2. Defined as….
Hyperbilirubinemia refers to
an excessive level of
accumulated bilirubin in the
blood and is characterized by
jaundice.
Jaundice is the yellowish
discoloration of the skin,
sclerae, mucous membranes
and nails.
5. Neonatal Hyperbilirubinemia
When the rate of bilirubin production exceeds elimination, the end result is
hyperbilirubinemia.
Jaundice is the most common transitional finding in the newborn period,
occurring in 60-70% of term and approx. 80% in preterms.
Significant jaundice occurs in approx. 6 % of term babies
An elevation of Sr. Bilirubin conc. >2mgdl is found in virtually all newborns
in the first few days of life. Jaundice becomes clinically apparent when it
exceeds >5mgdl.
Physiologic ranges of TSB remain controversial as these levels are
affected by several factors like gestational age, birth wt, disease state,
level of hydration, nutritional status and ethnic background.
INdirect – Unconjugated
Direct - Conjugated
7. Classification of neonatal jaundice
• Appears after 24 hours
• Maximum intensity by 4th-5th day in term & 7th day in
preterm
• TSB levels within normal centiles for age in hours based on
normogram.
• Clinically not detectable after 14 days
• Disappears without any treatment.
Physiologic
jaundice
• Appears within 24 hours of age
• Increase of bilirubin > 5 mg / dl / day or at a rate of >0.2mg/dl/hr
• Serum bilirubin >95 percentile for age in hours based on
normogram.
• Jaundice persisting after 14 days in fullterm babies.
• Stool clay / white colored and urine staining clothes yellow
• Direct bilirubin> 2 mg / dl or >20% of TSB.
Pathologic
jaundice
8. Causes of physiologic jaundice
1. Increased bilirubin load due to physiologic increased RBC mass,
decreased RBC life span.
2. Decreased immediate postnatal bilirubin uptake due to reduced
ligandin activity.
3. Hepatic enzyme immaturity for bilirubin conjugation.
4. Increased enterohepatic circulation due to lack of intestinal flora,
greater proportion of β-glucoronidase.
9.
10. First 24 hrs
• Hemolytic disease of Newborn : Rh, ABO
• Infections: TORCH, malaria, bacterial
• G6PD deficiency
24 – 72 hrs
• Physiological
• Sepsis
• Polycythemia
• Intraventricular hemorrhage
• Increased entero-hepatic circulation secondary to feeding issues, hirschsprungs, etc.
> 72hrs
• Sepsis
• Cephalhaematoma
• Neonatal hepatitis
• Extra-hepatic biliary atresia
• Breast milk jaundice
• Metabolic disorders (IEM, G6PD).
Differential Diagnosis ( as per time of presentation) :
11. Causes of pathologic jaundice
1. Excessive Red cell hemolysis.
2. Defective conjugation of bilirubin.
3. Breast milk jaundice.
4. Metabolic and endocrine disorders.
5. Increased enterohepatic circulation.
6. Miscellaneous.
13. Monitoring
All newborns should be routinely assessed for jaundice.
Jaundice is visible when Sr. Bilirubin >5mg/dl.
Newborns to be observed for 72 hrs for jaundice appearance. In case of
discharge before 48hrs, Bilirubin risk factors and Hyperbilirubinemia risk
as per Normograms should be assessed and followup to be advised
accordingly.
A predischarge TSB or Transcutaneous bilirubin reading to be done if discharge
is before 72 hrs of life.
14. Risk factors:
Jaundice within first 24 hrs of life
A sibling who was jaundiced as neonate
Unrecognized hemolysis
Non-optimal sucking/nursing
Deficiency of G6PD, Pyruvate kinase.
Infection
Cephalhematoma /bruising
East Asian/North Indian
J
A
U
N
D
I
C
E
16. Gestational age 35 to <38wks + Hyperbili risk factors
Predischarge TcB / TSB
Bilirubin risk zones ( as per normogram)
High High intermediate) Low intermediate Low
Evaluate for Phototherapy,
TSB in 4 – 8 hrs.
(As per PT normogram)
Evaluate for phototherapy,
TcB / TSB in 4 – 24 hrs.
( As per PT noprmogram)
If Discharge <72 hrs,
Followup in 2 days
+ TcB / TSB
If discharge < 72hrs,
Followup in 2 days
AAP Screening guidelines - Type 1
17. Gestational age 35 to <38wks +no risk factors
OR
Gestational age >38 wks + hyperbili risk factors
Predischarge TcB / TSB
Bilirubin risk zones ( as per normogram)
High High intermediate) Low intermediate Low
Evaluate for Phototherapy,
TSB in 4 – 24 hrs.
(As per PT normogram)
Evaluate for phototherapy,
TcB / TSB within 24 hrs
( As per PT noprmogram)
If Discharge <72 hrs,
Followup in 2 days
If discharge < 72hrs,
Followup in 2 – 3 days
AAP Screening guidelines - Type 2
18. Gestational age > 38wks
+ No hyperbili risk factors
Predischarge TcB / TSB
Bilirubin risk zones ( as per normogram)
High High intermediate) Low intermediate Low
Evaluate for Phototherapy,
TSB in 4 – 24 hrs.
(As per PT normogram)
Follow up in 2 days
TSB / TcB on f/u
If Discharge <72 hrs,
Followup in 2 – 3 days
If discharge < 72hrs,
Followup as per age of
Discharge or SOS.
AAP Screening guidelines - Type 3
19. History
Gestational age
Age of onset of jaundice / duration.
H/O lethargy, irritability, convulsion, posturing, shrill cry.
Feeding history
Antenatal history of APH, PPROM, maternal DM, Thyroid disorders, antenatal infections.
Birth history of Birth asphyxia, resuscitation needed.
Family history of Jaundice, anaemia, splenectomy, metabolic disorder.
Previous sibling history , H/O neonatal deaths or morbidities in family.
?? Time of first stool passage, colour of stools, frequency of stools.
Urine colour and frequency.
20. Clinical assessment
** Colour of the skin
(to be checked in naked baby, natural light, non- yellow background, minimum blanching
over bony surfaces)
Severity of jaundice (Krammers staging of Jaundice)
Anemia, Signs of dehydration.
Hepatosplenomegaly
Complete neurological examination to look for s/o kernicterus
Special look for cephalhematoma, bruisings or bulging AF.
Abdominal mass, distension, ?Ascitis.
23. Transcutaneous bilirubinometer ( TcB)
TcB is a useful adjunct to TSB measurement
and routine employement of TcB can reduce
the need for blood sampling.
TcB can be used in infants of 35 wks or more
gestation & after 24 hrs of life.
TcB has a good correlation with TSB levels
but becomes unreliable once the TSB level
goes beyond 14 mg/dl.
Trends in TcB values 12 hrs apart have a
better predictive value than a single reading.
A TcB value more than 12 – 14 mg/dl needs
confirmation by TSB examination.
24. Indications for TSB measurement :
1. Jaundice in first 24 hour.
2. Beyond 24 hrs:
If visually assessed jaundice is likely to be more than 12 to 14mg/dL
(as beyond this TSB level, visual assessment becomes unreliable)
or
Approachingthe phototherapy range or beyond.
3. If you are unsure about visual assessment
4. During phototherapy, for monitoring progress and after phototherapy
to check for rebound in select cases (such as those with hemolytic jaundice)
26. Perform visual assessment every 12 hrly for initial 3-5 days.
This can be supplemented by TcB measurements.
Does the baby have serious jaundice???
Yes
Start
phototherapy
Measure the TSB levels to determine whether the
infant needs phototherapy or exchange transfusion.
Determine the cause of jaundice and
provide further management and followup
care
No
Does the infant have significant
jaundice to require TSB
measurement ??
Yes No
Continue observation
every 12 – 24 hrs for
next few days.
Approach to jaundice baby
37. Phototherapy
Phototherapy remains the mainstay in treatment
of neonatal hyperbilirubinemia.
It acts by photooxidation, photoisomerisation &
structural Isomerisation ( i.e.) converting insoluble
bilirubin into soluble isomers , which are easily
excreted in urine & faeces.
The phototherapy units available in market have
variety of light sources including flourescent
lamps, halogen bulbs, high intensity LED lamps &
fibreoptic light sources.
With easy availibility and low cost, CFL is most
commonly used in India. In last few years, LED use
has increased tremendously.
38. Phototherapy – Equipment specifications
Wavelength range = 460 – 490 nm.
(Practically used are white, blue lights)
Irradiance = minimum 30 μW/cm2/nm.
Distance of baby from unit = 30 to 45 cm.
(as per manufacturer instructions if specified)
Ambient room temperature = 26 – 28 degrees.
Plastic cover or shield to be placed before
phototherapy lams to avoid accidental injury in
case lamp breaks.
39. Phototherapy – Patient specifications
Expose maximum surface area of the baby.
Remove all clothes of the baby except diaper.
Apply a small eye patch. Make sure it does not
cover baby’s nostrills.
Avoid blocking the lights by any equipment like
warmer parts, large diaper, cap, dressing,
electrodes, etc.
If in an incubator, light should be perpendicular
to the baby.
40. Phototherapy – Patient specifications
Ensure adequate nutrition & hydration of the
baby.
Minimise interruption during feeds or
procedures.
There is no need to supplement breastfeed with
any other feeds or fluids during phototherapy.
Monitor temperature of the baby 2-4hrly, TSB
levels 12-24 hrly. Watch for rebound bilirubin
clinically.
Monitor baby’s hydration status esp. urine
output.
41. Phototherapy – side effects…..
•Increased insensible water loss / dehydration: Frequent
Breast feeding.
•Loose green stools: weigh often and compensate with
breast milk.
•Skin rashes: Harmless, no need to discontinue
phototherapy.
•Bronze baby syndrome: occurs if baby has conjugated
hyperbilirubinemia. If so, discontinue phototherapy.
•Hypo or hyperthermia: monitor temperature frequently.
42. Exchange Transfusion
Exchange Transfusion is reserved for the most
severe forms of neonatal hyperbilirubinemia.
Double volume exchange transfusion has to be
performed if the TSB levels reach to age specific cut
offs for exchange transfusion or the neonate shows
signs of bilirubin encephalopathy irrespective of the
bilirubin levels.
Indications for DVET at birth for infants include :
1.) Cord bilirubin >4.5mg/dl.
2.) Cord Hb <11mg/dl
3.) Rate of bilirubin increase >1mg/dl/hr
4.) If Hb 11-13, rate of bili increase >0.5mg/dl/hr.
5.) Phototherapy fails to limit hyperbilirubinemia.
43. Exchange Transfusion
Type & Volume of blood for exchange transfusion
Sr. no Condition Type of blood
1 Rh Isoimmunization Rh negative and bld group ‘O’ or that of baby.
Cross matched with baby’s and mother’s blood.
2 ABO incompatibility Rh compatible & blood group ‘O’ (NOT THAT OF BABY)
Cross matched with baby’s and mothers blood.
3 Other conditions (G6PD
def, other hemolutic
conditions)
Baby’s group & Rh type.
Cross matched with mother and baby sample.
Volume of blood: Twice the blood volume of baby (total volume: 160 to 180 mL/kg)
Preferred preservative – CPD (citrate phosphate dextrose)
Blood should be < 72 hrs old (to ensure bld pH <7)
For hydrops fetalis, prefer fresh blood < 24 hrs old.
44. Exchange Transfusion
Assistant help - Maintain sterile field, monitor and assess
the infant , record the procedure and exchanged volumes.
Equipment needed - Radiant warmer/incubator,
pulseoximeter, resuscitation apparatus, UAC/UVC insertion
equipment, bivalves, NGT, Exchange transfusion circuit,
Blood for exchange to be warmed at room temperature.
Blood should be obtained for lab studies before and after
ET:
Total Serum bilirubin, calcium, sodium, potassium, chloride,
pH, pCO2,bicarb, Sr. glucose. Hemoglobin , platelet count,
WBC.
Blood culture is recommended after Exchange transfusion.
45. Exchange Transfusion - Procedure
Double volume exchange transfusion done
in hyperbilirubinemia in neonates.
Normal blood volume is 80ml/kg in fullterm baby.
Therefore, 160ml/kg of blood ( after blood grouping &
cross matching) will be needed for the procedure.
Procedure to be performed under complete aseptic precautions.
Baby placed in supine position.
Restraints can be given…. Snug but not tight.
Stomach decompression by nasogastric tube and left in situ.
Scrub and put on sterile gown and gloves.
Perform umbilical vein catheterisation and confirm position by
radiograph.
If isovolumetric double exchange to be done, umbilical artery
catheter to be inserted.
Have the unit of blood ready. Attach the bag of blood to the tubing and
stopcocks. According to the direction of the transfusion tray.
Check the orientation of the stopcock directions before starting the infusion and
withdrawl.
46. Exchange Transfusion - Procedure
Eastablish the volume of each aliquot.
Exchange transfusion can be done by the push –
and- pull technique through the umbilical vein.
The recommended duration is 1 hr.
After exchange transfusion , phototherapy is continued
and bilirubin levels are measured every 4 hrs.
Calcium gluconate , antibiotics are to be given
SOS (On individual basis)
Side effects : Hypoglycemia, Hypocalcemia,
hyperkalemia, Bleeding/coagulopathies,
Infections, late metabolic alkalosis.
Infant weight Aliquot (ml)
3 kg 20
2 – 3 kg 15
1 – 2 kg 10
850g – 1 kg 5
< 850 gm 1 - 3
47. Other Treatment modalities :
• Increases hepatic glucoronyltransferase activity & conjugation od bilirubin.
• Used to treat Criggler najjar , gilbert syndromes.
• Not effective as urgent treatment as it takes some time for effect.
• Sedation & neurologic side effects limits its use.
Phenobarbitone
• Tin (Sn) and zinc (Zn) are being used in trials.
• They work by decreaseing the production of bilirubin by competitive inhibition of heme
oxygenase.
• Their long term safety is still under study. Not yet approved by FDA.
Metal
metalloporphyrins
• This has been effective in infants with Rh & ABO hemolytic disease and reduces the
need for exchange transfusion.
• AAP recommends this in isoimmune hemolytic disease if TSB levels are rising despite
phototherapy or TSB levels are within 2-3mg/dl of exchange level.
• Dose is 500mg – 1gm/kg over 2 hrs, repeated in 12 hrs (only if necessary)
IVIG
• Can be given if albumin levels are low.Albumin
49. Kernicterus
Caused secondary to chronic bilirubin
encephalopathy.
Acute bilirubin encephalopathy may develop
during hazardous hyperbilirubinemia and
develop in chronic adverse neurodevelopmental
sequelae.
TETRAD of Kernicterus :
1. Choreoathetoid Cerebral Palsy.
2. High frequency central neural hearing loss.
3. Vertical gaze palsy.
4. Dental enamel hypoplasia.
50. Kernicterus (cont..)
Unconjugated Hyperbilirubinemia.
Bilirubin predilection to neurons & involvement of
basal ganglia, cochlea and oculomotor neuron.
Stages of Kernicterus :
STAGE 1 : decreased activity, poor sucking,
hypotonia, high pitched cry.
STAGE 2 : Stage 1 features + rigid extension of all 4
extremities, tight fisted posturing of arms, crossed
extension of legs, high pitched irritable cry.
Sometimes seizure, retrocolis, opisthotonus posture.
STAGE 3 : Hypertonia, retrocolis, opisthotonus, stupor,
coma.
51. Kernicterus – MRI findings
Abnormally high signal intensity on T1 weighted images of
basal ganglia , thalamus & internal capsule.
Similar, but less intense signal was seen on T2 weighted images
52.
53. Direct Jaundice
Defined as measure of direct reacting
bilirubin of >1mg/dl in TSB <5. OR more
than 20 % of the TSB levels.
Also known as Conjugated
hyperbilirubinemia.
It is a biochemical marker of cholestasis
& indicator of hepatobiliary dysfunction.
Always Pathological
57. Management
1.) Medical :
Special formulas (medium chain triglycerides)
Vitamin Supplements (Vit K, E, D, A)
Dietary restrictions (as per diagnosis)
2.) Pharmacological :
UDCA (Ursodeoxycholic acid)
Phenobarbitone
Cholestyramine
3.) Surgical : as per the diagnosis, SOS Liver transplantation.
58. AAP Guidelines
Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.
Pediatrics. 2004; 114:297-316 (July issue)
Key elements of the recommendations provided by this guideline.
Clinicians should:
1. Promote and support successful breastfeeding.
2. Establish nursery protocols for the identification and evaluation of
hyperbilirubinemia.
3. Measure the total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) level
on infants jaundiced in the first 24 hours.
4. Recognize that visual estimation of the degree of jaundice can lead to errors,
particularly in darkly pigmented infants.
59. AAP Guidelines
5. Interpret all bilirubin levels according to the infant’s age in hours.
6. Recognize that infants at less than 38 weeks’ gestation, particularly those who
are breastfed, are at higher risk of developing hyperbilirubinemia and require
closer surveillance and monitoring.
7. Perform a systematic assessment on all infants before discharge for the risk of
severe hyperbilirubinemia.
8. Provide parents with written and verbal information about newborn jaundice.
9. Provide appropriate follow-up based on the time of discharge and the risk
assessment.
10. Treat newborns, when indicated, with phototherapy or exchange transfusion.
