Cholestasis Of Pregnancy: What’s It About?

Overview: What’s Cholestasis In Pregnancy & How Common Is It?

Are you having severe itching on the palms of your hands or the soles of your feet in middle or late pregnancy? Talk to your healthcare provider. You might be experiencing cholestasis. (1)(2)(3)

It’s a rare pregnancy condition that only affects about 0.8% of pregnant women in the US and around 0.5 to 1.5% across Europe. This condition causes intense pruritus (itching), which can make you feel very uncomfortable and even affect your sleep in more serious cases. (1)

Cholestasis is a liver disorder characterized by higher levels of serum bile acids, which may be affected by pregnancy hormones (estrogen and progesterone). The higher the bile levels, the greater the risk of stillbirth and other complications. (1)(2)

Bile is a fluid formed by the liver that helps in digestion. In cholestasis, the flow of bile is reduced or even stopped. The blockage causes bilirubin (a waste product from red blood cells) to escape and accumulate in your bloodstream instead of getting eliminated properly from the body. (4)

Did you know that as many as 23% of pregnant women can experience pruritus at some point in their pregnancy, but only a small percentage is due to cholestasis? That’s why blood tests are also done to diagnose the condition. (1)

It’s unclear, however, why some ethnicities are more prone to cholestasis than others. (2)

Researchers still haven’t determined the exact reasons why this condition causes serious fetal complications. However, some studies indicate this might be because maternal bile acids can cross your placenta and accumulate in the amniotic fluid. (1)(2)

In this article, we’ll discuss the risk factors, causes, and symptoms of cholestasis. You’ll also find the diagnostic tests and treatment options available for those with this condition.

We’ll also discuss whether this condition can be prevented and how to minimize the risks to your baby.

How Serious Is Cholestasis?

Its rarity doesn’t make it less serious. Unlike other dermatoses (problems of the skin) in pregnancy, cholestasis can cause significant risk to your unborn baby: (1)

13.4% risk of premature births
18.7% risk of fetal distress, including meconium (first stool) passage and abnormal heart rate
0.91% risk of stillbirth
2.12% risk of NICU (neonatal intensive care unit) admission

When Does Cholestasis Of Pregnancy Usually Start?

This condition usually appears by the late second or early third trimester, though some women might experience this earlier in pregnancy. The good news is that it typically goes away shortly after giving birth. (1)(2)

Other Names For Cholestasis In Pregnancy

This medical condition is also known by these other terms: (1)(2)

ICP (intrahepatic cholestasis of pregnancy)
Obstetric cholestasis
Jaundice in pregnancy (because this symptom can appear around 1-4 weeks after the onset of itching in about 14-15% of patients)
Idiopathic jaundice of pregnancy
Recurrent jaundice in pregnancy
Obstetric hepatosis
Hepatosis gestationalis

Symptoms of ICP Or Cholestasis In Pregnancy

The most common symptoms of cholestasis: (1)(2)(3)

Mild to extreme itching without rashes or skin lesions (but these can appear later as an effect of scratching)
Dark urine
Light-colored, foul-smelling stools

Itching from cholestasis usually affects the soles of the feet or palms of the hands. However, you can also experience this in other parts of your body. The symptoms might even worsen at night and can affect your sleep. (3)

Other Signs You Might Notice

Some pregnant women might also experience the following symptoms: (1)(3)(4)

Jaundice (yellowish skin and/or the whites of your eyes)
Nausea
Oily, foul-smelling stools
Steatorrhea (high amounts of fat in the stool)
Loss of appetite
Nausea
Vomiting
Right upper quadrant pain
Sleep deprivation

What Causes Cholestasis In Pregnancy?

Pregnancy Hormones & Their Effect On Bile Transport

Increased levels of pregnancy hormones (e.g., estrogen and progesterone) are believed to affect bile transport. This is also the reason why oral contraceptives, known to contain these hormones, can also trigger cholestasis outside of pregnancy. (4)

Environmental Factors

The exact environmental factors that can cause cholestasis have not been established. However, some studies have shown that a lack of sun exposure, which can lead to reduced vitamin D levels, may be linked to cholestasis. (1)

Low selenium levels in your diet can also cause cholestasis. Foods rich in selenium include meat, poultry, organ meats, seafood, nuts, grains, and dairy products. (1)(5)

Genetics & Family History

Genetic predisposition is believed to be a common cause and risk factor for cholestasis. This may be apparent with the increased risks with: (1)

First-degree relatives
Recurrence rate for moms who had cholestasis in previous pregnancies
Same ethnic groups

Combination Of Everything

It’s also possible that cholestasis might be due to a combination of two or all of these factors. (1)

Risk Factors For Cholestasis In Pregnancy

Personal Medical History Of Cholestasis

Moms who’ve had a previous history of cholestasis may also be more prone to experiencing the same in future pregnancies (with a 60-70% risk of recurrence). (1)

ABCB11 Or ABCB4 Gene Mutations

Possible mutations with the following genes may also pose increased risks: (1)

ABCB4
ABCB11
ATP8B1
ABCC2
NR1H4

Genetics Or Family History Of Cholestasis

Up to as much as 50% of reported cholestasis cases have a family history of this condition. (1)

Multiple Pregnancies

Cholestasis can have a 20.9% chance of occurring with twin pregnancies. It’s higher than the 4.7% chance with singletons (pregnancy with one baby). (1)

Not surprisingly, triplet pregnancies may have a higher incidence of cholestasis (43%) than twin pregnancies (14%). (1)

Personal Medical History of Hepatitis Or Other Liver Disease

Because it’s a liver condition, it’s also unsurprising that moms who have had other liver diseases are more prone to experiencing cholestasis in pregnancy. Examples of these liver conditions include: (1)(4)

Alcohol-related liver disease
Acute hepatitis
Chronic hepatitis C virus infection
Primary biliary cholangitis (with possible scarring and inflammation of the bile ducts)
Cirrhosis from viral hepatitis B or C (also possible scarring and inflammation of the bile ducts)
Gallstones in the bile duct
Stricture or narrowing of a bile duct
Pancreatitis (inflammation of the pancreas)
Cancer of the bile duct
Cancer of the pancreas
Cancer in other parts of the body that has metastasized (spread) to the liver

Certain Medications

Drugs or medications that might trigger cholestasis: (4)

Amoxicillin/clavulanate (antibiotic and β-lactam drug combination)
Chlorpromazine (medication for bipolar disorder, acute psychosis, and schizophrenia; use only when needed during pregnancy)
Azathioprine (for rheumatoid arthritis or to prevent organ rejection after a transplant)

Certain Races Or Ethnicities

The number of cholestasis cases varies globally, ranging from less than 1 to around 27.6%. While the overall incidence is only at around 0.8% in the US, primarily Hispanic moms may have a 5.6% chance of developing this pregnancy condition. (1)

It can also be more prevalent in the following areas than in North America and Europe: (1)(2)

South America (especially Chile and Bolivia)
Scandinavia

The Araucanos Indians (Chile) have an incident rate of 27.6%, the highest globally. (1)

Surprisingly, the condition is more prevalent during the winter months than in other seasons of the year in these areas: (2)

Chile
Finland
Sweden
Portugal

Researchers are unsure why the incident rates vary greatly across different ethnicities and areas. However, they believe this might be due to exposure to different environmental factors or possibly differences in susceptibility among the ethnic groups. (1)

IVF Procedure

If you’ve undergone an IVF (in vitro fertilization) procedure to get pregnant, it might lead to ovarian hyperstimulation syndrome. This can increase your risks of cholestasis. (1)

Geriatric Pregnancy

Advanced maternal age (pregnancy at 35+ years old) may also increase your risks for cholestasis. (1)

Seeking Help For Cholestasis In Pregnancy

Where Should You Go?

Obstetrician and gynecologist (OB/GYN)
Your family doctor

When To See Your Doctor

As soon as possible after experiencing any of the symptoms

How To Prepare For Your Appointment

What To Bring & Do

List of Signs & Symptoms Experienced

All the symptoms you might have noticed, aside from itching
These symptoms can help your doctor determine if you might have cholestasis or possible complications

Your Medical History

Include previous history of cholestasis or even itching with previous pregnancies
Liver-related conditions, including possible liver damage or problems with liver function

Medicines & Treatments

All the medications you’re taking, including herbal medicines and supplements
All recent and past treatment procedures, including alternative treatments

Bring A Notebook Or Paper

You can use this to take notes or write down your questions
You can also use your phone for note-taking

Prepare A List Of Cholestasis Questions You Want To Ask

Some questions you might want to ask your doctor:

What are my risks with cholestasis of pregnancy?
Are there symptoms I need to watch out for?
What tests do you recommend to diagnose if I have cholestasis?
Do you think my condition is serious, and what are possible complications I might experience?
What are my intervention options, and is my baby going to be alright with our treatment plan?
Would you recommend an early delivery?
Will cholestasis of pregnancy affect my labor and delivery?
Will I need monitoring? If yes, how many times do I need to undergo tests?
Should I make lifestyle or diet changes to alleviate my symptoms and prevent the recurrence of cholestasis?
What are my risks of getting another cholestasis of pregnancy in the future?

Ask A Loved One Or Friend To Come With You

They can also be your support group

What Your Doctor Might Do & Recommend

Ask about your personal and family history, especially with cholestasis during pregnancy and/or liver conditions
Check your skin for signs of lesions or rashes
Recommend diagnostic tests (e.g., blood tests for total bile acids, bilirubin, serum aminotransferase, etc.)
Recommend a treatment plan to reduce your baby’s risks for preterm delivery or stillbirth

Tests & Diagnosis For Cholestasis In Pregnancy

Some tests that your healthcare provider might recommend to diagnose your condition: (4)

Blood tests
Ultrasound scan
Liver biopsy

Blood tests that show a high level of bile acids (more than 40 micromol/L) can indicate cholestasis. (1)

Your doctor might also check for the following blood test results: (1)

Serum aminotransferase – Can reach up to 1000 unit/L
Total and direct bilirubin concentrations
Serum concentration of GGT (gamma-glutamyl transpeptidase)

Treatment For Cholestasis In Pregnancy

Considerations Before Choosing A Treatment Plan

There are other possible reasons for itching during pregnancy. So, it’s essential to determine the cause of your condition to ensure that the right treatment plan will be implemented. (1)

Your doctor might suggest weekly monitoring or further tests (this depends on the results of your blood tests, the possible severity of your condition, and your medical history). (1)

The two main goals of cholestasis treatment: (1)

Ease the itching, especially with extreme pruritus
Reduce your baby’s fatality risks

Soothe The Itching

UDCA (Ursodeoxycholic Acid)

Your doctor will likely prescribe UDCA or ursodeoxycholic acid to manage your symptoms. Possible treatment plans until delivery: (1)

300 mg 3x times daily (or at 15 mg/kg per day)
300 mg 2x daily (or at 10 mg/kg per day)

The medication can help reduce your symptoms within 1-2 weeks. If your symptoms persist, your doctor might increase the dose to the maximum (up to 21 mg/kg daily). (1)

Studies have shown that UDCA can help reduce maternal pruritus but doesn’t appear to have fetal or newborn benefits. (1)

For example, maternal itching was reduced, and ALT (alanine aminotransferase) levels improved in a 2019 The Lancet randomized control trial. However, it had little effect on reducing adverse effects such as stillbirth or preterm labor. (1)(6)

Creams & Medications

Some creams and other medications to help soothe itching and help you sleep: (1)

Calamine lotion
Dexamethasone
Hydroxyzine

Home Remedies To Soothe Itching

Some home remedies that you might want to consider for itching: (1)

Charcoal
Herbal remedies (check with your doctor before use)

Clothes To Consider To Avoid Itching

Wear comfortable clothes, such as those made of cotton material.

Monitor Baby’s Condition

Fetal Nonstress Heart Rate Testing & Monitoring

NSTs (nonstress tests) are used to monitor your baby’s rate. However, some researchers recommend further testing and monitoring because fetal deaths have still been recorded despite good NST scores. This might be because fetal deaths in cholestasis are believed to be sudden instead of gradual events caused by placental or other problems. (1)

Fetal BPP (Biophysical Profile)

Tests for your baby’s biophysical profile might be done twice a week, with continuous monitoring until delivery. (1)

Amniocentesis Testing

Your amniotic fluid might also be tested for the presence of meconium (first stool), which can be a sign of fetal stress and can be dangerous to your baby. (1)

Early Delivery (If Needed)

High levels of total bile acid concentrations are associated with stillbirth. So, your doctor might recommend early delivery (or a nonspontaneous preterm birth). However, a preterm delivery has various risks, including breathing difficulties, because your baby’s lungs and other organs might still be developing. (1)

Preterm delivery is only recommended when absolutely necessary and must be avoided if bile acids are within or close to normal levels. (1)

Possible delivery timing, depending on your bile acid levels and other factors: (1)

<40 micromol/L: 37 to 38 weeks of gestation
40 to 99 micromol/L: 36 to 37 weeks of gestation
≥100 micromol/L: 36 weeks of gestation

Delivery before 36 weeks of gestation might be considered in the following cases: (1)

Previous history of fetal death before 36 weeks due to ICP (only if there’s recurring ICP in the current pregnancy)
Extreme itching that isn’t relieved by medications
Worsening liver function

However, delivery is typically delayed for as long as possible to at least 34 weeks of gestation. (1)

Note that in the absence of total bile concentration results, and especially if you’re at 39 weeks of gestation (full-term), your doctor might recommend labor induction if you have symptoms of cholestasis. (1)

Alternative & Complementary Medicine Options

Other medicines that your doctor might prescribe if itching doesn’t improve with the maximum UDCA dose: (1)

Cholestyramine (given orally from 2-4 mg/day to 16 mg/day; however, it can cause abdominal discomfort, constipation, and malabsorption of fat and fat-soluble vitamins like vitamin K)
S-adenosyl-methionine (given at 800-1000 mg/day; however, it can be inconvenient because it’s usually administered intravenously like dextrose rather than orally)
Rifampin or rifampicin (given at 300-1200 mg/day; however, this can cause decreased appetite, hemolytic anemia, nausea, renal failure, and hepatitis)

However, studies with these other medications have conflicting results and can also have side effects (as detailed above).

Treatments Or Medications That Must Be Avoided If You Have Cholestasis In Pregnancy

Antihistamines aren’t usually used for cholestasis treatment because an allergic reaction doesn’t cause the condition. However, they might still be prescribed to alleviate itching in some cases. (7)

Health Monitoring

Your OB/GYN might recommend weekly monitoring to check if your symptoms have improved after your treatment started. Monitoring might continue after delivery, especially if you remain symptomatic. (1)

Outlook When You Have Cholestasis In Pregnancy

Possible Complications: What Happens To The Baby If The Mom Has Cholestasis?

Preterm Labor & Birth

Cholestasis can lead to preterm birth (delivery before 37 weeks of pregnancy or gestation). (1)

Cases with an earlier onset of itching are more likely to lead to premature labor than those that start in late pregnancy. (1)

Researchers believe that early labor may be due to the higher levels of bile acids activating oxytocin receptors in the myometrium (the uterus’ muscular outer layer). Oxytocin induces labor contractions. (1)

Stillbirth Or Fetal Death

The higher the build-up of bile in the blood, the greater the risks for stillbirth or fetal death: (1)

0.3% risk for 40 to 99 micromol/L
6.8% risks for ≥100 micromol/L

The exact reasons for fetal death are unknown but can be attributed to the following, which may be due to higher bile acid levels: (1)

Fetal arrhythmia (abnormal heart rate)
Vasospasm (narrowed arteries)
Coexistent pregnancy complications, such as preeclampsia (characterized by high blood pressure, high protein levels in your urine, and swelling in your feet, legs, and hands) and gestational diabetes (diabetes that only happens during pregnancy)

Fetal Distress & Meconium Passage

Cholestasis can also cause fetal distress. Signs can include: (7)(8)

Abnormal heart rates: too fast (more than 100 beats per minute) or too slow (less than 60 beats per minute)
Decreased or slower movement
Abnormal levels of amniotic fluid
Thick meconium in the amniotic fluid

Respiratory Distress After Birth

Possible signs of respiratory distress: (8)

Breathing troubles
Wheezing
Flaring nostrils

Postpartum Hemorrhage Or Bleeding

The conditions that affect the bile can also cause poor absorption of vitamin K (needed for blood clotting), which can lead to postpartum bleeding or hemorrhage. (4)

Nutrient Deficiencies

Bile blockage can lead to nutrient deficiencies and clotting problems due to poor absorption of calcium and vitamin D. It may lead to bone tissue loss. (4)

Can You Still Have a Healthy Baby Even With A Cholestasis?

Yes. Maternal cholestasis during pregnancy might not affect your baby’s liver function. However, there may be a higher risk of stillbirth or problems associated with preterm birth (if delivered before full-term). (1)

Will Cholestasis Still Affect You After Birth?

Cholestasis in pregnancy usually goes away shortly after birth and isn’t likely to cause problems with breastfeeding. (1)

However, hepatology tests and monitoring might still be done if you continue to show symptoms even after delivery. (1)

Will You Experience Cholestasis Again In Future Pregnancies?

Possibly. Patients who experience cholestasis have a 60-70% chance of recurrence in future pregnancies. (1)

How To Prevent Or Avoid Cholestasis In Pregnancy

Is There A Way To Prevent Cholestasis In Pregnancy?

No. You can’t prevent cholestasis but can still reduce the risks during pregnancy (such as with birth control changes discussed below). (3)

What Foods Should You Avoid With Cholestasis Of Pregnancy?

Your doctor might recommend a low-fat diet. (9)

Changes In Future Birth Control Methods

Progestin-only oral contraceptives might be preferable to estrogen-progestin contraception to reduce the risks of recurrent cholestasis in future pregnancies. (1)(4)

Clinical Trials On Cholestasis Of Pregnancy Treatments

Clinical trials on cholestasis treatments, especially with UDCA, are limited and have a small sample size. However, UDCA has been shown to be effective in some of these studies, and there aren’t other medications with similar or better outcomes. So, they remain the treatment of choice unless future trials show better options. (10)

Other Pregnancy Concerns & Complications

References

(1) https://medilib.ir/uptodate/show/3560

(2) Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009 May 7;15(17):2049-66. doi: 10.3748/wjg.15.2049. PMID: 19418576; PMCID: PMC2678574.

(3) https://www.beaconhealthsystem.org/library/diseases-and-conditions/cholestasis-of-pregnancy?content_id=CON-20338994

(4) https://www.msdmanuals.com/home/liver-and-gallbladder-disorders/manifestations-of-liver-disease/cholestasis

(5) https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

(6) https://pubmed.ncbi.nlm.nih.gov/31378395/

(7) Pillarisetty LS, Sharma A. Pregnancy Intrahepatic Cholestasis. [Updated 2023 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.

(8) https://www.medicinenet.com/what_are_signs_of_fetal_distress/article.htm

(9) Send SR. Nutritional Management of Cholestasis. Clin Liver Dis (Hoboken). 2020 Feb 25;15(1):9-12. doi: 10.1002/cld.865. PMID: 32104570; PMCID: PMC7041952.

(10) https://www.cochrane.org/CD000493/PREG_interventions-treating-intrahepatic-cholestasis-pregnancy-icp