APPROACH TO NEONATAL

JAUNDICE
JAUNDICE
Defined as yellowish discolouration of skin and
sclerae and other tissues caused by deposition of
bilirubin.
Clinical jaundice apparent at TSB 5-7mg/dl

Progresses in a cephalo-caudal direction, hence

dermal staining of bilirubin can be used as a
clinical guide
BURDEN
Hyperbilirubinemia -common
-benign in most cases

Observed during first week of life.

60% term infants
80% in preterm infants
EVALUATION OF JAUNDICED
NEONATE
History and examination are directed towards
assessing the severity.complication and etiology
of jaundice.
Detailed history and clinical examinaion is
warranted in all neonates with suspected
pathological jaundice.
 APPROACH TO NEONATAL JAUNDICE

Jaundice in the Perform HISTORY and

PHYSICAL EXAMINATION
neonate

Obtain total direct

and indirect bilirubin Measure Bilirubin
levels

> 12 mg/dl and infant < 24 < 12 mg/dl and infant > 24 hr
hr old old

Predominantly Predominantly
direct/conjugated indirect/unconjugated Follow bilirubin level
hyperbilirubinemia hyperbilirubinemia
HISTORY
Onset of jaundice :-
<24hrs
24-72 hrs
>72 hrs
<24h 24-72h 3-7 D >7 D
Breast Milk
Rh Incompatibility Idiopathic
Jaundice
ABO Incompatibiloty sepasis
G6PD Deficienccy
Minor Blodd group Incompatibility
RBC membrane defect
Enclosed hemorrhage
Increased Enterohepatic Circulation
Hypothyroidism
CAUSES OF JAUNDICE
Appearing within 24 hours of age
Hemolytic disease of NB : Rh, ABO
Infections: TORCH, malaria, bacterial
G6PD deficiency

NJ -
7
CAUSES OF JAUNDICE

Appearing between 24-72 hours of life

Physiological
Sepsis
Polycythemia
Concealed hemorrhages-Intraventricular hemorrhage,
cephalhematoma, SAH
Increased entero-hepatic circulation

NJ -
8
CAUSES OF JAUNDICE
After 72 hours of age
Sepsis
Cephalhaematoma
Neonatal hepatitis
Extra-hepatic biliary atresia
Breast milk jaundice
Metabolic disorders (G6PD).

NJ -
9
JAUNDICE AFTER 1 WEEK
a) Prolonged direct b) Prolonged Indirect
Jaundice Jaundice

Neonatal hepatitis (common) Criggler Najjar Syndrome

Extra-hepatic biliary atresia Breast milk jaundice
Metabolic disorders Hypothyroidism
Intra-hepatic biliary atresia Pyloric stenosis
Amino acid toxicity Ongoing hemolysis
Inspissated bile syndrome Gilbert syndrome
(uncommon)
HISTORY

a) MATERNAL H/O:-

o Maternal Infection - congenital viral,

toxoplasmosis
o DM
o Polyhydramnios h/o
o Drug intake
o Blood groups of mother and baby
MATERNAL DRUGS
INTERFERE WITH HEMOLYSIS IN G6PD
BILIRUBIN BINDING TO DEFICIENT INFANT
ALBUMIN
SULFONAMIDES SULFONAMIDES
CEFTRIAXONE ANTIMALARIALS
ASPIRIN,IBUPROFEN NITROFURANTOIN
AMPICILLIN,TICARCILLIN VIT K, OXYTOCIN
BLOOD GROUP
MOTHER BABY
RH NEGATIVE RH POSITIVE
O A,B
b) BIRTH H/O:-

o Delivery complications:-
Trauma -Extravascular bleeding and hemolysis
o Oxytocin use
o Birth asphyxia
o Prematurity and
o Delayed cord clamping.
c) POSTNATAL H/O:-

1. Delayed infrequent stooling :-

Poor caloric intake and intestinal obstruction.
2. Delayed passaging of meconium:-
Hirschprungs disease,cystic fibrosis.
3. Vomiting:-
Sepsis
Pyloric stenosis
Galactosemia.
 Vomitings,
lethargy,
poor feeding,
failure to thrive

Inborn errors of
metabolism.
d) FAMILY H/O:-

Jaundice, Anemia, Heriditary hemolytic

H/O:- Splenectomy, anemia
Early gall bladder disease (spherocytosis, G6PD
deficiency).
Galactosemia,Alpha 1
Antitrypsin def,tyrosinosis,
Liver
Hypermethionemia, Gilbert,
Diseases:-
Criggler najjar 1 and 2,
Cystic fibrosis.
Sibling with jaundice and Blood group
anemia:- incompatability, Breast
milk jaundice, Lucey
dricall syndrome.
PHYSICAL EXAMINATION
VISUAL INSPECTION OF JAUNDICE
Examine in natural bright light
extent of jaundice - krammers rule

Depth of jaundice:
Deep yellow staining (even in absence of yellow sole or
palms)is often associated with severe jaundice and
therefore TSB should be estimated on such circumstances.
KRAMMER
SCORE
PHYSICAL EXAMINATION
Prematurity
Small for gestational age
Cephalhematoma, petechiae, ecchymoses-
Extravasation of blood

Pallor
Plethora

Hepatosplenomegaly

Microcephaly

Omphalitis

Chorioretinitis
 Baby lethargic, poor feeding, temperature
instability, with apnea: Sepsis
Cataract, rash: TORCH infections

Dysmorphic features, congenital heart disease

(pulmonary stenosis), Intra-hepatic biliary
atresia :Alagille syndrome
NEUROLOGIC EXAMINATION
The appearance of abnormal neurologic signs
heralds the onset of early bilirubin encephalopathy.
Initial signs - lethargy, poor feeding, vomiting, and
hypotonia.
The persistently hyperbilirubinemic infant may go on to
experience seizures
The progression of neurologic changes parallels the stages
of bilirubin encephalopathy from acute to chronic and
irreversible changes
Muscle tone
Cry PARAMETERS ASSESED
Mental status
NEUROLOGIC EXAMINATION
BILIRUBIN INDUCED NEUROLOGICAL DYSFUNCTION SCORE

MENTAL MUSCLE CRY

SEVERITY SCORE
STATUS TONE PATTERN
None 0 Normal Normal Normal
Mild 1 Sleepy, Neck High Pitched
Poor Feeding Stiffness,mild
Hyper/
Hypotonia
Moderate 2 Lethargic, Archingneck, Shrill
Irritable Retrocollis,
Arching
Trunk
Severe 3 Semi Coma, Bowing Inconsolable
Seizures, Trunk,
Coma Opisthotonus
SCORE INTERPRETATION

TOTAL SCORE CATEGORY MANAGEMENT

1-3 Mild ABE Reversed with DVET

4-6 Moderate Likely to reverse with DVET
7-9 Severe ABE Urgent DVET

ABE-acute bilirubin encephalopathy

DVET-double volume exchange transfusion
MEASUREMENT OF S.BILIRUBIN
S.bilirubin
Transcutaneous bilirubin screening
tool to identify infants at high risk for severe
hyperbilirubinemia.
Principle multiple wave lengths analysis

Used in >35weeks->24hrs

Trends in tcb values by measuring 12hr apart-

better predictive value

Tcb >12-14mg/dl confirmed by tsb measurement

Advantage reduce no of invasive blood tests

MEASUREMENT OF TSB
Indication of tsb measurement
Jaundice in first 24hrs
>24hrs if <12-14mg/dl
During phototherapy for monitoring progress

Frequency of tsb measurement

Hemolytic rh immunisation-> tsb measurement every 6-
8hrs
Non hemolytic term tsb <20-22mg/dl->every 12-24hrs
 METHODS

I. Biochemical
A. High performance liquid chromatography(hplc) gold
standard
B. vandenbergh reaction
II. Micro method- based on spectrophotometry
 Approach to neonatal jaundice

Jaundice in Perform HISTORY and

the neonate PHYSICAL
EXAMINATION

obtain total direct

Measure Bilirubin
and indirect
bilirubin levels

> 12 mg/dl and infant < 12 mg/dl and infant >

< 24 hr old 24 hr old

Predominantly Predominantly
direct/conjugate
d indirect/unconjuga Follow bilirubin level
hyperbilirubine ted
 Direct
hyperbilirubinemia
Conjugated
Bilirubin
>2mg/Dl
Or>20%total Causes:-
Infection/Sepsis
Congenital Infection
Neonatal Hepatitis
Anatomic Disorders
(Biliary Atresia,choledochal Cyst)
Other Obstructive Cholangiopathies
Cong Heart Disease
Alpha 1 Antitrypsin Deficiency
Cystic Fibrosis
Metabolic Disorders(galactosemia)
Genetic Syndromes(trisomy 21,alagille Syn)
CAUSES OF CONJUGATED HYPERBILIRUBINEMIA

Extrahepatic biliary disease

Biliary atresia

Choledochal cyst

Bile duct stenosis

Spontaneous perforation of the bile duct

Cholelithiasis

Neoplasms

Intrahepatic biliary disease

Intrahepatic bile duct paucity (syndromic or
nonsyndromic)
Progressive intrahepatic cholestasis

Inspissated bile
 Hepatocellular disease
Metabolic and genetic defects- a1-antitrypsin
deficiency, cystic fibrosis, Zellweger's syndrome,
Dubin-Johnson and Rotor's syndromes,
galactosemia
Infections
Total parenteral nutrition
Idiopathic neonatal hepatitis
Neonatal hemochromatosis
Miscellaneous
Shock Hypoperfusion State, ECMO
 INTRAHEPATIC CHOLESTASIS WITH NORMAL BILE DUCTS

Infection

Viral: hepatitis B virus; non-A, non-B hepatitis virus;

CMV, HSV, EBV; coxsackie virus; adenovirus
Bacterial: Treponema pallidum, Escherichia coli, group B
streptococcus, Staphylococcus aureus, Listeria; urinary tract
infection caused by E. coli or Proteus spp, pneumococcus
Other: Toxoplasma gondii
Genetic disorders and inborn errors of metabolism: Dubin-
Johnson syndrome, Rotor's syndrome, galactosemia, hereditary
fructose intolerance, tyrosinemia, a1-antitrypsin deficiency,
Byler disease, recurrent cholestasis with lymphedema,
cerebrohepatorenal syndrome, congenital erythropoietic
porphyria, Niemann-Pick disease, Menkes' kinky hair syndrome
Idiopathic neonatal hepatitis (giant cell hepatitis)
Total parenteral nutrition-induced cholestasis
 DIRECT BILIRUBIN

Evaluate for treatable causes

1.Infections-blood, urine culture, VDRL.
2.Metabolic disorders-urine reducing substances,
serum amino acids,T4,TSH.
If no abnormality ;screen for Identifiable causes
*-1 antitrypsin deficiency
*cystic fibrosis
*congenital viral infections
If no abnormality; evaluate for anatomical
abnormalities
*Stool color
*USG
*Hepato-biliary scintigraphy
*Liver biopsy

Sick or clinical setting
Urine for non-glugose
reducing substance,
GALT Blood and urine
culture CBC, malaria
parasite TORCH
serology AFP, urinary normal Galbladder (GB)
succinylacetone Serum
ferritin IEM work up
if necessary Liver
biopsy if indicated
Neonatal hepatitis: giant
cell transformation, lobular
disarry Bile duct paucity
Storge disorder
Jaundice, dark urine
acholic stool
Conjugated Give vitamins in enhanced
hyperbilirubinemia doses
Do LFT, PT, INR
Not sick & no specific
clinical clues
Look for stool color for 3d abdominal USG
Pigmented stool USG; Pale stools GB: small/non-
visulized Triagular cord
sign+ Urgency: Biliary
Atresia
Liver Biopsy
Liver Biopsy HIDA
Biliary atresia on liver biopsy
Biopsy equivocal and no excretion on HIDA
(Hepatobiliary Imino-Diacentic Acid)
Laparotomy and preoperative
cholangiography
Kasai portoenterostomy or
Hepaticojejunostomy
 Predominantly Indirect
Hyperbilirubinemia

Breast feeding
Onset of jaundice at >24hrs of age
Jaundice persisting-14 days (one month if
breast fed)
Unremarkable maternal h/o,birth h/o,family
h/o
Healthy infant,normal physical exam,
Total bilirubin<13mg/dl(15mg/dl if breast
fed)YES NO
Conjugated bilirubin<2mg/dl(or<20%total)
Observe,consider repeat total bilirubin levelCBC with smear
Observe,consider repeat total bilirubin level
reticulocyte count
Physiological jaundice
Infant and maternal
Breast feeding jaundice
blood type coombs test
 Isoimmune hemolytic
disease
ABO,RH INCOMPATIBILITY

YES
polycythemia
Coomb
s YE
positiv S
e
NO High
hematocrit
N
O
High
Reticulocy
te
count
 Breast feeding jaundice
Breast milk jaundice
Physiologic jaundice
Extravascular blood
Infection GI obstruction
Hypothyroidism
N Drugs/toxins
O Familial hyperbilirubinemia
syndromes like gilbert
High Crigler najjar syn,
Reticulocy lucey Driscoll syn
te
count

YE YE RBC MEMBRANE DEFECTS

S S

Characteristic abnormal
RBC morphology RBC ENZYME DEFICIENCIES
HEMOGLOBINOPATHY
NO
SEPSIS/DIC
CAUSES OF UNCONJUGATED
HYPERBILIRUBINEMIA

Physiologic jaundice
Hemolytic anemia

Congenital: red blood cell defects (hereditary

spherocytosis,infantile pyknocytosis, pyruvate kinase

deficiency, G6PD deficiency, and thalassemia)
Acquired: blood group incompatibilities (ABO or Rh
incompatibility), infection, and drug-induced hemolysis
CONTD..
Polycythemia
Blood extravasation
Defects of conjugation
Congenital: Crigler-Najjar syndrome (types I and II),
Gilbert syndrome
Acquired: Lucey-Driscoll syndrome

Breast-feeding and breast milk jaundice

Metabolic disorders: galactosemia, hypothyroidism
CONTD..
Increased enterohepatic circulaton of bilirubin
Substances pathologic conditions such as
CysticFibrosis,
Gastrointestinal Obstruction (Ie, Pyloric Stenosis,
Duodenal Atresia,annular Pancreas)
Ileus
Disorders affecting binding of bilirubin to
albumin:
Drugs, Fattyacids In Nutritional Products, Asphyxia,
Acidosis, Sepsis
Hypothermia, Hyperosmolality, Hypoglycemia
PROLONGED JAUNDICE
*COMMON
Inadequacy of breastfeeding
Breast milk jaundice
cholestasis
Continuing hemolysis .eg- RH,ABO
Rare
- extravasated blood eg-cephalhaematoma
-hypothyroidism
-criggler-najar synd
-GI obstruction
-gilbert synd
 Persistence of jaundice >2 wk in term & >3 wk in preterm babies

Check if the infant is passing high colored urine

(Staining nappies)

If Yes: manage as per If No:

cholestasis guidelines
1. Visually assess severity of jaundice (measure TSB, if
required)
2. Assess for and manage inadequate breastfeeeding
3. Perform clinical examination to ascertain the cause:
extravasated blood, hemolysis, hypothyroidism

Level of jaundice/TSB not TSB in PTx range:

in PTx range: Initiate PTx
Manage conservatively Perform: G6PD, thyroid screen, ABO of infant &
Follow up as needed until mother, if not done earlier
resolution of jaundice

TSB persistently high, unresponsive to PTx and hovering in exchange range: consider
cessation of breastfeeding for 48h (required in exceptional cases only)
TSB persistent high despite PTx/cessation of breastfeeding: consider phenobarbitone
trail to rule out CNS
PHYSIOLOGICAL JAUNDICE
Jaundice associated with following changes are
physiologic:-
1. Onset-2nd or 3rd day
2. Rate of rise- <5mg/dl/24hrs
3. Peak-between 2-4 th day
4. Peak level-5-6mg/dl [term-<12,preterm-15]
5. Decreases to <2mg/dl bet 5-7th day
6. Does not exceed 15 mg/dl
7. Clinically undetectable after 14 days.

No treatment is required but baby should be observed

closely for signs of worsening jaundice.
 MECHANISMS:-
1. Increased bilirubin production.
2. Increased enterohepatic circulation.
3. Defective uptake of bilirubin from plasma.
4. Defective conjugation.
5. Decreased hepatic excretion of bilirubin.
PATHOLOGICAL JAUNDICE
o Appears within 24 hours of age
o Increase of bilirubin > 5 mg / dl / day
o Serum bilirubin > 15 mg / dl
o Jaundice persisting after 14 days
o Stool clay / white colored and urine staining clothes
yellow
o Direct bilirubin> 2 mg / dl

NJ -
47
LABORATORY EVALUATION
Jaundice in first 24 h
Measure TcB and/or TSB
Jaundice appears excessive for infants age
Measure TcB and/or TSB
Infantreceiving phototherapy or TSB rising
rapidly (ie, crossing percentiles) and
unexplained by history and physical
examination:
Blood type and Coombs test, if not obtained with cord blood
Complete blood count and smear
Measure direct or conjugated bilirubin
It is an option to perform reticulocyte count, G6PD, and ETCOc,
if available
Repeat TSB in 424 h depending on infants age and TSB level
LAB EVALUATION (CONTD.)

TSB concentration approaching exchange

levels or not responding to phototherapy
Perform reticulocyte count, G6PD, albumin, ETCOc, if
available
Elevated direct (or conjugated) bilirubin level
Do urinalysis and urine culture.
Evaluate for sepsis if indicated by history and physical
examination
Jaundice present at or beyond age 3 wk, or
sick infant
Total and direct (or conjugated) bilirubin level
If direct bilirubin elevated, evaluate for causes of cholestasis
Check results of newborn thyroid and galactosemia screen,
and evaluate infant for signs or symptoms of hypothyroidism
MANAGEMENT
MANAGEMENT OF JAUNDICE
Infants born at gestation of 35 weeks or more -
American Academy Of Pediatrics (aap) criteria
should be used for making decision regarding
phototherapy or exchange transfusion.
AAP provides two age specific nomograms one
each for phototherapy and exchange transfusion
RISK FACTORS
Isoimmune hemolytic anemia
G6pd deficiency
Asphyxia
Temperature instability
Hypothermia
Sepsis
Significant lethargy
Acidosis
Hypoalbunemia
PRETERM BABIES
TOTAL SERUM BILIRUBIN LEVELS

HEALTHY BABY SICK BABY

EXCHANGE
EXCHANGE PHOTO
BIRTH PHOTO TRANSFUS
TRANSFUS THERAPY
WEIGHT THERAPY ION
ION

<1000GM 5-7 11-13 4-6 10-12

1001-
7-10 13-15 6-8 11-13
1500GM
1501-
10-12 15-18 8-10 13-15
2000GM
2001-
12-15 18-20 10-12 15-18
2500GM
PHYSIOLOGICAL JAUNDICE

Explain about benign nature of the

disease
Encourage to breastfeed frequently &
exclusively
Ask Mother to bring baby back if baby
looks deep yellow or palms & soles have
yellow staining.
PATHOLOGICAL JAUNDICE

Mainly 2 modalities of Treatment:

1. Phototherapy

2. Exchange Transfusion
1. PHOTOTHERAPY
Mainstay of treatment
Under blue-green light(460-490nm),
insoluble bilirubin is converted into soluble
isomers that can be excreted in urine &
feces.
To be effective, bilirubin must be present in
skin; hence nor role for prophylactic
phototherapy
PHOTOTHERAPY
MECHANISMS:
Configurational Isomerization

Structural Isomerization

Photo Oxidation
CONFIGURATIONAL ISOMERIZATION
Z-isomer converted to E-isomer
Reaction is instantaneous but reversible.
After exposure of 8-12 hrs, this constitutes about
25% of the TSB which is non-toxic.
Excreted slowly from the body; hence not a
major mechanism for decrease in TSB.
STRUCTURAL ISOMERIZATION
Irreversible reaction
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
Minor reaction
ADMINISTERING PHOTOTHERAPY:
Optimum ambient room temperature( 25-28celcius)
to prevent hypothermia.
Remove all clothes of baby except diaper
Cover babys eyes with an eye patch(to prevent
retinal degeneration) ensuring that it does not block
the babys nostrils.
Place the baby under the lights in a cot if weight is
more than 2kg or in an incubator if baby is
small(<2kg)
 Cont

Keep the distance between the baby & the light 30-
45cm.
Ensure optimum breastfeeding as intermittent
feeding sessions.
Monitor temperature of the baby every 2-4hrs
Measure TSB every 12-24hrs.
Discontinue, once 2 TSB values 12hr apart fall below
current age-specific cut-offs.
Monitor for rebound bilirubin rise within 24hrs.
COMPLICATIONS OF PHOTOTHERAPY
Loose stools
Erythematous macular rash
Purpuric rash associated with transient
porphyrinemia
Over-heating
Dehydration
Bronze baby syndrome
BRONZE BABY SYNDROME
Intense grey-brown
discoloration of the skin,
serum, and urine,
especially in premature
infants; when
phototherapy was used to
reduce hyperbilirubinemia.
Pre-existing hepatic
disease is suspected as a
cause of the jaundice and
may have prevented the
biliary excretion of the
photo oxidation products
EXCHANGE TRANSFUSION
Double Volume Exchange Transfusion (DVET) : 160-
180ml/kg; is to be performed if TSB levels reach age-
specific cut-offs or if the infant shows signs of
bilirubin encephalopathy, irrespective of TSB levels.
If baby shows signs of cardiac decompensation at
birth, partial exchange transfusion with 50ml/kg of
packed red cells should be done to quickly restore
oxygen carrying capacity of blood.
Umbilical venous route.
2. EXCHANGE TRANSFUSION
FOLLOWUP
Babies with serum bilirubin>20 mg/dl & those
who required ET should be kept under follow-up
in high-risk clinic for neuro-developmental
outcome.
Hearing assessment should be done at 3months
of age.