3. INTRODUCTION
Neonatal Jaundice (NNJ) or neonatal hyperbilirubinaemia is one
of the most common medical conditions in newborn babies.
All babies have a transient rise in serum bilirubin but only about
75% are visibly jaundiced
Jaundice can be detected clinically when the level of bilirubin in
the serum rises above 85 μmol/l (5mg/dl)
Hyperbilirubinemia is either unconjugated or conjugated
4. PATHOPHYSIOLOGY
Bilirubin is a yellow-orange compound that is produced by the
breakdown of haemoglobin from red blood cells
Unconjugated bilirubin: is an end product of heme protein
catabolism
Conjugated bilirubin: is an end product of unconjugated bilirubin
that has gone conjugation in the liver cell by uridine diphosphate
(UDP) – glucuronyl transferase
5.
6. CAUSES OF NEONATAL JAUNDICE
AGE OF ONSET <24 HOURS OF LIFE 24 HOURS – 2 WEEKS
OF LIFE
>2 WEEKS OF LIFE
CAUSES Haemolytic
disorders:
• Rhesus
incompatibility
• ABO
incompatibility
• Enzymopathy –
G6PD deficieny,
pyruvate kinase
deficiency
• Membranopathy
–spherocytosis
Congenital
infections
• Infection -
urinary tract
infection
• Haemolysis -
G6PD
deficiency
• ABO
incompatibility
• Physiological
jaundice
• Breastfeeding
jaundice
• Bruising
• Polycythaemia
• Crigler-Najjar
syndrome
Unconjugated:
• Breast milk
jaundice
• Infection-UTI
• Hypothyroidism
• Haemolytic
anaemia
• High GI
obstruction-
pyloric stenosis
Conjugated:
• Bile duct
obstruction
• Neonatal
hepatitis
8. PATHOLOGICAL JAUNDICE
(EARLY ONSET OF JAUNDICE)
Serum bilirubin rises > 5mg/dL(85umol/L) in 24 hours
Appears within 24 hours of Life
Causes:
I. Hemolysis – ABO incompatibility, rhesus isoimmunisation, G6PD
deficiency
II. Sepsis
III. Gastrointestinal tract obstruction: increase in entero hepatic
circulation.
IV. Cephalhaematoma, subaponeuritic haemorrhage
V. Infant of diabetic mother
VI. Polycythemia (hyperviscosity)
9. CAUSES OF PATHOLOGICAL JAUNDICE
PATHOLOGICAL
JAUNDICE
HAEMOLYSIS
TRAUMA
POLYCYTHEMIA
INFECTION
BREASTFEEDING
JAUNDICE
BREAST MILK
JAUNDICE
BILIARY TREE
OBSTRUCTION
10. PHYSIOLOGICAL JAUNDICE
Appears after 24 hours
Serum bilirubin rises > 5mg/dL(85umol/L)
Peaks at day 3-5 of life
Resolving after 1-2 weeks (3 weeks if preterm)
Is not associated with underlying disease and is usually benign
Causes:
I. 1. Increased bilirubin production resulting from an increased RBC mass
relatively polycythemic
II. 2. Shortened RBC lifespan
III. 3. Poor bilirubin clearance :
hepatic immaturity of ligandin and glucuronosyltransferase
11. RISK FACTORS FOR SEVERE
NEONATAL JAUNDICE
prematurity
low birth weight
jaundice in the first 24 hours of life
mother with Blood Group O or Rhesus Negative
G6PD deficiency
rapid rise of total serum bilirubin
sepsis
lactation failure in exclusive breastfeeding
high predischarge bilirubin level
cephalhaematoma or bruises
babies of diabetic mothers
family history of severe NNJ in siblings
13. HISTORY
Onset of jaundice
<24 hours
24hr – 2 weeks
>2 weeks
Symptoms of kernicterus
Lethargy
Poor feeding
Abnormal posture
Irritable
Inconsolable cry
High pitch cry
Convulsion
Mother’s blood group & Rhesus
14. Family history
Previous history of other siblings with neonatal jaundice
G6PD deficiency
Blood disorders
Liver diseases
History of pregnancy & delivery
Antenatal infections
Eg: TORCHES, Syphillis,
Drug intake/herbal remedies
Delayed cord clamping
Birth trauma with bruising / fractures
HISTORY
15. Postnatal history
Breastfeeding
Use of drug/remedies in lactating mother
Greater than average weight loss
Symptoms & signs of hypothyroidism
Symptoms & signs of metabolic disease
Eg: galactosemia
Exposure to total parental nutrition
HISTORY
16. PHYSICAL EXAMINATION
General condition, gestation and weight, signs of sepsis,
hydration status.
Level of jaundice
Using Kramers rule
To find causes & other associated signs
Cephalhematoma
Infections of umbilical cord
Hepatosplenomegaly
Signs of sepsis
Signs of intrauterine infection e.g. petechiae, hepatosplenomegaly.
20. TRANSCUTANEOUS BILIRUBINOMETER
(TCB)
Hand held device that measures the amount of bilirubin in the skin.
Used as a screening tool
Limitation:
1. If levels exceed 200 μmol/L (12 mg/dL), total serum bilirubin (TSB)
should be measured
2. Should not be used in preterm babies
3. Should not be used to monitor bilirubin levels in babies on
phototherapy
21. COMPLICATIONS
Acute Bilirubin encephalopathy
ABE result in changes of mental (behavioral) status and muscle
tone during the neonatal period when the baby is having
hyperbilirubinemia
Signs of acute bilirubin encephalopathy: drowsiness, poor feeding
and hypotonia followed by hypertonia affecting particularly extensor
muscles - opisthotonus, Retrocollis
Risk factors: Preterm infants, small for gestational age, sepsis,
acidosis,
hypoxic-ischemic encephalopathy, hypoalbuminaemia, jaundice less
than 24hours of age
22. COMPLICATIONS
Kernicterus (Bilirubin Encephalopathy)
Neurologic syndrome resulting from deposition of unconjugated
bilirubin in basal ganglia and brainstem nuclei
May be seen in babies who survive from ABE
The earliest clinical manifestations are lethargy, hypotonia,
irritability, poor Moro response, poor feeding, a high-pitched cry and
emesis
Early signs are noted after day 4 of life.
23. Signs of chronic bilirubin encephalopathy (irreversible
brain damage to basal ganglia): dystonia, choreo athetoid
cerebral palsy, paralysis of upward gaze, sensorineural
hearing loss
Early signs of kernicterus occasionally may be reversed
by immediately instituting an exchange transfusion
10% mortality and 70% morbidity
24. BLOOD INVESTIGATION
Test Why?
Serum bilirubin (SBV/SBC)
• Total
• Unconjugated
• Conjugated
1. Bilirubin level (narrow down dx)
2. Severity
3. Monitoring
Further Investigations:
G6PD testing G6PD deficiency
TSH status Hypothyroidism
FBC ± peripheral blood count
Reticulocyte count
1. Haemolytic disorders
2. Infections
Blood grouping (maternal & baby)
Direct Coomb’s test
1. ABO incompatibility
2. Rhesus incompatibility
Septic workout (if infection is
suspected)
• Blood culture & sensitivity
• Urine culture & sensitivity,
UFEME, Urinalysis
Infections/Sepsis
26. CPG management of neontal jaundice 2nd edition
Predischarge screening:
-clinical risk factor assessment
-predischarge bilirubin levels –
TCB
-G6PD Deficiency should be
admitted and monitored for NNJ
during first 5 days of life and
check TSB if clinical jaundice
-Term, BW >2.5kg, may be
discharged earlier at day 4 of life
if TSB <160umol/L (9mg/dL) and
follow up closely
-All babies discharged < 48H
after birth should be seen by
healthcare provider within 24H of
discharge
-Severe jaundice, early follow up
is needed to detect rebound
jaundice after discharge
27. PHOTOTHERAPY
It is the mainstay of treatment in NNJ
No sunlight exposure (risk of dehydration and sunburn)
Types of devices : flouroscent tubes, Light Emitting Diode (LED),
fibreoptic and halogen bulbs
Mechanism of action:
bilirubin (water insoluble) is transformed into photoisomers that are
water soluble , and are easily excreted in the urine as they do not
require hepatic conjugation
Commenced when total serum bilirubin reaches the phototherapy
threshold
28.
29.
30.
31.
32. EFFECTIVE PHOTOTHERAPY
Achieved with optimal irradiance and adequate exposed body
surface rather than number of phototherapy units
Supine position
Blue light range (400-500 nm)
Irradiance of minimum of 15uW/cm2/nm for conventional
phototherapy
Irradiance of minimum of 30uW/cm2/nm for intensive
phototharapy
Distance of the light source not exceeding 30-50 cm from baby
*Visual observation unreliable. Serum bilirubin levels must guide the
management
33. CARE OF BABIES DURING
PHOTOTHERAPY
Adequately exposed
cover eyes (prevent retinal damage)
Babies should be regularly monitored for vital signs including
temperature and hydration status
Monitor urine output and weight
Breastfeeding should be continued.
Turn off photolights and remove eyepads during feeding and blood
taking
36. • Failure of phototherapy is defined as an inability of decline in
bilirubin of 17-34 umol/L (1-2mg/dL) after 4-6 hours and/or
to keep the bilirubin below the exchange transfusion level
37. EXCHANGE TRANSFUSION (ET)
Indicated for severe hyperbilirubinemia to reduce risk of brain
damage associated with kernicterus.
Various methods :femoral vein (FV), umbilical vein(UV), umbilical
artery/vein (UA/V), peripheral artery (radial artery).
38. INDICATIONS
DOUBLE VOLUME EXCHANGE PARTIAL EXCHANGE
TRANSFUSION
1. To lower serum bilirubin level and
reduce risk of brain damage
associated with kernicterus
1. To correct polycythemia with
hyperviscosity
2. Hyperammonia 2. To correct severe anemia without
hypervolemia
3. To remove bacterial toxins in
septicemia
4. To correct life threatening electrolyte
and fluid disorders in acute renal
failure
39. • Signed consent fromparents
• Ensure resuscitation equipment is ready and available
• Stabilise the patient, maintain temperature, pulse, respiration, O2
saturation
• Obtain peripheral venous access for IV fluid maintenance
• Proper gentle restraint
• Omit the last feed before ET (if < 4 hours from last feed, empty
gastric contents by NGaspiration)
• Types of blood to be used;
RH isoimmunisation: ABO compatible, Rh negative blood
Other conditions: Cross match with baby and mother’s blood
In emergency (unknown blood type): O Rh negative blood
• Volume to be exchanged is 2x the infant’s total blood volume
(2x80ml/kg)=160ml/kg
• Fresh whole blood, less than 5 days old
or reconstituted Packed Red blood cells and FFP in a ratio of 3:1
PREPARATIONS
40.
41. • Pre-warm blood to body temperature using water bath
• Connect baby to cardiac monitor
• Neonatal Exchange Blood Transfusion Sheet
Take baseline observation (heart rate, respiration, oxygen saturation) and
record down
following observations are recorded every 15-30 minutes
• Perfom under aseptic technique using a gown, mask and headcap.
• Cannulate the umbilical vein not > 5-7cm depth
• Aliquot for removal and replacement 5ml/kg per cycle (not more than 5-8%
of blood volume):
20ml for term
not more than 5ml/kg for ill/preterm
• Begin with an initial removal, so that there is always deficit, to avoid cardiac
overload
PROCEDURE OF ET
42. PROCEDURE OF ET
• Syringe should be held vertically during infusion ‘in’ to prevent air
embolism
• Total exchange duration should be 90-120 minutes utilizing 30-35
cycles
• Rate of exchange: 3-4 min per cycle (1 min out, 1 min in, 1-2
min pause)
• Record the amount of blood given or withdrawn, and
medications given
• Anemic hb pre-ET < 12: at the end of procedure, give extra
aliquot vol of blood 10cc/kg at a rate 5 cc/kg/h
43. • Investigations
– Pre-ET (the 1st vol. of blood removed)
• FBC, blood c+s, HIV ,hep B, hep C,SBV
– Post-ET
• SBV, FBC, renal profile, capillary blood sugar, blood c+s
• Post-ET management
–continue Intensive Phototherapy
–Monitor vital signs (BP
, HR, spo2) hourly x 2, 2 hourly x 2, then
4 hourly ifstable
–Monitor dscan hourly x 2 ,then 4 hourly if stable
–repeat SBV 2 hours post ET, then 4-6hly
–NBM with IVD (can allow feeding if well)
-readministered medication after ET
-repeat ET may be required in 6H if high rebound serum
bilirubin
44. COMPLICATION OF ET
CATHETER RELATED HEMODINAMIC
PROBLEMS
ELECTROLYTE/METAB
OLIC DISORDERS
• Infection
• Hemorrhage
• Necrotising
enterocolitis
• Air embolism
• Vascular events
• Portal, splenic vein
thrombosis (late)
• Overload cardiac
failure
• Hypovolemic shock
• Arrythmia (catheter tip
near sinus node in
right atrium)
• Hyperkalemia
• hypocalcemia
• Hypo/hyperglycemia
45. • Intravenous Immunoglobulin (IVIG)
–high dose IV Immunoglobulin (0.5-1g/kg over 2h) reduces the
rate of haemolysis in babies with rhesus haemolytic disease.
–give as early as possible in haemolytic disease with +ve
Coombs test or when the serum bilirubin is increasing despite
intensive phototherapy
• Clofibrate
• Human albumin
• Tin-mesophorphyrin
• Phenobarbitone
PHARMACOTHERAPY
46. FOLLOW UP
Acute bilirubin encephalopathy • Long term follow up, to monitor
neurodevelopment sequelae
TSB > 342umol/L (20mg/Dl)/ done
ET
• Auditory Brainstem Response
(ABR) test (3 month of life)
• Referred to audiologist
• Neurodevelopmental follow up
Prem babies with Jaundice • Follow up for neurodevelopment
sequelae (as per prem follow up
plan)
48. PROLONGED JAUNDICE
Visible jaundice that persists beyond :
14 days of life in term infant (≥37 weeks)
21 days in preterm infant (≥35 weeks to < 37 weeks)
Causes of prolonged jaundice
Conjugated or Unconjugated hyperbilirubinemia
conjugated hyperbilirubinemia:
direct bilirubin more than 34umol/L(2mg/dL) or >15%of total
bilirubin
*All babies with conjugated hyperbilirubinaemia must be referred to a
paediatrics department urgently to exclude biliary atresia
49. Conjugated
hyperbilirubinaemia
Unconjugated
hyperbilirubinaemia
Biliary tree abnormalities:
Biliary atresia
Choledochal cyst
Paucity of bile duct
Alagille syndrome
Idiopathic neonatal hepatitis syndrome
Septicemia
UTI
Congenital infection (TORCHES)
Metabolic disorder
Progressive familial intrahepatic
cholestasis (PFIC)
Alpha-1 antitrypsin deficiency
Total parenteral nutrition
Septicemia
UTI
Breast milk jaundice
Hypothyroidism
Hemolysis:
G6PD deficiency
Congenital spherocytosis
Galactosemia
Gilbert syndrome
*Early diagnosis and treatment of biliary atresia and hypothyroidism is
important for favourable long term outcome of patient
50. • Common and remain a diagnosis of exclusion
(Infant is well, gaining weight, breast feed well, stool
normal yellow with normal physical examination)
• Interruption of breastfeeding for 1 to 2 days results in a
rapid decline of bilirubinlevels.
• Breast milk may contain an inhibitor of bilirubin
conjugation
• Management :
-continue breast feed and review periodically
-Increase breastfeeding to 8-12 times/day ,recheck
serum bilirubin levels in 12-24 hours.
BREAST MILK JAUNDICE
51. BREASTFEEDING JAUNDICE
• Manifests in the first 3 days of life ,peaks by 5-15 days of
life, dissapears by week 3 of life.
• Caused by:
-insufficient production or intake of breast milk
-Maternal breastfeeding issues (engorgement,cracked
nipples, and fatigue)
-Neonatal factors (ineffective sucking)
• In contrast with breastmilk jaundice, infants generally
exhibit mild dehydration and weight loss in the first few
days of life
• Management:
-Increase breastfeeding, make sure proper
breastfeeding technique is adheredto.
52.
53. • Needs earlydiagnosis
• Clinical features ;
- persistent or late onset
jaundice
-conjugated
hyperbilirubinaemia
-pale stool
-firm liver
-hepatosplenomegaly
• Better prognosis if Kasai
procedure
(hepatoportoenterostomy) is done
within first 2 months of life
• Diagnosis -US liver
,raised GGT ,
palestool
BILIARY ATRESIA
54. serious, rare, autosomal recessive , permanent
deficiency of glucuronyl transferase
results in severe unconjugated hyperbilirubinemia
Type I : does not respond to phenobarbitol and
manifests as persistent indirect hyperbilirubinemia,
often leading to kernicterus.
Type II : responds to enzyme induction by
phenobarbitol , producing an increase in enzyme
activity and reduction of bilirubin levels.
CRIGLER-NAJJAR SYNDROME
55. • mutation of promoter region of glucuronyl
transferase , resulting in mild indirect
hyperbilirubinemia
GILBERT DISEASE
56. ALAGILLE SYNDROME
Consider in infants who have cardiac murmurs or dysmorphism.
One of the parents is usually affected (AD inheritance, variable
penetrance)
Affected infants might not have typical dysmorphic features at
birth due to evolving nature of the syndrome.
Important screening tests include :
Vertebral x ray: To look for butterfly vertebrae
Echocardiography: look for branched pulmonary artery stenosis.
Slit eye lamp examination: look for posterior embryotoxon
May also help to rule out other aetiologies in neonatal hepatitis
syndrome, e.g. retinitis in congenital infection, cataract in
galactosaemia.
Other known abnormalities - ASD, valvular pulmonary stenosis.
Gene test: JAG1 gene mutation which can be done at IMR (EDTA
container).(Consult Genetist Prior to Testing)
57. APPROACH TO PROLONGED
JAUNDICE
All babies must be screened for prolonged jaundice (clinical
jaundice)
Clinical assessment :
feeding method, weight, stool colour, hepatosplenomegaly
Risk stratification:
direct and total serum bilirubin
Once diagnosed refer to MO on the same day/next working day
58. INVESTIGATIONS
most important lab
investigation:
Total serum bilirubin with direct
and indirect
Work up for Prolonged Jaundice :
- FBP + reticulocyte count
- Thyroid Function test, e.g. TSH
- Liver function test
- Urine FEME & culture and sensitivity
* Observe stool colour for 3 days
*No Phototherapy needed in Prolonged jaundice
62. FOLLOW UP FOR
PROLONGED JAUNDICE
• Treat any treatable conditions (biliaryatresia,
hypothyroidism, UTI, IEM, syphilis)
• Follow up 2-8weekly with LFT
• Watchout for worsening LFT
• No need for regular serum bilirubin monitoring once
investigations for prolonged jaundice is done and the
serum bilirubin is not increasing in trend.
Associated with unconjugated hyperbilirubinemia without evidence of hemolysis during first to second week of life, persists longer than physiological jaundice (can persist up to 4 months of age)
Periodically,during 1 and 2 mo immunisazation
Phototherapy not needed because of bbb already fully functional by 2 weeks and 3 weeks in preterm babies