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Neonatal JaundiceDr. Karuppiah Pandi
Neonatal Jaundice (Hyperbilirubinemia)
Definition: Hyperbilirubinemia refers, excessive level of bilirubin in the blood.
Characterized by jaundice, a yellowish discoloration of the skin, sclera, mucous membranes and nails.
Visible form of bilirubinemiaAdult sclera >2mg / dlNewborn skin >5mg /dl
Unconjugated = IndirectConjugated = Direct bilirubin.
•Why am I learning this?
• Is it important?
Why?
Jaundice more common in newbornFull term infants: at least 60%.Preterm infants: over 80%.6-10% require phototherapy/ other
therapeutic options.
Is it important?
Most Importantly…Kernicterus: Unconjugated bilirubin deposits
in the brain = Yellow staining + degenerative lesions
Hyperbilirubinemia & Clinical Outcomes
Deposits in skin and mucous membranes
Unconjugated bilirubin deposits in the brain
Permanent neuronal damage
JAUNDICE
ACUTE BILIRUBIN ENCEPHALOPATHY
KERNICTERUS
Kernicterus:
*Bilirubin deposits typically in basal ganglia, hippocampus, substantia nigra, etc.
Clinical Symptoms:
• Acute Bilirubin Encephalopathy/Kernicterus: • Irritability, jitteriness, increased high-pitched crying• Lethargy and poor feeding• Back arching• Apnea• Seizures • Long-term: Choreoathetoid CP, upward gaze palsy,
SN hearing loss, dental dysplasia
Stages of Kernicterus
I :- Unable to suck, hypotonia, lethargy
II :- Seizures, opisthotonus, spasticity
III :- Spasticity, shrill cry, apnea and seizures
IV :- Athetosis, deafness, up gaze palsy, dental dysplasia and mental retardation
Causes of jaundice based on age at onset Within 24 hours
a. Hemolytic disease of new borna. Rh incompatibilityb. ABO incompatibility
b. Intra uterine infectiona. Toxoplasmosis, CMV, Rubella
c. Deficiency of red cell enzymea. G6PD deficiency, pyruvate kinase deficiency
d. Others
Onset- 24 to 72 hours of life
• Physiological jaundice• Can be aggravated & prolonged by
i. Immaturity ii. Cephalhematomaiii. Birth asphyxiaiv. Hypothermia v. Breast feedingvi. infection
Onset – after 72 hours of age
a. Septicemiab. EHBAc. Breast milk jaundiced. Metabolic causes
i. Galactosemia ii. Tyrosinemia iii. Hereditary fructosemiaiv. Gilbert syndromev. Organic acidemia
Physiological versus pathological jaundice
Physiological jaundice• Jaundice due to physiological immaturity of
neonates to handle increased bilirubin production.
Pathological jaundice• When TSB concentrations are not in
‘physiological jaundice’ range
Why does physiological jaundice develop?
Increased RBC’s (Polycythemia)
Shortened RBC lifespan
Immature hepatic uptake & conjugation
Increased enterohepaticCirculation
Physiological versus pathological jaundice PHYSIOLOGICAL PATHOLOGICAL
Onset More than 24 hours Less than 24 hours
Duration Term - <2 wksPreterm- <3 wks
Term - >2 wksPreterm- >3 wks
Serum bilirubin concentration
Raise < 0.2 mg/dl/hr or < 5 mg/dl / day
Raise > 0.2 mg/dl/hr or > 5 mg/dl / day
TSB < 15mg/dl > 15mg/dl
Involvement of palm and soles
No Yes
Signs of acute bilirubin encephalopathy
No Yes
Direct bilirubin Less than 2mg/ dl more than 2 mg/dl
Bhutani Curve- phototherapy
Bhutani Curve- Exchange transfusion
Causes of pathological jaundice
Common causes: Haemolysis:
Blood group incompatibility - ABO, Rh and minorEnzyme deficiencies- G6PD deficiency
Decreased conjugationPrematurity
Increased enterohepatic circulation Breastfeeding jaundice, GI obstruction
Extravasated blood Cephalhematoma, extensive bruising etc
Risk factors for jaundice
JAUNDICE J - jaundice within first 24 hrs of lifeA - a sibling who was jaundiced as neonateU - unrecognized haemolysisN – non-optimal sucking/nursingD - deficiency of G6PD I – infectionC – Cephalhematoma /bruisingE - East Asian/North Indian
Where do you look for jaundice in newborn
1. Forehead2. Tip of nose3. Chest4. Knee5. Palms and soles
Clinical assessment of jaundice
• Visual inspection of jaundice1. Examine the baby in bright natural light or
white fluorescent light. No yellow or off white background
2. Make sure the baby is naked3. Examine blanched skin and gums4. Note the extent of jaundice (Kramer’s rule) 5. Depth of jaundice (degree of yellowness)
Kramer’s rule
Kramer’s rule
Zone 1= 5mg/dl Zone 2 = 5-10 mg/dlZone 3 = 10-12 mg/dlZone 4 = 15mg/dlZone 5 = >15mg/dl
Measurement of serum bilirubin
Transcutaneus bilirubinometry (TcB)• Advantage:
• Reduce invasive blood test
• Disadvantage:• Costly, • unreliable- less than 35 weeks, during initial 24 hr of
age & TSB more than 14mg/dl
• Measured by using multiple wave length analysis
Measurement of TSB
Indicationsi. Jaundice in first 24 hourii. Beyond 24 hr: if visually assessed jaundice more than 15
mg/dLiii. If you are unsure about visual assessmentiv. During phototherapy, for monitoring progress and after
phototherapy Methods:
v. Biochemical: High performance liquid chromatography (HPLC)
vi. Micro method: Based on spectrophotometry
Questions
1. Name four modality of treatment for jaundice?
2. What are the lights used in phototherapy?3. Which is the best light for phototherapy?4. Can babies with jaundice shown in sunlight?
Management of Indirect Hyperbilirubinemia
• Careful assessment and monitoring – Visual assessment– Blood level monitoring per hospital
protocol at 24 hr of life or sooner as indicated
– Interpretation of risk levels and need for treatment• Phototherapy• IVIg• Exchange Transfusions• Phenobarbital
Therapeutic Management
Purposes: reduce level of serum bilirubin and prevent bilirubin toxicity
Modalities :1. Phototherapy- Reduction of bilirubin levels2. Exchange transfusion- Reduction of bilirubin levels3. IV IG- prevent- Lysis of RBC’s by blocking immune
mediated antibody4. Metalloporphyrin tin/ zinc- Prevent breakdown of Hb
by heme oxidase5. Phenobarbitone/ UDCA- Conjugation of bilirubin
Phototherapy
Safe and effective method for treatment of neonatal jaundice
Bilirubin absorbs light maximum at 420-460 nm
Phototherapy
Mechanism of Action
• Conversion of insoluble Bilirubin into soluble bilirubin Excretion of bilirubin
1. Photo- isomerisation
2. Structural isomerisation
3. Photo- oxidation
Photo-isomerisation
Reversible reaction.Conversion of insoluble, toxic form Z
isomer non toxic polar (water soluble) E isomer diffuses into the blood excreted easily into bile
Structural isomerisation
Irreversible reactionBilirubin lumirubinRapidly excreted in bile and urineMain responsible for phototherapy induce
decline of TSBReduction of bilirubin directly proportional to
dose of phototherapy
Photo-oxidation
Minor reactionPhoto-oxidation of Bilirubin to water soluble
polymersColourless by productRiboflavin- catalyze the dermal photo-
oxidation
Phototherapy
Indications for Phototherapy
TSB > 18 mg % in termTSB > 15 mg% in pretermAdjuvant to exchange transfusionProphylactic PT
- ELBW- Extreme preterm babies, - Bruised babies- Babies with DCT positivity- Babies whose mother is ICT positive
Procedure Best is narrow spectral blue lights (425- 475nm) White lamps (380-700nm) Distance from skin – 45cm Intensive PT – 15-20 cm Shield eyes & genitalia Change position once in every 2-4 hrs Level to be checked every 10-12 hrs Frequent temperature monitoring & daily weight
check
Side Effects
Immediate:i. Loose stoolsii. Dehydrationiii. Hypo or hyperthermiaiv. Rashesv. Bronze baby syndrome
Late:vi. Risk of skin malignanciesvii. Damage to intracellular DNAviii. Retinal damageix. Testicular damage
Exchange transfusion
• The procedure involves the incremental removal of the patient's blood and simultaneous replacement with fresh donor blood, saline or plasma
• Indications- infants with Rh isoimmunnisation include:
i. Cord bilirubin 5mg/ dl or moreii. Cord Hb 10g/ dl or less
Exchange transfusion
• Complications• Hypocalcaemia and Hypomagnesaemia - Citrate in
CPD blood• Hypoglycaemia• Metabolic alkalosis or acidosis• Hyperkelemia• CVS: overload and arrhythmias• Infections: HBV HIV• Haemolysis• Hypothermia, NEC.
Prevention
Breastfeeding
Case #1:• FT baby girl born at 40 weeks to
primi mother• BW 3200 g; APGAR 8,9• Pregnancy and delivery without
complications• Currently DOL #2 (48h of life)• Nurses noted that she looks like
this and call you to the Well-Baby Nursery to evaluate her:
Case #1:
• What else would you want to know?– How is she feeding? How is it going?– Is she stooling and voiding? How often?– What is her current weight?– How is she doing otherwise?– Does she have any risk factors?– Has she had her TcB checked?– Has she had blood bilirubin levels checked?
Case #1:• Her mother is breastfeeding her. She thinks it is going
well but this is her first baby and she is not sure if her milk is in yet. She is feeding for 20 minutes every 4 hours.
• Voided once and stooled several times since birth.• Current weight is 2850 g (about 11% less than BW).• She seems less active and is sleeping more today.• No known risk factors. Mother and baby are both B
positive.• Total/direct bilirubin is 18/1 mg/dL.
Case #1:
• What is your working diagnosis?
– BREASTFEEDING JAUNDICE
Case #1: • What would you do
next?– Initiate phototherapy – Monitor serial bilirubin
levels– Encourage increased
frequency of feedings (q 2-3h ATC) and consider supplementation prn
– Request lactation consult
Bhutani Curve: Phototherapy Indication
Breast feeding jaundice Breast milk jaundice
Incidence 5-10 % of newborn 2- 4 % of newborn
Etiology & pathogenesis Decrease intake of breast milk leads to increased enterohepatic circulation
Due to unknown( substance in breast milk blocks destruction of bilirubin
Day of appearance Similar to physiological jaundice 4 to 7 days of age
Duration of jaundice Less than 3 weeks 3 – 10 weeks. Bilirubin level may reach upto 20-30 mg/dl
Treatment Adequate breast feeding Not harmful
Aggravating factors Dehydration Nil
Case #2:• Late pre-term baby boy born
at 35 weeks• BW 2500g; Apgars 8,9• Pregnancy and delivery
without complications• Currently DOL #1 (12 h of life)• Nurses noted that he looks
like this and called you into Room 1 to evaluate him:
Case #2:
• What else would you want to know?– How is he feeding? How is it going?– Is he stooling and voiding? How often?– What is his current weight?– How is he doing otherwise?– Does he have any risk factors?– Has he had his TcB checked?– Has he had blood bilirubin levels checked?
Case #2:• He is taking Neosure formula 2 ounces q 2-3 hours.• Voided twice and stooled several times since birth.• Current weight is 2500 g (same as BW).• He is less active and sleeping more today.• Mother is O positive and baby is A positive.• Total/direct bilirubin is 18/1 mg/dL.• Coombs positive.
Case #2:
• What is your working diagnosis?
– ABO INCOMPATIBILITY
Case #2:• What would you do next?
– Exchange transfusion
Bhutani Curve: Phototherapy Indication Exchange Transfusion Indication
Prolonged jaundice
• Definition :• Persistence of significant jaundice for more
than 2 weeks in term
or More than 3 weeks in preterm babies
Causes of prolonged jaundice
Common:i. Inadequacy of breast feedingii. Breast milk jaundiceiii. Cholestasis
Rare causes:iv. Hypothyroidism v. Criggler-Najjar syndromevi. GI obstruction due to malrotationvii. Gilbert syndrome
Summary:• Hyperbilirubinemia is a common and potential
serious issue in neonates• Important to recognize and diagnose early in order
to initiate prompt treatment when possible