NEONATAL JAUNDICE (JAUNDICE IN NEWBORN)

What is jaundice?

Increase in Bilirubin (yellow pigment) in blood beyond the normal range is defined as jaundice. Bilirubin is produced from breakdown of red blood cells. Before it is processed by the liver it is in indirect form. The rise of this form of bilirubin leads to Indirect jaundice. After processing into the liver it is converted to direct form which passes into the intestine through the bile duct. Bile duct is a tube like structure which connects the liver to small intestine. From intestine the direct bilirubin is absorbed into the blood and excreted by the kidneys. Any problem in the liver or bile duct can result into direct or cholestatic (absence of bile flow) jaundice.

What is physiological (normal) jaundice of Newborn?

After birth, liver function is insufficient to convert the indirect bilirubin to direct bilirubin. This jaundice is seen by 2-4th day and increases in next 2 days after which it gradually subsides. Routine consultation with the pediatric doctor 48-72 hours after discharge from hospital is required to detect the severity of jaundice. Some babies may require investigations and phototherapy for treatment of this type of jaundice. Phototherapy converts indirect bilirubin to soluble form so that it is excreted by the kidneys. High level of indirect jaundice may cause brain damage.

When should cholestatic jaundice be suspected?

Cholestatic (direct) jaundice should be suspected when the jaundice last beyond 2 weeks of life. Parents may observe that the stool color is pale (clay colored) and the urine stains the diaper or nappy yellow. Normally urine of newborn is colorless (like water). The color of the baby skin and eyes usually has a yellowish tinge.

Why jaundice is a concern for the babies?

High level of indirect jaundice may cause brain damage. Direct jaundice can be a sign of liver disorder that can be life threatening if not treated urgently. Direct jaundice can lead to deficiencies of fat soluble vitamins like Vitamin A, D, E, K. Vitamin K deficiency can lead to bleeding disorder. In case of poor development of bile duct (Biliary Atresia) there can be liver damage if not corrected surgically. If surgical correction is done within 60 days of life the success rate of achieving bile flow is higher.

What information should I give to the doctor on consultation?

The following information can be useful to the doctor for evaluation of the jaundice in your baby:

• Whether your spouse is closely related to you?
• Was TORCH screening done during pregnancy?
• Parents and baby’s blood group.
• Weight gain record.
• Stool pattern and color
• Color of the urine
• Bleeding from any site
• Activity of the baby
• Similar disease in siblings or family members

How will the doctor evaluate my baby?

Your doctor will take a complete history and do the physical examination. He will look for signs of poor weight gain (record weight, length), severity of jaundice and examination of abdomen to look for size of liver, enlargement of spleen (organ on the left side of abdomen which is a part of immune system) and collection of fluid within the abdomen (ascites).

Does my baby require multiple tests?

The investigations of direct jaundice are usually done if the jaundice last for more than 2 weeks. The first step is to measure the blood level of total bilirubin and direct bilirubin. If it suggests direct jaundice (i.e. direct bilirubin > 2 mg/dl), then evaluation starts in a staged manner if baby is less than 6 weeks and non sick. If otherwise then parallel investigations are advised to reach early diagnosis.

The doctor should first assess the liver function by measuring liver enzymes (SGPT, SGOT,GGT), serum albumin and prothrombin time. A baby with high enzyme level, low albumin and prolonged prothrombin time can become sick rapidly and hence should be admitted in hospital and managed further.

In staged approach rapid diagnosis of treatable conditions like infection (blood counts, blood culture and urine culture), low thyroid hormones (T3, T4, and TSH), and inborn error of metabolism (genetic disorder due to enzyme defects like galactossemia) is done first. Once diagnosed this should be treated accordingly.

Diseases requiring early surgery like Biliary atresia has to be ruled out next by doing USG abdomen, HIDA scan and liver biopsy. If the above tests are non diagnostic then complete battery of tests are done which include:

• Congenital infections (acquired during pregnancy): TORCH screening.
• Metabolic diseases (inherited genetic defect): Tyrosinemia (alpha fetoprotein level in blood and urine for succinyl acetone), Allagille syndrome (JAG 1 mutation) and neonatal hemochromatosis (serum ferritin and buccal mucosal biopsy).
• Viral infections: Hepatitis B, Hepatitis C virus, HIV.
• Eye examination: congenital infection and metabolic disorder.
• Liver biopsy
• Liver enzyme: GGTP (gamma glutamyl transpeptidase)
• Alpha antitrypsin deficiency (rare in India)
• Sweat chloride test (Cystic fibrosis)

When should the baby be referred to higher centre?

Once common causes are ruled out or the baby shows signs of poor liver function, baby should be referred to pediatric gastroenterologist in a tertiary care centre?

Is liver biopsy always required?

Liver biopsy may be recommended for babies with direct jaundice especially if cause of jaundice remains undetermined. It is over all a safe procedure with occasional risk of bleeding within the liver. It helps in establishing the diagnosis like in idiopathic neonatal hepatitis where other tests are negative. It helps in assessment of liver damage (cirrhosis). In cases where diagnosis is already made by other test (infection, galactossemia) liver biopsy may not be indicated.

When is liver biopsy contraindicated?

In presence of coagulopathy (blood does not clot) there is chance of bleeding at the site of biopsy. In such cases Vitamin K and Fresh frozen plasma (white blood) is given to correct coagulopathy after which liver biopsy can be done.

What is the medical management for direct jaundice?

Specific treatment is required for specific disorder. In general supportive care plays an important role in management of these babies.

• Nutrition: Due to poor absorption of fat by the intestine, the caloric requirement is 1.5 times the normal requirement. To increase the calorie intake, Simyl MCT oil can be added to the milk. The protein intake should be 3-4 gm/kg/day. Fat soluble vitamins like K and E is given orally but vitamin A and D should be given intramuscularly. B complex vitamins should be given 2-3 times the recommended daily allowance.
• Prevention and management of infections: antibiotics
• Choleretics: These are the drug which makes the bile to flow easily. UDCA is used in the dose of 15-30 mg/kg/day in 2 divided doses.
• Regular follow up and monitoring
• Vaccination as per schedule (take precaution during injection in muscle, inform the doctor/nurse regarding bleeding tendency, press for 5 min, do not rub)

When is surgery indicated?

Surgery is indicated only for biliary atresia and choledochal cyst. For Biliary atresia it is done as early as possible once the diagnosis is made preferably within 60 days.

What is the outcome? Can direct jaundice be life threatening? What are the danger signals?

Cholestatic jaundice outcome will depend upon its cause. It can be life threatening especially if there are signs of liver failure. The danger signals are:

• Blood in vomitus/ stools
• Increase in abdomen size (ascites)
• Alteration in sensorium (baby may become dull with poor feeding or may have abnormal movements)
• Low blood sugar
• Secondary infection: Fever with poor activity.

References:

1.http://www.ncbi.nlm.nih.gov/pubmed/9057403

Bhave SA, Bavdekar AR, Pandit AN. Neonatal cholestasis syndrome in India- a diagnostic and therapeutic challenge. Indian Pediatr. 1996 Sep; 33(9):753-62.

http://www.ncbi.nlm.nih.gov/pubmed/11132478

Yachha SK, Mohindra S. Neonatal cholestasis syndrome: Indian scene. Indian J Pediatr. 1999; 66(1 Suppl):S94-6.

http://www.indianpediatrics.net/aug2001/aug-893-898.htm

Matthai J, Paul S. Evaluation of cholestatic jaundice in young infants. Indian pediatrics 2001; 38: 893-898

<>4.http://www.indianpediatrics.net/august2000/august-845-851.htm http://www.ncbi.nlm.nih.gov/pubmed/10951633

Indian Academy of Pediatrics. Pediatric Gastroenterology Subspecialty Chapter.Consensus report on neonatal cholestasis syndrome. Pediatric Gastroenterology Subspecialty Chapter of Indian Academy of Pediatrics. Indian Pediatr. 2000 Aug; 37(8):845-51.