London, UK—A drug pharmacists regularly dispense for a common pregnancy liver disorder might not be effective after all.

In fact, a study published in The Lancet suggests that the use of ursodeoxycholic acid, commonly known as urso, is ineffective and should be reconsidered for intrahepatic cholestasis of pregnancy (ICP). Expectant mothers with the condition are at risk for preterm birth and stillbirth.

To reach that conclusion, Kings College London–led researchers conducted a trial at 33 hospital maternity units in England and Wales between December 2015 and September 2018. Participants included 605 pregnant women with ICP—half received urso and half were given a placebo.

The study team collected blood tests and samples, measured the women's level of itching, and recorded birth information. They determined that urso did not affect pregnancy outcomes, including preterm birth, neonatal unit admission, and stillbirth. It also didn’t improve the itching or bile-acid levels for most women, according to the report.

Background information in the study points out that intrahepatic cholestasis of pregnancy—with symptoms including maternal pruritus and increased serum bile acid concentrations—is associated with increased rates of stillbirth, preterm birth, and neonatal unit admission.

“Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base,” the study team asserted. “We aimed to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.”

For the study, participants 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. Clinicians, at their discretion, could increase or decrease the dosage to a maximum of four tablets and a minimum of one tablet a day. Researchers urged that treatment should be continued from enrollment until the infant’s birth.

Defined as the primary outcome was a composite of perinatal death (in-utero fetal death after randomization or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks’ gestation), or neonatal unit admission for at least 4 hours (from birth until hospital discharge).

The authors report that 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, 0·62-1·15]). While two serious adverse events were reported in the ursodeoxycholic acid group and six serious adverse events were reported in the placebo group, no serious adverse events were regarded as being related to treatment, they note.

“Treatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy,” the researchers conclude. “Therefore, its routine use for this condition should be reconsidered.”

“We want to find a safe and effective treatment for women with cholestasis of pregnancy, so that we can prevent stillbirths in this condition,” said lead author Lucy Chappell, PhD, of the Department of Women & Children's Health at King’s College London. This trial has shown that the widely used drug ursodeoxycholic acid is not the answer. It is essential that we share these findings with pregnant women and clinicians so that we can avoid unnecessary medication in pregnancy. We now need to focus on finding a treatment that does work.”

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