Neonatal Jaundice

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Neonatal Jaundice

• Ruben Bromiker
• Department of Neonatology
• Shaare Zedek Medical Center

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Physiologic Jaundice

• Healthy infants
• up to 12mg in 3rd day in premature, 5th day.
• No hemolysis or bleedings
• No underlying metabolic disease

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Mechanism

• Production
• Volemia,
• RBC span (90 days)
• Ineffective erythropoyesis
• Turnover of non Hb heme proteins

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Mechanism

• Enterohepatic recirculation
• Glucuronidase
• Bilirubin monoglucuronide
• Intestinal bacteria
• Intestinal motility and stooling

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Mechanism

• Bilirubin Uptake ligandin
• Conjugation UDPG-T activity
• Hepatic excretion of bilirubin

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Neonatal Hyperbilirubinemia

• Visible jaundice
• Adults gt2mg
• Newborns gt6mg
• Up to 50 of all newborns may develop jaundice

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Source of Bilirubin

• Metabolism of heme. 6-10 mg/kg/day. (adults
  3-4mg/kg/day)
• 1gr Hemoglobine produces 34mg of bilirubin
• 75 from old RBCs released from RES
• 25 from ineffective erythropoyesis, myoglobine,
  cytochromes, catalase, peroxidase.

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Metabolism
Heme Oxygenase O2
Heme Biliverdin CO Fe
Biliverdin reductase
Indirect (unconjugated) bilirubin
Binds to albumin in plasma
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Conjugation
Indirect bilirubin

• Liver Uptake (binds to ligandin)
  Endoplasmic reticullum
• Bilirubin Mono and
  diconjugated bilirubin

UDPG-T
Liver
Excretion
Gut

• Elimination
• Enterohepatic recirculation
• Urobilinoids

• Stool
• Beta glucuronidase
• Bacteria

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Jaundice Physical examination

• Blanch skin with a finger ? Jaundice
• Significant when appears at palms or below
  knees.
• Transcutaneous bilirubinometer
• Bruising, cephalohematoma, others.
• Organomegaly

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Dermal Zones of Jaundice
After leaving RES bilirubin binds to albumin,
initially with low affinity, thus bilirubin
precipitates in the proximal parts of the body
before it does it distally. So jaundice appears
first proximally, and later distally.
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Jaundice Laboratory

• Total serum bilirubin
• Blood type, Rh, Coombs infant and mother
• Smear (morphology and reticulocytes)
• Hematocrit

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Jaundice Laboratory

• Antibody identification
• Direct bilirubin
• When more than 2 weeks old or signs of
  cholestasis
• If prolonged
• LFT, TORCH, sepsis work-up, metabolic, thyroid
• G6PD

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Non Physiologic Jaundice

• Onset at lt 24 hs
• Bilirubin ? over levels for phototherapy
• Bilirubin rise gt 0.5 mg/hr
• Signs of underlying illness
• Vomiting, lethargy, poor feeding, ?? weight
• Age gt 8 days in term or 15 days in premature

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Non Physiologic Jaundice Anamnesis

• Familial
• G6PD, spherocytosis, metabolic, enzymes.
• Siblings
• Immune, breast milk.
• Pregnancy
• Infections, drugs, diabetes.
• Delivery
• Trauma, cord clumping, asphyxia.

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Bilirubin toxicity
Cerebral Penetration As free indirect bilirubin
or bound when disrupted BBB

• Disrupted BB barrier
• Hyperosmolarity
• Anoxia
• Hypercarbia
• Prematurity

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Bilirubin toxicity Factors

• ?Unbound indirect bilirubin
• ? Albumin concentration
• 1gr albumin binds 8.5mg bilirubin
• Displacement from albumin site
• FFA
• Drugs Sulfonamides
• Correction of acidosis

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Bilirubin toxicity Kernicterus
Neuronal injury yellow staining of brain ?
incidence in hemolytic disease (especially RH)
Localization

• Basal ganglia
• Cranial nerve and cerebral nuclei
• Hippocampus
• Anterior horn of spinal cord

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Bilirubin toxicity Acute encephalopathy

• I) Hypotonia, lethargy, high pitched cry, poor
  suck
• II) Hypertonia of extensor muscles
• opistotonus, rigidity, oculogyric crises,
  retrocollis
• III) Return of hypotonia after 1 week

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Bilirubin toxicity Chronic complications

• Athetosis
• Sensorial deafness
• Limited upward gaze
• Intellectual deficits
• Dental dysplasia

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Bilirubin toxicity

• Healthy full-term infants
• Abnormality in ABR
• Hypotony reverses with ? bilirubin levels
• Very rarely kernicterus
• Low birth weight infants
• Damage most probably due to accompanying factors
  than to high bilirubin.

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Breast Feeding Jaundice

• Bilirubin ? after 4 days of age. Healthy infants
• Resolves after holding breast milk for 1-2 days
• Presentation
• Early 2-4 days of age
• Late after 4 days of age

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Breast Feeding Jaundice Mechanism

• Interference with hepatic conjugation
• Beta glucuronidase in milk
• Reduced bacterial colonization of gut
• ?Caloric intake ? ?intestinal motility ?
  ?recirculation
• FFA suggested to reduce bilirubin metabolism

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Treatment Options for Jaundiced Breast-fed Infants
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Isoimmune hemolytic disease of the newborn

• Rh , or minor types (Kell, Duffy, E, C,c)
• 15 of people are Rh-
• Coombs
• Maternal sensitization d/t previous pregnancy,
  transfusion, amniocentesis, abortion

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IHDN Pregnancy Management

• Coombs titers gt1/16 or previous history of severe
  disease ? Amniocentesis for optical density
• High levels, and clinical signs of hydrops ?
  Intrauterine transfusion
• Intraperitoneal, intravascular or intracardiac
• Repeated transfusions ? switched fetal blood type

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IHDN Newborn Management

• Check immediately after birth
• Hematocrit
• Bilirubin
• Blood type
• 50 will only need phototherapy
• 24 will be anemic and cord bilirubin gt4mg ?
  exchange transfusion

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IHDN Prevention

• Anti D (Rh) immune globulin indications
• At 28 weeks
• within 72 hours since birth.
• Procedures or suspected transplacental hemorrhage.

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ABO hemolytic disease of the newborn

• 15 of pregnancies mother O infant A or B
• 20 will develop significant jaundice
• 10 will need phototherapy.
• Presentation
• Early jaundice (lt24hs of life)
• Many times Combs -, but there are antibodies
• Blood smear spherocytes

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Treatment Phototherapy

• Bilirubin best absorbs light at 450 hm.
• The best is to provide it with blue light.
• White range 380-700 hm also adequate.
• Irradiation generates photochemical reaction in
  the extravascular space of the skin
• A higher illuminated area increases effectiveness

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Treatment Phototherapy Mechanism

• Photoisomerization
• Natural Isomer 4Z,15Z ? 4Z,15E hydrosoluble ?
  blood ? biliar secretion (unconjugated)
• Slow excretion and fast reisomerization
  ? reabsorbed.
• Photooxydation Small polar products. Slow

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Treatment Phototherapy mechanism

• Structural isomerization
• Ciclization to lumirubin (irreversible) ? bile
  and urine
• Fast excretion not reabsorption.
• Related to dose of phototherapy (intensity of
  light)

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Treatment Phototherapy mechanism
Main Pathway
Bilirubin
Lumirubin
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Phototherapy Technique

• Fluorescents ,spots or biliblankets
• More than 5mw/cm2 at 425-475hm
• Naked , covering eyes
• Increase fluids 10-20
• Check bilirubin every 12-24hs
• Stop 131mg in term, 101mg in preterm
• Check 12-24hs later for rebound

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Phototherapy Side effects

• Increased water loss
• Diarrhea
• Retinal damage
• Bronze baby, tanning
• Mutations in DNA? ? shield scrotum
• Disturb of mother-infant interaction.

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Exchange transfusion Technique

• Irradiated PC lt 7 days FFP. Warmed
• Double of blood volume.
• Open incubator, monitors
• Route
• UV push-pull, over gt 1hr
• Artery-vein Isovolumetric

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Exchange transfusion Complications

• Hypocalcemia-hypomagnesemia (CPD)
• Hypoglycemia (monitor Dx after exchange)
• Acid base disturbances
• Hyperkalemia
• Cardiovascular
• Embolizations, arrhythmia, perforation, arrest.

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Exchange transfusion Complications

• Bleeding
• Thrombocytopenia, loss of factors.
• Infections
• Hemolysis
• GVHD
• Other
• Fever, hypothermia, NEC?

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Neonatal JaundiceOther treatments

• Phenobarbital ? conjugation
• Oral agar ? enterohepatic circulation
• Metalloporphyrins inhibit bilirubin production.
• Competitors of heme oxygenase
• IVIGg inhibits hemolysis.
• Binds to FC receptor of reticuloendothelial cells

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Management of Hyperbilirubinemia in the Healthy
Term Newborn
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Diagnostic approach to neonatal jaundice
Jaundice
Measure Bilirubin
Non physiologic
Blood type, Rh, Coombs Hematocrit, Smear,
Reticulocytes
Increased direct bili
Increased indirect bili
Coombs
Coombs -
Sepsis TORCH Biliary Atresia Cholestasis Inspissat
ed Bi Hepatitis CF Tyrosinosis Galactosemia
Hematocrit
ABO Rh minor group
Polycytemia
N or Hematocrit
RC shape
Normal
Bleedings Enterohepatic Metabolic Drugs Other
Abnormal
Specific and non specific Abnormalities