1. Ruben Bromiker Department of Neonatology Shaare Zedek Medical Center
Neonatal Jaundice
Ruben Bromiker
Department of Neonatology
Shaare Zedek Medical Center

2. Physiologic Jaundice Healthy infants
up to 12mg% in 3rd day; in premature, 5th day.
No hemolysis or bleedings
No underlying metabolic disease 5

3. Mechanism Production: Volemia, RBC span (90 days)
Ineffective erythropoyesis
Turnover of non Hb heme proteins 6

4. Mechanism Enterohepatic recirculation: Glucuronidase
Bilirubin monoglucuronide
Intestinal bacteria
Intestinal motility and stooling 7

5. Mechanism Bilirubin Uptake : ligandin Conjugation : UDPG-T activity
Hepatic excretion of bilirubin 8

6. Neonatal Hyperbilirubinemia
Visible jaundice:
Adults: >2mg%
Newborns: >6mg
Up to 50% of all newborns may develop jaundice

7. Source of Bilirubin
Metabolism of heme 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. 2

8. Metabolism Heme Biliverdin + CO + Fe Indirect (unconjugated) bilirubin
Heme Oxygenase + O2
Heme Biliverdin + CO + Fe
Biliverdin reductase
Indirect (unconjugated) bilirubin
Binds to albumin in plasma 3

9. Conjugation Indirect bilirubin Liver Gut
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 4

10. Jaundice: Physical examination
Blanch skin with a finger  Jaundice
Significant when appears at palms or below knees.
Transcutaneous bilirubinometer
Bruising, cephalohematoma, others.
Organomegaly 13

11. 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.

12. Jaundice: Laboratory Total serum bilirubin
Blood type, Rh, Coombs infant and mother
Smear (morphology and reticulocytes)
Hematocrit 14

13. 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 15

14. 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 9

15. Non Physiologic Jaundice: Anamnesis
Familial:
G6PD, spherocytosis, metabolic, enzymes.
Siblings:
Immune, breast milk.
Pregnancy:
Infections, drugs, diabetes.
Delivery:
Trauma, cord clumping, asphyxia. 10

16. Bilirubin toxicity: Disrupted BB barrier Hyperosmolarity Anoxia
Cerebral Penetration:
As free indirect bilirubin or bound when disrupted BBB
Disrupted BB barrier
Hyperosmolarity
Anoxia
Hypercarbia
Prematurity 16

17. Bilirubin toxicity: Factors
Unbound indirect bilirubin
 Albumin concentration
1gr albumin binds 8.5mg bilirubin
Displacement from albumin site
FFA
Drugs: Sulfonamides
Correction of acidosis 17

18. 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 18

19. 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 19

20. Bilirubin toxicity: Chronic complications
Athetosis
Sensorial deafness
Limited upward gaze
Intellectual deficits
Dental dysplasia 20

21. 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. 21

22. 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 11

23. 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 12

24. Treatment Options for Jaundiced Breast-fed Infants

25. 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

26. 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

27. 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

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

29. 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

30. Treatment: Phototherapy
Bilirubin best absorbs light at 450 hm.
The best is to provide it with blue light.
White range: hm also adequate.
Irradiation generates photochemical reaction in the extravascular space of the skin
A higher illuminated area increases effectiveness 22

31. 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 23

32. Treatment: Phototherapy mechanism
Structural isomerization:
Ciclization to lumirubin (irreversible)  bile and urine
Fast excretion not reabsorption.
Related to dose of phototherapy (intensity of light) 23

33. Treatment: Phototherapy mechanism
Main Pathway
Bilirubin
Lumirubin 24

34. Phototherapy: Technique
Fluorescents ,spots or biliblankets
More than 5mw/cm2 at hm
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

35. Phototherapy: Side effects
Increased water loss
Diarrhea
Retinal damage
Bronze baby, tanning
Mutations in DNA?  shield scrotum
Disturb of mother-infant interaction.

36. 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

37. Exchange transfusion: Complications
Hypocalcemia-hypomagnesemia (CPD)
Hypoglycemia (monitor Dx after exchange)
Acid base disturbances
Hyperkalemia
Cardiovascular:
Embolizations, arrhythmia, perforation, arrest.

38. Exchange transfusion: Complications
Bleeding
Thrombocytopenia, loss of factors.
Infections
Hemolysis
GVHD
Other
Fever, hypothermia, NEC?

39. 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

40. Management of Hyperbilirubinemia in the Healthy Term Newborn*

41. Diagnostic approach to neonatal jaundice
Measure Bilirubin
Non physiologic
Blood type, Rh, Coombs
Hematocrit, Smear, Reticulocytes
Increased direct bili
Increased indirect bili
Coombs +
Sepsis
TORCH
Biliary Atresia
Cholestasis
Inspissated Bi
Hepatitis CF
Tyrosinosis
Galactosemia
Coombs -
­Hematocrit
ABO Rh
minor group
Polycytemia
N or ¯Hematocrit
RC shape
Normal
Bleedings
Enterohepatic
Metabolic
Drugs
Other
Abnormal
Specific and non specific
Abnormalities