Patient's question:
Description of the problem: I am 15 weeks pregnant, and 20 days ago, I noticed some itching on my legs, back, and abdomen, especially at night. I had liver function tests and liver function test 2 done at the hospital, which were normal, but the individual test for glycocholic acid showed a value of 2406 (the normal value on the report is less than 300). The doctor said it could be intrahepatic cholestasis of pregnancy and prescribed Ursodiol Ursodeoxycholic Acid Capsules for me. Could you please advise on how to handle this situation? Is the medication prescribed by the doctor suitable for me?Doctor's answer:
Normal serum glycocholic acid (CG) levels: 1.3 ± 0.8 mg/L, range 0.4–2.98 mg/L, with a lower diagnostic threshold for hepatitis of 3.Clinical significance:
(1) In acute hepatitis, chronic active hepatitis, primary liver cancer, cirrhosis, and chronic persistent hepatitis, blood CG levels are significantly higher than in normal individuals and show progressive increases.
(2) In patients with cholelithiasis and jaundice, impaired excretion function of the bile duct and gallbladder leads to significantly elevated serum CG levels.
(3) In cirrhosis, obstructive liver disease, and intestinal–hepatic circulation disorders, serum CG levels are higher than in normal individuals.
4. Clinical significance of glycocholic acid in obstetrics
Glycocholic acid is the predominant bile acid component in serum during late pregnancy. During normal pregnancy, a woman’s serum CG levels gradually increase with gestational age, rising by 30%–60% compared to non-pregnant levels at term. As pregnancy progresses, elevated progesterone levels reduce smooth muscle tone, leading to decreased gallbladder contractility and impaired bile excretion, causing varying degrees of bile stasis. Thus, serum CG levels may physiologically rise in some pregnant women without significant icteric cholestasis (ICP) symptoms. However, as CG levels increase, they cause varying degrees of harm to both mother and fetus, with higher levels posing greater risks.
Multiple studies suggest that during pregnancy, the placenta synthesizes and secretes large amounts of estrogen and progesterone, increasing metabolic load and potentially inducing changes in the liver and biliary system, making pregnant women susceptible to ICP. In ICP patients, serum CG levels are significantly elevated, sometimes up to 10–100 times higher than in normal pregnant women. Elevated CG levels in ICP are associated with increased rates of amniotic fluid contamination, preterm birth, fetal distress, and cesarean delivery. When CG levels exceed 10-fold, these risks further escalate.
In ICP, bile stasis and cholestasis plugs are observed in the central hepatic lobules and capillaries, impairing bile excretion and causing the accumulation of bile acids in the peripheral circulation, leading to elevated serum CG levels and symptoms such as pruritus. Elevated bile acids in both maternal blood and amniotic fluid expose placental villous veins to high concentrations of bile acids, causing vasoconstriction, spasms in placental villous vessels, reduced oxygenated blood flow, and fetal hypoxia, which may result in complications such as fetal distress and preterm birth.
Domestic reports indicate preterm birth rates of 13%–42.4% and fetal distress rates of 44%–60.6%. ICP significantly impacts perinatal outcomes, primarily causing preterm birth and fetal distress. International studies report preterm birth rates of 20%–60% and fetal distress rates of 20%–30%, with perinatal mortality rates of 1%–3%. Some research suggests that elevated serum bile acids stimulate and enhance smooth muscle motility, increasing the risk of spontaneous preterm birth.
ICP has become a major contributor to rising cesarean delivery and preterm birth rates. Current studies indicate that high maternal serum levels of bile acids and bilirubin can cross the placenta into the fetus, damaging mitochondrial membranes through cytotoxic effects and generating reactive oxygen species, directly harming fetal cells and tissues, leading to respiratory dysfunction and impaired fetal oxygen utilization. Bilirubin also enhances the cytotoxic effects of bile acids, increasing their toxicity, while bilirubin itself has cytotoxic properties, inhibiting oxidative phosphorylation and reducing ATP production. As serum CG and bilirubin levels rise, perinatal outcomes worsen.
For ICP patients, timely termination of pregnancy remains a challenging issue for obstetricians. Premature termination increases perinatal morbidity and mortality, while delayed termination carries risks of fetal distress or stillbirth. Early detection of ICP and assessment of its severity are crucial for appropriate management. Most experts now advocate for intrapartum monitoring and timely intervention to reduce adverse perinatal outcomes.
ICP patients can be classified into mild and severe groups based on CG and total bilirubin (TBIL) levels, facilitating clinical monitoring and management. Pregnant women (≥37 weeks) followed in high-risk clinics should undergo proactive intervention and early termination of pregnancy, ideally before 40 weeks. For recurrent ICP or those with a history of neonatal death, termination of pregnancy at 35 weeks may be considered to reduce perinatal mortality.