Intrahepatic cholestasis of pregnancy (ICP) is a condition found in fewer than 1% of pregnant women in most countries. ICP typically develops in the second half of pregnancy as the result of defective bile acid transport, which leads to the release of liver enzymes and bile acids into the maternal circulation. Itching—the commonest symptom—may interfere with sleep, but in other respects the maternal disorder is benign and does not predispose to liver failure. The fetus, however, is at increased risk of preterm birth, intrauterine demise or stillbirth, and mecomium aspiration.
This study compared two drugs, given separately and in combination. Both S-adenosyl-L-methionine (SAMe) and ursodeoxycholic acid (UDCA) enhance the excretory function of hepatocytes, stimulate choleretic activity, and dilute toxic bile acids in the enterohepatic circulation. UDCA also reduces the accumulation of bile acids in the fetus, and SAMe increases trans-sulfuration of bile acids, which increases their excretion. One or both of these drugs were given to 78 women with singleton pregnancies at less than 36 weeks’ gestation who had moderate or severe ICP as evidenced by high self-reported symptom scores. One group of 25 patients received SAMe at a dose of 500 mg twice daily by slow running infusion for 12 days, followed by 500 mg daily by mouth until delivery. Another 26 women received UDCA orally in a dose of 250 mg 3 times a day. The remaining 27 women received both these treatments. The treatment groups were similar obstetrically at the outset.
Although all 3 treatments resulted in improvement of maternal symptoms, more women had a favorable response to UDCA alone or in combination with SAMe than to SAMe alone. UDCA given alone or combined with SAMe resulted in greater decreases in the concentrations of bile acids and transaminases compared to SAMe alone, and a favorable response in most women (85% to UDCA alone and 89% to combined therapy). Monotherapy with SAMe did not significantly alter biochemical parameters. Only one patient, treated with UCA alone, became worse. The response was also more rapid—within 7 days of initiating treatment—with UDCA alone or in combination than in SAMe alone, but was fastest with combination therapy. However, by two weeks of therapy there was no difference between the two UDCA groups. There were no significant group differences in the duration of treatment, which ranged from 1 to 12 weeks. All treatments were well tolerated and no adverse side effects were recorded. No perinatal deaths occurred, but premature deliveries before 36 completed weeks of gestation exceeded the population average in all treatment groups. Birth weights below the 10th centile of national growth curves were, however, within the limits of the population average in all groups.
UDCA, alone or combined with SAMe, appears to be an effective treatment for ICP. Antepartum and intrapartum monitoring of the fetus should be routine when severe ICP is present.