Intrahepatic Cholestasis of Pregnancy
Intrahepatic cholestasis of pregnancy (ICP), or obstetric cholestasis, is a relatively rare condition that occurs when bile salts build up in a woman’s circulation causing extreme itching (no rash).
The condition likely occurs due to hormonal effects on the liver, gallbladder, and bile duct system which is also responsible for the increased risk of gallstones during pregnancy.
By itself, itching is very common during pregnancy; itching related to ICP is described as relentless, extreme, intense, and even debilitating. Fortunately, this condition resolves after delivery.
Women should call their HCP if they are concerned about intense itching, if they notice any additional symptoms described below, or if they need help managing even moderate skin itching during pregnancy.
Intrahepatic cholestasis of pregnancy (ICP) is a potentially serious liver disorder characterized by severe, intense itching from a build up of bile (also known as obstetric cholestasis, cholestasis of pregnancy, jaundice of pregnancy or pruritus/prurigo gravidarum).
Intrahepatic: occurring with or within the liver
Cholestasis: the obstruction of the flow of bile from the liver cells
Bile: released by the liver, stored in the gallbladder, and helps digestion; if the bile duct is blocked, it builds up in the liver, causing intense itching and jaundice
Bilirubin: a yellowish byproduct of the normal breakdown of red blood cells; passes through the liver and then excreted in urine and stool
Jaundice: yellowing of the skin and eyes, caused by a build up of bilirubin
Normally, bile acids flow from the liver to the stomach and intestines to help digest food. In ICP, obstruction occurs in the liver which blocks the flow of bile. This back up of bile acids is theorized to cause severe itching by accumulating in body tissues and triggering an itching sensation (the exact mechanism for this trigger is unknown). However, some research disputes bile as the specific cause for itching.
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.
Incidence of ICP is varies widely, to a reported 1 in 100 to 1 in 5,000 pregnancies. ICP requires medical attention to avoid possible complications.
ICP is likely caused by a combination of hormonal, genetic, and environmental factors.
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.
Signs and Symptoms
The most obvious symptom of cholestasis of pregnancy is itching (no rash) all over the body that usually begins in the second and third trimesters but has been reported to occur as early as 8 weeks of pregnancy. (Note: Intense itching does not always indicate ICP.) A rash could occur, but is more likely the result of intense scratching, rather than a direct result of ICP.
The itching is often:
Mild to completely disabling
More noticeable on the hands and feet (where it may start), as well as the limbs, back, and abdomen
Worse at night, which can dramatically impact sleep and functional ability during the day
Other symptoms can include:
Pale/oily bowel movements (increases risk of Vitamin K deficiency and therefore an increased hemorrhage risk)
Jaundice (can develop before or after the itching, occurs in 10% to 15% of women with ICP)
HCPs may request lab work and will usually see elevated liver enzymes and/or increased level of total serum bile acids.
Complications and Management
Gallstones: Pregnant women already have an increased risk of developing gallstones compared to women who are not pregnant.
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.
Gestational Diabetes: A study published in June 2021 indicated that women diagnosed with ICP have an increased risk of also being diagnosed with gestational diabetes. The authors noted the two conditions may have biological similarities.
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.
Preterm birth: With untreated/unmanaged ICP, it is estimated 30% to 60% of women will go into spontaneous preterm labor.
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.
Recurrence of the condition in subsequent pregnancies occurs in 70% of women with a history of ICP. The condition could also recur with the use of oral contraceptives; a risks and benefits discussion of method of birth control after delivery should be discussed with an HCP.
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.
Women should call their HCP anytime they are experiencing unmanageable and intolerable itching. Although itching is common, HCPs will want to perform a physical assessment to rule out conditions such as ICP and Polymorphic Eruption of Pregnancy (also known as PUPPP).
Women should also consider sharing and submitting their experience below regarding ICP during pregnancy. This can help other women learn additional perspectives regarding this concern, how to potentially manage symptoms, and what they should ask their HCP.
Intrahepatic Cholestasis of Pregnancy (American Liver Foundation)
Obstetric Cholestasis (Royal College of Obstetricians and Gynaecologists)
Skin Conditions During Pregnancy (American College of Obstetricians and Gynecologists)