What are the effects of cholestasis on a fetus and mother in late-term pregnancy?

Effects of Cholestasis in Late-Term Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) significantly increases the risk of stillbirth in the third trimester, with the risk escalating dramatically when bile acid levels exceed 100 μmol/L, particularly after 35 weeks gestation, necessitating early delivery to prevent fetal death. 1

Fetal Effects

Stillbirth Risk

• The most critical fetal complication is sudden intrauterine fetal death, which occurs predominantly in the third trimester and represents a sudden event rather than a chronic placental process. 1
• Stillbirths in ICP typically occur in appropriately grown fetuses without structural abnormalities, distinguishing this from other placental insufficiency conditions. 1
• The mechanism is thought to involve bile acid cardiotoxicity, as animal studies demonstrate that elevated bile acids have direct toxic effects on fetal cardiac tissue. 2
• When bile acids reach ≥100 μmol/L, the stillbirth risk increases substantially after 35 weeks gestation, which is why delivery at 36 0/7 weeks is mandated at this threshold. 1

Other Fetal Complications

• Spontaneous preterm birth occurs at increased rates in ICP, with ursodeoxycholic acid treatment shown to reduce this risk. 1, 3, 4
• Fetal anoxia and meconium-stained amniotic fluid are common complications, likely related to bile acid-induced fetal distress. 1, 3, 2
• Meconium staining occurs without the typical features of chronic placental insufficiency such as fetal growth restriction or oligohydramnios. 1
• Perinatal morbidity increases overall, though recent data suggest improved outcomes with intensive fetal surveillance and timely delivery. 1, 3, 2

Maternal Effects

Immediate Pregnancy Effects

• The primary maternal symptom is generalized pruritus, typically affecting palms and soles and worsening at night, which significantly reduces quality of life but does not cause direct maternal mortality. 5, 6, 7, 3, 2, 4
• Pruritus occurs in the absence of a primary rash, with only excoriations from scratching visible on examination. 5, 6, 2, 4
• Elevated liver transaminases (typically <500 U/L) and bile acids (>10 μmol/L diagnostic) are hallmark laboratory findings. 5, 6, 8, 3
• Mild jaundice occurs in only 10-15% of cases, with bilirubin typically remaining <5 mg/dL. 5

Vitamin K Deficiency and Bleeding Risk

• Cholestasis can lead to vitamin K deficiency due to impaired fat-soluble vitamin absorption, increasing maternal bleeding risk. 1
• This risk is exacerbated by cholestyramine use, which further impairs vitamin K absorption. 1
• Regular monitoring of prothrombin time (PT) during pregnancy is recommended in patients with cholestasis, with prompt parenteral vitamin K supplementation if deficiency develops. 1

Long-Term Maternal Health Consequences

• Women with ICP history face significantly elevated risks of future hepatobiliary disease, including chronic hepatitis (HR 5.96), liver fibrosis/cirrhosis (HR 5.11), hepatitis C (HR 4.16), and cholangitis (HR 4.2). 5
• These risks are particularly elevated within the first year after diagnosis. 6
• ICP may unmask underlying genetic bile acid transporter defects (ABCB11, ABCB4, ATP8B1 mutations) that predispose to chronic liver disease. 5, 2

Recurrence Risk

• The recurrence rate in subsequent pregnancies approaches 90%, requiring early counseling and monitoring in future gestations. 5, 6

Critical Management Implications

Bile Acid-Stratified Risk

• Bile acids ≥100 μmol/L: Deliver at 36 0/7 weeks due to substantially increased stillbirth risk. 1
• Bile acids 40-99 μmol/L: Deliver between 36 0/7 and 39 0/7 weeks. 1
• Bile acids <40 μmol/L: Consider delivery at term (39 weeks), though delivery between 36-39 weeks is still recommended. 1, 5

Monitoring Requirements

• Weekly bile acid monitoring from 32 weeks gestation is essential, as levels can rise rapidly and unpredictably near term. 1, 6, 7
• Antenatal fetal surveillance should begin when delivery would be performed in response to abnormal testing, with more frequent testing for bile acids ≥100 μmol/L. 1
• Continuous fetal monitoring during labor is mandatory due to increased stillbirth risk. 1

Treatment Impact

• Ursodeoxycholic acid (UDCA) 10-15 mg/kg/day reduces maternal pruritus, lowers bile acid levels, and decreases adverse outcomes including spontaneous preterm birth and possibly stillbirth. 1, 5, 6

Common Pitfall

• Never deliver before 37 weeks based on clinical suspicion alone without laboratory-confirmed elevated bile acids, as this exposes the neonate to unnecessary prematurity risks. 1, 5, 6