Cholestasis Symptoms: Causes of Itching in Pregnant Women

Cholestasis Symptoms: Causes of Itching in Pregnant Women

Pregnancy can bring about various changes in a woman's body, and one uncommon but potentially serious condition is cholestasis. This liver disorder occurs in late pregnancy and is characterized by intense itching, particularly on the palms and soles of the feet. Cholestasis symptoms can be distressing for expectant mothers and may have implications for both maternal and fetal health.

Understanding cholestasis and its symptoms is crucial for pregnant women and healthcare providers alike. This article explores the causes of itching in pregnant women related to cholestasis, delves into diagnosis methods, and discusses treatment options. It also examines potential complications for mother and baby, including the risk of jaundice in newborns. By shedding light on this condition, we aim to help expectant mothers recognize the signs and seek timely medical attention.

Diagnosing Cholestasis in Pregnant Women

Diagnosing intrahepatic cholestasis of pregnancy (ICP) involves a combination of clinical symptoms, physical examination, and laboratory tests. This condition typically develops during the third trimester, although it may occur as early as the end of the first trimester 1.

Physical examination

During a physical examination, healthcare providers assess the patient's symptoms, particularly the presence of pruritus (intense itching) in the third trimester. They also evaluate the patient's medical history, including any previous occurrences of ICP or family history of the condition 2. The skin is inspected to rule out other causes of itching, such as eczema or scabies 2.

Blood tests

Blood tests play a crucial role in diagnosing ICP. The most sensitive and specific marker for ICP is the total serum bile acid test, with a sensitivity of 91% and specificity of 93% 3. A diagnosis is confirmed when total bile acids are 10 micromoles per liter or above 4. Most studies use an upper limit of bile acids between 10 and 14 micromoles/L for diagnosis 3.

Other liver function tests are also conducted:

1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): These enzymes are usually mildly elevated, not exceeding two times the upper limit of normal value in pregnancy 3 5.
2. Alkaline phosphatase: This can be elevated physiologically up to four times the upper normal value but has little diagnostic significance in ICP 3.
3. Bilirubin: Elevated in about 25% of cases, rarely exceeding 6 mg/dL 3 5.
4. Prothrombin time: May be elevated due to vitamin K deficiency 3.

It's important to note that approximately 60% of people with ICP will have elevated liver functions during their pregnancies 5. Blood tests are typically conducted weekly if normal, or bi-weekly if abnormal 2.

Ultrasound and other imaging

Ultrasound scans are often used to examine the liver and gallbladder, as they are safe during pregnancy 2. These scans help to rule out other liver abnormalities and detect the presence of gallstones, which are observed in 13-20% of ICP cases 1.

In some cases, magnetic resonance cholangiopancreatography (MRCP) may be performed to demonstrate intra- and/or extrahepatic cholelithiasis 1.

Throughout the diagnostic process, healthcare providers also monitor fetal well-being through ultrasound scans and cardiotocograph monitoring 2. Regular antenatal visits are scheduled every two weeks in suspected cases to closely monitor the condition 2.

Treatment Options for Cholestasis

Medications

The primary treatment for intrahepatic cholestasis of pregnancy (ICP) is ursodeoxycholic acid (UDCA). This naturally occurring bile acid competes with more toxic bile acids, facilitating their elimination 6. UDCA is the first-line treatment recommended by the Society for Maternal-Fetal Medicine (SMFM) 6. The recommended daily dosage ranges from 600-2000 mg, with an initial starting dose of 300 mg twice daily 3. If symptoms persist, the dose can be increased to a maximum of 21 mg/kg/day 3.

UDCA has shown beneficial effects for both the fetus and the pregnancy, including reducing the risk of meconium staining, protecting the baby's heart against bile acid-induced changes, and restoring the placenta's ability to transport bile acids away from the baby 6. Most patients experience symptom relief within two weeks of starting treatment 3.

In cases where UDCA is ineffective or contraindicated, alternative medications may be considered. These include:

1. Rifampin: Increases bile acid detoxification and excretion 3
2. Cholestyramine: Decreases ileal absorption of bile salts 3
3. S-adenosyl-L-methionine (SAMe): Administered intravenously 6 3
4. Antihistamines: Such as diphenhydramine or hydroxyzine, to alleviate pruritus and insomnia 7

Lifestyle Changes

While no diet or medication can prevent cholestasis of pregnancy, certain dietary modifications may help reduce bile acid levels during pregnancy 8. These include:

1. Consuming plenty of protein and fiber
2. Eating foods with medium-chain fatty acids (MCFAs)
3. Increasing intake of vitamins A, C, E, and K
4. Consuming extra omega-3 fatty acids
5. Staying hydrated

It's also recommended to avoid alcohol, highly preserved and processed foods, and foods high in oxalates 8.

Early Delivery Considerations

Early delivery is often considered the only known intervention to reduce the risk of stillbirth in ICP cases 9. The timing of delivery should balance the risk of fetal death against the potential risks of prematurity 3. Current recommendations for delivery timing include:

1. For bile acids under 100 μmol/L: Delivery between 36 0/7 and 39 0/7 weeks gestation 6
2. For bile acids over 100 μmol/L: Delivery at 36 0/7 weeks gestation 6

In cases with unrelieved itching, a prior stillbirth, or worsening liver disease, delivery may be considered between 34-36 weeks gestation 6. Betamethasone is recommended for pregnancies delivered before 37 weeks to aid fetal lung maturity 6.

Potential Complications for Mother and Baby

Maternal risks

Intrahepatic cholestasis of pregnancy (ICP) primarily affects the mother's liver function but generally has few long-term consequences for maternal health. The most common long-term risk for women who have experienced ICP is an increased likelihood of developing gallstones and other gallbladder diseases 10. In some cases, women with ICP may have their gallbladders removed either before or after pregnancy. It's important to note that ICP does not decrease life expectancy compared to the general population 10.

Fetal risks

ICP poses significant risks to the developing fetus. The most concerning complication is sudden intrauterine fetal demise (IUFD), which has an odds ratio of 1.46 compared to healthy pregnancies 3. This risk increases with higher levels of maternal bile acids, particularly when they exceed 100 micromol/L 3. Other fetal complications associated with ICP include:

1. Meconium-stained amniotic fluid (odds ratio 2.60)
2. Spontaneous preterm birth (odds ratio 3.47)
3. Iatrogenic preterm birth (odds ratio 3.65)
4. Neonatal ICU admission (odds ratio 2.12) 3

Babies born to mothers with ICP are also nearly three times more likely to experience respiratory problems at delivery compared to those born to mothers without ICP 11. This may be due to high bile acid levels interfering with the normal synthesis of surfactant, which is crucial for lung development 11.

Long-term effects

Recent studies have revealed potential long-term effects on children born to mothers with ICP. By age 16, boys born from cholestatic pregnancies had a significantly higher body mass index, up to four points higher than those born from normal pregnancies 12. They also showed elevated fasting insulin levels, a symptom associated with type 2 diabetes 12. Girls born to mothers with ICP had increased waist measurements (up to 9cm) and hip measurements (up to 5cm) compared to their peers 12.

Research using mouse models has supported these findings, showing that offspring from cholestatic pregnancies are more prone to obesity and diabetes 12. These metabolic changes may result from alterations in placental fat metabolism and nutrient supply during pregnancy, potentially leading to epigenetic changes in the offspring 12.

In summary

Cholestasis during pregnancy is a complex condition that has a significant impact on both maternal and fetal health. The diagnosis, treatment, and management of this disorder require a careful balance between addressing the mother's symptoms and ensuring the baby's safety. Early detection through proper testing and monitoring is key to mitigate risks and implement timely interventions.

As research continues to uncover potential long-term effects on children born to mothers with cholestasis, healthcare providers must stay informed and provide comprehensive care. This condition serves as a reminder of the intricate connection between maternal health and fetal development. To wrap up, cholestasis in pregnancy highlights the need for vigilant prenatal care and collaborative efforts between obstetricians, hepatologists, and pediatricians to ensure the best possible outcomes for both mother and child.

FAQs

1. How severe is the itching from cholestasis during pregnancy?
Intense itching without any accompanying rash is the primary symptom of cholestasis in pregnancy. This sensation is most commonly felt on the palms and soles, but it can occur all over the body. The itching typically worsens at night and can be severe enough to disrupt sleep.

2. What causes itching during pregnancy?
Itching during pregnancy can occur as the skin stretches, particularly over the abdomen, which becomes itchy as the bump grows. However, itching can also be a sign of a liver disorder known as intrahepatic cholestasis of pregnancy (ICP), or obstetric cholestasis (OC), which requires medical treatment.

3. When does cholestasis typically begin in pregnancy?
Intrahepatic cholestasis of pregnancy usually starts in the late second trimester or early third trimester, often becoming noticeable after the 30th week. The most frequent symptom is widespread severe itching, particularly affecting the palms and soles, and is more intense during nighttime.

4. What are the treatment options for cholestasis in pregnancy?
To alleviate severe itching caused by cholestasis during pregnancy, healthcare providers may prescribe ursodiol (Actigall, Urso, Urso Forte), which helps reduce bile acid levels in the blood. Additionally, other medications to help relieve itching may be considered.

References

[1] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899155/
[2] - https://www.news-medical.net/health/Diagnosis-of-intrahepatic-cholestasis-of-pregnancy-(ICP).aspx
[3] - https://www.ncbi.nlm.nih.gov/books/NBK551503/
[4] - https://my.clevelandclinic.org/health/diseases/17901-cholestasis-of-pregnancy
[5] - https://icpcare.org/intrahepatic-cholestasis-pregnancy/diagnosis/
[6] - https://icpcare.org/intrahepatic-cholestasis-pregnancy/treatment/
[7] - https://emedicine.medscape.com/article/1562288-medication
[8] - https://zayacare.com/blog/cholestasis-of-pregnancy-diet/
[9] - https://www.contemporaryobgyn.net/view/should-women-intrahepatic-cholestasis-pregnancy-be-delivered-early
[10] - https://icpcare.org/considerations-after-icp-pregnancy/
[11] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9681709/
[12] - https://www.news-medical.net/news/20130625/Study-examines-long-term-effects-on-babies-born-to-mothers-with-obstetric-cholestasis.aspx