Hyperbilirubinemia

Neonatal Hyperbilirubinemia

Jaundice• Yellow discoloration of skin due to

elevated serum bilirubin level

• > 5mg/dl in neonates

• > 2 mg/dl in older children

Bilirubin• Produced in the reticuloendothelial

system as the end product of heme catabolism

• Isomers: Z (cis) – lipid-soluble

E (trans) – water-soluble

• Sources: hemoglobin (75%), myoglobin, catalase, cytochromes, cyclooxygenase, guanyl cyclase

Hyperbilirubinemia in Neonates• Predisposing factors

– Increased RBC mass– Decreased red cell survival (70-90 days)– Immature hepatic function– Decreased hepatic blood flow– Breastfeeding

Pathophysiology

hemoglobin

biliverdin

binds with ligandin intracellularly

Cis-bilirubin

heme oxygenase

+ albumin

unconjugated bilirubin

Bilirubin + glucuronic acid

urobilinogen

UDPGTB-glucuronidase

enters hepatocyte

reabsorbed in small intestine

excreted

Kernicterus• Sequelae due to non-albumin bound

indirect bilirubin depositing on the basal ganglia at 15-20 mg/dl

• S/Sx: poor suck, hypotonia, extensor hypertonia, decreased sensorium, fever

• Also results to cerebral palsy with athetosis, oculomotor damage & high frequency hearing loss

• 10% mortality, 70% long-term morbidity

Kramer’s Classification (Cephalopedal Progression)

Zone Jaundiced Areas Serum Bilirubin (mg/dl)

I Head/Neck 6-8

II Upper trunk 9-12

II Lower trunk/Thigh 12-14

IV Arms/Legs/Elbows/Knees 15-18

V Hands/Feet >18

Neonatal JaundiceFactors PHYSIOLOGIC PATHOLOGIC

Onset >24 hour of life <24 HOL or >1 week

Duration <2 week >1 week (term)

>2 weeks (preterm)

Total Bilirubin <12mg/dl (term)

<15mg/dl (preterm)

>12mg/dl (term)

>15mg/dl (preterm)

Increase Rate of TB

>5mg/dl/day

Direct Bilirubin

>2mg/dl or 15% of TB

Signs & Symptoms

Vomiting, lethargy, poor suck, apnea

Physiologic JaundiceFactor BREASTFEEDING BREASTMILK

Onset 3rd-4th day of life 4th-6th day of life

Duration <1-2 week Peaks at 2nd-3rd week

<10-12 weeks

Pathophysiology Decreased milk intake increases enterohepatic circulation

Due to a compound in breastmilk which competitively inhibits glucuronyl transferase

Diagnostics• Total bilirubin, direct bilirubin, indirect

bilirubin

• Fetal and maternal blood typing

• Coomb’s test

• Hemoglobin, Hematocrit

• Reticulocyte count

• RBC morphology

• Urinalysis

• Liver UTZ

Management• Adequate hydration and nutrition

• Phototherapy

• Exchange transfusion– indicated if phototherapy is inadequate

or if at high risk of developing kernicterus

Phototherapy• Recommended range 5-10

mcw/nm/cm2• Photoisomerization – isomer is

converted to less toxic, polar isomer; excreted in bile

• Structural Isomerization – conversion to lumirubin, which is rapidly excreted, reaction is irreversible and not reabsorbed

• Photooxidation – conversion to small, polar products, excreted in urine

Phototherapy• Indications:

– Prophylactic. In preterm infants or those with hemolytic disease to prevent a significant rapid rise in serum bilirubin

– Therapeutic. In late-preterm and full-term infants to reduce excessive bilirubin levels and avoid development of kernicterus

Bhutani Chart

Bhutani Chart

Bhutani Chart

Bhutani Chart Summary

Phototherapy ends when…• TSB became low at levels: 13+/-

0.7mg/dl (term), 10.7+/-1.2mg/dl (preterm)

• No risk factors for reaching toxic levels of bilirubin

• Direct bilirubin level is increasing

Note: check total bilirubin 12-24hours after phototherapy

Side Effects of Phototherapy• Increased insensible water loss (add

10% to TFR while on phototherapy)• Watery diarrhea• Hypocalcemia in preterm• Retinal damage• Skin tanning• Bronze-baby syndrome• Mutations (shield genitalia)

Fluid Requirement• Add 10% more to the TFR because

there is increased insensible water loss due to phototherapy

Nutritional Requirement • Early feeding since patient is large

for gestational age

• LGA neonates are prone to hypoglycemia

• Hyperbilirubinemia result also from inadequate feeding