This document discusses neonatal jaundice and hyperbilirubinemia. It begins by defining jaundice and hyperbilirubinemia. It then describes the metabolism of bilirubin, including transport to the liver, hepatic uptake, conjugation in the liver, and excretion in bile and stool. Causes of increased bilirubin production are discussed, including increased red blood cell production or breakdown. The document also discusses approaches to evaluating and managing neonatal jaundice and hyperbilirubinemia, including assessing risk factors, monitoring bilirubin levels, and guidelines for initiating phototherapy.

1. NEONATAL JAUNDICE

2. OBJECTIVES
• Defination of jaundice
• Defination of hyperbilirubinemia
• Metabolism of bilirubin

4. BILIRUBIN CLEARANCE AND EXCRETION
1. TRANSPORT
- Bilirubin is non polar
- It is transported to liver cell, bound to serum albumin
( low albumin can cause bilirubin toxicity)
2. HEPATIC UPTAKE
- Bilirubin crosses the hepatic plasma membrane and binds to
cytoplasmic ligandin ( Y Protein) for transport to smooth endoplasmic
reticulum

5. 3. BILIRUBIN CONJUGATION
- Enzyme uridine diphosphogluconurate glucuronosyltansferase
(UGT 1A1) catalyses the conjugation of bilirubin.
4. EXCRETION
- Conjugated bilirubin is secreted into bile and then excreted into the GI
tract where it is eliminated in the stool.
- Intestinal enzyme beta-glucuronidase can deconjugate the bilirubin
which can be reabsorbed and delivered back to the liver. This is called
enterohepatic circulation.
- Intestinal bacteria can prevent enterohepatic circulation of bilirubin
by reducing conjugated bilirubin to urobilin, which is not a substrate
for beta glucuronidase

6. CAUSES OF INCREASED BILIRUBIN
PRODUCTION
1. Increased production
- Increased RBC volume per kg
- Decreased RBC survival
- Ineffective erythropoiesis and increased turnover of non-hemoglobin
heme protein
2. Decreased uptake
- Defective uptake of bilirubin from plasma

7. 3. Decreased conjugation
- Decreased UGT 1A1 activity
A. Crigler-Najjar
B. Gilbert’s syndrome
C. Organic anion transporter protein OATP-2
4. Increased enterohepatic circulation
- Any pathological condition leading to increased enterohepatic
circulation
- Impaired intestinal motility eg: intestinal atresias, meconium ileus, or
Hirschsprung’s disease

8. What is Neonatal Hyperbilirubinemia?
• -It is universal (normal infant TSB>2 mg/dl)
• Newborn jaundice is a a commonest sign in >80% of all babies.
• BENIGN NEONATAL HYPERBILIRUBINEMIA
• Mostly benign manifestations (when screened):>75%of well babies
• Most repond to nutrional support (promote enteral elimination)
• CLINICAL NEONATAL HYPERBILIRUBINEMIA
• Need for serial monitoring ;complicated with hemolysis and GA wks.
• Some may need phototherapy (6 to 8 % of monitored babies)

9. • SEVERE NEONATAL HYPERBILIRUBINEMIA
• Few need readmission , after discharge (8 to 12 per 1000 discharges).
• Rare need of an Exchange Transfusion (<4/100,000 live births in
California)
• Most likely due to G6PD deficiency (both males and females).

10. Clinical risk factors for developing significant
hyperbilirubinemia(ranked by evidence)
• Lower gestational age.(i.e ,each additional week of prematurity)
• Jaundice at age <24 hours
• Predischarge TcB /TSB level that anticipates phototherapy
• Risk of neonatal haemolysis as suggested by rapid rate of rise in the TSB or TcB (>0.3
mg/dl/hour at age <24 hours and >0.2 mg/dl/hour thereafter)
• Use of phototherapy before discharge.
• Parent or sibling requiring phototherapy or exchange transfusion.
• Family history or genetic ancestry suggestive of inherited RBC disorders.
• Excusive breastfeeding with suboptimal intake.
• Scalp hematoma or significant bruising
• Down syndrome.
• Macrosomic infant of a diabetic mother.

11. PHYSIOLOGICAL VS PATHOLOGICAL JAUNDICE
PHYSIOLOGICAL PATHOLOGICAL
ONSET AND DURATION 1. Appears after 24 hr of age
2. Maximum intensity at 4 -5 day in term
and 7 th day in pre term
3. Disappears by 14 days
1. Appears within 24 hr of age
2. TSB increasing by more than
0.2 mg/dl/hr or 5 mg/dl/day
3. Persist for more than week in
term and 2 weeks in pre term
neonate
CAUSES • Polycythaemia
• Reduced life span of RBC
• Paucity of bacterial flora in intestine
• Increases in activity of beta glucoronidase
enzyme
• Immaturity if X and Y acceptors and
glucoronyl transferase enzyme
1. Hemolysis
2. Decreased conjugation
3. Extravasated blood

12. Breast feeding VS Breast milk jaundice

13. BREAST MILK JAUNDICE
• Due to lactation failure
• Can be associated with insufficient intake, weight loss or
hypernatremia
• May be due to genetic predisposition
• Peaks within 2-3 weeks of age
• Bilirubin levels falls rapidly in 48hrs, if breastfeeding stopped
• Affected infants have good weight gain, normal LFT and no evidence
of haemolysis
• Cessation of breastfeeding is not advised
BREASTFEEDING JAUNDICE

14. APPROCH TO NEONATAL
HYPERBILIRUBINEMIA

15. HISTORY
WITHIN 24 HOURS
• HEMOLYTIC DISEASE OF
NEW BORN
• INTRAUTERINE
INFECTION
• DEFICENCY OF RED
CELL ENZYMES
• ALPHA THALASEMIA
• HERIDATORY
SPHERICYTOSIS
• CRIGLLAR NAJJAR
SYNDROM
• LUSCEY DRISCOLL
SYNDROM
BETWEEN 24 TO 72
HOURS
• PHYSIOLOGICAL JAUNDICE
•CONGENITAL
SPHEROCYTOSIS
•MILD HEMOLYTIC DISEASE
AFTER 72 HOURS OF
AGE(WITHIN 2 WEEKS)
•SEPTISEMIA
•NEONATAL HEPATITIS
•EXTRA HEPATIC BILIARY
ATRESIA
•BREAST MILK JAUNDICE
•PREMATURITY
•METABOLIC DISEASE

16. Haemolytic disease of newborn
• Clinical features
• Jaundice appear
within 24 hours
• Anaemia
• Gross
hepatosplenomegaly
• Generalised anasarca
(hydropes foetalis)
• Diaper is not
coloured despite
jaundice because the
jaundice is due as it is
indirect bilirubin
• The baby may die in
utero.
Diagnosis
•Cord blood for Rh and ABO
typing
•Haemoglobin level
•Reticulocyte count
•Positive direct Coombs test
in a Rh-positive baby
suggests HDN.
•False negative may be seen
if blood is contaminated
with Warthon’s jelly or due
to laboratory error.
MANEGMENT
•Moniter –level of anti D
antibodies and optical
density difference(ODD)
of amniotic fluid
•If ODD at 450 is > O.1,
s/o severely affected
baby
•Treated with 50 ml of O
negative PRC infused
intraperitoneally once in
2-3 wk until baby
matures.

17. ABO Haemolytic diseases
• Early onset of jaundice in babies with blood group A or B and
mother is O.
• Disease is milder.
• Anaemia is absent
• Serum bilirubin in cord blood is elevated
• Reticulocytosis ,spherocytosis is seen with increased fragility
of RBC.
• Direct Coobs test is negatively or weakly positive.

18. Drugs causing neonatal jaundice
Large doses of
vitamin k
Haemolysis by
depressive
action on
glutathione and
it also blocks the
Y receptor
protein.
Oxytocin
haemolysis .
Movobiocin,
gentamicin,
kanamycin,
chloramphenicol.
Drugs competing with
glucoronyl transferase
enzyme
Sulphonamides,
caffeine,
furosemide,
indomethacin and
kanamycin.
Drugs that block the
binding sites of
albumin

19. Haematological disorders causing jaundice
G6PD deficiency
• X linked recessive
diseases.
• Wearing clothes
protected with
napthalene balls may
initiate haemolysis
• Sudden dramatic and
unexplained elevation
of serum bilirubin in a
newborn baby is a
characteristic
manifestation of G6PD
deficiency.
Hereditary spherocytosis
•Autosomal dominant disorder
•It is characterised by anaemia ,
hyperbilirubinemia and mild
splenomegaly at any time
during neonatal period
•Laboratory finding s/o–
spherocytosis and increased
fragility of erythrocytes.
Homozygous alpha
thalassemia
Infant with severe anemia
with gross hepatomegaly
and anasarca with out any
evidence of Rh iso
immunization
Coombs test is negative

20. Approach to a Case of Neonatal Jaundice
Family history
Parent or sibling with history of jaundice
or anaemia
Suggest hereditary haemolytic anaemia such as
hereditary spherocytos
Previous sibling with neonatal jaundice haemolytic disease due to ABO or Rh
isoimmunisation
History of liver disease in siblings or
disorders such as cystic fibrosis,
galactosemia ,tyrosinaemia, criglar Najjar
syndrome
All are associated with neonatal
hyperbilirubinemia

21. Maternal history
Unexplained illness during pregnancy Consider congenital infections like TORCH
Diabetes mellitus Increased incidence of jaundice in infants born to
diabetic mother
Drug ingestion during pregnancy Ingestion of sulfonamides, nitrofurantoins,
antimalarial may initiate hemolysis in G6PD-
deficient infants
History of labour & delivery: Vacuum extraction Increased incidence of cephalhaematoma and
jaundice
Oxytocin-induced labour Increased incidence of hyper bilirubinaemia by
haemolysis
Delayed cord clamping Increased incidence of hyperbilirubinaemia
among polycythaemic infants

22. INFANT HISTORY
Delayed passage of meconium and infrequent stool Increased enterohepatic circulation suggestive of
intestinal atresia, annular pancreas Hirschsprung's
disease, meconium plug, drug induced ileus.
Inadequate caloric intake Delay in bilirubin conjugation
Vomiting Suspect sepsis,galactosemia,pyloric stenosis

23. Examination
• VISUAL INTERPRETATION OF JAUNDICE
• Examine the baby in bright natural light.
• Alternatively, the baby can be examined in bright white
fluorescent light.
• Make sure there is non yellow background.
• The baby should be naked.
• Examine blanched skin and gums and sclerae

24. Kramer’s rule
Note the extent of jaundice Mild jaundice (yellow
lemon colour)
Deep jaundice (Orange
yellow )
Face and neck 5 to 7 mg/dl 7 to 9 mg/dl
Chest and upper abdomen 7 to 9 mg/dl 9 to 11 mg/dl
Lower abdomen and thigh 9 to 11 mg/dl 11 to 13 mg/dl
Legs and arm/forearms 11 to 13 mg/dl 14 to 16 mg/dl
Palms and sole 13 to 15 mg/dl 17 mg/dl or more

25. TRANSCUTANEOUS BILIRUBINOMETER (TCB)

26. Infant's physical Examination
Small for gestational age Polycythemia is very common.
Plethora Polycythaemia
Cephalhaematoma Entrapped haemorrhage may be hyperbilirubinemia
Head size Microcephaly seen in intrauteine infection associated
with jaundice
Appearance of umbilical stump Omphalitis and sepsis
Pallor Suspect hemolytic anemia
Hepatosplenomegaly Haemolytic anaemia or congenital infection
Optic fundus Chorioretinitis indicates congenital infection

28. Hour-specific Bilirubin testing
• TSB is the definitive test to guide phototherapy and escalation.
• Any newborn age <24 hrs with jaundice .Mandatory TSB.
• TcB , valid and reliable screening test ,validate with TSB.
• Routine TSB/TcB test in all newborns age 24-48hours or at discharge.
• TSB/TcB rise (>0.3 at <24h or >0.2mg/dl/h at >24h) is severe.
• These high rates of rise suggest hemolysis and excessive bilirubin production.
• Inability to arrange timely TSB at follow –up may delay discharge.
• TSB+ direct should be measured if jaundice persist beyond age 1 week.
• Cholestasis cut-offs-direct bilirubin >1.0 mg/dl unconjugated bilirubin >0.3
mg/dl are abnormal.
• TSB VARIABILITY IN YOUR LAB ;CV SHOULD BE <6%

29. AAP CPG Recommendations [2022]
I. Prevention of Hyperbilirubinemia
A. Prevent hyperbilirubinemia associated with iso-immune hemolytic
disease (prenatal screening of ABO/Rh)
B. Assesment of feeding support.
II. Assesment and monitoring
A. Identify clinical risk factors
B. Identify need for treatment
C. Do not visually estimate TSB
D. Transcutaneous bilirubin screens TSB values
E. Evaluate direct/conjugated bilirubin by age >7 days, if jaundice persists.
III. Treatment : TSB based on age in hours, GA(weeks) and neurotoxicity risk
IV. Post discharge Follow-up during the first week after birth
V. Hospital Policies and procedures : implement systems practices.

30. Predicting adverse outcome of
hyperbilrubinemia
• Biomarker considered
• Clinical risk factors
• Hour –specific bilirubin alone
• Hour specific bilirubin +GA (week)
• Rate of bilirubin rise (per hour)
• Bilirubin/Albumin ratio
• Bilirubin –binding capacity
• Unbound bilirubin
• Measures of increased bilirubin production (incl.ETOCc)
• Auditory brainsteam response
• Early clinical sign of bilirubin neurotoxicity.

31. 2.Gestational age (weeks) Guides Treatment
• Know GA: Clinical exam, LMP and /or Fetal U/S in first trimester.
• Category of babies as term, near term or late preterm needs to be
specific.
• Use completed weeks.
- 40 weeks or more
- 39 weeks
- 38 weeks
- 37 weeks
- 36 weeks
- 35 weeks

32. 3. Neurotoxicity Risk Factors Guide Treatment
• Gestational Age <38 weeks and risk increases with the degree of
prematurity
• Serum Albumin <3.0 g/dl
• Isoimmune hemolytic disease (i.e. positive DAT ) predischarge G6PD
deficiency, other familial risk of inherited hemolytic disorders.
• Viral or bacterial sepsis
• Significant hemodynamic instability in the precedind days
DAT , Direct antiglobulin test: G6PD glucose 6 phosphate
dehydrogenase.
CPG. III Bilirubin Neurotoxicity Risk Factors

33. How to identify need for phototherapy?
Now, you MUST ask yourself
1. What is the best estimate of GA, in weeks (your exam, LMP,
fetal U/S)
2. Do you wish to offer home phototherapy?
3. Is the baby’s serum albumin <3g/dl? (Neurotoxicity risk)
4. Do you know the baby’s G6PD deficiency status? (Neurotoxicity
risk)
5. Have you assessed for race,ethnicity,ancestry and country of
origin)
6. Any family history suggestive/indicative of inherited RBC
disorders?
7. Is there any risk of concurrent viral or bacterial illness?

34. TSB thresholds adjusted: age(h),GA & Neurotoxicity
GA(wks) None 1 or more None 1 or more
40 or more 21.6 18.2 27.0 23.5
39 21.5 18.2 27.0 23.5
38 20.7 18.2 27.0 23.5
37 20.0 17.9 26.6 23.1
36 19.3 17.0 25.5 22.1
35 18.6 16.1 24.5 21.1
PHOTOTHERAPY EXCHANGE

36. BHUTANI CHART FOR PHOTOTHERAPY

37. BHUTANI CURVE- EXCHANGE TRANSFUSION

38. PRETERM INFANT: <35WEEKS OF GESTATION

39. Web- based tools to determine TSB threshold
1. Pedia-tool.org
2. BiliTool.org
3. Uptodate Calculator
4. Others

40. TREATMENT MODALITIES
PHOTOTHERAPY
INCREASING
BILIRUBIN
CONJUGATION
DECREASING
EXTEROHEPATIC
CIRCULATION
INHIBITING
BILIRUBIN
PRODUCTION
EXCHANGE
TRANSFUSION

41. PHOTOTHERAPY
1. MECHANISM
• Structural isomerization- by light converts bilirubin to lumirubin is
main mechanism
• Configurational isomerization- rapidly converts 15% of 4Z , 15z
bilirubin isomer to less toxic 4Z, 15E form
• Photo oxidation is a slow process converts small polar products, but
least important mechanism

44. 2. OPTIMIZING PHOTOTHERAPY
-Fix eye shades
-Use blue light and appropriate intensity of phototherapy (>30 µW/cm2
per nm)
-Light-emitting diode (LED) and compact fluorescent lamps (CFL) most
often deliver the required intensity for a long duration.
-Place phototherapy as close to baby as possible without causing
hyperthermia.
-Expose maximum area of body.
-Ensure optimal breastfeeding and stool output
-Monitor bilirubin level

46. Introduction
• Validated phototherapy practices have drastically curtailed the use of
exchange transfusion
• Initiation & duration of phototherapy is defined by specific range of
TSB & Neurotoxicity risk factors
• Clinical response depends on efficacy of phototherapy device & infant
rates of bilirubin production & elimination
• Phototherapy perse does not improve neurodevelopmental outcome
&cognitive performance in recipients.
• There is nothing like prophylactic Phototherapy

47. Standard for phototherapy devices
(A)Light Wave length
• Visible white light spectrum 350-800nm
• Bilirubin absorbs in blue region (460nm).
• Most effective wave length (460-490nm)
• Newer LED have longer life time (>20,000 hrs)
o Lower heat output, low infrared & no Ultraviolet emission
(B) Irradiance
• Refers to photons (Spectral energy)
• Ideal Irradiance is atleast 30uW/cm2/nm at 460-490nm
• Use flux meter regularly to monitor output
• irradiance decrease with use

48. PARAMETER
1) Irradiance
2) Lightwave length (nm)
3) Body surface area (bsa)
GA (Weeks)
>35 28-35 <28
25-35 15-25 10-15
460 460 460
30% to <80% 30% - 80% <30%
 Emit light ( 460-490nm)
Produce irradiance 30µ W/cm2/nm
Illuminate maximal bsa (80%)
Parameters for T……… in phototherapy

49. Factors affecting phototherapy
• Spectrum of light emitted
 Best effective at 450-470 nm maximal absorption by bilirubin
 Skin penetration maximum at 460nm
 Torquoise lights of 497nm tried in research – no better
• Irradiance of source
• Std 8- 10 and Intense > 30µ W/cm2/nm
• Increasing surface area exposed (Spectral power)
• Cause of Jaundice- Less effective in hemolysis
• Level at start of PT- more the level, greater the reduction
• Cycling 12hr shown as effective as conventional PT-useful in ELBW

50. Safety &preventive measures
• Ensure adequate hydration, Nutrition & temperature control
• Interruption of phototherapy- After ensuring decrease TSB
• Use of eye masks to prevent retinal damage
• Diapers are used for hygiene, but not essential
• Ensure electrical & fire hazard safety standards

51. PRACTICE CONSIDERATION FOR OPTIMAL
ADMISNISTRATION OF PHOTOTHERAPY
CHECKLIST RECOMMENDATION IMPLEMENTATION
Light source (nm) Wavelength spectrum in 460-490 nm blue-
green light region
Know the spectral output of the lightsource
Light irradiance Use optimal irradiance >30 nm within the
460 to 490 nm waveband
Ensure uniformity over the light footprint area
Body surface area Expose maximal skin area Reduce blocking of light
Timeliness of
implementation
Urgent or “crash cart “ intervention for
excessive hyperbilirubinemia
May conduct procedures while infant is on
phototherapy
Continuity of therapy Briefly interrupt for feeding parental
bonding, nursing care
After confirmation of adequate bilirubin
concentration decrease
Efficacy of intervention Periodically measure rate of response in
bilirubin load reduction
Degree of total serum/plasma bilirubin
concentration decrease
Duration of therapy Discontinue at desired bilirubin
threshold be aware of possible rebound
increase
Serial bilirubin measurements based on rate of
decrease

52. PHOTOTHERAPY- ADVERSE EFFECTS
• More Common
oGreen Loose stools
oSkin rashes
oInterfere with bonding
oWater loss
o Temperature instability
oCircadian rhythm disturbed
• Less Common
oRisk for Asthma/Allergy
oRisk for epilepsy in boys
o5% Increase risk in mortality in
500-800 gms babies- Aggressive
PT
oIncrease risk for photo oxidation
Injury
oIncrease risk of malignancies

53. Can you prescribe home phototherapy?
• Gestational age >/= 38 weeks, postnatal age >48 hours
• Clinically well with adequate oral feeding
• No known clinical risk for significant hyperbilirubinemia other
than TSB level
• No discernible bilirubin neurotoxicity risk factors
• No previous use of phototherapy
• TSB level no more than 1mg/dl above the phototherapy
treatment threshold(see below)
• An LED based phototherapy device implemented at home
without delay
• Capacity for daily TSB measurement.

54. Exchange transfusion
• Aim
• 1. To remove the bilirubin from the blood to prevent kernicterus.
• 2. To treat anemia.
• Type of blood to be selected-
• Before birth: 'O'-negative blood with low titers of anti-A and Anti-B, cross-
matched against mother's blood
• After birth: 'ABO group of the baby, preferably 0. negative blood cross-
matched against baby's and mother's serum.
• Amount of blood
• Double the volume of the baby's blood is required for exchange transfusion.
• 2 x 85 ml x weight of the baby in kg.

55. • https://www.youtube.com/watch?v=42xzmYqkjB4

56. Volume for DV-ET
a) 80 cc/kg
b) 100 cc/kg
c) 180 cc/kg
d) 200 cc/kg
Aliquot size
a) < 1kg
b) 1- 2kg
c) > 2kg
Best choice
a) Fresh PCV
b) Whole blood
c) Irradiated, CMV –
ve, O Rh
compatible
suspended in AB
plasma

59. Complications
Early complications
Transient bradycardia, cyanosis, vasospasm, thrombosis, apnoea with bradycardia require
resuscitation.
Infection like CMV, HIV, hepatitis.
Necrotizing enterocolitis.
Late complications
Mild graft versus host reaction characterized by diarrhoea, rash, hepatitis, eosinophilia.
Inspissated bile syndrome.
Portal vein thrombosis.

60. • Adjuvant therapies:
• Intravenous immunoglobulin: Usage of intravenous immunoglobulin (IVIG) in
immune-mediated hemolysis where TSB continues to rise despite intensive
phototherapy or whose TSB is within 2-3 mg/dl. of the exchange level is now not
a standard of care. However, clinical practice is yet to change and many continue
to use in the absence of robust evidence supporting or refuting the use of IVIG.
• Intravenous hydration: Studies have shown that infants receiving intensive
phototherapy when given intravenous fluid, decreased the duration of
phototherapy. The recommended fluid is 0.45 DNS 50 mL/kg given over 12 hours.
• Phenobarbitone: Phenobarbitone induces micro- somal enzymes, increases
bilirubin conjugation and excretion, and increases bile flow. It is used in treating
the hyperbilirubinemia of Crigler-Najjar syndrome type II.

61. BILIRUBIN TOXICITY

62. NEONATAL JAUNDICE
● visible form of bilirubinemia
-Adult sclera >2mg/dl
-Newborn skin >5mg/dl
●Occurs in 60% of term and 80% of preterm
neonates
●However significant jaundice occurs in 6% of
term babies

63. • Hyperbilirubinemia is the most common clinical condition requiring
evaluation and treatment in the newborn and a frequent reason for
hospital readmission during the first week of life.

64. Every baby is to be tested for Bilirubin.
Who?
What?
Why?
When?
Where?
How?
& Then?

65. CPG addresses routine well baby newborn
Case study
Clinically, Casey is a healthy baby born to a 34 year old primigravida following a
normal pregnancy with an unremarkable prenatal course and screening results.
Postnatally,in the well baby nursery,there has been no significant birthing events or
risk of sepsis.CCHD screen,immunizations,ABR screen and routine metabolic screen
for CA have been ordered. Mother is being counselled for breast feeding.
• Casey is >35 weeks AGA in the well baby nursery, specifically, @37 2/7 GA weeks.
• No jaundice has been documented. You learn that Mom’s mother is Punjabi,Indian.
• You anticipate to discharge her to parents @ ~48hours after birth and request
follow up.
• At discharge,your inent is to counsel, reassure and anticipate normal infancy and
childhood outcomes(athletic and academic) with continued pediatric care.
Bilirubin test guides phototherapy , follow up and escalated care.

66. When should you “Escalate Care”….
At TSB is 2mg below exchange transfusion threshold (age in hours,
GA (weeks), bilirubin neurotoxicity risk factors)
• NICU care,increase 2 intensive phototherapy (dose,surface area,
homogenous LED light distribution)
• STAT labs (CBC, chem, TSB(+direct), Albumin, Type and Cross)
• STAT blood bank orders
• STAT procedures under phototherapy
• IVIG (optional)
• Bilirubin / Albumin (optional)
• Prepare for urgent exchange transfusion (facility,expert
technique)

67. When to consider Exchange Transfusion
• At “Escalation of Care”
• Treat if you exceed designated Bilirubin :Albumin ratio.
• Preparation of exchange commences with escalated care.Obtain
informed consents ,order STAT lab/blood bank requirements)
• Preparation should take <2 hours (escalated care buys you time)
• Exchange at any sign of clinical neurotoxicity, treat to SAVE LIFE.
• Exchange for rising TSB in spite of phototherapy.
• Exchange does not always prevent bilirubin neurotoxicity or kernicterus.

68. Guidelines for discharge and follow -up

69. When a newborn baby reaches your hospital
• Assess and document urgent clinical signs
- ‘’Looking yellow , lethargy , poor feeding, inconsolable shrill cry
Irritability’’
- History :onset of clinical signs ; birthing history ; last bilirubin test ;
document facts; was a G6PD screening test done?
- Exam :a) assess progression of jaundice ; b) signs of ABE ; c)breathing
pattern ; d)risk of respiratory failure.
- TEST:a) TcB (if you have a device ;ERR?) b) Pulse –ox .

70. • How do you refer for further medical care?
• Time matters!
• Laboratory :where can you get a STAT TSB test?
• Emergency room for testing ? For phototherapy? Neo access? AVOID.
• NICU: call neo ;call nearest NICU ; coordinate with with Neonatologist
• URGENT TRANSPORT : arrange for medical supervision (must coordinate)

71. Hospital Jaundice policies: before discharge
• All families should receive written and verbal education.
• Provide parents written information for post-discharge care including the date
,time , and place of the follow-up appointment.
• Prescription and appointment for a follow-up for TcB /TSB,as needed.
• Birth hospitalization information , last TcB /TSB and age when tested and DAT
results (if any) are transmitted to the follow-up primary care provider.
• When uncertain about follow-up care provider , provide documented medical
information to families.

72. Every baby is to be tested for bilirubin
Physician Lead implementation
Nurse: Access unfettered testing
Parent: Bedside education
Hospital: Systems practices
Community: Awareness
Public Health: Retire Exchange Tx
Society: Ensure safer care
National: Implement guidelines

73. LEARNING OBJECTIVES
• Introduction & background based on Technical report
• Mechanism of bilirubin reduction by Phototherapy
• Commercial light sources
• Factors influencing effects of Phototherapy –
1. Wave length
2. Irradiance
3. Optimal Body Surface Area (BSA)
4. Rate of reduction
• Adverse effects - Newer insights.
• Take home message.

74. Screening, Prevention and Management of
Neonatal Hyperbilirubinemia
1.
a. Either the American Academy of Pediatrics (AAP) guidelines based on
postnatal age, gestation and presence or absence of risk factors or the
National Institute for Health and Care Excellence (NICE), UK guidelines
are used for deciding the need for phototherapy and exchange
transfusion in neonates of gestation 35 weeks and more).
b. Either Maisel’s operational thresholds or the NICE, UK guidelines
are used in preterm neonates born before 35 weeks of gestation.

75. 2.Transcutaneous bilirubin (TcB) measurement may be
used to screen for hyperbilirubinemia in term and
preterm neonates.
If TcB values fall within 2.9 mg/dL (~50 µmol/L) below
or above the age appropriate phototherapy
threshold, total serum bilirubin (TSB) should be
measured to decide on the need for phototherapy
or exchange transfusion.
3. Discontinuation of breastfeeding is NOT recommended either for
diagnosis or for treatment of breast milk jaundice in neonates.

76. 4. Prophylactic phototherapy is not recommended for management of
neonates with Rh immunization or ABO incompatibility.
5. Stable neonates with no other morbidity but having
hyperbilirubinemia requiring phototherapy do not need to be admitted
in the neonatal intensive care unit (NICU) or special care newborn unit
(SCNU) for initiation of phototherapy; phototherapy should be initiated
in them by their mothers’ side.
6. Intensive phototherapy using either single or multiple phototherapy
devices is to be employed in neonates requiring phototherapy. Multiple
phototherapy devices may be preferred when irradiance from a single
device is low, or if serum bilirubin rises rapidly or fails to reduce as
expected despite phototherapy.

77. 7. a. There is no role of routine fluid supplementation in neonates
under phototherapy.
b. In neonates presenting with severe hyperbilirubinemia and requiring
exchange transfusion, intravenous fluid supplementation may be
considered while awaiting exchange transfusion. However, exchange
transfusion should not be delayed for this purpose, particularly in
presence of features of acute bilirubin encephalopathy.
8. Routine periodic changes in body position – from
supine to prone and vice versa – are not
recommended in neonates receiving phototherapy.
9. Continuous phototherapy – except for interruptions during breast
feeding and nappy changes – is employed in neonates with
hyperbilirubinemia requiring phototherapy.

78. 10 a. In neonates with bilirubin value near exchange transfusion
threshold, total serum bilirubin (TSB) may be measured every 4-6 hours
after initiation of intensive phototherapy; once TSB starts declining and
is no longer near exchange transfusion threshold, subsequent TSB may
be measured every 8-12 hours.
b. A follow-up total serum bilirubin (TSB) measurement may be done
12-24 hours after discontinuation of phototherapy in neonates with
features of hemolysis.

79. 11. Total serum bilirubin (TSB) is preferred over transcutaneous bilirubin (TcB) for
monitoring of hyperbilirubinemia during phototherapy or in the first 24 hours after
discontinuing phototherapy in term and preterm neonates.
12. Intravenous immunoglobulin (IVIG) is NOT recommended, either prophylactically or
therapeutically, in neonates with hyperbilirubinemia secondary to alloimmune
hemolytic disease.
13. Phototherapy can be discontinued when TSB value is at least 2.9 mg/dL (nearly 50
µmol/litre) below the treatment threshold. A single value below this threshold is
sufficient to discontinue phototherapy in neonates with nonhemolytic jaundice; two
consecutive values below the threshold are usually required in neonates with
hemolytic jaundice.
14. Albumin priming prior to or during exchange transfusion is not recommended in
neonates with hyperbilirubinemia.

80. Indirect Hyperbilirubinemia
• Case study: A male infant is brought to the clinic on
the fourth day after birth with complaints of yellowish
discoloration of skin for last 1 day. Baby is active and
on exclusive breastfeeds.

81. IMMEDIATE QUESTIONS
How are the onset, progression, and severity of jaundice?
1.Onset of jaundice in the first 36 hours of life is pathological and
warrants immediate admission. The majority of infants develop
jaundice after 48 hours to peak by day 5-7 and disappear by day 10-14
after birth. Jaundice up to palms and soles, associated with poor
feeding, pallor, altered sensorium or convulsions is severe jaundice.
Many hospitals at discharge do transcutaneous bilirubin (TCB)
screening. Based on the hour-specific bilirubin nomogram, one can
predict the risk for subsequent severe jaundice.

82. • 2. Are there any associated complaints?
Presence of fever, vomiting, eve-ear-umbilical discharge, change in
feeding-sleep-voiding pattern, fast breathing, abnormal cry posture, or
convulsions suggest pathological jaundice, and warrants
hospitalization.

83. 3.Are there any risk factors for jaundice?
All infants at hospital discharge should have a universal risk screen:
(a) Setting for blood group incompatibility; (b) Primigravida mother;
(c) Exclusively breastfed; (d) History of jaundice/ phototherapy in
previous sibling; (e) Preterm or late preterm gestation;
(f) Weight loss > 10% from birth; and (g) Geographical prevalence of
glucose-6- phosphate dehydrogenase (G6PD) deficiency. More the risk
factors more are the chances of developing severe jaundice.
All infants with risk factors must have a scheduled follow up after 24
hours of Hospital discharge.

84. 4. Are there any perinatal risk factors?
Maternal blood group (0) or Rh-ve), use of oxytocin during labor, drugs
(aspirin, sulfonamides), prematurity, intrauterine growth restriction
(IUGR), difficult prolonged or assisted delivery, perinatal treatment.
asphyxia, and chorioamnionitis are risk factors predisposing to
jaundice. Family history of jaundice, splenectomy, blood transfusions,
and consanguinity should raise suspicion of hematologic, metabolic or
genetic cause for jaundice.

85. 5. How is the feeding of the baby?
All infants at every contact must be asked for sufficiency of feeding-
weight gain/loss, color of urine, frequency of stools, and fullness of the
breast. Inadequate breast milk feeding increases enterohepatic
circulation and increases the risk of severe jaundice. Breastfeeding
jaundice is milk insufficiency jaundice seen during the first week of life.
Breast milk jaundice is late onset, prolonged Jaundice secondary to
substances in the milk aggravating jaundice. Any loss of 3% of weight
daily or cumulative loss of >10% of birth weight suggests feeding
inadequacy

86. CLINICAL EVALUATION
• General features:
Note the general well-being, activity, posture, tone, cry, and color of urine and stools.
Identify "danger signs"-poor weight gain, vomiting, tense distended abdomen, alternating
drowsiness, decreased urination, decreased responsiveness, fever, inconsolable
cry,abnormal movements, bruises or swelling over the body or severe pallor.
Vital parameters: Document weight, temperature, heart rate, respiration, and oxygen
saturation.
Physical examination: High-colored urine and pale stools reflect conjugated
hyperbilirubinemia. Assess the intensity of jaundice in broad daylight and evaluate the
face, back, trunk, legs, arms, hands and feet. Jaundice follows a cephalocaudal progression.
Cephalhematoma/subgaleal bleed increase the bilirubin load and result in jaundice. Pallor,
splenomegaly suggests hemolytic jaundice. Lethargy, temperature instability, umbilical
discharge, tachypnea suggests sepsis or early bilirubin-induced neurological dysfunction.
Poor suck, poor feeding, shrill cry, and reduced tone are early signs of acute bilirubin
encephalopathy (ABE). Fever, seizures, hypertonia, hung up Moro reflex, and opisthotonus
are late signs of ABE.

87. Differential Diagnosis
• Physiological jaundice: Around 80% of newborns will develop some jaundice during the first week
of life, most of whom will not need any treatment.
• Pathological jaundice: Up to 5% of infants may have a pathological cause and will require
evaluation and treatment.
• Increased bilirubin production:
• Isoimmune hemolytic jaundice: ABO, RH, minor blood group incompatibility.
• RBC enzyme deficiency: G6PD deficiency, pyruvate kinase deficiency.
• RBC membrane defects: Hereditary spherocytosis ,elliptocytosis.
• Hemoglobinopathies: Hemoglobin F, alpha-thalassemia.
• Sequestration of blood: Cephalhematoma, sub-galeal bleed, intra-abdominal hematoma
■ Polycythemia infection: Sepsis, urinary tract infection (UTI).
Decreased bilirubin clearance: Crigler-Najjar syndrome type I and II. Gilbert syndrome, congenital
hypothyroidism.
Laboratory investigations: (See Flowchart I for an approach to jaundice)
.

89. • A proper history and examination should guide the investigations.
Total and direct serum bilirubin level will determine the severity and
differentiate between direct and indirect hyperbilirubinemia. Baby's
blood group, blood counts, direct Coombs test (DCT), the peripheral
blood film will determine the most common causes of pathological
jaundice. Some cases may require further evaluation for G6PD
deficiency and other rare causes of indirect hyperbilirubinemia

90. MANAGEMENT
Screening:
American Academy of Pediatrics (AAP) recommends that all newborns 235 weeks gestational age at birth,
should undergo screening total serum bilirubin (TSB) or TCB before discharge from birth hospital, and followed
up as per Bhutani nomogram.
• Predischarge hour-specific TSB/TcB predicts which infant is at high risk, intermediate risk, and low risk for
developing clinically significant jaundice.
• Infants with screen TSB/TcB above >95th percentile (high risk) on the hour-specific Bhutani nomogram
should be considered for phototherapy or repeating TSB within next 4-8 hours and treatment decided on the
basis of AAP guideline nomograms for phototherapy and exchange transfusion.
• Infants with predischarge TSB/TcB in high intermediate range (between 95th and 75th percentile) on hour
specific Bhutani nomogram should be followed up within next 24 hours. Infants with predischarge TSB/TCB
in low intermediate (between 75th and 40th percentile) and low risk (<40th percentile) on the hour- specific
Bhutani nomogram need routine follow-up within next 2-3 days.
• For infants 235 week's gestational age at birth, presenting with significant hyperbilirubinemia, AAP
guidelines for phototherapy and exchange transfusion should be used to decide the treatment.
• For infants <35 weeks gestational age, Maisel's chart or National Institute for Health and Care Excellence
(NICE) guidelines should be used for treatment of indirect jaundice. The treatment modalities available are
as under:

91. DEFINITIVE CARE
• Phototherapy. The effectiveness of phototherapy depends on
irradiance, the surface area exposed and the intensity of the light
source used. Intensive phototherapy implies irradiance in the blue-
green spectrum (wave length 430-490 nm) of at least 30 μw/cm²/nm.
Phototherapy helps by causing configurational photoisomerization of
bilirubin, which occurs almost instantaneously after starting intensive
phototherapy. These photoisomers can account for up to 20-30% of
the total unconjugated bilirubin and are less lipophilic than native
bilirubin, therefore are less likely to cross the blood-brain barrier
Structural photoisomer lumirubin and to a small extent photo-
oxidation is primarily responsible for the ultimate bilirubin lowering
effect of phototherapy.

92. • Exchange transfusion:
• Exchange transfusion is an important intervention to prevent or reduce the risk for kernicterus.
The donor blood of higher plasma volume [hematocrit (HCT)-40] to enhance the amount of
bilirubin-free albumin introduced into the infant's circulation during the exchange is preferred.
Studies have shown that single-volume exchange transfusion is equally effective as double-
volume exchange transfusion.
• The preferred method is push-pull of small aliquots (5-10 mL) through the umbilical venous
catheter.
• The indication for exchange transfusion are: (a) TSB in the exchange transfusion range on the AAP
nomogram despite intensive phototherapy, and (b) infant manifesting signs of intermediate to
advanced stage of ABE (hypotonia, arching, retrocollis, opisthotonus, fever, high-pitched cry) even
if TSB is falling.
• The medical decision to select the donor blood type is dependent on the mother's and infant's
blood and Rh grouping (Table 1).

93. Follow-up
• All infants who receive treatment for indirect hyper- bilirubinemia
(phototherapy/exchange transfusion) should be followed up within 24-48 hours
of discharge to evaluate for rebound hyperbilirubinemia. All these infants are also
at risk for neurodevelopmental sequel and sensorineural hearing loss, hence
many require long-term follow-up.
Parental Counseling
• All the parents should be counseled about the risk of development of jaundice in
their newborn, during the first week after birth. Structured follow-up schedule
should be given to all with written and verbal instructions. Though in the majority
the jaundice is benign, parents should understand the potential of severe
jaundice that exists; hence periodic evaluation is a must. Need for exclusive and
on-demand breastfeeding needs to be emphasized.

94. CASE RESOLUTION
• The infant was noted to have jaundice up to abdomen. The delivery
was uneventful with no setting for blood group incompatibility.
Breastfeeding was found to be adequate There was no pallor,
plethora, rash, cephalhematoma or hepatosplenomegaly.
• A clinical diagnosis of physiologic hyperbilirubinemia was made and
parents assured, danger signs explained and breastfeeding re-
emphasized.

95. Neonatal Critical Care Workshop
Jaundice Workstation

97. Pallor, plethora
s/o sepsis
(thermal +, pustule,
discharge, petichae, purpura)
Hepato-
splenomegaly
Drowsy
Poor suck
Is it pathologic jaundice?
Urine/stool
color
Gestation
Weight loss
Non-physiologic jaundice
• Sick newborn
• Jaundice < 24 hours
• Jaundice > 14 days
• Rate of rise of bilirbuin > 5mg/dl/day
• TcB > 95th percentile on nomogram
• TSB > 75th percentile on nomogram
• Direct bilirubin > 2 mg% or 20% of
TSB

98. Stool Chart

99. 3.5-5.4 TSB by 24-48 hr
> 5.5
< 3.4 TSB by 8-24 hr
• Preterm
• Hemolysis
• Sepsis
• Unstable over 24 h
• Albumin < 3 g/dl
Preterm
Suboptimal BF
Down’s sy
Cephal, IDM
Onset of jaundice < 24h
Family history of PT, ET
FU by 48-72 hr

100. Score Mental Status Muscle tone Cry
0 Normal Normal Normal
1 Poor feeding
Sleepy-arousable
Mild Hypotonia High pitched
2 Lethargy
Poor suck
Irritability
Moderate Hypo or
Hypertonia
Shrill
3 Seizures
Apnea
Coma
Retrocolis
Opisthotonus
Bicycling
Inconsolable
Weak
Absent
BIND Score
Pediatrics. 1999; 104 (Supplement): 746-747

101. Beware of BIND !
Research and Reports in Neonatology, 8:33-44, 2018
Shrill cry Setting sun sign
Dystonia Opisthotonus

102. BIND Score Action Outcome
0-3 Intensive
phototherapy
Good
4-6 Exchange transfusion Fair, Reversible
7-9 Exchange transfusion Guarded, Irreversible
Interpreting BIND Score
Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity
in Newborn Infants J Pediatr 2017 Apr;183:51-55.e1
Prediction (BIND score ≥4)
Specificity (87.3%), Sensitivity (97.4%)

103. Phototherapy (AAP Charts)
Pediatrics. 2004 Jul; 114(1):297-316.
x <24 hrs x >7d
Not for < 35w Use Total bili For intensive PT

104. PT Chart
• Preterm
• Hemolysis
• Sepsis
• Unstable over 24 h
• Albumin < 3 g/dl
Gestation Specific
Neuro Risk factors
0-14 days
1-2 mg/dl > PT
Not for < 35w
Use Total bili
For intensive PT

105. Indication for ET (AAP Chart)
Pediatrics. 2004 Jul; 114(1):297-316.

106. Exchange
Transfusion

107. https://www.youtube.com/watch?v=42xzmYqkjB4
• ET Procedure : Preterm Baby Package

108. https://bilitool.org/

109. Escalation of Care
When?
What?
Inv?
IVIG?
Exit?

110. Clinical Judgment
Risk factors?
Neurotoxic
Risk factors?
Examination ?
P
T
E
T
Follow
up

111. Preventing Kernicterus
TcB / TSB
Screening
(24-48 hr)
Visual screen
Risk Factor
Neuro-toxicity
Breast feeding
Assess, Support
Counsel parents
3.5-5.4 TSB by 24-48 hr
> 5.5
PT Chart
Gestation
Neurotoxic
risk
Phototherapy
ESCALATION
OF CARE
ET Chart
Gestation
Neurotoxic
risk
TcB > 15 or <
3mg/dl of PT
threshold
Do Total S Bili
2 mg/dl
of ET
< 3.4 TSB by 8-24 hr
FU by 48-72 hr
Suspect hemolysis
>0.3 mg/dl/h (< 24h)
>0.2 mg/dl/h
Preterm
Hemolysis
Sepsis
Unstable over 24 h
Albumin < 3 g/dl

112. Manegment of Hyperbilirubinemia

113. SERIOUS JAUNDICE:
a. Presence of visible jaundice in first24 hour
b. Yellow palms and soles anytime
c. Signs of acute bilirubin encephalopathy or kernicterus:hypertonia,
abnormal posturing such as arching, retrocollis, opisthotonus or
convulsion, fever, high pitched cry)
d. TcB/TSB value more than 95 centile as per age specific nomogram

114. RISK FACTORS:
• Isoimmune hemolytic disease
• G6PD deficiency
• Asphyxia
• Lethargy
• Temperature instability
• SepsisAcidosis
• Albumin <3 g/dL (if measured)

115. Phototherapy
Indications of phototherapy
1. It is not a treatment but is used to prevent kernicterus.
2. It is not a substitute for exchange transfusion.
3. It is mainly indicated in:
◦ a) Rh incompatibility and ABO incompatibility
◦ b) Physiological jaundice with complications like septicaemia, acidosis, birth asphyxia etc.
◦ c) Concealed haemorrhages

116. • DOSE
• The blue light in the range of 420-470 nm with irradiance of 15
MW/cm²/nm is ideal to decrease the serum bilirubin level.

117. Methods to be followed for phototherapy
• 1. In one photo therapy unit,4 CFL must be in working condition.
• 2. The distance between the source of light and baby is 35 cm.
• 3. Flexiglass must cover the tube lights to prevent ultra violet irradiation
and injury to the baby either due to breakdown or dislodgement of tube
lights.
• 4. Eyes and genitalia must be covered to prevent injuries to the retina and
testis.
• 5. The baby must be naked.
• 6. The baby's posture must be changed once in two hours.
• 7. 20% extra amount of fluid to be given.
• 8. The baby must be observed every 6 hours.

118. Complications
• 1. Dehydration: Baby require 20% more amount of fluids.
• 2. Cell damage: Intermittent phototherapy supposed to damage the DNA and
prone for carcinoma
• 3. Retinal damage.
• 4. Infertility.
• 5. Skin changes: Increased tanning of skin.
• 6. Bronze baby syndrome: Lumirubin is responsible for this syndrome,
characterised by dark greyish brown discoloration of skin and urine.
• 7. GIT: Increases faecal water loss.
• 9. Metabolic: Decrease in levels of calcium.

119. 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- ATRASIA, CHOLEDOCHAL CYST,
MALFORMATION
HIDAS SCAN- HEPATOBILIARY SCINTIGRAPHY
LIVER BIOPSY

120. 1. Obstructive bile duct disorders.
• Biliary atresia: frequent cause and must be identified promptly so
that intervention (hepatoportoenterostomy) can be performed
before 2 months of age. This condition may be associated with situs
inversus, polysplenia or asplenia, and cardiac anomalies.
• Alagille syndrome :characterized by unusual facial appearance, ocular
abnormality (posteriorembryotoxon), cardiac abnormalities
(pulmonic stenosis), and vertebral anomalies (butterfly vertebrae).
Choledochal duct cysts are an uncommon but surgically treatable
cause of cholestasis.
• 2. Infectious causes Include sepsis and urinary tractinfections
as well as infections caused by numerous viral, bacterial, and other
organisms.

121. 3. Metabolic disorders include a1-antitrypsin deficiency, cystic fibrosis,
galactosemia, tyrosinemia, galactosemia, storage diseases (Gaucher,
Niemann-Pick), Zellweger syndrome, mitochondrial disorders, and
congenital disorders of glycosylation
4. Immunologic disorders include gestational alloimmune liver disease
(formerly neonatal hemochromatosis) and neonatal lupus erythematosus.
5. Endocrine disorders include hypothyroidism and panhypopituitarism.
6. Toxic disorders. A frequent cause of cholestasis in the NICU occurs in
infants unable to take enteral feeding who have prolonged courses of TPN
including lipid. This condition typically resolves with Introduction of
enteral feedings.

122. THANK YOU