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