients receiving ursodeoxycholic acid compared to placebo.