JC113 (Paediatrics) - A Jaundiced Child: Neonatal Jaundice Flashcards
Define neonatal jaundice
Define level of bilirubin for jaundice
Prevalence of neonatal jaundice
Neonatal period = first 28 days of life
Jaundice results from bilirubin accumulation in skin and sclera
neonates: jaundice is visible when it reaches 80-100 μmol/L (4.5-6.0 mg/dL)
Clinical jaundice within the first few days of life:
>50% of term infants
80% of preterm infants
Difference between jaundice with yellow color vs jaundice with yellow + green hue
Yellow – unconjugated bilirubin
Yellow with green hue – conjugated bilirubin
Normal physiology of bilirubin processing
heme metabolism:
RBC broken down in reticuloendothelial system:
Heme processed to biliverdin»_space; unconjugated bilirubin»_space; binds to albumin and enters hepatic circulation
Liver: Unconjugated bilirubin processed by UDGPT»_space; conjugated bilirubin
Large intestine: Conjugated bilirubin processed by Intestinal B-glucuronidase»_space; Unconjugated bilirubin for excretion or retenter enterohepatic circulation
Causes of physiological* neonatal jaundice
- Upstream:
- High Hb load in neonates (mean 17-19 g/dL)
- Short RBC lifespan with faster turnover (half-life 80 days) - Downstream: Immature liver metabolic function:
- Low ligandin = low uptake of bilirubin into liver cells
- Low conjugation enzyme activity (UDGPT) = poor conjugation function - Enterohepatic circulation:
- High amount of bilirubin recycled from gut when feeding is minimal in the first 2-3 days of life
Neonatal jaundice
- Typical time span
- Investigations for confirmation
Natural history:
Apparent from day 2-3 of life
Peaks at day 4-5
Subsides by day 7-14
Laboratory tests:
Unconjugated hyperbilirubinemia (commonly >170 umol/L)
Absent/minimal conjugated fraction
Normal hepatic ductal and parenchymal enzymes
Blood smear: no evidence of haemolysis (if yes»_space; watch out for kernicterus)
Severe NNJ (unconjugated hyperbilirubinemia)
main causes
A. Exaggeration of mechanisms responsible for normal neonatal physiologic jaundice
B. Specific underlying pathological conditions:
- Hemolysis of various causes***
- Inadequate feeding (higher enterohepatic circulation)
- Sepsis
C. Breast milk jaundice
Causes of neonatal hemolysis a/w severe NNJ
i. Immune causes, e.g. Rhesus incompatibility (Caucasian), ABO incompatibility
ii. Non-immune, e.g. G6PD deficiency
iii. Extravasation of blood and breakdown e.g. cephalhematoma, intraventricular hemorrhage, birth trauma with extensive bleeding
iv. Polycythemia (high RBC load and breakdown)
Differentiate underlying cause of breastmilk jaundice and breastfeeding jaundice
Breastmilk jaundice:
Certain ingredients in breast milk slow down conjugation e.g. nonesterified long chain fatty acids, glucuronidase, B-diol)
Presentation: more delayed
Breastfeeding jaundice
- Inadequate breastfeeding in first few days of life
- Less bilirubin excretion in stool
- Bilirubin deconjugated by intestinal B-glucuronidase and reabsorbed into blood (Higher enterohepatic circulation)
Presentation: First few days oflife
Breast milk jaundice
- Time span
- Effect on baby’s health
- Ix and Tx
Jaundice may be prolonged (i.e. beyond 14 days of life), even up to 2-3 months old
= benign condition: baby healthy otherwise, thriving
Ix: all unconjugated (do fractional bilirubin – direct and indirect)
Tx: self-limiting, advise mothers to continue breastfeeding
Complication of severe NNJ *****
Presentation in early, late and end-stage
Encephalopathy/ kernicterus:
- Unconjugated bilirubin can cross lipid layers and blood brain barriers
- Cause damage to neural tissue (bilirubin neurotoxicity)
Early: Hypotonia Hypertonia Opisthotonus (like severe tetanus) Poor feeding Lethargy Fever Convulsion
Late:
Extrapyramidal signs (acute dystonia, akathisia, Parkinsonism, tardive dyskinesia)
Hearing loss
End:
Death
Long-term morbidity: Dystonic cerebral palsy, Upward gaze palsy, Hearing loss
Risk factors of severe NNJ/ kernicterus
- Very high unconjugated bilirubin level in blood for a prolonged period
- High “free” bilirubin with insufficient albumin
Low albumin
Competitive binding to albumin (e.g. drugs) - Hemolysis
- Sepsis (albumin = negative acute phase reactant)
- Acidosis
- Hypoglycemia
- Prematurity
Management of severe NNJ and bilirubin toxicity
- Regularly screen for neonatal jaundice in first 2 weeks of life
- Monitor total bilirubin for severity (“free” bilirubin is not readily measurable)
- Intervene before plasma bilirubin reaches “risky” level:
Term: <20mg/dl (340 mol/L)
Preterm: lower
- Phototherapy, Mesoporphyrin, Exchnage transfusion, IvIg - Avoid risk factors for kernicterus: prolong hyperbilirubinemia, low albumin, acidosis, hypoglycemia, sepsis, hemolysis…
Conjugated hyperbilirubinemia in neonate
- Cut-off of bilirubin level
- Associated biochemical derangement
Direct bilirubin:
>2mg/dL (35μmol/L); or
>15% of total serum bilirubin
Associated with other evidence of hepatobiliary disease:
Elevated parenchymal/ductal enzymes
Deranged synthetic functions, e.g. deranged clotting factors, low albumin
Deranged detoxification functions, e.g. hyperammonemia
Deranged metabolic function, e.g. hypoglycemia
Causes of conjugated hyperbilirubinemia in Neonatal period
Neonatal period:
Neonatal hepatitis (etiological agents mostly unknown)
Obstructive: biliary atresia/ choledochal cyst
Metabolic diseases, e.g. citrin deficiency, galactosemia
Prolonged parenteral nutrition associated cholestasis
Syndromal disorders
Neonatal hemochromatosis (rare)
Causes of Conjugated hyperbilirubinemia beyond neonatal period
Viral hepatitis (A-E)
Drug-induced hepatotoxicity (e.g. paracetamol)
Wilson’s disease
Hemochromatosis, other metabolic diseases
Others (e.g. choledochal cyst, hereditary hyperbilirubinemia)
Cystic fibrosis
Biliary atresia in neonate
Presentation
Complication
Ix
Present during or beyond neonatal period with:
Prolonged jaundice (obstructive: yellowing of sclera with tinge of green hue)
Clay-coloured stool
Tea-coloured urine
Poor growth
Enlarged (or shrunken) liver and spleen / abdominal distension
Complication:
progressive obliterative cholangiopathy due to ductal obstruction:
- atresia (closure) of biliary tract
- continuing inflammation of duct epithelium
- hepatitis (hepatic parenchymal damage) and cirrhosis
Ix: conjugated hyperbilirubinemia
Biliary atresia in neonate
Management options
Outcomes
portoenterostomy (Kasai operation) - Best effect before 12 weeks
- Jaundice clear
- Jaundice recur due to liver failure
Paediatric liver transplant - refractory to Kasai operation
- 90% 10-year survival
Paediatric liver transplant
- Indications
- Source of liver
Indication:
- Mostly done for biliary atresia; failed Kasai operation
- Effects of biliary atresia
Progressive liver failure (no improvement)
Growth retardation
Recurrent cholangitis
Portal hypertension
Source:
LDLT (living donor) or DDLT (deceased donor)
Outline history taking questions for neonatal jaundice
- Compatible with natural course of “physiologic” jaundice? (jaundice within 24h of life is never physiological)
- Find pathological causes:
- Preterm, low birth weight
- Prenatal complications e.g. gestational DM causing chronic intrauterine hypoxia and polycythaemia
- Feeding habits and urine/ bowel output (TPN/ low feeding increases enterohepatic circulation)
- Blood group (ABO incompatibility and Rh)
- G6PD status
- Sepsis
- Age of life
- Birth trauma (extravasation of blood and breakdown, e.g. IVH, Cephalohematoma)
P/E for neonatal jaundice
Severity of jaundice:
Skin, sclera
Transcutaneous bilirubinometer: measure at forehead and sternum
General exam:
- Hydration
- Pallor (hemolytic anemia)
- Plethora (polycythemia)
Etiology:
- Cephalhematoma/bruises (birth trauma > increased red cell load)
- Size of liver and spleen - Hematosplenomegaly (hemolysis/ obstructive jaundice e.g. biliary atresia)
- Neurological exam - signs of neurotoxicity (kernicterus)
First-line investigations for neonatal jaundice
- Total serum bilirubin
- Fractional bilirubin (direct, indirect)
- LFT
- Blood smear (hemolysis)
Define low, medium and high risk NNJ by total serum bilirubin levels
Higher risk = more premature + risk factors (e.g. sepsis, hypoglycemia, hemolysis, hyperbilirubinemia, acidosis, birth trauma, low albumin) = lower ‘photo level’ i.e. give PDT at a lower bilirubin level than normal
Treatment options for neonatal jaundice
Unconjugated hyperbilirubinemia: A. Phototherapy B. Exchange transfusion C. IVIg - for Immune Hemolytic Jaundice D. Mesoporphyrins
Obstructive jaundice = surgical treatment by Kasai operation
Phototherapy for NNJ
- Indication
- MoA
- S/E
Indication: Serum bilirubin above photo level
Mechanism:
Photo- isomerisation of bilirubin to less toxic (hydrophilic) and readily excretable forms (in bile and urine)
Administration:
Wavelength: 460 ul (blue light spectrum)
Side effects Mild: Corneal/ retinal damage (use eye shield) Dehydration Skin rash (transient) Loose stool (transient)
Exchange transfusion for NNJ
- Indication
- MoA
- S/E
Indication:
- Plasma bilirubin reaches a dangerous level (e.g. >380 umol/l); or
- Child already shows signs of neurotoxicity
MoA
- exchange of patient’s blood to rapidly remove plasma bilirubin to safe level
- Insertion of central line
S/E: high risk, avoid if necessary by regular screening
