Neonatal Jaundice - Dubai Pediatric Clinic

• Jaundice is yellow coloration of the skin and sclera and is the result of accumulation of bilirubin.
• In most infant, hyperbilirubinemia reflects a normal transitional phenomenon, but in some infants, serum bilirubin levels may rise excessively which can be cause for concern because unconjugated bilirubin is neurotoxic and can cause death in newborn and lifelong neurologic sequelae in infants ( kernicterus).
• For this reason, the presence of neonatal jaundice requires immediate diagnostic evaluation.

Differential Diagnosis

• It is important to differ between the physiologic jaundice and the other cause (pathologic) by clinical examination, laboratory and radiologic examination.

Physiologic jaundice:

• Physiologic jaundice is transient phenomenon which results from the 2 phenomenon. Bilirubin production is elevated because of increased breakdown of fetal erythrocytes and the higher erythrocyte mass in neonate. Hepatic excretory capacity is low.
• Physiologic jaundice presents on the second or third day of life. Jaundice that is visible during the first 24 hours of life is likely to be non-physiologic and further evaluation is suggested. Infants who present with jaundice after 3-4 days of life requires closer monitoring.
• Physiologic jaundice usually disappears within the first 2 weeks of life, so jaundice that persists for more than 2 weeks of life needs further investigation.
• In Physiologic jaundice usually TB does not  rises more than 13mg/dl in full term baby and 15 mgldl in pre term baby , so higher values need  more investigations.

Etiology of Indirect Hyperbilirubinemia

Physiologic Jaundice:

• Full term newborn with peak TB 12mg/dl in the third day of life or premature baby with peak TB 15mg/dl and occurs later (5^th day).
• The peak level of physiologic jaundice maybe higher in breast milk fed infant (15-17 mg/dl) which is the result of decreased fluid intake.
• Jaundice is pathologic if it is evident on the first day of life. Bilirubin level increased more than 0.5mg/dl/hr. Peaks more than 13mg/dl in term infants; direct bilirubin more than 1mg/dl, if hepatosplenomegaly or anemia is present.
• Crigler-Najjar syndrome is a serious rare permanent deficiency of glucoronyl transferase and severe indirect hyperbilirubinemia. The autosomal dominant type of this disease responds to phenobarbital while the autosomal recessive form does not respond to phenobarbital and often lead to kernicterus.
• Gilbert disease results from mutation and manifest as a mild indirect hyperbilirubinemia.
• Breastmilk feeding associated with unconjugated hyperbilirubinemia without evidence of hemolysis during the first 2 weeks of life, interruption of breastfeeding for 24hrs; 48hrs reduce the level of bilirubin.
• Jaundice in the first day of life is always pathologic and need immediate attention. (Hemolysis – internal hemorrhage or infection).
• Jaundice present after 2 weeks of age is pathologic and suggests direct reacting hyperbilirubinemia.

Etiology of Direct Hyperbilirubinemia

Direct hyperbilirubninemia is not neurotoxic but signifies a serious underlying disorder:

• Cholestatsis
• CMV infection
• TORCH
• Inspissated bile from prolonged hemolysis
• Neonatal hepatitis
• Sepsis
• Inborn errors of metabolism
• Cystic fibrosis
• Biliary atresia
• Choledochal cyst
• Antitrypsin deficiency
• Alagille syndrome
• Byler syndrome

After specific diagnostic tests are performed, the supportive treatment depends on the severity of hepatocellular dysfunction and cholestasis.

Hepatocellular dysfunction  predisposes the patient to complications such as bleeding, encephalopathy, and hepatorenal syndrome, bile salt deficiency lead to fat soluble vitamin deficiencies, Rickets, hypocalcemia, hemorrhage, and peripheral neuropathy.

Retention of bile salt may produce pruritis.

Supportive therapy involves medium chain triglyceride and fat soluble vitamin supplementation, cholestyramine to decrease reabsorption of bile salts from the gut.

Phenobarbital to increase the hepatic excretion of bile.

Definitive treatment depends on the underlying process and may involve an exclusion diet (lactose in galactosemia), surgery in extrahepatic biliary atresia or coledochal cyst, or liver transplantation.

Important Points in the Medical History

• Previous sibling with neonatal jaundice.
• Other family members with jaundice.
• Anemia – splenectomy – bile stones.
• Liver disease.
• Maternal illness.
• Maternal drug intake.
• Delay cord clamping
• Birth trauma
• Loose of stool color
• Breastfeeding
• Use of drug
• Symptoms of hypothyroidism
• Symptoms of metabolic disease
• Expose of total parenteral nutrition.

Physical Examination

• Neonatal jaundice first becomes visible in the face and gradually become visible on the trunk and extremities.
• Neurologic findings such as change in the muscle tone; seizure in significant neonatal jaundice is danger signs and requires immediate attention to prevent kernicterus.
• Hepatosplenomegaly, petechiae, microcephaly are signs of other cause rather than physiologic jaundice such as infections.
• Metabolic disorders require more investigations.

Lab Studies

• In infants with moderate jaundice who presents on the typical second or third day of life without a history and physical findings is suggestive of a pathologic process.
• A total bilirubin level test is the only one required additional studies which is indicated in the following studies.
  • Jaundice in the first day of life.
  • Infants who are anemic at birth.
  • Infants who appear ill.
  • Infants with TB level are elevated enough to trigger treatment.
  • Significant jaundice persists beyond the first 2 weeks of life.
  • Family history of pathologic jaundice.
  • Hepatosplenomegaly, neurologic signs and symptoms.

The other lab tests are:

• Blood type and Rh in mother and infant.
• Direct Coombs test.
• Hg and Hct
• Blood smear
• Reticulocyte count
• Direct bilirubin
• Liver function test
• Blood culture
• Screen for IUI
• Thyroid function
• Reducing substance in the urine

Imaging Studies

• Ultrasonography of the liver and bile ducts is warranted in infant with laboratory or clinical signs of cholestatic disease. (hepatosplenomegaly, elevated direct bilirubin)
• Radionuclide liver scanning for uptake of (HIDA) is indicated if extrahepatic biliary atresia is suspected.
• AABR: Brainstem auditory evoked potentials should be obtained in severe neonatal jaundice to exclude sensorineural hearing loss.

Treatment:

Phototherapy; IV Ig; exchange transfusion are the most used therapeutic modalities.

• Phototherapy is the primary treatment in the neonate with unconjugated hyperbilirubinemia. Photo oxidation of the bilirubin changes some of the predominant bilirubin isomers to water soluble isomers, the photo isomers of bilirubin are excreted in bile and urine and they have half-life shorter than bilirubin. Water soluble isomers are not able to cross the blood brain barrier so photo therapy reduces the risk of bilirubin induced neurotoxicity as soon as the light turns on.
• Exchange transfusions when phototherapy failed to control serum bilirubin levels.
  • IV Ig  in infant with Rh or AbO isoimmunization can significantly reduce the need for exchange transfusion.
• There is a special chart to show the recommendation for phototherapy and blood exchange according to TB level, age and associated risk factor.
• The infant with phototherapy  should be naked except for diapers.
• Follow up the TB level every 6-12 hrs.
• Discontinuation of phototherapy when TB level is lower than 3mg/dl below the level that triggered the initiation of phototherapy and follow-up tests should be obtained within 6-12 hours after discontinuation because serum bilirubin may rebound after treatment has been discontinued.

Other Therapies:

• Infants with breastmilk jaundice: interruption of breastfeed for 24-48 hours helps to reduce the bilirubin level.
• Prophylactic treatment of Rh mothers with Rh immunoglobulin has significantly decreased the incidence of Rh hemolytic disease.
• Surgical therapy is indicated for bile duct atresia.

Prognosis:

Prognosis is excellent if the patient receives treatment. Brain damage due to kernicterus remains true risk. Kernicterus is neurologic abnormalities associated with hyperbilirubinemia.

Acute bilirubin encephalopathy

• First stage: Hypotonia - poor feeding.
• Second stage: Hypertonia - (backward arching of the neck), Opisthotonus
• Third stage: Hypotonia                                                           

Chronic bilirubin encephalopathy

• Extrapyramidal abnormalities: Athetosis – Chorea
• Visual abnormalities
• Auditory abnormalities
• Cognitive defect 

Infants with cholestasis have prognosis that differs according to the underlying cause. In the idiopathic neonatal hepatitis, most of the patient recovers within 6-8 months.

In biliary atresia, the prognosis is better when Kasai procedure is used before 3 months of age. Over 90% of patients survive 5 years after the procedure. Untreated cases die from cirrhosis before 2 years of age. For some cases of biliary hypoplasia, cirrhosis and liver failure occur before adolescent.

Dubai Pediatric Clinic at Dr Rami Hamed Center provides one of the leading pediatricians in Dubai.