NEONATAL JAUNDICE

PRESENTED BY:

Dr. Mohammed Hamza Baig

Pharm D

DEFINITION

PHYSIOLOGIC JAUNDICE (non-pathologic unconjugated hyperbilirubinemia):

1. Term Infants:

• 50-60 % of all newborns are jaundiced in the first week of life.
• Total serum bilirubin peaks at age 3–5days (later in Asian infants).
• Mean peak total serum bilirubin is 6 mg/dL (higher in Asian infants).

2. Preterm Infants:

• Incidence of visible jaundice is much higher than in term infants.
• Peak is later (5-7d).
• Because of ↑ risk of bilibubin encephalopathy, “physiologic” jaundice is more difficult to define and jaundice should be followed closely.

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DEFINITION of NON-PHYSIOLOGIC JAUNDICE:

• Jaundice in the first 24 hours
• Bilirubin rising faster than 5 mg/dL in 24 hours
• Clinical jaundice >1 week
• Direct bilirubin >2 mg/dL

• In healthy term infants total serum bilirubin concentration >15 mg/dL

• Lower levels in preterm infants, “sick” infants, and hemolytic disease

BILIRUBIN METABOLISM

• As red blood cells are lysed, they release hemoglobin. Heme molecules (from hemoglobin) are converted to bilirubin.
• Unconjugated bilirubin is bound to serum albumin and transferred to the liver where it is conjugated to glucuronate by glucuronyl transferase.
• Conjugated bilirubin is excreted into bile. A fraction of bilirubin from the stool is reabsorbed into the blood via the portal circulation (enterohepatic circulation).

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ETIOLOGY

UNCONJUGATED (HEMOLYTIC)

Intrinsic causes of hemolysis

• Membrane conditions
• Spherocytosis
• Hereditary elliptocytosis
• Enzyme conditions
• Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)
• Pyruvate kinase deficiency

• Globin synthesis defect
• sickle cell disease
• Alpha-thalassemia, e.g. HbH disease

Extrinsic causes of hemolysis

• Systemic conditions
• Sepsis
• Arteriovenous malformation

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• Alloimmunity (The neonatal or cord blood gives a positive direct Coombs test and the maternal blood gives a positive indirect Coombs test)
• Hemolytic disease of the newborn (ABO)
• Hemolytic disease of the newborn (anti-Kell)
• Hemolytic disease of the newborn (anti-Rhc)

Non-hemolytic causes

• Breastfeeding failure jaundice
• Breast milk jaundice
• Cephalohematoma
• Polycythemia

• Urinary tract infection
• Sepsis
• Hypothyroidism
• Gilbert's syndrome
• Crigler-Najjar syndrome
• High GI obstruction (Pyloric stenosis, Bowel obstruction)

CONJUGATED (DIRECT)

• Liver causes
• Infections
• Sepsis
• Hepatitis A
• Hepatitis B
• TORCH infections
• Metabolic
• Galactosemia
• Cystic fibrosis

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• Dubin-Johnson Syndrome
• Rotor syndrome
• Post-liver
• Biliary atresia or bile duct obstruction
• Alagille syndrome
• Choledochal cyst

RISK FACTORS

The risk of developing significant neonatal jaundice is increased in

• Low birth weight: Premature
• Breast-fed babies.
• A previous sibling with neonatal jaundice requiring phototherapy.
• Infants of mothers who have diabetes.
• Male infants.
• East Asians.
• Populations living at high altitudes.

CLINICAL PRESENTATION

• Neonatal jaundice first becomes visible in the face and forehead. Blanching reveals the underlying colour. Jaundice then gradually becomes visible on the trunk and extremities.
• In most infants, yellow colour is the only finding on physical examination. More intense jaundice may be associated with drowsiness.

• Neurological signs –

eg, changes in

muscle tone,

seizures, or

altered crying - require immediate attention to avoid kernicterus.

• Hepatosplenomegaly, petechiae and microcephaly are associated with haemolytic anaemia, sepsis and congenital infections.
• Hepatitis (eg, congenital rubella, CMV, toxoplasmosis) and biliary atresia cause a raised conjugated bilirubin and have a marked jaundice and pale stools and dark urine, usually presenting in the third week of life.

INVESTIGATIONS

Bilirubin level:

• Use a transcutaneous bilirubinometer in babies with a gestational age of 35 weeks or more and postnatal age of more than 24 hours.
• If a transcutaneous bilirubinometer is not available, measure the serum bilirubin.
• If a transcutaneous bilirubinometer measurement indicates a bilirubin level greater than 250 μmol/L check the result by measuring the serum bilirubin.

• Measurement of conjugated bilirubin is particularly important for babies with hepatosplenomegaly, petechiae or thrombocytopenia (or any other indication of liver or biliary disease, metabolic disorder or congenital infection) and for babies with prolonged jaundice.
• Do not measure bilirubin levels routinely in babies who are not visibly jaundiced.

• LFTs: Hepatitis, Cholestatic disease.
• Infection screen (must be excluded in any baby who is unwell or presents in the first 24 hours or after day 3):
• TORCH syndrome (toxoplasmosis, other, rubella, CMV and herpes simplex)
• Congenital infection screen,
• Surface swabs including umbilicus, throat swabs, urine culture, blood culture, lumbar puncture, CXR.

Haemolysis:

• Blood type and Rh determination in mother and infant.
• Reticulocyte count.
• Direct Coombs' testing in the infant.
• Haemoglobin and haematocrit values.
• Peripheral blood film for erythrocyte morphology.

• Red cell enzyme assays: G6PD activity (G6PD deficiency), pyruvate kinase deficiency.
• Reducing substance in urine: Screening test for galactosaemia (provided the infant has received sufficient quantities of milk).
• TFTs.

• Ultrasound, hepatobiliary iminodiacetic acid (HIDA) radionuclide scan, liver biopsy and laparotomy may be required for cholestatic jaundice in the differentiation between hepatitis and biliary atresia

MANAGEMENT FOR CONJUGATED HYPERBILIRUBINEMIA

1. Healthy Term Newborn

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2. Sick Term Newborns: Start above therapies at lower total serum bilirubin levels. Consult attending physician for specific values.

3. Preterm Infants: Because of ↑ risk of bilibubin encephalopathy, therapy should be started at lower bilirubin concentrations. In general, bilirubin shoud not be allowed to exceed the infant’s weight in kg x 10 (e.g., for 1.0 kg infant, keep bilirubin <10 mg/dL).

MANAGEMENT FOR CONJUGATED HYPERBILIRUBINEMIA

• Conjugated bilirubin is not toxic.
• Management is treatment of cause.
• Phototherapy will cause “bronzing” with conjugated hyperbilirubinemia.

REFERENCE

• Neonatal jaundice. Intensive care nursery house staff manual; The regents of University of California. Pg:118-20
• Thor WR Hansen. Neonatal Jaundice: Background, Pathophysiology, Etiology. Medscape; Mar 04, 2016
• Dr Colin Tidy. Neonatal Jaundice. Patient; 1-5. (patient.info/doctor/neonatal-jaundice-pro)