1.Overview
Intrahepatic cholestasis: intrahepatic cholestasis of pregnancy (ICP) is a unique complication of mid- and late pregnancy, characterized by pruritus and jaundice as the main clinical manifestations and elevated serum bile acids. It mainly affects the fetus and increases the rate of perinatal morbidity and mortality. The greatest risk to pregnancy is the sudden and unpredictable death of the fetus. The incidence of ICP ranges from 0.1% to 15.6%, with significant geographical and ethnic differences. The incidence is higher in intelligence, Sweden and the Yangtze River basin in China.
2.Clinical manifestations
Typical symptoms: The first symptom is pruritus without skin damage occurring in late pregnancy, which occurs after 30 weeks in about 80% of patients, or even earlier in some cases. The degree of itching varies and is often persistent, light during the day and increasing at night. Pruritus usually begins on the palms of the hands and feet and then gradually extends to the proximal extremities and may even progress to the face, but rarely invades the mucous membranes. This pruritic symptom is present for an average of about 3 weeks, but also for several months, and is relieved 24-48 hours after delivery, and rarely in 1 week or more.
Other symptoms: 10%-15% of patients develop mild jaundice, the appearance of jaundice is closely related to the prognosis of the fetus, and there is a significant increase in amniotic fluid contamination, neonatal asphyxia and perinatal mortality in those with jaundice. Generally there are no obvious gastrointestinal symptoms, a few pregnant women present with epigastric discomfort and mild steatorrhea.
Signs: striped scratches on the skin due to itching and scratching.
3. Detailed explanation
3.1 Etiology
It is still unclear and may be related to female hormones, genetics and environmental factors.
Effects of ICP on pregnant women: Typical symptoms of ICP are itching, which can cause unbearable itching and insomnia, and reduced absorption of vitamin K in ICP patients, resulting in abnormal coagulation and postpartum hemorrhage.
Effects of ICP on infants: Perinatal morbidity and mortality are significantly higher due to the toxic effects of bile acids. Fetal distress, preterm delivery, and contamination of amniotic fluid with placenta and feces can occur. In addition, there are unpredictable sudden fetal deaths and intracranial hemorrhage in newborns.
In other pregnancy complications and complications, fetal death is often preceded by many signs, such as abnormal fetal movement and fetal heart changes, but in ICP patients, fetal death is often sudden and without any signs, sometimes fetal heart monitoring is normal in the morning, but the fetus may die suddenly in the afternoon, which is often difficult for pregnant women and their families to accept, so it is important to raise awareness of the dangers of ICP.
3.2 Examination methods
(1) Serum bile acid measurement.
Serum total bile acid determination is the most important laboratory basis for the diagnosis of ICP and an important indicator for monitoring the condition and the effect of treatment, as well as the main specific evidence of ICP. Pruritus without causation and serum TBA >10umol/L can be used as a diagnosis of ICP, and serum TBA ≥40umol/L suggests a more severe condition. Serum glycopyrrolate is highly sensitive and can be used as an indicator for screening and follow-up of ICP.
(2) Liver function measurements.
Most patients with ICP have mild to moderate elevation of portal aminotransferase (AST) and alanine aminotransferase (ALT), which are 2 to 10 times the normal level, and ALT is more sensitive than AST; some patients have mild-moderate elevation of serum bilirubin.
(3) Hepatitis virus assay.
Hepatitis virus testing was negative in patients with simple ICP.
(4) Ultrasound of the liver.
There are no characteristic changes in the liver of ICP, so liver ultrasound is of little significance for the diagnosis of ICP, and is only of some significance in ruling out the presence of underlying diseases of the hepatobiliary series in pregnant women.
(5) Liver pathology.
The examination is only performed when the diagnosis is unclear and the disease is serious
(6) Placental pathology examination.
ICP placental intervillous cavity is narrowed, but whether the placental weight, volume and thickness are different is unknown.
3.3 Diagnosis
Based on typical clinical symptoms and laboratory findings, the diagnosis of ICP is not difficult. However, other diseases causing abnormal liver function or pruritus need to be excluded.
4.Treatment
The goals of treatment are to relieve pruritus symptoms, improve liver function, lower blood bile acid levels, enhance monitoring of intrauterine conditions of the fetus, prolong gestational weeks and improve pregnancy outcome.
(1) General treatment: appropriate bed rest in the left lateral position to increase placental blood flow, intermittent oxygen, hypertonic glucose, vitamins and energy combination to both protect the liver and improve fetal tolerance to hypoxia. Regularly retest liver function and serum bile acids to understand the condition.
(2) Drug therapy: Drugs that can reduce the clinical symptoms of pregnant women and improve the biochemical indicators of cholestasis and the prognosis of the perinatal baby are
Ursodeoxycholic acid: it is the first-line drug for ICP treatment. Pruritic symptoms and biochemical parameters can be significantly improved. Liver function is checked every 1-2 weeks during treatment to detect changes in biochemical parameters.
S-adenosylmethionine: clinical second-line drug for the treatment of ICP.
Dexamethasone: It can promote fetal lung maturation and avoid respiratory distress syndrome in preterm infants, and is used before 34 weeks of gestation for those estimated to be likely to deliver prematurely within 7 days.
(3) Adjunctive therapy.
Hepatoprotective therapy: Hepatoprotective therapy using oral or intravenous drugs on top of bile acid lowering therapy ;
Improvement of pruritus symptoms: giving certain topical medications (e.g., glycolic lotion) can improve pruritus symptoms;
Application of vitamins: To prevent postpartum bleeding, vitamins can be given.
Chinese medicine treatment
(4) Obstetric management.
Prenatal monitoring: weekly non-stimulated fetal heart monitoring (NST) test from 34 weeks of gestation, fetal biophysical scoring if necessary for early detection of occult fetal hypoxia. In severe cases, early admission to hospital for delivery is indicated. Count fetal movements daily. If there are less than 10 fetal movements in 12 hours, the fetus should be alerted to intrauterine distress. Regular ultrasound examination to note any amniotic fluid hypotension.
Terminate pregnancy at the right time: ICP is not an indication for cesarean delivery. However, because ICP is prone to acute fetal hypoxia and stillbirth, there is no effective monitoring means to predict fetal hypoxia. Most scholars recommend inducing labor at 37-38 weeks of gestation in ICP patients, actively terminating the pregnancy, and strengthening fetal monitoring during delivery. For severe ICP with ineffective treatment, combined with multiple fetuses and severe pre-eclampsia, cesarean section is feasible to terminate the pregnancy.
5. Precautions after treatment
At 6 to 12 weeks after the birth of the baby, the pregnant woman should go for a liver function check, which can help her determine the correctness of the diagnosis of obstetric cholestasis at the time of pregnancy. If the lab results are still abnormal, then the pregnant woman should see a liver disease specialist for further treatment.
6.Preparation for medical consultation
When a pregnant woman develops itchy skin during pregnancy she should pay special attention to it and needs to go to the obstetrics department in time for positive laboratory tests. ICP needs to be identified with a variety of diseases and these need to be referred to a specialist, but there is no need to be overly worried and to pay enough attention to understand the dangers of the disease and to listen to the doctor’s advice to minimize the impact of ICP on the mother and child as much as possible.
7.The most frequently asked questions
(1) Can a pregnant woman with ICP have a normal delivery?
Patients with mild ICP, with no contraindications to vaginal delivery, can have a vaginal trial of labor after the full term of pregnancy, depending on the condition of the cervix and active induction of labor. If there is ineffective treatment for severe ICP; previous history of stillbirth, neonatal asphyxia or stillbirth; severely reduced placental function or high suspicion of fetal distress; combined twin or multiple births, severe preeclampsia, etc.; and other contraindications to vaginal delivery, cesarean delivery should be chosen to terminate the pregnancy.
(2) Who is prone to ICP?
Maternal factors: maternal age >35 years or older; having chronic hepatobiliary disease; having ICP in the family; history of ICP in the previous pregnancy.
Current pregnancy factors: significantly higher prevalence of ICP in twin pregnancies compared to singleton; increased relative risk of ICP development in pregnant women after artificial insemination.