Transcript Neonatal Hyperbilirubinemia

Neonatal Jaundice
Prof. Sirota Lea
Department of Neonatology
Shnaider Children’s hospital
Physiologic Jaundice
Healthy infants
up to 12mg% in 3rd day; in premature,
5th day.
No hemolysis or bleedings
No underlying metabolic disease
Mechanism
Production:
Volemia,
RBC span (90 days)
Ineffective erythropoyesis
Turnover of non Hb heme proteins
Mechanism
Enterohepatic recirculation:
Glucuronidase
Bilirubin monoglucuronide
Intestinal bacteria
Intestinal motility and stooling
Mechanism
Bilirubin Uptake : ligandin
Conjugation : UDPG-T activity
Hepatic excretion of bilirubin
Neonatal Hyperbilirubinemia
Visible jaundice:
Adults: >2mg%
Newborns: >6mg
Up to 50% of all newborns may develop
jaundice
Source of Bilirubin
Metabolism of heme. 6-10 mg/kg/day. (adults 34mg/kg/day)
1gr Hemoglobine produces 34mg of bilirubin
75%: from old RBCs released from RES
25%: from ineffective erythropoyesis,
myoglobine, cytochromes, catalase, peroxidase.
Metabolism
Heme Oxygenase + O2
Heme
Biliverdin + CO + Fe
Biliverdin reductase
Indirect (unconjugated) bilirubin
Binds to albumin in plasma
Conjugation
Indirect bilirubin
Liver Uptake (binds to ligandin)
Endoplasmic reticullum
UDPG-T
Bilirubin
Mono and diconjugated bilirubin
Liver
Elimination
Enterohepatic recirculation
Urobilinoids
Stool
Gut
Beta glucuronidase
Bacteria
Jaundice: Physical examination
Blanch skin with a finger  Jaundice
Significant when appears at palms or below knees.
Transcutaneous bilirubinometer
Bruising, cephalohematoma, others.
Organomegaly
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.
Dermal Zone Bilirubin range (mg%)
1
4.5-8
2
5.5-12
3
8-16.5
4
11-18
5
> 15
Jaundice: Laboratory
Total serum bilirubin
Blood type, Rh, Coombs infant and mother
Smear (morphology and reticulocytes)
Hematocrit
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
Non Physiologic Jaundice
Onset at < 24 hs
Bilirubin  over levels for phototherapy
Bilirubin rise > 0.5 mg%/hr
Signs of underlying illness
Vomiting, lethargy, poor feeding,  weight
Age > 8 days in term or 15 days in premature
Non Physiologic Jaundice: Anamnesis
Familial:
G6PD, spherocytosis, metabolic, enzymes.
Siblings:
Immune, breast milk.
Pregnancy:
Infections, drugs, diabetes.
Delivery:
Trauma, cord clumping, asphyxia.
Bilirubin toxicity:
Cerebral Penetration:
As free indirect bilirubin or bound when disrupted BBB
Disrupted BB barrier
Hyperosmolarity
Anoxia
Hypercarbia
Prematurity
Bilirubin toxicity: Factors
Unbound indirect bilirubin
 Albumin concentration
1gr albumin binds 8.5mg bilirubin
Displacement from albumin site
FFA
Drugs: Sulfonamides
Correction of acidosis
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
Bilirubin toxicity: Chronic complications
Athetosis
Sensorial deafness
Limited upward gaze
Intellectual deficits
Dental dysplasia
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.
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
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
Treatment Options for Jaundiced
Breast-fed Infants
Observe
Continue breast-feeding; phototherapy
Supplement with formula with or without phototherapy
Interrupt breast-feeding; substitute formula
Interrupt breast-feeding; substitute formula; phototherapy
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
IHDN: Pregnancy Management
Coombs titers >1/16 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
IHDN: Newborn Management
Check immediately after birth
Hematocrit
Bilirubin
Blood type
50% will only need phototherapy
24% will be anemic and cord bilirubin >4mg%
 exchange transfusion
IHDN: Prevention
Anti D (Rh) immune globulin indications
At 28 weeks
within 72 hours since birth.
Procedures or suspected transplacental
hemorrhage.
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 (<24hs of life)
Many times Combs -, but there are antibodies
Blood smear: spherocytes
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
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
Treatment: Phototherapy mechanism
Structural isomerization:
Ciclization to lumirubin (irreversible)  bile
and urine
Fast excretion not reabsorption.
Related to dose of phototherapy
(intensity of light)
Treatment:
Phototherapy mechanism
Main Pathway
Bilirubin
Lumirubin
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: 13±1mg% in term, 10±1mg% in preterm
Check 12-24hs later for rebound
Phototherapy: Side effects
Increased water loss
Diarrhea
Retinal damage
Bronze baby, tanning
Mutations in DNA?  shield scrotum
Disturb of mother-infant interaction.
Exchange transfusion: Technique
Irradiated PC < 7 days + FFP. Warmed
Double of blood volume.
Open incubator, monitors
Route
UV: push-pull, over > 1hr
Artery-vein: Isovolumetric
Exchange transfusion:
Complications
Hypocalcemia-hypomagnesemia (CPD)
Hypoglycemia (monitor Dx after exchange)
Acid base disturbances
Hyperkalemia
Cardiovascular:
Embolizations, arrhythmia, perforation, arrest.
Exchange transfusion:
Complications
Bleeding
Thrombocytopenia, loss of factors.
Infections
Hemolysis
GVHD
Other
Fever, hypothermia, NEC?
Neonatal Jaundice:
Other 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
Management of Hyperbilirubinemia in
the Healthy Term Newborn*
Age,hours
TSB Level, m g/dL (pm ol/L)
Consider
Phototherapy
Phototherapy
<=24§
Exchange
Transfusion if
Intensive Photo
therapy Fails
Exchange
Transfusion and
Intensive
Phototherapy
...
...
...
...
25-48
>12 (170)
>15 (260)
>20 (340)
>25 (430)
49-72
>15 (260)
>18 (310)
>25 (430)
>30 (510)
>72
>17 (290)
>20 (340)
>25 (430)
>30 (510)
* TSB mdicates total serum bilirubin .
§ Term infants who are clinically jaundiced at <= 24 hours old are not
considered healthy and require further evaluation.
Diagnostic approach to neonatal
jaundice
Jaundice
Measure Bilirubin
Non physiologic
Blood type, Rh, Coombs
Hematocrit, Smear, Reticulocytes
Increased direct bili
Sepsis
TORCH
Biliary Atresia
Cholestasis
Inspissated Bi
Hepatitis
CF
Tyrosinosis
Galactosemia
Increased indirect bili
Coombs +
ABO
Rh
minor group
Coombs N or ¯Hematocrit
RC shape
Abnormal
Specific and non specific
Abnormalities
Normal
Hematocrit
Polycytemia
Bleedings
Enterohepatic
Metabolic
Drugs
Other