Approach to neonatal jaundice - Simplified references : Cloherty And Stark's Manual Of Neonatal Care AIIMS Protocol In Neonatology Care Of The Newborn – Meherban Singh

1. APPROACH TO NEONATAL
JAUNDICE
Dr CHETHAN CHANNEGOWDA
PEDIATRIC RESIDENT
MRMC,GULBARGA

2. - Yellowish discoloration of skin , sclera , nails due to
hyperbilirubinemia
- INCIDENCE : TERM → 60%
PRETERM → 80%
- 2mg/dl by 1st week – UNIVERSAL finding
- However, significant jaundice occurs in 6 % of term babies
- ICTERUS + @ neonates → >5mg , Adult > 2mg
- Cephalocaudal progression of icterus

3. 1gm Hb – 34mg bilirubin
1g albumin binds 8mg bilirubin
Newborn : 6-10mg/kg/day
Adult : 3-4 mg/kg/day

4. Types of bilirubin
Unconjugated
bilirubin (Indirect )
• Bind to albumin in plasma
• Non polar ,Fat soluble
• Can cross B-B-B (KERNICTERUS !)
• High mol wt cannot filter in
kidney
• Toxic in high level to brain
Conjugated bilirubin
(Direct )
•In bile
• Conjugated with glucuronic acid
• Polar ,Water soluble , cannot cross B-B-B
• Excreted in urine and stool

5. • AFTER 24 HOURS
• SLOW RISE < 5MG/DL/DAY
• MAX – TERM @5TH DAY , PT @ 7TH DAY
• RARELY > 15mg
• Goes off by 14th day
PHYSIOLOGICAL
JAUNDICE
• Appear within 24 hrs
• Rapid rise > 5mg/dl/day
• S bili > 15mg/dl → DIRECT BILIRUBIN >2mg
• High colored urine + clay colored stools
• May persist >PND14
PATHOLOGICAL
JAUNDICE

6. PHYSIOLOGICAL JAUNDICE
• Physiological immaturity of neonates to handle increased bilirubin
production
• High haematocrit / reduced RBC life span → Increased bilirubin
synthesis
• Less efficient binding and transport of bilirubin
( low ligandin levels )
• Less efficient hepatic conjugation and excretion (low UDP-GT)
• Enhanced absorption of bilirubin via enterohepatic circulation
• NO Rx needed (just followup for worsening)

8. BREAST FEEDING JAUNDICE
[FAILURE]
BREAST MILK JAUNDICE
OCCURS WITH LACTACTION FAILURE IN 1ST
WEEK
? GENETIC PREDISPOSITION -2.4%
PEAK IN 2 WEEK
INSUFFUCIENT INTAKE → SLOWER
BILIRUBIN ELIMINATION
WEIGHT LOSS +
PRESENCE OF beta – GLUCURONIDASE ,
DECONJUGATES INTESTINAL BILIRUBIN ,
PROMOTES EH circulation
INCREASED ENTEROHEPATIC CIRCULATION GOOD WEIGHT GAIN
NO HEMOLYSIS

9. PATHOLOGICAL JAUNDICE
1. HEMOLYSIS : ABO, Rh and minor groups incompatibility , enzyme
deficiencies such as G6PD deficiency, autoimmune hemolytic anemia
2. Decreased conjugation such as prematurity
3. Increased enterohepatic circulation such as lack of adequate enteral
feeding that includes insufficient breastfeeding or the infant not being
fed because of illness, GI obstruction
4. Extravasated blood: cephalhematoma, extensive bruising etc
5. TORCH inf

11. Hemolytic disease of newborn [Rh]

12. Hemolytic disease of the newborn due to ABO
incompatibility
• Mother – O , BABY - A/B
• IgM anti – A , anti – B doesn’t cross placenta
but rarely few mothers have IgG [1/3rd ]
• NOT SEVERE AS Rh Incompatibility, why ?
✓ Fetal RBC surface A and B antigens are not
fully developed during gestation and so there
are a smaller number of antigenic sites on
fetal RBCs
✓ A , B antigen is seen in other tissues so Few
ANTIBODIES available for RBCs

13. DEPENDING TIME OF ONSET OF JAUNDICE
1. WITHIN 24 HOURS : Rh and ABO incompatibility , G6PD and PK
enzyme deficiency , Infections: TORCH, Bacterial, Malaria
2. Appearing within 24‐72 hours after birth :
• Physiological
• Sepsis
• Polycythemia
• Concealed hemorrhage
• Intraventricular hemorrhage
• Increased entero-hepatic circulation

14. 3 . Appearing after 72 hours after birth
Sepsis
Cephalhaematoma
Neonatal hepatitis
Extra-hepatic biliary atresia
Breast milk jaundice
Metabolic disorders – Criggler Najjar , Gilbert syn

16. CLINICAL ASSESSMENT OF JAUNDICE
• Determine birth weight, gestation and postnatal age
• Examine the naked baby in bright natural light [every 12 hr until first
3 to 5 days of life for occurrence of jaundice.]
• Assess ILL / WELL ?
• Examine blanched skin and gums, and sclerae → physiological /
pathological
• Note the extent of jaundice (Kramer’s rule)
• Depth of jaundice (degree of yellowness) should be carefully
Deep icterus in sclera >> palms & soles
• Watch for kernicterus signs
Icteric baby photos

17. • IDENTIFY @ RISK INFANTS
✓ Gestation < 38 WEEKS
✓ Visible jaundice in first 24 hr
✓ Previous baby with significant jaundice
✓ Age specific TSB level being above 95th centile (if measured)
• AAP recommends routine s bilirubin in all babies but not feasible in
resource limited settings
• Visual inspection may be supplemented by transcutaneous
bilirubinometer but not reliable

18. KRAMER’S RULE / ZONES

19. WORK UP
• Maternal & perinatal history
• Physical examination
• Laboratory tests (must in all)*
• Total & direct bilirubin*
• Blood group and Rh for mother and baby*
• Hematocrit, retic count and peripheral smear*
• Sepsis screen
• Liver and thyroid function
• TORCH titers, liver scan when conjugated hyperbilirubinemia

20. Family history : jaundice , anemia, liver ds → G6PD def , spherocytosis
alfa 1 antitrypsin def
ANTENATAL : TORCH , GDM
Maternal drug intake : sulphonamides , anti malarial [interfere in bilirubin
binding]
LABOR : birth trauma , HIE , delayed cord clamp
INFANT : infrequent stool -→ inc EH circulation of bilirubin
poor calorie intake may decrease bilirubin uptake by liver

21. CLINICAL CLUES
Small for gestational age - polycythemia , IU infection
MICROCEPHALY – Cong infecgtion
PALLOR – Hemolytic anemia , extravascular blood loss
PETECHIAE – Sepsis , erythroblastosis
Hepatosplenomegaly - Hemolytic anemia , cong infection , Liver ds
Evidence of hypothyroidism

22. SCREENING TOTAL BILIRUBIN
➢ Heel prick , serum levels
➢ Trancutaneous
• non invasive
• cannot be used during / after phototherapy
if TB >15mg/dl
• OVERESTIMATES IN DARK infants , underestimates in light pigmented
• confirm by serum if >75th percentile in nomogram
➢ End tidal CO → Screen for hemolytic conditions

23. Management
• Aims
1. To prevent STB from rising
2. To reduce STB level
3. To prevent neurotoxicity

24. PREVENTION
• Early and frequent breast feeding
• Adequate hydration
• Administration of Anti‐D injection to Rh negative mother (when the baby
is Rh positive)
REDUCTION of BILIRUBIN LEVELS
- PHOTOTHERAPY
- EXCHANGE TRANSFUSION

25. USAGE OF BHUTANI NOMOGRAMS
• NEED ? - Initiation of therapy is directed by the hour-specific TB
value, modified by the presence of any risk factors
• RISK factors should be considered strictly
• As these interfere with binding of bilirubin to albumin, increase
permeability of the blood-brain barrier, or make brain cells more
susceptible to damage by bilirubin
RISK FACTORS
IMMUNE HEMOLYTIC DISEASE
ASPHYXIA
SEPSIS
ACIDOSIS
LETHARGY, TEMPERATURE INSTABILITY
ALBUMIN [<3GM]

30. Maisel’s chart

31. MAISEL CHART help in Decision making in treatment of pathological
jaundice
In the presence of following, treat as in next higher bilirubin category
• Perinatal asphyxia
• Respiratory distress
• Metabolic acidosis
• Hypothermia
• Low serum protein
• Birth weight <1500g
• Signs of clinical or CNS deterioration

32. PHOTOTHERAPY
• Mainstay of treating hyperbilirubinemia , Cost effective , excellent safety track
record
• Native bilirubin 460 to 490nm Photo isomers of bilirubin
Insoluble Soluble
Acc to AAP technical report : CHARACTERISTICS of devices
❖BLUE – GREEN SPECTRUM 460-490 nm , bilirubin best absorbs light at 460nm
❖IRRADIANCE of min – 30microwatts/cm/m2
❖Maximum body surface illumination
❖Should dec Bilirubin in 4-6 hrs

33. MECHANISM
1] STRUCTURAL PHOTOISOMERIZATION
BILIRUBIN TO LUMIRUBIN {irreversible}; SOLUBLE , NO CONJUGATION NEEDED
2] PHOTOISOMERIZATION
4Z,15Z ISOMER → 4Z ,15E form {reversible}
3] PHOTO OXIDATION ; small polar products

34. LIGHT SOURCES
1. Fluorescent blue light : most effectively because they deliver light in
the blue-green spectrum, providing maximal absorption and good
skin penetration. 1500 hours , cheap but irradiance changes with
time .
2. Blue light-emitting diodes (LEDs) - optimal high-intensity light in the
absorption spectrum of bilirubin , 3,000 hours life span ,better than
Fluorescent bulbs . m/c used nowdays
3. Fiberoptic blankets or pads can be placed directly under the infant,
generate little heat, but provide lower irradiance → not in intensive PTx
4. Halogen lights
Usage of CFL is not recommended

36. How to increase efficacy ?
- Regularly check irradiance [direct dose–response relationship]
- Distance between baby and light
- The lamps should be changed if the lamps are flickering or ends are
blackened
- Expose maximal surface area of the baby
- Ensure optimum breast feeding and hydration [More frequent breast
feeds or 10‐20% extra IV fluids are provided]
Safety
- Eye pad , temperature monitor , avoid sunlight exp [sunburn !!]
MONITORING ;
- Bilirubin 4-6 Hrs after starting , next 8 – 12 hrs
- 24 hrs After stopping
FLUOROSCENT 30-45 cm
LED 20cm

37. Adverse effects
• Increased insensible water loss
• Loose stools
• Skin rash
• Bronze baby syndrome – photoproducts of bile pigment [more in direct ], self limiting
• Retinal degeneration
• Hyperthermia
• Upsets maternal baby interaction
• May result in hypocalcemia

38. When to avoid phototherapy
• congenital erythropoietic porphyria
• photosensitizing drugs - ibuprofen , furosemide , fluroquinolones

39. PHARMACOTHERAPY ?
• IVIG has been used in infants with hemolytic disease caused by Rh or ABO
incompatibility to prevent Exchange transfusion
• Raising trend even on Intensive phototherapy
• IVIG may act by occupying the Fc receptors on macrophages, decreasing removal of
antibody-coated red cells from the circulation → reduces hemolysis
• 0.5 to 1 g/kg IVIG over 2 hours
• Phenobarbitone, clofibrate, or steroids → NOT recommended

40. EXCHANGE TRANSFUSION
• most effective method for rapid removal of bilirubin
• Phototherapy fail
• Toxic range of bilirubin levels
• Infants with neurologic signs suggestive of bilirubin toxicity
• Double volume exchange transfusion (about 160 to 180 mL/kg)
• Indications for DVET at birth in infants with Rh isoimmunization include
1. Cord bilirubin is 5 mg/dL or more
2. Cord Hb is 10 g/dL or less

41. Reducing total bilirubin load.
Increasing the binding sites of plasma albumin
Shifting bilirubin out of plasma
Providing erythrocytes less apt to haemolyse
Removes sensitized RBC.
How does it work ?

43. The ET should be performed by pull and push technique using umbilical
venous route

44. isovolumic procedure
Push pull technique : withdraw @ 2-4ml/kg/minute of blood , max 20ml
Albumin infused 1 to 2 hours prior to the exchange transfusion promotes removal
of more bilirubin because more extravascular bilirubin is drawn into the
circulation.
Intensive phototherapy should be resumed after the transfusion
Measure bilirubin @ 2,4,6th hour
COMPLICATIONS:
COMMON RARE
Thrombocytopenia NEC
Coagulation Abnormalities Portal vein thrombosis
Hypoglycemia, Cardiac arrythmias
Hyperkalemia, And Hypocalcemia Sepsis

45. PROLONGED JAUNDICE
• TERM > 2 weeks
• Preterm babies > 3 weeks
• Always rule out CHOLESTASIS →
dark colored urine

46. • u
PERSISTENT JAUNDICE

47. BILIRUBIN TOXICITY
• Unconjugated bilirubin that is not bound to albumin is a potential
toxin → APOPTOSIS/NECROSIS in Brain tissue
FFA , DRUGS
ACIDOSIS
DISPLACE BILIRUBIN
FROM ALBUMIN
ASPHYXIA
HYPEROSMOLARITY
HYPERCARBIA
PREMATURITY
B-B-B DISRUPTION

48. Bilirubin deposited in the brain can result in BILIRUBIN-INDUCED
NEUROLOGIC DYSFUNCTION (BIND)- subtle neurodevelopmental
disabilities without classical findings of kernicterus.
Severe hyperbilirubinemia (TB >25 mg/Dl)
Areas affected
Basal Ganglia – globus pallidus
Subthalamic nuclei
Cerebellum
The Brainstem Nuclei For
Oculomotor And Auditory
Function.
White Matter

49. Acute bilirubin encephalopathy [ABE]
• Clinical manifestation of bilirubin toxicity seen in the neonatal period.
• EARLY PHASE - Signs are subtle and may include lethargy, hypotonia, high-
pitched cry, and poor suck.
• INTERMEDIATE PHASE : hypertonia of extensor muscles, oculogyric
crisis,seizures .
• ADVANCED PHASE : pronounced opisthotonus and retrocollis , apnea,
seizures, and coma
Death d/t intractable seizures or respiratory failure.

50. AT RISK ?
• Premature birth
• Rh incompatibility
• Polycythemia
• Sulfonamides , ceftriaxone
• Crigler-Najjar syndrome type I
• G6PD deficiency

51. KERNICTERUS
• Yellow Staining (Icterus) Of The Deep
Nuclei Or “Kernel” Of The Brain
• CHRONIC and PERMANENT SEQUELAE of
bilirubin toxicity that develop during the first
year of age - CHRONIC BILIRUBIN
ENCEPHALOPATHY

52. Problems in kernicterus
• CHOREOATHETOID CEREBRAL PALSY with neuromotor
impairments
• Sensorineural hearing loss (auditory neuropathy),
characterized by abnormal BERA with normal OAE
• Limitation of upward gaze
• Dental enamel dysplasia

53. CONJUGATED HYPERBILIRUBINEMIA / CHOLESTASIS
• Direct bilirubin level >1 mL/dL or >15% of the TB level
• Defects in intrahepatic bile production
• Defects in transmembrane transport of bile or mechanical
obstruction to flow
CLINICAL POINTERS
Pale Stools
Dark Urine
Hepatomegaly, Splenomegaly
LAB
Abnormal LFT , Raised GGT
USG – atresia , choledochal cyst , malformations
HIDA scan – Hepatobiliary Scintigraphy
Liver biopsy

54. 1] BILIARY ATRESIA : Hepatoportoenterostomy [KASAI] → before 2 months
2] Metabolic disorders : α1-antitrypsin deficiency, cystic fibrosis,
galactosemia, tyrosinemia, galactosemia, storage diseases (Gaucher,
Niemann-Pick), Zellweger syndrome
3] Endocrine disorders - hypothyroidism and panhypopituitarism
4] Prolonged courses of total parenteral nutrition (PN) including lipid

55. Metabolic disorders asc with JAUNDICE
HYPOTHYROIDISM
▪ Quiet baby , protruding tongue
▪ Enlarged fontanelle
▪ Gen hypotonia , protruded abdomen
▪ Dry skin
▪ late onset and persistent jaundice
▪ why ? – delayed maturation of Glucuronide conjugation

56. OTHERS
i. Α1-ANTITRYPSIN DEFICIENCY
ii. CYSTIC FIBROSIS
iii. GALACTOSEMIA
iv. TYROSINEMIA
v. GALACTOSEMIA
vi. STORAGE DISEASES (GAUCHER, NIEMANN-PICK)

57. Inherited dieseases
UNCONJUGATED HYPERBILIRUBIN CONJUGATED HYPERBILIRUBIN
GILBERT SYN DUBIN JOHNSON SYN
CRIGLER NAJJAR SYN ROTOR SYN
GILBERT SYN : M/C , REDUCED production of UDP – glucuronyl transferase , not lethal

59. Recent advances
• Heme oxygenase inhibitors : rate limiting step heme → biliverdin
TIN-MESOPORPHYRIN (SNMP) for phototherapy resistant jaundice .
• Fiberoptic phototherapy devices:
The light from the bulb passes through a fiberoptic bundle into a pad of
woven optic fibers

60. KEY POINTS
• Visual inspection is NOT a reliable measure
• Jaundice <24hrs – consider aggressive approach
• Measure bilirubin , identify risk factors before discharging
• Need for using NOMOGRAMS
• Breast feeding jaundice – educate the mother
• Work up for persistent jaundice is a must
• Early and effective Phototherapy prevents Devastating BIND ,
KERNICTERUS

61. References
• Cloherty And Stark's Manual Of Neonatal Care
• AIIMS Protocol In Neonatology
• Care Of The Newborn – Meherban Singh