3. Facts & figures
Commonest abnormal physical finding during I week of life
> 2/3 of NBBs develop clinical jaundice
Visible form of bilirubinemia
– Adult sclera >2mg / dl
– Newborn skin >5 mg / dl
Occurrence - 25 – 50% of term, 80% of preterm NBBBs
Yellow discoloration –
First evident on skin of face, naso-labial folds and tip of nose
Masked by physiological plethora
Assess by blanching
Assess in good daylight – No yellow light, clothes or curtains
4. Clinical assessment of jaundice
With increase in jaundice – Cephalo-pedal progression of
yellow discoloration of skin -
Area of body Bilirubin levels
mg/dl
Face 4-8
Upper trunk 5-12
Lower trunk & thighs 8 - 16
Arms & lower legs 11 - 18
Palms & soles > 15
Imp! – Screen all NBBs x BD in good day light
6. Sources of Bilirubin
Haem containing proteins
RBC Hb – Major source. 1 gm Hb 34 mg
of Bilirubin
- Haem from ineffective erythropoiesis in bone
marrow
- Other haem containing proteins – myoglobin,
cytochromes, catalase, peroxidase
- Free haem
7. Bilirubin
turnover in
Newborn
Hb Haem + Globin
Other sources
BILIRUBIN
UCB binds to S albumin
Dissociates from albumin
UDPG - T
Bil monoglucoronide +
Bil Diglucoronide
Water sol Bil
Binds to cytoplasmic
Ligandin (Y protein)
Excreted into bile canaliculi
Enters Gut
Excreted in stool
Biliverdin + CO + Fe
Bilirubin Reductase
Haem oxygenase
Beta Glucoronidase
UCB
Production
Transport
Uptake
Excretion
Conjugation
8. Physiological handicaps causing
increased Bilirubin turnover
1. Increased production of bilirubin
Physiological Polycythemia
Shorter life span of HbF (90 days)
1ml/kg (approx 1% ) of blood hemolyse everyday
0.15 gm/ kg of Hb released everyday
1 gm Hb yields 35 mg of bilirubin
Hence, a 3 kg infant produces 15 mg bil/ day from Hb sources
+ 1 mg/kg from non Hb sources
Thus, daily load to the liver – 20 mg bil
2. Defective uptake from plasma
Non availability of albumin binding sites
9. Physiological handicaps…
3. Defective conjugation
Transient deficiency of Y & Z acceptor proteins
4. Reduced hepatic clearance
Reduced UDPG enzymes
>ed unconjugated bil in early days of life in preterms
5. Enhanced enterohepatic circulation
100 – 200 mg of bil in gut as 1 mg/gm of meconium
Reduced gut motility & poor evacuation
Paucity of bacterial flora in gut of NBB
Over activity of intestinal glucoronidase enzyme
Conj Bil rapidly deconjugated and recirculated through blood to liver
for reconjugation
10. Bilirubin load causing jaundice in
Newborn
>ed RBC vol & <ed RBC survival
>ed Bil monoglucoronide
<ed Bil Diglucoronide
UCB
Production
Transport
Uptake
Excretion
Conjugation
>ed Ineffective erythropoiesis & >ed Heam
turnover
Non availability of Albumin
binding sites
Defective conjugation
<ed LIigandin
Decreased excretion
<ed gut motility
Poor evacuation
>>ed beta glucoronidase, <ed
intestinal bacteria
>ed BILIRUBIN load
Defective uptake from plasma
>ed Entero-hepatic circulation
12. Within 24 hours of birth
Hemolytic disease of newborn - due to feto-maternal
group incompatibility (Rh, ABO, other minor blood
group systems)
Intra-uterine infections (TORCH)
Deficiency of red cell enzymes – G6 PD, pyruvate
kinase, heokinase, phospho-glucose isomerase, unstable
Hbs
Admn of drugs in excess – Vit K, salycilates,
sulfisoxazole to mother
Hereditary spherocytosis
Criggler Najjar syndrome
Lucey Driscoll syndrome
Homozygous alpha thalassemia
13. Between 24 – 72 hours of age
Physiological jaundice
May be aggravated/ prolonged by –
Immaturity, birth asphyxia, acidosis, hypothermia,
hypoglycemia, drugs, cephalhematoma, hge’/
bruising, Polycythemia, high altitude, cretinism,
breast feeding, infections
Mild hemolytic states – Feto maternal blood gp
incompatibility, spherocytosis, deficiency of cell
enzymes
14. After 72 hrs of age ( and within
first 2 weeks)
Septicemia
Neonatal hepatitis
Extra hepatic biliary atresia
Breast milk jaundice
Metabolic diseases – Galactosemia, tyrosinemia,
fructosemia, organic acidemia, cyctic fibrosis,
alpha 1 anti trypsin deficiency
Hypertrophic pyloric stenosis & intestinal
obstruction
15. Drugs causing increase in
bilirubin
Drugs Nature of action
Vit K in larg doses Hemolysis
Vit K and kanamycin Block Y acceptor protein
Novobiocin, Moxalactam, Gentamycin,
Kanamycin, Chloramphenicol
Compete for Glucoronyl
transferase
Salicylates, long acting sulphonamides,
sodium benzoate, furosamide,
indomethacin, radiographic contract media
Block bilirubin binding sites in
albumin
Oxytocin (induced labour) Hyponatremia & hypo
osmolality
Spinal block for mother using Bupivacaine
16. Risk factors for jaundice
J - jaundice within first 24 hrs of life
A - a sibling who was jaundiced as neonate
U - unrecognized hemolysis
N – non-optimal sucking/nursing
D - deficiency of G6PD
I - infection
C – cephalhematoma /bruising
E - East Asian/North Indian
17. Common causes in Sri Lanka
Physiological
Blood group incompatibility
Intrauterine and postnatal infections
G-6PD deficiency
Bruising and cephalhematoma
Breast milk jaundice
19. Physiological jaundice
Appears between 30 – 72 hrs of age in term babies (earlier in
preterms)
Maximum intensity by 4th-5th day in term & 7th day in preterm
Serum level less than 15 mg / dl
Disappears by 10 days of life (reaches 15 days in preterms)
Disappears without any treatment
Note:
Baby should, however, be watched for worsening jaundice
Alert in preterms…danger of brain damage!
20. Features of physiological jaundice (all of
the following
Jaundice that first appears between 24-72 hours of
age
Maximum intensity is seen on 4-5th day in term
and 7th day in preterm neonates
Does not exceed 15 mg/dl (255μmol/l)
Clinically undetectable after 14 days
Physiological jaundice is a diagnosis by exclusion. No treatment is
required but baby should be observed closely for signs of worsening
jaundice
21. Pathological jaundice
In 5% of newborns
Appears within 24 hours of age
Serum bilirubin > 15 mg / dl after 24h
Jaundice persisting after 14 days
Stool clay / white colored and urine staining clothes yellow
Direct bilirubin> 2 mg / dl
Total serum bilirubin (TSB) increasing by > 5mg/dl/day(85
μmol/l/day) or 0.5 g/dl/hr (8.5μmol/l/hr)
22. Dangers of hyperbilirubinemia
Unconjugated hyperbilirubinemia Bil encephalopathy/
Kernicterus
C/F – Refusal of feeds, shrill cry, setting sun sign,
convulsions, retrocollis and opisthotonus
- Sluggish Moro’s response, lethsrgy, poor feeding
- Preterms – Non specific. Die due to apneic attacks
- Infancy – Athetoid cerebral palsy, choreo-athetosis,
brownish staining of teeth, dental dysplasia, deafness,
paralysis of upward gaze, intellectual retardation &
learning disabilities
23. Pathogenesis of kernicterus
Related to –
Unconjugated bilirubin levels
Gestational maturity of infant
Integrity of blood-brain barrier
Biochemical determinants –
Bilirubin protein ratio – 3.5 or more
HBABA (hydroxybenzene azo benzoic acid) dye
binding capacity - < 50%
Salicylate saturation index – 8 or moreRBC biuding
of bilirubin - >4 mg%
26. Approach to a jaundiced baby
Ask 4 questions -
What is the birth weight?
What is the gestation?
What is the postnatal age in hours?
Is the jaundice physiological or pathological?
If jaundice is physiological and baby is well – only
observe
If deep jaundice – Assess for bil toxicity
(kernicterus)
27. Indication for lab investigations
(In high risk infants)
H/O Jaundice, Exchange Blood transfusion /
Kernicterus in previous sibling
Mother – O group or Rh –ve
Jaundice – Within 24 hrs or after 72 hrs
Trunk distinctly yellow stained
Sick jaundiced baby
Jaundice persisting > 2 weeks
Yellow coloured urine or clay coloured stools
28. Workup
Maternal & perinatal history
Physical examination
Laboratory tests (must in all)
Total & direct bilirubin (Total : 0.3 to 1.9 mg % , Direct : 0 to 0.3
mg %)
Bil: protein ratio (< 3.4)
Blood group and Rh for mother and baby
Blood - Hematocrit, retic count and peripheral smear, Sepsis
screen, Carboxy Hb
Liver function - Vanden Bergh test
Thyroid function
TORCH titers, liver scan when conjugated hyperbilirubinemia
Tests for –
Pulmonary excretion rate of CO, OR
End tidal CO (Etco) breath level
29. Assessment of severity of
jaundice
Assess in natural daylight for cephalo-
pedal progression
(Unreliable after phototherapy)
Use of ‘Icterometer’
Transcutaneous bilimeter
Bilimeter with microcentrifuge
32. Management of jaundice
A medical emergency
Aim –
Keep S bilirubin at a safe level and prevent bil
toxicity
Prevent brain damage
Methods –
Preventive and supportive measures
Reduction of bilirubin levels – Phototherapy,
Exchange transfusion (-most effective and reliable
method), drugs
33. Preventive and supportive
measures
Prevention of Rh isoimmunization
Withhold drugs that aggravate jaundice or
block bilirubin binding sites in albumin
Prevent perinatal distress factors
Avoid phenolic detergents in nursery
34. Adequate feeding and hydration
Aspiration of cephalhematoma (bil > 18
mg%)
Treatment of sepsis and hepatitis
Phenobarbitone
Clofibrate – Enhances glucoronyl
transferase
37. Measures to reduce S Bilirubin -
Phototherapy
Safe and effective
Bil absorbs light maximally at 420 –
460 nm
Causes photo-oxidation & photo-
isomerization of bilirubin
Enhances hepatic exertion of
unconjugated bil into the intestinal
lumen
Single & double surface system
38. Phototherapy equipment
White light tubes 6-8*/ 4 blue light
tubes
Cradle or incubator
Eye shades
*May use 150 W halogen bulb
40. Phototherapy
Safe and effective
Bil absorbs light maximally at 420 – 460 nm
Causes photo-oxidation & photo-isomerization of bilirubin
Enhances hepatic exertion of unconj bil into the intestinal lumen
Single & double surface system
6 - 8 daylight tubes or 4 blue/ white tubes mounted on a stand with
grounded electrical outlets.
Change tubes every 1000 hours or after 3 months of use
Alternate - 150 watt halogen bulb (life 1000 hours) OR Blue CFL
lamps - change every 3000 h..
Maintain flux at 6-8 mw/cm2/nm with help of fluxmeter.
Have Plexiglas shield to cover the tube lights.
Nurse in cradle or incubator
41. Phototherapy
Perform hand wash
Place baby naked 45 cm away from the tube lights in a crib or incubator
Fix eye shades - to prevent damage to the retina. Also cover gonads
Keep baby at least 45 cm from lights, if using closer monitor temperature of
baby
Start phototherapy
Frequent extra breast feeding every 2 hourly
Turn baby every two hours or after each feed (in single surface)
Monitor – Temp - 2 to 4 hourly, wt -daily, urine frequency, bilirubin - 12
hrly
More frequent breastfeeding or 10-20% extra fluid is provided.
Discontinue phototherapy - if two serum bilirubin values are < 10 mg/dl.
Measure rebound bilirubin 6-8 hours after stopping phototherapy.
42. Turn baby every two hours or after each feed (in single
surface)
Monitor temperature of the baby x 2 – 4 hrly..
Monitor daily - Urine frequency and body wt
More frequent breastfeeding or 10-20% extra fluid is
provided.
Monitor Serum bilirubin at least every 12 hours
Measure rebound bilirubin 6-8 hours after stopping
phototherapy.
Remember - Baby appears bleached when under phototherapy. Hence
clinical assessment of jaundice not reliable. Monitor S bilirubin.
43. Repeat serum bilirubin measurement 4–6 hours after initiating
phototherapy.
Repeat levels 4-6 hourly if serum bilirubin is rising or is not falling
while under phototherapy.
Repeat serum bilirubin measurement every 12-24 hours when the
serum bilirubin level is stable or falling.
• Stop phototherapy once bilirubin levels are below the phototherapy
level by 2 -3 mg/dl (35 - 50μmol/l) as per postnatal age.
• In case of haemolytic jaundice, check bilirubin levels after 12
hours of stopping phototherapy to check for rebound increase.
44. Side effects of phototherapy
Increased insensible water loss
Loose stools
Skin rash
Bronze baby syndrome
Hyperthermia
Upsets maternal baby interaction
May result in hypocalcemia
45.
46. Drugs blocking entero-hepatic
circulation of bilirubin
Drug Action
Charcoal, Agar, Bind unconj bilirubin in gut and prevents entero-
hepatic circulation
Cholestyramine Enhances fecal exrcretion of bilirubin by binding
unconj bil and bile salts
Orotic acid Used to conjugate bilirubin
Tin-mesoporphyrin
(SnMP)
Inhibit heam oxygenase & reduce productin of
bilirubin
Albumin infusion Improves bilirubin binding capacity
47. Exchange transfusion
Most effective and reliable method to
reduce serum bilirubin.
Anticipation and early referral to a higher
centre is important
Indications –
Cord Hb 10 gm% or less
Cord bilirubin 5 mg% or more
Unconj S bil 10 mg% within 24 hrs or 15
mg% within 48 hrs or rate of rise of 0.5 mg%
per hr
48. Choice of blood for exchange
blood transfusion
ABO incompatibility
– Use O cells of same Rh type, ideal - O cells
suspended in AB plasma.
Rh isoimmunization
– In emergency 0 -ve blood. Ideal 0 -ve suspended in
AB plasma or baby's blood group but Rh –ve blood
also
Other situations
– Baby's blood group
50. The exchange equipment
The volume of blood required - .
1. Single blood volume exchange for anaemia:
– Term infant – 80 -100mls /kg
– Preterm infant – 100mls/kg
– Volume exchanged (ml) = Wt (kg) x Blood Volume x
(Hb desired – Hb initial)
2. Double volume exchange for jaundice: (Approx 2 x 85
mls/kg)
- Term infant – 200 -250 mls/kg or 80 – 85 mls/kg x
2/3
- Preterm infant – 300 mls/kg or 100 – 120 mls/kg x 2/3
51. Procedure
'PUSH-PULL METHOD’ via the umbilical vein.
- Serial withdrawal and injection of aliquots (5-20 mls)
– 1 mt for each cycle. Takes 60 – 120 minutes.
- Used when arterial arterial access is a problem.
‘ISOVOLUMETRIC METHOD’ - slow removal of
aliquots (10mls usually) from an artery (central or peripheral)
and simultaneous infusion into a vein (central or peripheral).
- preferred method
- Does not cause wide fluctuations of blood volume and
pressure.
- Takes 60 – 90 minutes
52. First out specimen tested for -
Haemoglobin, film, PCV
Group, Rhesus, Direct Coomb's test
PGL
Urea and electrolytes, calcium, SBR, total and
conjugated
Blood gas
Coagulations profile
Newborn screening test
Hold samples for other tests as indicated, eg. G6PD
deficiency, Viral infection, hereditary
spherocytosis, metabolic studies.
53. Set up for Push Pull method
UAC tray and catheters
Sterile drapes
Blood administration set
3-way taps X 2 (white blood in, red for blood out to waste)
Exchange transfusion recording sheet
Blood warmer with appropriate coil
Extension tubing, long - must be wide bore
Drainage connecting tube
5ml, 10ml, and 20ml syringes depending on size of aliquots to be
used
Waste bag
Calcium gluconate 10% ampoules
Heparin ampoules1000 IU/ml or heparinised NaCl 0.9% 50 ml
syringe