1. Neonatal Hyperbilirubinemia

2. Jaundice
Yellowish discoloration of skin +/- sclera of newborns due to bilirubin
Affects nearly all newborns
Peak: hours, typically 5-6 mg/dL, usually does not exceed mg/dL
Pathologic: TSB exceeds age (in hours) specific 95th percentile according to Bhutani nomogram

3. Effects of hyperbilirubinemia
Bilirubin toxicity
Toxicity due to unbound (free) form
Focal necrosis of neurons and glia
Acute bilirubin encephalopathy
Chronic= kernicterus
Most often affects basal ganglia and brainstem nuclei
Movement disorders
Impaired upward gaze
Auditory abnormalities

4. Effects Bilirubin toxicity At risk when TSB > 25-30 mg/dL
Premature and sick infants
Albumin level
Drugs- silfisoxazole, moxalactam, ceftriaxone
Acidosis
Near term (35-37) weeks
Breast fed
Hemolytic disease
Discharge before 48 hours

5. Manifestations Phase one- 1st few days Phase two- end of 1st week
Lethargy, hypotonia, poor suck, high pitched cry
Phase two- end of 1st week
Irritable, hypertonia, retrocollis, opisthotonus
Phase three- after 1st week
Stupor, coma, shrill cry

6. Evaluation Transcutaneous bilirubin Total serum bilirubin
End-tidal carbon monoxide
Blood type, direct Coombs test
CBC, peripheral blood smear
Reticulocytes, G6PD screen
Serum albumin

8. Special circumstances
Jaundice in 1st 24 hours
Frequently due to hemolysis
Require immediate evaluation and close surveillance
Other reasons for increased bilirubin production
Cephalohematoma, extensive bruising, conjugation disorders

9. Management Phototherapy Mechanisms Irradiance
Structural isomerization
Photoisomerization
Photo-oxidation
Irradiance
Initiation if bilirubin exceeds the 95th percentile for hour-specific TSB concentration and risk category

10. Risk categories-phototherapy
Lower risk: at least 38 weeks gestation, no risk factors
>12 mg/dL at 24 hours, >15 mg/dL at 48 hours, >18 mg/dL at 72 hours
Medium risk: at least 38 weeks with risk factors or weeks without risk factors
>10 mg/dL at 24 hours, >13 mg/dL at 48 hours, >15 mg/dL at 72 hours
Higher risk: weeks with risk factors
>8 at 24 hours, >11 at 48 hours, >13.5 at 72 hours

11. Management Rate of decline of TSB Discontinuation Irradiance
Surface area
Initial TSB
Discontinuation
TSB level below 95th percentile for age
Is less than 13 mg/dL

12. Management Exchange transfusion
Hyperbilirubinemia unresponsive to phototherapy
Especially useful with immune-mediated hemolysis
Removal of circulating antibodies and sensitized RBCs
For TSB > 25 mg/dL
Presence of bilirubin neurotoxicity

13. Risk categories- exchange transfusion
Lower risk: at least 38 weeks gestation, no risk factors
>19 mg/dL at 24 hours, >22 mg/dL at 48 hours, >24 mg/dL at 72 hours
TSB/Albumin>8.0
Medium risk: at least 38 weeks with risk factors or weeks without risk factors
>16.5 mg/dL at 24 hours, >19 mg/dL at 48 hours, >21 mg/dL at 72 hours
TSB/Albumin>7.2
Higher risk: weeks with risk factors
>15 at 24 hours, >17 at 48 hours, >18.5 at 72 hours
TSB/Albumin>6.8

14. Summary Assess for jaundice every 8-12 hours Assess risk factors
If discharging, appropriate follow-up is necessary
Treatment should be initiated immediately upon identifying significant hyperbilirubinemia

15. Approach to the management of Hyperbilirubinemia in Term Newborn Infant

16. 2004 AAP Guidelines
Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation
Subcommittee on Hyperbilirubinemia
Pediatrics 2004; 114;

17. Prevention Breastfeeding Should be encouraged for most women
Separate AAP guidelines
8-12 times/day for 1st several days
Assistance and education
Avoid supplements in non-dehydrated infants
Do not decrease level & severity of hyperbili

18. Prevention
Ongoing assessments for risk of developing severe hyperbilirubinemia
Monitor at least every 8-12 hours
Don’t rely on clinical exam
Blood testing
Prenatal (Mom): ABO & Rh type, antibody
Infant cord blood
Mom not tested, Rh (-): Coomb’s, ABO, Rh
Mom O or Rh (+): optional to test cord blood

19. Laboratory investigation
Indicated (if bilirubin concentrations reach phototherapy levels)     
Serum total or unconjugated bilirubin concentration    
Serum conjugated bilirubin concentration   
Blood group with direct antibody test (Coombs’ test)
Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances)
    Complete blood count including manual differential white cell count     
Blood smear for red cell morphology
Reticulocyte count     
Glucose-6-phosphate dehydrogenase screen
  Serum electrolytes and albumin or protein concentrations

20. Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Nomogram for designation of risk in 2840 well newborns at 36 or more weeks' gestational age with birth weight of 2000 g or more or 35 or more weeks' gestational age and birth weight of 2500 g or more based on the hour-specific serum bilirubin values
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:
Copyright ©2004 American Academy of Pediatrics

21. Risk Factors for Severe Hyperbilirubinemia
Minor risk factors 
Bili in high intermed-risk zone
Gestational age 37–38 wk
Jaundice before discharge
Previous sibling with jaundice
Macrosomia infant with diabetic mother
Maternal age ≥ 25
Male
Decreased Risk
Bili in low-risk zone
≥ 41 wks gestation
Exclusive bottle feed
Black race
D/c from hospital > 72hrs
Major risk factors 
Predischarge bili in high-risk zone
Jaundice in 1st 24 hrs
Blood group incomp with + direct antiglobulin test, other known hemolytic disease (eg, G6PD deficiency)
Gestational age 35–36 wk
Previous sibling received phototherapy
Cephalohematoma or significant bruising
Exclusive breastfeeding
East Asian race

22. Discharge Assess risk Predischarge bili
Use nomogram to determine risk zone
And/or Assessment of risk factors
TSB Zone
Newborns (%)
% with TSB >95th %
High risk 6
39.5
High intermed
12.5
12.9
Low intermed
19.6
2.26
Low
61.8

23. Discharge Close follow-up necessary Individualize based on risk
Weight, % change from BW, intake, voiding habits, jaundice
Infant Discharge
Should be Seen by
< 24 hours
72 hours
24-48 hours
96 hours
48-72 hours
120 hours

24. Algorithm for the management of jaundice in the newborn nursery
Jaundice < 24 hours = pathologic; check TSB or TcB
Jaundice appears excessive for age = TSB or TcB
The need for and timing of a repeat bili depends on the zone in which TSB falls, age of infant
Interpret all bili levels according to infant’s age in hours
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:
Copyright ©2004 American Academy of Pediatrics

25. Phototherapy
Mechanism: converts bilirubin to water soluble form that is easily excreted
Forms
Fluorescent lighting
Fiberoptic blankets
Goal is to decrease TSB by 4-5 mg/dL or < 15 mg/dL total
Breastfed infants are slower to recover

26. Phototherapy Severe rebound hyperbilirubinemia is rare Intensive
Average increase is 1 mg/dL
Intensive
Special blue tube with light in blue-green spectrum
Close to infant
Expose maximum surface area

27. Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation
Use total bili
Risk factors = isoimmune hemolytic disease, G6PD deficiency, asphyxia, significant lethargy, temperature instability, sepsis, acidosis, or albumin < 3.0
Can use home phototherapy if no risk factors
Based on limited evidence
Use intensive phototherapy when TSB exceeds line
If TSB doesn’t decrease or rises strongly suggests hemolysis
If TSB > 25 or at level recommending exchange transfusion it is a med emergency and requires admission
Isoimmune hemolytic disease: IV gamma globulin (.50-1 g/kg over 2 hrs) if TSB rising on phototherapy or within 2-3 mg/dL of exchange transfusion recommendations. Can repeat dose in 12 hours. Shown to decrease need for exchange transfusion
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:
Copyright ©2004 American Academy of Pediatrics

28. Exchange Transfusion
Mechanism: removes bilirubin and antibodies from circulation and correct anemia
Most beneficial to infants with hemolysis
Generally never used until after intensive phototherapy attempted

29. Risk of Kirnicterus TSB level > 25-30 mg/dl Acidosis
Increased free bilirubin
low albumin, drug displacement
Blood-brain barrier disruption
prematurity, sepsis, ischemia

30. Kernicterus cases potentially correctable causes
 Early discharge (<48hrs) without f/u within 48 hrs
Failure to check bilirubin level if onset in first 24 hours
Failure to note risk factors
Visual assessment underestimate of severity
Delay in testing jaundiced newborns or treating elevated levels
Lack of concern for presence of jaundice or parental concern
Pediatrics 2001; 108:

31. Common Clinical Risk Factors for Severe Hyper-bilirubinemia
Jaundice in the first 24 hours
Visible jaundice at discharge
Previous jaundiced sibling
Near term gestation weeks
Exclusive breastfeeding
East Asian (4), Mediterranean (1), African origin (12) (G6PD deficiency), 19/61 kernicterus cases = G6PD
Bruising, cephalohematoma, birth trauma
Hemolysis risk, O + maternal blood type, sepsis 

32. Medications increasing bilirubin toxicity
Sulfisoxazole (displacement or G6PD hemolysis)
Ceftriaxone (displacement from albumin)

33. Trans cutaneous bilirubin
Older devices affected by skin pigmentation
Newer multi-wavelength spectral reflectance correlate 0.88 with the serum value,
example SpectRx, ± 3 mg/dl
? Confirm values > 40% per age
Carbon monoxide exhaled

34. Direct Coombs Testing Strongly positive: Negative or “weakly positive:Rh
Kell
Kidd
Duffy 
Negative or “weakly positive:
Anti-A  

35. Hemolysis consider present
Hct < 45%
Abnormal blood smear with 3-4+ spherocytes
Reticulocyte count is 4.5% in the first 72 hrs, or
Reticulocyte count is >1-2% in the first 1-2 wks

36. References
American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics ;114:
Johnson LH, Bhutani VK, Brown AK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr ;140:
American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Classification of recommendations for clinical practice guidelines. Pediatrics ;114:
Gartner LM, Herschel M. Jaundice and breastfeeding. Pediatr Clin North Am ;48:
Moyer VA, Ahn C, Sneed S. Accuracy of clinical judgment in neonatal jaundice. Arch Pediatr Adolesc Med ;154:
Ip S, Glicken S, Kulig J, Obrien R, Sege R, Lau J. Management of Neonatal Hyperbilirubinemia. Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Research and Quality; AHRQ Publication 03-E011
Bhutani VK, Johnson LH, Sivieri EH. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent hyperbilirubinemia in healthy term and near-term newborns. Pediatrics ;103:6-14.
American Academy of Pediatrics, Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Pediatrics ;108:
Mohammadh Khassawneh MD accessed online 2009