Intrahepatic Cholestasis of Pregnancy

Despite this conflict, there is further causal evidence pointing toward bile acids. The most effective drug for ICP and its intense itching is a drug called ursodeoxycholic acid (more below). The drug works by reducing bile acids in cord blood, colostrum, and amniotic fluid, and subsequently relieves itching.

Progesterone’s “relaxation” effects on muscle (necessary to inhibit contractions) likely slows the movement of bile from the liver through the bile ducts as a “side effect”. This slow down promotes obstruction and/or collection, leading to complications of buildup (read more in Gallstones).

Additionally, in one small study of progesterone supplementation of 12 women at risk for preterm labor, 11 of the 12 women developed ICP; these results have been replicated in other studies, further indicating a potentially significant role of progesterone in the condition.

Estrogen is another hormone at play: multiple pregnancies (twins or higher) have a five-fold greater prevalence of ICP, likely due to higher levels of estrogens. Oral contraceptives with high estrogen levels can also lead to cholestatic conditions similar to ICP.  Further, women who had ICP during pregnancy can develop ICP symptoms if they use oral contraceptives after delivery (see below).

There may also be a seasonal component of ICP, as it appears the condition may occur most often in the winter months; more research is needed to determine an explanation, but selenium deficiency has been hypothesized since selenium levels tend to be lower in winter months.

Women with ICP who are pregnant for the first time have an additional 2.7-fold increased risk of developing gallstones compared to pregnant women without cholestasis.

Further, a study published in November 2021 determined that gestational diabetes was more common in women diagnosed with mild ICP.

A retrospective cohort study of patients diagnosed with ICP between 2012 and 2019 at a tertiary referral center published in October 2021 determined those with pre-gestational diabetes, history of ICP, prior cholecystectomy (gall bladder removal), and tobacco use were more likely to develop severe ICP disease.

There is much debate about if or how much the fetus may be affected when the mother has ICP.  It is possible the build up of bile salts in the mother can pass to the fetus, causing fetal distress, meconium-stained amniotic fluid, or preterm labor. Stillbirth has also been documented to occur.

A December 2020 study indicated that ICP can cause abnormal fetal heart function due to elevated bile acids in untreated ICP. The study noted that treatment with ursodeoxycholic acid (UDCA) (see more below) can partially prevent/treat this result.

Complications for both mother and baby are prevented with early treatment and induction/delivery between 36 to 40 weeks if the fetus’ lungs are mature. Early delivery depends on the mother’s liver function tests and her individual history. Symptoms resolve almost immediately after delivery.

For itching control, antihistamines offer little help with ICP compared with general itching during pregnancy. UDCA is reported to be the only known effective treatment of ICP, is taken by mouth, and has a good safety profile.

However, not all studies agree on its effectiveness. A study published in October 2020 found no beneficial effect of treatment with UDCA on bile acid concentration or itch score in women with ICP. These researchers indicated that the routine use of UDCA should be reconsidered, but that the medication could be effective in specific groups of women.

A study published in May 2021 determined that patients with severe ICP displayed a higher recurrence rate in their second pregnancies. Being less than 28 weeks at the time of ICP diagnosis and having Hepatitis B infection in the previous delivery also appear to be independent predictive factors for ICP recurrence.