Important topic

1. APPROACH
TO
NEONATAL
JAUNDICE
MODERATOR- DR KIRTI VISHWAKARMA
PRESENTER- DR PALLAVI GUPTA

2. REFERENCES
• NELSON TEXTBOOK OF PEDIATRICS -:Volume First 21st edition
• O.P GHAI ESSENTIAL PEDIATRICS 9TH Edition
• CLOHERTY & STARKS MANUAL OF NEONATAL CARE-8TH EDITION
• AIIMS PROTOCOLS IN NEONATOLOGY-2ND EDITION
• MEDICAL EMERGENCIES IN CHILDREN-: MEHARBAN SINGH 5th edition

3. CONTENTS
• INTRODUCTION
• PATHOPHYSIOLOGY
• ETIOLOGY
• CLINICAL PRESENTATION
• MANAGEMENT
• PREVENTION

4. INTRODUCTION
• JAUNDICE is the yellowish discoloration of the skin, sclera and mucous
membrane.
• The yellow color usually results from the accumulation of unconjugated,
nonpolar, lipid-soluble bilirubin pigment in the skin..
• Jaundice is an important problem in the first week of life.
• 60% of term infants and 80% of preterm infants.

5. • Almost all newborn infants have a serum or plasma total bilirubin (TB) level
>1 mg/dL in contrast to normal adults in whom the normal TB level is <1
mg/dL.
• A normal newborn produces 6 to 10 mg of bilirubin/kg/day, greater than the
adult production of 3 to 4 mg/kg/day.
• High bilirubin levels may be toxic to the developing central nervous system
and may cause neurological impairment even in term newborns.
REEFERENCE:CLOHERTY & STARKS MANUAL OF NEONATAL CARE-8TH EDITION

8. URIDINE
DIPHOSPHOGLUCONURATE
GLUCURONOSYLTRANSFERASE

10. PHYSIOLOGICAL JAUNDICE
• Physiological jaundice represents physiological immaturity of the neonates to handle increased
bilirubin
production.
• Visible jaundice usually appears between 24-72 hours of age.
• Total serum bilirubin (TSB) level usually peaks 12 to 15 mg/dL by 3 days of age and then falls in
term neonates.
• In preterm infants, the peak level occurs on the 3 to 7 days of age and TSB can rise over 15 mg/dL.
• Conjugated bilirubin never passes 2mg/dL or 20% of TSB.
• TSB levels are below the designated cut-offs for phototherapy.
• It does not require any treatment.

11. PREDISPOSING FACTORS LEADING TO PHYSIOLOGICAL JAUNDICE:-
• Shorter RBC lifespan (~90 Days)
• Increased RBC mass
• Ineffective erythropoiesis
• Decreased uptake of bilirubin into liver due to low ligandin levels
• Decreased hepatic conjugation secondary to decreased UDPGT activity.
• Increased enterohepatic circulation.

12. PATHOLOGICAL JAUNDICE
• TSB levels have been arbitrarily defined as pathological if it exceeds 5 mg/ dl on first day,
10 mg/dl on second day, or 15 mg/ dl thereafter in term babies.
• Appearance of jaundice within 24 hr, TSB levels above the expected normal range,
presence of clinical jaundice beyond 3 weeks and conjugated bilirubin (dark urine staining
the nappy) would be categorized under this category.
• Such jaundice warrants investigation for the cause and therapeutic intervention such as
phototherapy.

13. Presence of one or more of following conditions would qualify a neonate to
have pathological jaundice:
• 1. Visible jaundice in first 24 hours of life .
• 2. Presence of jaundice on arms and legs on day 2
• 3. Yellow palms and soles anytime
• 4. Serum bilirubin concentration increasing more than 0.2 mg/dL/hour or more than 5 mg/dL in 24
• hours
• 5. If TSB concentration more than 95th centile as per age-specific bilirubin nomogram
• 6. Signs of acute bilirubin encephalopathy or kernicterus
• 7. Direct bilirubin more than 1.5 to 2 mg/dL at any age
• 8. Clinical jaundice persisting beyond 2 weeks in term and 3 weeks in preterm neonates
REFERENCE:AIIMS PROTOCOLS IN NEONATOLOGY-2ND EDITION

14. ETIOLOGY
Important causes of jaundice in neonates include:
• i. Hemolytic: Rh incompatibility, ABO incompatibility,
G6PD deficiency,
ii. Non-hemolytic: Prematurity, extravasated blood,
inadequate feeding, polycythemia, idiopathic,
breast milk jaundice
(Blood incompatibility: ABO>Rh incompatibility, OA incompatibility is more due to immune based
hemolysis by anti A)

15. Causes are usually classified based on the time of onset
of jaundice
APPEARING WITHIN 24 HOURS OF
AGE
Hemolytic disease of newborn: Rh &
ABO incompatibility, G6PD
Deficiency.
Infections: Intrauterine viral,
bacterial, malaria
BETWEEN 24 AND 72 HOURS OF
LIFE
Physiological
Sepsis
Polycythemia
Concealed hemorrhages:
Cephalohematoma, subarachnoid
bleed, IVH
Increased enterohepatic circulation
AFTER 72 HOURS
Sepsis
Neonatal hepatitis
Extrahepatic biliary Atresia
Breast Milk Jaundice
Metabolic disorder

16. This is defined as persistence of significant jaundice (10 mg/dl) beyond three weeks in a term
baby.
Common causes:
• inadequate feeding
• breast milk jaundice
• extravasated blood (cephalohematoma)
• Ongoing hemolytic disease
• G6PD deficiency
• Hypothyroidism
If the baby has dark urine or significant jaundice, investigations should be initiated to rule out:
• i. Cholestasis (stool color, urine color, direct and indirect bilirubin levels)
• ii. Ongoing hemolysis, G6PD screen
• iii. Hypothyroidism
• iv. Urinary tract infection
PROLONGED JAUNDICE

17. Risk Factors for Development of Severe
Hyperbilirubinemia

18. BREASTFEEDING
JAUNDICE
BREAST MILK
JAUNDICE
This is related to inadequate breastfeeding. Approximately 2-4% of exclusively breastfed term babies
have jaundice in excess of 10 mg/ dL 3rd-4th weeks of life
Jaundice in breastfed babies usually appears
between 24-72 hr of age, peaks by 5-15 days of
life and disappears by the third week of life.
The mechanism of breast milk jaundice is a factor in
human milk, possibly β-glucuronidase, that
deconjugates intestinal bilirubin and promotes its
absorption
Decreased intake of milk leads to slower bilirubin
elimination & increased enterohepatic
circulation.
A diagnosis of breast milk jaundice should be considered, if
this is unconjugated and other causes for have been ruled
out.
Ensuring optimum breastfeeding would help
decrease this kind of jaundice.
If breastfeeding is stopped, the bilirubin level may fall
rapidly in 48 hours.
If nursing is then resumed, the bilirubin may rise by 2
to 4 mg/dL

19. Neurologic manifestations of bilirubin toxicity
a. Early phase: lethargy, hypotonia, high-
pitched cry, and poor suck.
b. Intermediate phase: hypertonia of
extensor muscles (rigidity, opisthotonos),
irritability, fever, and seizures. Some
infants die in this phase
c. Advanced phase :pronounced
opisthotonos ,cry that can be weak or
shrill, apnea, seizures, and coma. Affected
infants die from intractable seizures or
respiratory failure.
ACUTE BILIRUBIN
ENCEPHALOPATHY
KERNICTERUS
Yellow staining of the brain due to
bilirubin accumulation ( Unconjugated
bilirubin)
Parts of brain affected: Basal ganglia,
brainstem nuclei, hippocampus,
cerebellar nuclei

20. The signs of kernicterus are as follows:
a. Choreoathetoid cerebral palsy with neuromotor impairments
b. Sensorineural hearing loss (auditory neuropathy),
characterized by abnormal brainstem auditory evoked
response with normal otoacoustic emission testing
c. Limitation of upward gaze
d. Dental enamel dysplasia

21. APPROACH TO JAUNDICED BABY
• Determine the birth weight, gestation and post natal age.
• Assess clinical condition and degree of jaundice.
• Decide whether jaundice is physiological or pathological.
• Look for evidence of kernicterus in deeply jaundiced newborn.

22. ETIOLOGY OF JAUNDICE BASED ON
HISTORY

23. ETIOLOGY OF JAUNDICE BASED ON
PHYSICAL EXAMINATION

24. CLINICAL ESTIMATION OF BILIRUBIN
LEVELS
• Dermal staining described by Kramer may be used as a clinical guide to the
level of Jaundice.
• Dermal staining in newborn progresses in a cephalocaudal direction
( Newborn infants preferentially perfuse their head & proximal parts first and there
is diminished capillary blood flow in distal parts of the body in the first few days)
• The newborn should be examined in good daylight.
• The skin of forehead chest, abdomen, thighs, legs, palms and soles should be
blanched with digital pressure and the underlying color of skin and
subcutaneous tissue should be noted.

25. ZONE 1 4-6mg/dL
ZONE 2 6-8 mg/dL
ZONE 3 8-12 mg/dL
ZONE 4 12-14mg/dL
ZONE 5 >15mg/dL

26. Transcutaneous bilirubinometry (TcB):
• Total serum bilirubin can be assessed non invasively by a transcutaneous handheld device.
• We routinely perform TcB measurement in infants of 35 wk or more gestation to screen for
hyperbilirubinemia.
• This method is based on the principle of multi wavelength spectral reflectance from the bilirubin
staining in the skin. The instrument perform spectral analysis at more than 100 different wavelengths
and by subtraction of spectral combination of known components, bilirubin absorbance is quantified.
• The sensitivity & specificity of this instrument to pick up bilirubin >13mg/dL is 69% & 89.3%
respectively. Sensitivity is lower at higher cut offs.
• . A TcB value of greater than 12 to 14 mg/dL is confirmed by TSB measurement.

27. • Forehead and the upper end of sternum are the commonly used sites.
• Hyperemia at the test sites may affect results.

28. INVESTIGATIONS
First line
• Total serum bilirubin (and its fractions, if jaundice is prolonged or there is yellow staining of nappies )
• Blood groups of mother and baby (if the mother is 'O'or Rh negative): detects any incompatibility
• Peripheral smear: evidence of hemolysis
Second line
• Direct Coombs test: detects presence of antibody coating on fetal RBC
• Haematocrit: decreased in hemolysis
• Reticulocyte count: increased in hemolysis
• G6PD levels in RBC
• Others: sepsis screen; thyroid function test; urine for reducing substances to rule out galactosemia

30. THERAPEUTIC OPTIONS
• PHOTOTHERAPY
• EXCHANGE TRANSFUSION
• MISCELLANEOUS INTERVENTIONS- INTRAVENOUS IMMUNOGLOBULIN
IV HYDRATION
PHENOBARBITAL
METALLOPORPHYRINS

31. REFERENCE:O.P GHAI ESSENTIAL PEDIATRICS 9TH Edition

32. REFERENCE:O.P GHAI ESSENTIAL PEDIATRICS 9TH Edition

36. PHOTOTHERAPY
• Phototherapy remains the mainstay of treating hyperbilirubinemia in neonates.
• It acts by converting insoluble bilirubin (unconjugated) into soluble isomers that can be
excreted in urine and faeces.
• Phototherapy acts by several ways:
• Configurational isomerization: Here the Z-isomers of bilirubin are converted into E-
isomers. The reaction is instantaneous but reversible as bilirubin reaches into the bile duct.
After exposure of 8-12 hr of phototherapy, this constitutes about 25% of TSB, which is
nontoxic. Since this is excreted slowly from body this is not a major mechanism for decrease
in TSB.
• Structural isomerization: This is an irreversible reaction where the bilirubin is
converted into lumirubin . This product forms 2-6% of TSB which is rapidly excreted from
body thus is mainly responsible for phototherapy induced decline in TSB.
• Photo oxidation: This is a minor reaction, where photo-products are excreted in urine.

37. Types of Phototherapy lights:
• The phototherapy units have a variety of light sources - florescent lamps of different colors
(cool white, blue, green, blue-green or turquoise) and shapes (straight or U-shaped
commonly referred as compact florescent lamps, i.e. CFL), halogen bulbs, high intensity
light emitting diodes (LED) and fibro-optic light sources.
• With the easy availability and low cost in India, CFL phototherapy is being most commonly
used device.
• CFL devices have four blue and two white but this combination can be replaced with 6 blue
CFLs in order to increase the irradiance output.
• In last couple of years, blue LED is making inroads in neonatal practice and has been
found equally effective. LED has advantage of long life (up to 50,000 hr) and is capable of
delivering higher irradiance than CFL lamps.
• The wavelength range of 460 to 490 nm must be ensured.

38. Make sure that ambient room
temperature is optimum 25°to 28°C to prevent
hypothermia or hyperthermia in the baby.
Remove all clothes of the baby except the diaper.
Cover the baby's eyes with an eye patch, ensuring
that it does not block baby's nostrils.
Place the naked baby under the lights in a cot or
bassinet if weight is more than 2 kg or in an
incubator or radiant warmer if the baby is small ( <2
kg).
Keep the distance between baby and light 30 to 45
cm.
Ensure optimum breastfeeding.

39. DOUBLE SURFACE PHOTOTHERAPY
• Double light system where infant is
exposed from both above and below is
available and is more effective.
• For effective double surface
phototherapy, infant is placed on a
fiber-optic cool biliblanket and provided
phototherapy from top with halogen
bulbs.

40. MONITORING AND STOPPING
PHOTOTHERAPY
• Monitor temperature of the baby every 2 to 4 hr. Measure TSB level every
12 to 24 hr.
• Discontinue phototherapy once two TSB values 12 hr apart fall below
current age specific cut offs.
• The infant should be monitored clinically for rebound bilirubin rise within 24
hr after stopping phototherapy for babies with hemolytic disorders.

41. COMPLICATIONS
• Loose stools( Due to transient lactose intolerance & irritant effect of photocatabolites causing
increased colonic secretory losses)
• erythematous macular rash
• overheating
• Dehydration (increased insensible water loss, diarrhea) Can be assessed with weight
monitoring.
• Hypothermia from exposure
• Corneal damage (The infant's eyes should be closed and adequately covered )
• Bronze baby syndrome refers to a dark, grayish brown skin discoloration sometimes noted in
infants undergoing phototherapy, have significant elevation of direct reacting bilirubin and
other evidence of obstructive liver disease.

42. EXCHANGE TRANSFUSION
• Double volume exchange transfusion (DVET) should be performed if the
TSB levels reach to age specific cut-off for exchange transfusion or the
infant shows signs of bilirubin encephalopathy irrespective of TSB levels.
• Indications for DVET at birth in infants with Rhisoimmunization include:
i. Cord bilirubin is 5 mg/ dl or more
ii. Cord Hb is 10 g/ dl or less

43. • The ET should be performed by pull and push technique using umbilical
venous route. Umbilical catheter should be inserted just enough to get free
flow of blood.
• We use fresh type O Rh-negative irradiated packed RBCs that are
resuspended in AB plasma and cross-matched against maternal plasma
and cells.
• The volume ordered should be twice the infant's estimated blood volume.

44. Complications:
• Thrombocytopenia
• Coagulation abnormalities
• Hypoglycemia
• Hyperkalaemia
• Hypocalcaemia
• Acid-base abnormalities
• Infection

45. Intravenous immunoglobulins (IVIG)
• IVIG reduces hemolysis and production of jaundice in isoimmune hemolytic anemia (Rh
isoimmunization and ABO incompatibility) and thereby reduces the need for phototherapy and
exchange transfusion.
• We give IVIG (0.5 to 1 gm/kg) in all cases of Rh isoimmunization and selected case of ABO
incompatibility with severe hemolysis.
• IVIG administration can cause intestinal injury and necrotizing enterocolitis.
IV hydration
• Infants with severe hyperbilirubinemia and evidence of dehydration (e.g. excessive weight loss) should
be given IV hydration.
• An extra fluid of 50 mL/kg of N/3 saline over 8 hr decreases the need for exchange transfusion.

46. FOLLOW-UP
• Babies with serum bilirubin 20 mg/dl and those who require exchange
transfusion should be kept under Follow up in the high-risk clinic for
neurodevelopmental outcome.
• Hearing assessment (BERA) should be done at 3 months of age.
• With prompt treatment, even very elevated serum bilirubin levels within the
range of 25 to 29 mg/ dl are not likely to result in long term adverse effects
on neurodevelopment.

47. PREVENTION
• Antenatal investigation should include maternal blood grouping. Rh positive baby born to a
Rh negative mother is at higher risk for hyperbilirubinemia and requires greater monitoring.
Anti D (Rhogam) injection after first obstetrical event ensures decreased risk of
sensitization in future pregnancies.
• Ensuring adequate breastfeeding
• Parent education regarding danger signs should include yellowish discoloration below
knees and elbows or persistent jaundice beyond 15 days as reason for immediate checkup
by health personnel.
• High risk babies such as ones with large cephalohematoma or family history of jaundice
should be followed up after 2-3 days of discharge.