neonatal jaundice

introduction
• Jaundice is observed during the 1st week after birth in approximately 60% of term
infants and 80% of preterm infants
• It is apparent clinically when the level of bilirubin in the serum >
5mg/dL(85micromol/L)
• The yellow colour usually results from the accumulation of unconjugated, nonpolar,
lipid-soluble bilirubin pigment in the skin.
• Indirect bilirubin are potentially neurotoxic.
• Direct hyperbilirubinemia indicates a potentially serious hepatic disorders or a systemic
illness.
 bilirubin metabolism
1. Production: Bilirubin is produced mainly from old RBCs

1. Transport: Bilirubin(UB) is carried on albumin

2. Uptake by hepatocytes: UB bind to cytoplasmic ligandins (Z and Y proteins) to
deliver it to the endoplasmic reticulum (where conjugation occur)
3. Conjugation: Conjugation of bilirubin is stimulated by glucoronyl transferase
enzyme → conjugated bilirubin (water soluble)
4. Secretion: Active secretion of CB by liver cells into bile canaliculi
5. Excretion: Excretion of CB and bile salts into the intestine
6. Bilirubin in intestine:
• Some CB → deconjugated by mucosal enzyme(B glucuronidase) 🡪 UB 🡪 reabsorbed to
the liver (enterohepatic circulation)
• Some CB → changed into stercobilinogen by bacterial protease 🡪 brown colour stool
• Some CB → changed into urobilinogen → urine
IN NEWBORN:

• Hepatic uptake, conjugation and excretion is limited due to transient

deficiency of: -
• Z-acceptor protein
• UDP glucoronyl transferase
• Mostly unconjugated bilirubin because of the: -
• Lack of gut bacteria
• Overactivity of intestinal beta-glucuronidase (deconjugates bilirubin)
• So conjugated bilirubin is rapidly deconjugated and recirculated in the blood
 risk factors
Prematurity
Low birth weight
Mother with blood group O or Rh –ve
G6PD deficiency
Rapid rise of TSB
Sepsis
Lactation failure in EBF
Cephalhematoma or bruises
Babies of diabetic mothers
Family history of severe NNJ in siblings
CLASSIFICATION
 Based on time of onset of jaundice:

Within 24 hours of age Between 24 and 72 hrs After 72 hours

• Haemolytic disease of • Physiological • Sepsis

newborn: Rh, ABO and • Sepsis • Neonatal hepatitis
minor group • Polycythaemia • Extrahepatic biliary
incompatibility • Concealed atresia
• Infections: intrauterine haemorrhage: • Breastmilk jaundice
viral, bacteria, malaria, cephalohematoma, • Metabolic disorders
G6PD deficiency SAH, IVH
• Increased
enterohepatic
circulation
A 3-day-old term male neonate is brought to the pediatric outpatient department with complaints of yellowish discoloration of the
skin and sclera noticed by the mother since the last 24 hours. The baby was delivered by normal vaginal delivery at term, with an
uneventful antenatal, perinatal, and immediate postnatal period.
The neonate is feeding well, active, and passing urine and stools normally.
On examination, icterus is present up to the face and upper trunk. There is no hepatosplenomegaly or signs of sepsis. Vital
parameters are stable.

Laboratory investigations:
CLASSIFICATION
Total serum bilirubin: 9 mg/dL
Blood group (mother and baby): O positive

What is the most likely diagnosis?

 physiological jaundice
Incidence Commonest cause of neonatal jaundice
Aetiology • Decreased glucuronyl transferase enzyme activity (main cause)
• Decreased Z and Y protein (for bilirubin uptake)
• Short life span of neonatal RBC's (40- 60 days).
Characters • Appears after 24-72 hours of life
• Usually peaks by 3 days of life
• Clinically not detected after 14 days
• Disappears without treatment

Diagnosis • By exclusion (No anemia, normal liver function)

Treatment • Usually need no treatment; especially in full term
• Phototherapy may be needed for very low birth weight
 pathological jaundice
·

• Jaundice is considered pathological if its appearance, duration, or

pattern varies significantly from that of physiological jaundice.
Features:
• Appears within 24 hours
• TSB exceeds 5mg/dl on 1st day, >10mg/dl on 2nd day or 15mg/dl
thereafter in term babies
• Clinically jaundice present beyond three weeks
• Stool clay/white coloured and urine staining clothes yellow (conjugated
bilirubin)
• Direct bilirubin >2mg/dl at any time
 prolonged neonatal jaundice
• DEFINITION: Visible jaundice (SB >85 μmol/L or 5 mg/dL) that persists beyond 14 days of life in a term baby
(≥ 37 weeks) or 21 days in a preterm baby (≥35 weeks to < 37 weeks)
 breastfeeding jaundice
• Appears between 24-72 hrs of age

• Peaks by 5-15 days of life

• Disappears by the 3rd week of life

• Cause: decreased milk intake

• Treatment: ensure optimum BF rooming-in

with night feeding, and ongoing lactation

support
 breastmilk jaundice
Incidence • Affects 2-4% of breast fed, healthy full term
• Recurrence rate 79% in subsequent pregnancies
Clinical picture • Instead of the usual fall of serum bilirubin by the end of 1 st week, it continues to
rise
• With maximal level of 10-30mg/dL
• Peaks by 10-25 days of age
• Slowly decline by 3-12 weeks of age
Etiology • Breastmilk contain pregnanediol and non-esterified FFA  inhibit glucoronyle
transferase enzyme
• B-glucuronidase in breast milk  enhance enterohepatic circulation
Diagnosis • By exclude other causes
Treatment • Continue breastfeeding at frequent intervals and TSB levels usually decline over a
period of time
• Some babies may require phototherapy.
• Breastfeeding should not be stopped either for diagnosis or treatment of breast
milk jaundice.
Diagnostic approach to neonatal jaundice
 Congenital Hypothyroidism
• - Clinical syndrome resulting from deficiency of thyroid hormone activity
• - Results in generalised slowing of all bodily function (↓basal metabolic rate)
• - Hypothyroidism occuring during the critical period of brain growth (<2 years old)
• - Retards physical growth, development, irreversible intellectual retardation
• - Delayed maturation of foetal lungs and bones
Neonatal Hepatitis Syndrome UTI
- Intrahepatic inflammation and cholestasis of
multiple aetiologies (idiopathic, infectious
hepatitis or intrahepatic bile duct paucity) which
leads to prolonged jaundice in neonates
- Infants may have IUGR & hepatomegaly at birth (in
contrast to biliary atresia)
- Liver biopsy non-specific, showing giant cell hepatitis
- Comprises of:

Urine FEME and C&S to be done

Biliary atresia
- Destruction/ absence of the extrahepatic biliary tree &
intrahepatic biliary duct
- Obliterative cholangiopathy may be divided into 2 major types:

- Most common form of biliary atresia is obliteration of entire

extrahepatic biliary tree at/above
porta hepatis (85-90%)
- More common in East Asian countries, 1/10,000-15,000 live
births
COMPLICATION OF
HYPERBILIRUBINAEMIA
• If untreated, it will lead to acute & chronic bilirubin encephalopathy,
eventually kernicterus d/t deposition of unconjugated bilirubin in basal
ganglia (>20 mg/ dL)
• Conditions that alter BBB such as infection, acidosis, hypoxia, sepsis,
prematurity & hyperosmolarity may affect entry of bilirubin into brain
• C/F :
a) Earliest clinical manifestations : lethargy, hypotonia, irritability, poor
Moro response, high pitched cry, poor feeding and vomiting.
b) Later signs : bulging fontanelle, opisthotonic posturing, fever,
hypertonicity, paralysis of upward gaze and seizures.
• Spasticity resolves in surviving infants , he could manifest later nerve
deafness, choreoathetoid cerebral palsy, mental retardation, enamel
dysplasia and discoloration of teeth.
 INVESTIGATION
1ST LINE 2ND LINE
Total serum bilirubin Direct Coombs test
- Detect presence of Ab coating on fetal RBC
Blood groups of mother and baby Hematocrit
-Detect incompatibility - ↓ in haemolysis
Peripheral smear Reticulocyte count
-Evidence of haemolysis - ↑ in haemolysis
G6PD levels
Others:
- Sepsis screen – UTI
- TFT – hypothyroidism
- Genetic study – Crigler-Najjar
 PHYSIOLOGICAL JAUNDICE
- Explain to the parents on benign nature of jaundice
- Encourage frequent & exclusive breastfeeding
- If baby looks deep yellow or the palms & soles have yellow staining, they need to
come to hospital
- No need to expose baby to direct sunlight to reduce hyperbilirubinemia
- If the mother & baby is discharged before 72 hours of life, the baby should be
evaluated again in the next 48 hours to assess the adequacy of breastfeeding &
progression of jaundice
 MANAGEMENT OF
NEONATAL JAUNDICE

IRFAN SYAMIL
 PHOTOTHERAPY

Mainstay of treating hyperbilirubinemia in neonates

• It converts insoluble bilirubin (unconjugated) into soluble isomers

that can be excreted in urine and feces
• Bilirubin molecule isomerizes to harmless forms under blue-green
light (460-490nm)

• For phototherapy to be effective, bilirubin needs to be present in

the skin, so there is no role for prophylactic phototherapy
 ADMINISTERING PHOTOTHERAPY

Ensure ambient temperature is 25C to 28C to

prevent neonate from becoming hypothermic or
hyperthermic

Remove all clothes except the diaper

Cover baby’s eyes with an eye patch to prevent retinal

damage, ensuring it does not block the nostrils

Put in a cot if the neonate weights more than 2 kg

or in incubator or radiant warmer if the neonate is
less than 2 kg

Distance between neonate and light to 30 to 45cm

 MAXIMIZING THE EFFIC ACY OF
PHOTOTHERAPY

Expose maximal surface area of the neonate

Light should fall on the neonate perpendicularly

Avoid blocking the lights with any equipment (e.g. radiant warmer)

Ensure good hydration by frequent breastfeeding

Minimize interruption of phototherapy during feeding

sessions or procedure
 G U I DE LINES FO R
PHOTOTHERAPY
[A A P]

• Phototherapy should be commenced

when total serum bilirubin reaches
the phototherapy threshold for
neonatal jaundice

Risk factors:
• Isoimmune haemolytic disease
• G6PD deficiency
• Asphyxia
• Significant lethargy
• Sepsis
• Acidosis
• Hypoalbuminemia
CUT-OFFS FOR PHOTOTHERAPY IN
PRETERM NEONATES [NICE]

Phototherapy should be started at a lower threshold in

preterm and low birth weight babies
 MONITORING AND STOPPING
PHOTOTHERAPY

• Monitor temperature every to 2 to 4 hour

• Measure TSB level every 12 to 24hr
• Discontinue phototherapy once two TSB values hour apart fall below
current – age specific cut-offs
• Infant should be monitored clinically for rebound bilirubin rise within 24
hours after stopping phototherapy for neonates with hemolytic disorders

• Once the baby is on phototherapy, visual observation as means

of monitoring is unreliable
• Serum bilirubin levels must guide the management
 PH OTOTHERAPY
CO MPL I CATIO NS

• Loose stools
• Erythematous macular rash
• Purpuric rash
• Transient porphyrinemia
• Overheating
• Dehydration
• Bronze baby syndrome • Bronze baby syndrome refers to a
dark, grayish brown skin discoloration
• Corneal damage
• It occurs due to photo-induced
modification of porphyrins which are
often present during cholestatic jaundice
• It may last for many months
 EXCHANGE TRANSFUSION

Double-volume exchange transfusion is performed if intensive phototherapy

has failed to reduce bilirubin levels to a safe range and the risk of kernicterus
exceeds the procedural risk

Indications;
• TSB levels reach the age-specific cut-off for exchange transfusion or
• Infant shows sign of bilirubin encephalopathy, irrespective of TSB levels
 G U I DE LINES FO R
E X C HANGE T RANSF USION
[A A P]
 Rh isoimmunization; Other conditions
ABO compatible Cross match with baby
Rh-negative blood and mother’s blood

TYPE OF BLOOD
TO BE USED In Emergencies if
Blood Type unknown
[rarely]
‘O’ Rh negative blood
 Volume to be exchanged is 2x the infant’s total
blood volume (2x80mls/kg)
PROCEDURE
[E XCHANGE Use Fresh Whole Blood preferably less 5 days old or
TRANSFUSION] reconstituted Packed Red Blood Cells and FFP in a
ratio of
Connect baby to a cardiac monitor

Take baseline observations and record down on the

Neonatal Exchange Blood Transfusion Sheet

The following observations are recorded every 15

minutes; apex beat, respiration, oxygen saturation
 Cannulate the umbilical vein to a depth of
PROCEDURE not > 5-7 cm in a term infant for a catheter
tip to be proximal to the portal sinus
[E XCHANGE
TRANSFUSION] Aliquot for removal and replacement –
5-6ml/kg

Maximum volume per cycle -20mls for term

infants, not to exceed 5ml/kg for ill or
preterm infants
At the same time, the nurse keeps a record
of the amount of blood given or withdrawn
and medications given
Administration of IVIG is an adjunctive
treatment for hyperbilirubinemia caused by
isoimmune hemolytic disease

Its use is recommended when serum

bilirubin is approaching exchange level I N T RAVENOUS
despite maximal interventions, including I M M UNOGLOBULIN
phototherapy

IVIG (0.5-1.0 g/kg/dose; repeated in 12 hr)

reduces the need for exchange transfusion
in both ABO and Rh hemolytic disease
 METALLOPORPHYRINS

A possible adjunct therapy for hyperbilirubinemia

It acts a competitive enzymatic inhibition of the rate-limiting conversion of heme-protein

to biliverdin by heme-oxygenase
A single intramuscular dose on the 1st day of life may reduce the need for subsequent
phototherapy
Data on efficacy, toxicity and long-term benefit are still being evaluated
REFERENCES