Cholestasis of Pregnancy, Intrahepatic

Description

• Intrahepatic cholestasis of pregnancy (ICP) is characterized by generalized pruritus without skin lesions in pregnancy, accompanied by elevated serum bile acid levels +/− elevated serum transaminase levels (1,2).
• It occurs classically in the 3rd trimester but may begin in the 2nd trimester.
• It is a self-limited condition that resolves shortly after delivery.
• ICP is associated with adverse fetal outcomes, including premature delivery, meconium-stained amniotic fluid, respiratory distress, and fetal death (1,2).

Epidemiology

Incidence

• Varies between 0.2% and 25% worldwide (1)
• ICP is most common in China, Latin American, and Scandinavian countries.

Prevalence
Reports vary between 0.5% and 6.0% according to geography and ethnicity (2).

Etiology and Pathophysiology

• Genetic, endocrine, and environmental factors influence the risk of developing ICP (2).
• Its onset coincides with rising progesterone levels (2).
• Maternal pruritus may be related to a TGR5-mediated signaling pathway in sensory nerves, induced by bile acid (3).
• Sulfated progesterones and lysophosphatidic acid also play a role in pruritus (2,3).
• Some fetal complications may be due to bile salt accumulation in fetal tissues, leading to fetal arrhythmias and liver damage (4).
• Bile acids may vasoconstrict the chorionic veins, leading to decreased perfusion to the fetus (4).
• Bile acids may also increase oxytocin activity, leading to preterm delivery (4).

Genetics

• Heterozygous mutations in the ABCB4 gene, which encodes a hepatocanalicular transporter, have been implicated in many cases (3).
• Heterozygous mutations of other transporter genes, such as ABCB11 play a smaller role (3).

Risk Factors

• 2nd or 3rd trimester of pregnancy
• Multiple gestation (1)
• Family history of biliary disease (5)
• History of ICP in a previous pregnancy
• Advanced maternal age (1)
• Hepatitis C (1)
• Winter season/low vitamin D level (1)
• Low selenium level (1)
• Pregnancy achieved with in vitro fertilization (5)

Commonly Associated Conditions

• Oral contraceptive–induced pruritus (3)
• Incidence of concomitant hepatitis C infection is higher in women with ICP (1).
• Pregnancy complications: postpartum hemorrhage (4), preeclampsia (2), gestational diabetes (2), and 19–60% increased risk preterm delivery (6)
• Neonatal complications: 17.9% risk of meconium passage, 29% risk of respiratory distress syndrome (6)