Dr. Geetha Balsarkar

Gilbert’s Syndrome and pregnancy

A 31 year old telephone operator presented at 30 weeks gestation referred from private for management of Gilbert’s syndrome in pregnancy.

Before pregnancy, during the past 3 years, she had 3 episodes of jaundice with bilirubin ranging from 1.5 – 2, each time. At the last episode of jaundice, she was hospitalized and investigated, even underwent liver biopsy which was normal. All infective etiology screening like HbSAg, Hbe Ag, HIV was nonreactive. There she was diagnosed to have Gilbert’s syndrome.

During this pregnancy, she had a normal first trimester. Her bilirubin was in the range of 1 to 1.5gm%. Her haemoglobin was 10 gm percent. She was Rh positive.

At 30 weeks of gestation, she had a bout of severe upper respiratory tract infection, following which her jaundice deepened and she was referred to tertiary care center.

The patient also complained of diffuse symptoms like feeling tired all the time (fatigue), difficulty maintaining concentration, loss of appetite, abdominal pain, no gain in weight.

After she tided over the upper respiratory tract infection for which needed antibiotics, she settled for the rest of the pregnancy.

At 37 weeks she came in spontaneous labour. Her serum bilirubin was 2 gm%, SGOT and SGPT mildly raised, prothrombin time INR was 1.2. Her baby weight was 2.6 kg clinically. She was allowed to progress normally. When artificial rupture of membranes was done, the liqiour colour was deep yellow. She delivered normally, vaginally a female child of 2.65 Kg, the baby’s skin was tinged yellow. The baby was observed for 5 days for hyperbilirubinemia and then discharged.

Gilbert’s syndrome (named after a French gastroenterologist) is a condition caused by certain changes in the liver. It could be discovered accidentally or jaundice may be a symptom. This condition is inherited and is one of the commonest syndromes. People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal. Virtually all patients have decreased level of UDP-Glucuronosyltransferase, but there also is evidence for a defect in hepatic uptake of bilirubin as well.

 The hyperbilirubinemia is mild and by definition < 6 mg/dl. However, most patients exhibit levels of 3 mg/dl. Considerable daily and seasonal variations are observed and bilirubin level occasionally may be normal in as many as one-third of patients.

The characteristics of Gilbert syndrome are normal liver function tests, normal liver histology, delayed clearance of bilirubin from the blood, and mild jaundice that tends to fluctuate in severity, particularly after fasting.

Patients with Gilbert syndrome tend to have total serum bilirubin levels from 1-6 mg/dL. They show predominantly elevated unconjugated bilirubin, while conjugated is usually within normal ranges and form less than 20% of the total. This is distinguished from Crigler-Najjar syndrome type II, in which patients have total serum bilirubin levels between 6 and 20 mg/dL, and Crigler-Najjar syndrome type I, in which patients have total serum bilirubin levels from 20 to 45 mg/dL.

 Important points in management of pregnant patients with Gilbert’s syndrome

• A subset of people with Gilbert’s Syndrome may have an increased risk of paracetamol toxicity. Use of paracetamol should be avoided as pain relief during pregnancy and post delivery.
• Fasting  usually results in a 2- to 3-fold rise in the plasma unconjugated bilirubin level within 48 hours of a fast that returns to normal levels within 24 hours of resuming a normal diet. Hence fasting should be avoided in such patients.
• Dehydration also increases the hyperbilirubinemia. Dehydration should be avoided antenatally and during labour.
•  Intercurrent illness, such as a viral infection
• Stress, such as trauma and overexertion.
• Intravenous administration of 50 mg of nicotinic acid results in a 2- to 3-fold rise in plasma unconjugated hyperbilirubinemia within 3 hours. Hence nicotine consumption in any form should be avoided.
• Phenobarbital and other enzyme inducers of the bilirubin-UGT system will normalize plasma bilirubin in patients with Gilbert syndrome. This is predominantly due to accelerated bilirubin clearance from enzyme induction but is also due to reduced bilirubin turnover.
• Steroids can also reduce plasma bilirubin levels in Gilbert syndrome by increasing hepatic uptake and storage of bilirubin.
• Diet - Diet is normal.
• Activity - No activity restrictions are necessary.
• Inpatient care is not required.

The most important aspect of treatment once the diagnosis is established is reassurance. Patients with Gilbert syndrome should be informed of its benign nature and that hyperbilirubinemia is not associated with increased morbidity. It has an excellent prognosis and is associated with normal life expectancy, which must be made perfectly clear to the patient. During delivery watchful expectancy should be the dictum.

Uploaded in March 2010