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

  • ┬áIntra-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.