Jaundice in Pregnancy

Jaundice in pregnancy is rare but potentially serious to maternal and fetal health. It can be caused by pregnancy or occur intercurrently.

Commonest cause of jaundice in pregnancy with infections due to hepatitis viruses A, B, C, D and E.
Incidence of hepatitis varies greatly around the world: in developed countries, the incidence is around 0.1%, whereas in developing countries it can range from 3-20% or higher.
The course of most viral hepatitis infections (A, B, C, D) is unaltered by pregnancy, although in developing countries there is a higher incidence of infant mortality with fulminant hepatitis. The exception is hepatitis E where pregnant women who contract the disease exhibit fatality rates of 10-20%.

Hepatitis A

• Transmitted through contaminated food or water or by faecal-oral contact.
• After incubation period of 15-50 days, woman develops flu-like symptoms with weakness, fatigue, fever, anorexia, joint pain and headaches. This is followed by jaundice, dark urine, light stools and right-upper-quadrant tenderness.
• Disease usually lasts 2-3 weeks with death in <1% of patients and no chronic form.
• With symptoms, ALT and AST are elevated with IgM antibody detectable in serum (remains for 3-6 months followed by IgG antibodies that last for life).
• Isolate infected patient to prevent spread.
• Symptomatic treatment includes maintenance of adequate hydration and nutrition. Pregnant women exposed to the virus can be given immune globulin within 2 weeks of exposure together with vaccine.
• Not clear if virus transmitted from mother to baby and if IgM is present in mother during third trimester, prophylactic treatment of the neonate is probably unnecessary. However, if illness occurred in last month of pregnancy, neonate should receive immune globulin.

Hepatitis B³

• Commonest cause of acute viral hepatitis in pregnancy. Can occur in acute, subclinical or chronic form.
• Symptoms are similar to those of hepatitis A but symptoms of serum sickness, nephritis, essential mixed cryoglobulinaemia and aplastic anaemia are more frequent.
• Transmission is sexually, IV drug use, acupuncture, tattooing and via blood products.
• HBsAg (viral surface antigen) appears soon after onset of infection, reaches a maximum early in the disease and becomes undetectable in most cases a few weeks after recover. If it persists after 6 months, patients are chronic carriers. HbeAg is detectable in serum soon after HBsAg and then disappears within approximately 2 weeks with the appearance of its antibody HbeAb. The presence of HBeAg is associated with a very high risk of neonatal infection.
• All women should now be offered Hepatitis B screening as part of routine antenatal screening.
• Infants of HBsAg ve women should receive hepatitis B immune globulin immunoprophylaxis at birth and hepatitis B vaccine at one week, one month and six months old. This regime reduces the incidence of hepatitis B vertical transmission to less than 3%.
• The prevalence of neonatal infection depends on the time during gestation that maternal infection takes place: rare in first trimester, 6% in second trimester and 67% of those in the third trimester.

Hepatitis C

• Transmission similar to HBV but infection usually sub-clinical, so jaundice not present.
• No therapy has been shown to influence the neonatal transmission of hepatitis C virus.
• Interferon should not be used during pregnancy because of possible adverse effects on the fetus.

Hepatitis D

Develops as co-infection of superinfection with hepatitis B. When present it increases the incidence of acute hepatic failure.

Hepatitis E⁴

• Rare in the developed world, but in developing worlds where it is more common, responsible for high level of fulminant hepatic failure and mortality in pregnant women.
• It is a waterborne virus spreading through faecal-oral transmission. Outbreaks occur after flooding.

Epidemiology

May affect as many as 6% of pregnant women. Pregnancy alters bile composition and gall bladder emptying slows in the second trimester increasing the risk of gall stones.
Risk factors are multiparity and previous gallbladder disease.

Signs and symptoms

Symptoms are similar in pregnant and nonpregnant women. Usual presentation is with pain in the right-upper-quadrant or epigastrium peaking at 12-24 hours. This may radiate towards the back. and there may be epigastric or right-upper-quadrant tenderness. Murphy's sign (right-sided tenderness at tip of 9th costal cartilage as patient breathes in) is much less common in pregnancy.
Jaundice occurs only in 5% of occasions. Choledocholithiasis accounts for approximately 7% of patients with jaundice in pregnancy.

Management

Obstructive jaundice requires surgical intervention usually via laparoscopic cholecystectomy. Uncomplicated cholecystectomy is safer in first and second trimesters with fetal loss approx. 5% but with common bile duct exploration, especially with pancreatitis, 15 % maternal and 60% fetal mortality⁵.

Chronic liver disease in pregnancy is associated with an increased risk of fetal loss. In patients with primary biliary cirrhosis (PBC), ursodeoxycholic acid can be safely continued. Cholestasis may worsen during pregnancy with PBC. Infants of patients with marked hyperbilirubinaemia during pregnancy may require exchange transfusion at birth.

Can present with an acute attack, serum bilirubin increase is dependant upon type of disease, presence of antinuclear, small muscle, liver-kidney microsomes antibodies or antibodies to soluble liver antigen/liver pancreas antibodies. Can be treated with azathioprine during pregnancy. Usually, a favourable outcome in terms of mother and baby.

Hepatic dysfunction with preeclampsia has long been recognised but more recently it has been strongly associated with HELLP syndrome which complicates 3-10% pre-eclamptic pregnancies.

Investigations

In HELLP, haemolysis occurs (with elevated BR and LDH), moderately elevated transaminases and a drop in the platelet count. Jaundice may occur due to DIC and haemolysis. Lab abnormalities peak 1-2 days postpartum and then return to normal within 3-11 days.

Management

The most effective treatment for HELLP is prompt delivery. There is currently insufficient evidence to support the use of adjunctive steroids to reduce maternal and perinatal mortality and major morbidity⁷⁸.

Complications

Maternal mortality associated with HELLP is 2% - with DIC, placental abruption, pulmonary oedema and liver haematoma/rupture the most serious complications. Perinatal mortality rate is 33%.
Risk of recurrence in future pregnancies is 3-4%.

Epidemiology

Rare, <1 in 10,000 pregnancies.
Risk factors: nullips, pre-eclampsia, twin pregnancies, male births.
May be associated with a mutant gene producing a defect in mitochondrial fatty acid oxidation.

Signs and symptoms

Presents as acute illness with nausea, vomiting and abdominal pain, fevers, headache and pruritis usually beginning at 35th week of pregnancy but can occur much earlier. May also appear immediately after delivery.
Jaundice appears soon after onset of symptoms and can become intense in large proportion of patients. Can become fulminant with GI bleeding, hepatic coma and renal failure. May be complicated by pancreatitis, hypoglycaemia and DIC.

Investigations

WCC often elevated, AST and ALT moderately high, increased serum bilirubin. With coagulopathy, prolongation of prothrombin and partial thromboplastin times with depression of fibrinogen levels. May also be neutrophilia and thrombocytopenia.
Biopsy would be diagnostic but coagulation problems often preclude it. CT/MRI may show reduced attenuation in the liver. No specific treatment has proved successful.

Management

Consider early delivery as after delivery, condition resolves with complete recovery usual. Supportive ITU care is usually required.

Complications

Acute fatty liver of pregnancy is a life-threatening condition with a 18% maternal and 23% fetal mortality rate (up to 85% if associated with pre-eclampsia).

Reversible form of cholestasis developing in the third trimester of pregnancy and usually resolving rapidly after delivery.

Epidemiology

Complicates 0.5-1.8% of pregnancies
Increased prevalence in certain populations (eg Chile) and family clusters.
Dominant inheritance likely.
Likely to represent a pre-existing subclinical defect in a bile transport system which is unmasked in pregnancy by the effect of high levels of circulating hormones during the last trimester. This is supported by the fact that women with a history of ICP are prone to cholestasis induced by oral contraceptives and vice versa.

Symptoms

Symptoms are pruritis alone (80%), or with jaundice(20%).

Investigations

Serum bile salts are increased, minimal or no transaminase elevation, mild to moderate steatorrhoea.

Management

Medical treatment of ICP is controversial. Ursodeoxycholic acid is used where pruritis can be very severe and provides safe and effective relief.
Ensure close fetal surveillance prior to and during delivery.

Complications

No increased risk to mother but increased risk of preterm delivery, fetal distress and increased perinatal mortality rate (1-3.5%).
ICP recurs in 60-70% of subsequent pregnancies.