Feto-Maternal Effects of Adding Rifampicin to Ursodeoxycholic Acid in the Treatment of Intrahepatic Cholestasis of Pregnancy

Background Various pharmacological agents are used to manage intrahepatic cholestasis of pregnancy (ICP) for maternal pruritus and to lower serum bile acids in fear of adverse fetal outcomes. Ursodeoxycholic acid (UDCA) is the most widely used drug, but some patients do not respond to it. Neither UDCA nor any other drug being used for ICP is based on a high level of evidence. Methods A total of 108 pregnant women with ICP who were receiving UDCA with or without rifampicin were included in a prospective observational study from December 2018 to November 2020. Seventy-eight patients receiving UDCA only were labeled as group A, and 30 patients receiving UDCA with rifampicin were labeled as group B. Results The study subjects were comparable in both groups with respect to demographic factors. Pruritus, being the major symptom of ICP, has a mean (standard deviation (SD)) onset at 30.02 (2.93) weeks and 26.70 (4.56) weeks of gestation in groups A and B, respectively. Group B patients had earlier onset of symptoms and earlier mean (SD) gestational age at diagnosis at 28.89 (4.29) weeks compared to 32.47 (2.93) weeks in group A. Therefore, the mean (SD) gestational age to start UDCA was early in group B (29.32 (4.24) weeks). Relief in itch from UDCA was seen in 93.59% (73) in group A and 10% (3) in group B (partial relief). The mean (SD) duration for receiving only UDCA was 3.84 (2.07) weeks and 2.86 (1.58) weeks, respectively, for groups A and B. The mean (SD) gestational age at starting rifampicin was 32.11 (3.4) weeks for group B (n = 30). UDCA plus rifampicin was given for a mean (SD) duration of 3.48 (1.42) weeks. The mean (SD) dosage of UDCA given per day was 911.54 (229.05) mg in group A and 880 (260.50) mg in group B (p value = 0.563). The mean (SD) dosage of rifampicin used in group B was 700 (363.89) mg/day. The mean (SD) of baseline bile acids (pretreatment) was 36.94 (13) umol/L and 42.50 (15.23) umol/L in groups A and B, respectively (p value = 0.274). At the two-week follow-up, the mean (SD) value of serum bile acids was 22.92 (10.67) umol/L and 14.88 (10.27) umol/L in groups A and B, respectively (p value = 0.039). Group B having an earlier onset of ICP also had early gestational age at delivery at 35.70 (2.57) weeks versus 37.011 (1.18) weeks in group A. Of the babies in groups A and B, 63% and 50% were born full term, respectively. There was no significant difference in the mode of delivery for both study groups. The mean (SD) birth weight of babies was 2,706.85 (206.19) grams for group A and 2,522.67 (342.20) grams in group B. Adverse neonatal outcomes for both groups were comparable (68.5% in group A and 70% in group B) (p value = 0.881). Of the patients, 9% and 6.7% had antepartum stillbirth in groups A and B, respectively. Of the babies in groups A and B, 10.3% and 6.7% were born with dark-colored meconium or placental membranes and cord stained with meconium, respectively. In groups A and B, 9% and 6.7% of the babies were born with thin/light green meconium-stained liquor, respectively. Conclusion Rifampicin, if added to UDCA for the management of ICP, does not cause any adverse fetal outcome. It is a useful adjunct to UDCA for severe and/or resistant ICP, and it helps improve pruritus and serum bile acids.