Ursodeoxycholic Acid is of Limited Benefit in Obstetric Cholestasis

Intrahepatic cholestasis of pregnancy, or obstetric cholestasis, is a condition that generally occurs in late pregnancy and involves intense pruritus, usually on the hands and feet but can occur elsewhere on the body, otherwise unexplained altered liver enzyme levels, and elevated serum bile acid levels. There are no long-term risks for the mother, but the dangers for a developing fetus include preterm birth, meconium in the amniotic fluid, and death.

Cholestasis refers to any condition in which the flow of bile slows or stops. The cause of obstetric cholestasis is unknown but may involve pregnancy hormones affecting the functioning of the gallbladder. Risk factors for cholestasis are a family or personal history of the condition, liver damage, twin pregnancy, and a pregnancy that involved in vitro fertilization.

Despite insufficient evidence to support the practice, many physicians treat obstetric cholestasis with ursodeoxycholic acid (UDCA) to reduce pruritis and hepatic impairment. In the largest trial to date comparing UDCA with placebo in women with obstetric cholestasis and the first-ever trial studying the timing of delivery in this group of women, researchers found that use of ursodeoxycholic acid significantly reduces pruritus.¹

In the UDCA trial, the initial dosage of UDCA was 500 mg/d, but if no improvement of itching was noted, the daily dose was increased by 500 mg every 3 to 14 days until the maximum dosage of 2 g/d was achieved. A 30-millimeter improvement in the pruritic rash was predetermined to be a clinically significant outcome. Compared with women in the placebo group (n = 37), women in the treatment group (n = 44) reported an overall 16-millimeter improvement. Although this difference was significant (P = 0.003), the predetermined treatment outcome was not achieved. Women in the treatment group had significantly reduced levels of alanine transaminase, gamma-glutamyltransferase, and bilirubin. Babies in the treatment group were significantly less likely to have meconium-stained amniotic fluid.

In the timing of delivery trial (n = 62), women were randomized to either early-term delivery (scheduled induction or delivery between 37 weeks 0 days and 37 weeks 6 days) or to expectant management. If delivery had not occurred by 40 weeks 0 days, obstetricians could arrange delivery. Women in the early-term delivery group gave birth 0.6 weeks earlier than the women in the expectant management group. Maternal and fetal outcomes, including cesarean section, were similar for both groups.

Pertinent Points:
- Ursodeoxycholic acid significantly reduces pruritus, but the benefit may be too limited for physicians to recommend it or for patients to want to take it.
- Planned early delivery as a means to reduce risks to the fetus and to alleviate pruritis in the mother does not seem to be associated with an increase in cesarean section incidence.

References:

1. Chappell LC, Gurung V, Seed PT, et al, for the PITCH Study Consortium. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ. 2012;344:e3799. doi: 10.1136/bmj.e3799.