This document defines neonatal jaundice and describes its causes, presentation, risk factors, and management. Physiologic jaundice occurs in 50-60% of term infants and peaks at 3-5 days of life, while preterm infants have a higher incidence and later peak. Non-physiologic jaundice is defined as jaundice in the first 24 hours, rapid bilirubin rise, prolonged jaundice, or elevated direct bilirubin levels. Jaundice can be unconjugated (hemolytic) due to intrinsic or extrinsic causes, or conjugated due to liver or post-liver issues. Management involves phototherapy or exchange transfusion depending on infant risk factors and bilir

1. NEONATAL JAUNDICE

2. 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).

3. 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.

4. 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

5. 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).

6. Neonatal jaundice
Un conjugated
bilirubin
Pathologic
Hemolytic
Intrinsic
causes
Extrinsic
causes
Non
hemolytic
Physiological
jaundice of
Neonates
Conjugated
bilirubin
Hepatic Post hepatic

7. ETIOLOGY
UNCONJUGATED (HEMOLYTIC)
Intrinsic causes of hemolysis
• Membrane conditions
• Spherocytosis
• Hereditary elliptocytosis
• Enzyme conditions
• Glucose-6-phosphate dehydrogenase deficiency (G6PD
deficiency)
• Pyruvate kinase deficiency

8. • Globin synthesis defect
• sickle cell disease
• Alpha-thalassemia, e.g. HbH disease
Extrinsic causes of hemolysis
• Systemic conditions
• Sepsis
• Arteriovenous malformation

9. • 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)

10. Non-hemolytic causes
• Breastfeeding failure jaundice
• Breast milk jaundice
• Cephalohematoma
• Polycythemia

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

12. CONJUGATED (DIRECT)
• Liver causes
• Infections
• Sepsis
• Hepatitis A
• Hepatitis B
• TORCH infections
• Metabolic
• Galactosemia
• Cystic fibrosis

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

14. 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.

15. 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.

16. • Neurological signs –
eg, changes in
muscle tone,
seizures, or
altered crying - require immediate attention to avoid
kernicterus.

17. • 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.

18. 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.

19. • 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.

20. • 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.

21. 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.

22. • 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.

23. • 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

24. MANAGEMENT FOR CONJUGATED
HYPERBILIRUBINEMIA
1. Healthy Term Newborn
Treatment
Age (h)
Bilirubin
(mg/dL) Phototherapy
Exchange
Transfusion
≤ 24 Visible Jaundice Consult attending physician
25-48 ≥ 15 X
≥ 20 X X
49-72 ≥ 18 X
≥ 25* X X
> 72 ≥ 20 X
≥ 25* X X

25. 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).

26. MANAGEMENT FOR CONJUGATED
HYPERBILIRUBINEMIA
• Conjugated bilirubin is not toxic.
• Management is treatment of cause.
• Phototherapy will cause “bronzing” with conjugated
hyperbilirubinemia.

27. 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)