Neonatal Jaundice Flashcards
List the causes of unconjugated/indirect hyperbilirubinemia
o Physiologic jaundice (Factors related to immaturity)
o Breastfeeding failure jaundice (“Exaggerated physiologic jaundice”)
o Breast milk jaundice
o Hemolysis
o Hereditary defects of bilirubin conjugation:
• Gilbert’s Syndrome
• Crigler-Najjar Syndrome
Describe breastfeeding jaundice
(“Exaggerated physiologic jaundice”)
• In 1st week of life (peaks 3-5 days) = occurs early
• Common
• Usually resolves by 10 days
• Related to lower fluid intake and fecal excretion in breast-fed babies
Describe breast milk jaundice
- From some unknown factor in breast milk → decreased conjugation
- UGT1 inhibition
- Peaks at 2 weeks = occurs later
- Declines slowly
Gilbert’s Syndrome
o Hereditary defects of bilirubin conjugation
• Mutation in UGT-1A1 gene for bilirubin conjugation
• Leads to mild enzyme deficiency
Crigler-Najjar Syndrome
o Hereditary defects of bilirubin conjugation
• Rare
• Significant deficiency in UGT-1A1
• Leads to neurotoxicity → death
Complications of high levels of unconjugated bilirubin
High levels of unconjugated bilirubin → bilirubin neurotoxicity (Kernicterus)
• Free bilirubin = crosses BBB → deposits in basal ganglia → encephalopathy
• Initial signs: Lethargy, hypotonia, poor suck
• Progression: hypertonia, opisthotonus, high-pitched cry
• Later sequelae: sensorineural hearing loss, athetosis, dental dysplasia, limited upward gaze, developmental delays
List the causes of Conjugated/direct hyperbilirubinemia
Extrahepatic biliary atresia
Idiopathic neonatal hepatitis (30-35% cases)
Various inborn errors: • Galactosemai Tyrosinemia • Dubin-Johnson Syndrome • Rotor syndrome (error in hepatocyte cytoplasmic binding to glutathionS-transferase) • Alpha-1-Antitrypsin deficiency • Cystic fibrosis
Abnormal intrahepatic Bile ducts
• Alagille’s
• Caroli’s
Neonatal infections
• Sepsis
• UTI
• TORCH infections
Endocrine diseases
• Hypopituitarism
• Hypothyroidism
Iatrogenic
• TPN-associated cholestasis
Maternal drugs
• Carbamazepine
• Metamphetamine
Extrahepatic biliary atresia
30-35% of cases (most common cause)
Progressive inflammatory fibrosis of extrahepatic bile duct
• Cholestasis → inflammation → progressive degeneration of intra-hepatic ducts → biliary cirrhosis
Clinical presentation • Normal at birth Develop jaundice by 2 months: o Progressively acholic stools, choluria, HM o Weight gain slows down o Tbi ~6-10 mg%, 50-80% conjugated. o ALP, GGT greater than AST, ALT o Synthetic function OK ±vitamin K malabsorption
Evaluation: • Ultrasound: Gallbladder present? • Biopsy: see bile plugs and duct proliferation • Surgical exploration • Intraoperative cholangiogram
If untreated = fatal by 1 year
Treat: Kasai Procedure (porto-enterostomy)
• For best surgical outcome, need to diagnose EHBA by 7-8 weeks
Dubin-Johnson Syndrome
- Error in export into bile canaliculus
- Bilirubin retention
- Liver enzymes are normal
Alagille’s Syndrome
- Paucity of intrahepatic bile ducts
- Characteristic face (broad forehead, pointed mandible), vertebral anomalies (cleft in vertebral body = “butterfly vertebrae”), posterior embryotoxon, peripheral pulmonic stenosis (murmur); pigment on inner cornea near junction with iris
Hyperbilirubinemia Evaluation
History & exam
Timeline
• Urgent if develop jaundice within 1st 24 hours (higher risk of kernicterus, blood group incompatibility, hemolytic disease?)
• Icterus at >2 weeks always requires evaluation (conjugated hyperbilirubinemia?)
Degree of jaundice:
• Scleral jaundice at ~2 mg/dl
• Skin at ~5 mg/dl
• Progresses in descending (head → toe) pattern
Other factors:
• Feeding and elimination
• Weight compared to height
• Evaluate for sites of bleeding
Labs:
o Blood type/Coombs, CBC, total bilirubin
Bilirubin fractionation (unconjugated vs. conjugated) if:
• Ill-appearing infant
• Prolonged jaundice (>2 weeks)
• Development of acholic stools and dark urine (suggests biliary obstruction)
If conjugated hyperbilirubinemia = liver enzymes and INR
Imaging/other
o If conjugated hyperbilirubinemia = ultrasound (Usually no gallbladder in biliary atresia)
o Liver biopsy
o If suspect biliary atresia = exploratory laparotomy with cholangiogram
Differentiate between physiologic vs. pathologic jaundice in the newborn
Physiologic
o In 60% full-term; 80% of premature infants
o Increased bilirubin due to immaturity:
• Low conjugating activity
• Delayed excretion
• Increased reabsorption from intestine
o Onset after 36 hours of life
o Rate of increase < 5 mg/dl per day
o Peaks at 3-5 days
o Total bilirubin peaks 12-15 mg/dl (unconjugated)
o Clinical resolution by 1 week (full-term) or 2 weeks (pre-term)
o Otherwise healthy
o Resolves without intervention
o Note: a potentially severe disease may masquerade as physiological jaundice
Pathologic o Develops before 36 hours of age o Persists >10 days o Total bilirubin > 12 mg/dL o Pale stools, dark urine o Direct (conjugated) bilirubin > 1 mg/dL if total less than 5 OR 20% if total >5
Treatment for unconjugated hyperbilirubinemia
Goal: decrease bilirubin; prevent toxicity
Phototherapy
Blue light → isomerization of bilirubin to water soluble form
• Excreted in urine
Decide when to treat based off:
• Total bilirubin
• Postnatal age
• Risk group: gestational age, isoimmune hemolysis, G6PD deficiency, asphyxia, sepsis, acidosis, albumin less than 3, lethargy, temperature instability
Formula trial for breast milk jaundice
• Recheck after 2-3 days of formula-feeding (bilirubin should drop)
Exchange transfusions
• For infants with high risk of kernicterus (bilirubin greater than 20-25)
• Especially when hemolysis present
• When premature, may have lower cut-off (bilirubin 11-19)
Treatment for conjugated hyperbilirubinemia
Surgical or medical treatment of underlying condition
In extrahepatic biliary atresia = portoenterostomy (Kasai) procedure
• Attach segment of intestine to porta hepatis
• Try to reestablish biliary flow from liver and prevent cirrhosis
• Curative ~20% of cases
• Most require liver transplant in infancy or childhood
