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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