Jaundice in Pregnancy

Introduction

Jaundice in pregnancy usually indicates a liver/biliary disorder and becomes clinically apparent when the serum bilirubin exceeds 2 – 2.5 mg/dL.

Many indicators of liver disease in the non pregnant State are normal findings in pregnancy. These include:

• Spider naevi
• Decreased plasma albumin
• Increased serum lipids

Prothrombin time, transaminases and bilirubin are unaltered in normal pregnancy.

Jaundice occurs in about 1 in 1,500 to 2,000 pregnancies

Aetiology

Aetiology peculiar to pregnancy

• Hyperemesis gravidarum
• Pre-eclampsia and eclampsia as seen with HELLP syndrome
• Acute yellow atrophy (acute fatty liver in pregnancy; acute hepatic failure)
• Intra-hepatic cholestasis of pregnancy
• Cholestasis in pregnancy
• Gallstones

Aetiology not peculiar to pregnancy

• Viral hepatitis
• Haemolytic jaundice
• Adverse reactions to drugs e.g. chlorpromazine, tetracycline
• Congenital hyperbilirubinaemias such as Dubin-Johnson syndrome
• Liver cirrhosis

Clinical features

1. Acute yellow atrophy
2. Cholestasis of pregnancy
3. Dublin Johnson syndrome
4. Intrahepatic cholestasis of pregnancy
5. Viral hepatitis

1. Acute yellow atrophy

• A rare and serious disorder associated with high mortality
• Occurs in the order of 1: 10,000 pregnancies
• Unknown aetiology
• Typically noted in primigravidae, occurring after the 30 week of pregnancy or few days after birth
• The jaundice is classically obstructive
• Onset usually sudden with
  • Abdominal pain (right upper quadrant)
  • Headaches
  • Nausea and vomiting
  • Progressive jaundice
  • Encephalopathy
  • Hypertension is not uncommon

Histology

• Perilobular fatty infiltration of the liver cells
• There is no place for liver biopsy because of risk of severe bleeding complications

Management

Early diagnosis is mandatory

• Clinical features with evidence of
  deranged LFTs and of renal failure
• The management requires a combined team of obstetrician, physician and anaesthetist

Definitive treatment

• Deliver the baby as soon as possible (frequently by Caesarean section)

Supportive measures

• Transfusion with blood, fresh frozen plasma, platelets as indicated
• Renal dialysis

Complications

• Disseminated intravascular coagulopathy
• Hypotension
• Significant risk of maternal and fetal death due to:
  • Maternal liver failure
  • Metabolic disturbance
  • Encephalopathy
  • Overwhelming haemorrhage associated with clotting defects

Prognosis

• Good
• Post-natally, liver function returns to normal over a few weeks and there is no evidence of long-term liver dysfunction

2. Cholestasis of pregnancy

• This is uncommon, in the order of 1: 2,000 pregnancies.
• Common in certain southern American countries particularly Chile
• Presents commonly in late third trimester, after 36 weeks.
• Clinically significant because of its association with intra-uterine fetal growth retardation (IUGR) and intra-uterine fetal death (IUFD) (mechanism unclear).
• It is not as a rule associated with maternal complications

Clinical features

• Generalized pruritus
• Decreased fetal movements
• Upper abdominal pain
• Dark urine
• Steatorrhea
• Occasionally there is jaundice (particularly in the later stages of the disease)

Investigations

• Liver function tests:
  • Mildly deranged
  • Serum bilirubin and bile salts may be elevated

Differential diagnoses

• Viral hepatitis
• Early HELLP syndrome
• Acute fatty liver

Management

• Careful maternal follow-up with LFTs
• Fetal surveillance:
  • by growth (serial ultrasound biometry) and
  • wellbeing (cardio tocographic fetal) monitoring
• If all is well induce at 38 weeks

Management of associated pruritus:

• (Difficult to manage)
• Topical agents offer little help

Colestyramine

• To bind bile salts.

Vitamin K

• To decrease bleeding tendencies
• (Colestyramine binds fat soluble vitamins)

Antihistamines

• May offer brief respite

Ursodeoxycholic acid and colestyramine
(orally) decrease itching and normalize liver function

• Adult: 10- 15 mg/kg daily in 2 – 4 divided doses
• Child:
  • 1 month -18 years: 10- 15 mg/kg twice daily; total dose may be given in 3 divided doses

Recurrence

• Quite high

Prognosis

• Good
• Complete recovery in days to weeks

3. Dubin-Johnson syndrome

• Intermittent bilirubinaemia (conjugated)
• Often chronic and familial
• No itching, usually asymptomatic
• Cause is unknown

Treatment

• None is required

3. Intra-hepatic cholestasis of pregnancy

•  Intra-hepatic cholestasis of pregnancy is also termed ‘recurrent obstructive jaundice or ‘idiopathic cholestasis.
• Thought to be due to the effect of high estrogen levels on the liver, which results in decreased conjugation of bilirubin
• A rare condition
• Incidence of 1:500 pregnancies
• More commonly seen in among Scandinavians
• Its exact etiology is unknown

Clinical features

• Intense pruritus due to retention of bile salts
  • The most common presenting symptom and may occur in the absence of other symptoms
• Onset of symptoms usually in the third trimester.
• Jaundice is not often seen.

Investigations

• Elevated bile acids
• Bilirubinuria
• Elevated alkaline phosphatase
• Elevated liver transferase enzymes
• Prothrombin time

Always exclude viral disease, gallstones
treatment with chlorpromazine

Complications

Maternal

• Haemorrhage
• Preterm labour
• Steatorrhea

Fetal

• Fetal distress
• Still-birth
• Perinatal death
• Prematurity and its problems
• Meconium staining of the liquor

Management

• Careful maternal follow-up with LFTs
• Fetal surveillance:
  • by growth (serial USS biometry) and
  • well-being (CTG) monitoring
• If all is well, induce at 38 weeks

Management of pruritus

See Cholestasis of pregnancy

Recurrence

• Risk of recurrence is 50%
• Can be precipitated by estrogen-containing oral contraceptive pills

4. Viral hepatitis

• The most common cause of jaundice in pregnancy, accounting for about 40% of cases
• Incidence during pregnancy is probably no more than in the normal population
• Pregnancy does not alter the course of the disease
• Hepatitis A virus does not affect the fetus, but hepatitis B and C can cross over the placenta to affect the fetus.
  • Unlike other hepatotrophic viral infections, which carry a significant risk of vertical transmission (particularly in the third trimester)
• A severe attack may influence fetal outcome
  • Slight increase in premature labour and stillbirths (as seen in any severe medical illness)

Treatment

• Avoid any further damage to the liver by drugs
• Bed rest
• Adequate nutrition
• If hepatitis B is present then the infant requires protection with immunoglobulins against HBsAg
• Hepatitis B immunoglobulin by intramuscular Injection
  • Neonate: 200 units as soon as possible after birth
  • Child 1 month -5 years: 200 units;
  • 5-10 years: 300 units;
  • 10-18 years: 500 units
• Avoid breastfeeding
• Delivery room personnel must exercise great care in dealing with these patients, as all their
  body fluids are highly infectious
• Immediate delivery if hepatitis becomes fulminant
• Ideally, all women should be tested for hepatitis B and C antibodies at the first antenatal visit.
• And women should be
  immunized against these viruses before pregnancy.