Hyperbilirubinemia
Case 1
• 5 day old former term male infant born to a
23 y.o. G1P0->1 woman. Is exclusively
breastfeeding. Has total bilirubin of 25,
direct is 0.7. Both mother and baby are O+,
and coombs is negative.
• Phototherapy is started and baby is fed, 6
hours later the total bilirubin level is 19.
• Breastfeeding consult is done.
Physiologic Hyperbilirubinemia
• Increased production
– Short RBC lifespan
– Increased shunt bilirubin
• Decrease clearance
– Portal vein shunting via ductus venosus
• Decreased conjugation
– Decreased UDPGA synthesis
– Decreased UDPG transferase
• Increased enterohepatic circulation
– High concentration of bilirubin in
meconium
– Decreased bowel motility
Hyperbilirubinemia: Elevation in disease states
• Undersecretion
• Overproduction
– Hemolysis
• Isoimmunization
• Genetic
– Sequestered Blood
– Polycythemia
– Increased
Enterohepatic
Circulation
• Bowel obstruction
• Intestinal
hypomotility
– Decreased conjugation
• Congenital
– Impaired hepatic transport
• Congenital
• Liver disease
– Biliary obstruction
• Mixed
– Infections
• Congenital infections
• Bacterial sepsis
– Prematurity
– Infant of a Diabetic Mother
– Hypothyroidism
Bilirubin Neurotoxicity
• What is kernicterus?
– Yellow staining of the brain
– Neuronal necrosis microscopically
• Getting bilirubin from the blood to the brain
cell isn’t easy
• “The numbers” keep changing
• Bilirubin encephalopathy vs. minor CNS
deficits
Clinical Features of Kernicterus
•
Acute
–
–
–
•
Phase 1 (first 1-2 days): poor sucking, stupor,
hypotonia, seizures
Phase 2 ( mid first week): hypertonia of extensors,
opisthotonus, retrocollis, fever
Phase 3 (after first week): hypertonia
Chronic
–
–
First year: hypotonia, active DTRs, obligate tonic
neck refles, delayed motor skills
After first year: movement disorders (choreoathetosis,
ballismus, tremor), upward gaze, sensorineural
hearing loss.
Vigintiphobia*: Fear of “20”
• Based on retrospective analysis of infants
with hemolytic Rh disease…in the dark
ages before intrauterine transfusion.
– Hsia, et al. NEJM 1952;247:668-71
– Mollison and Cutbush. Blood 1951:777-88
*Term coined by the late Frank Oski, MD
% with Kernicterus
Serum Bilirubin Level and Kernicterus in 229
Infants with Erythroblastosis
Hsia, et al. NEJM 1952;247:668-71
100
90
80
70
60
50
40
30
20
10
0
<5
6-15
16-30
Serum Bilirubin
>31
AAP Guidelines for
Hyperbilirubinemia - 2004
• AMERICAN ACADEMY OF PEDIATRICS
CLINICAL PRACTICE GUIDELINE
Subcommittee on Hyperbilirubinemia
Management of Hyperbilirubinemia in the
Newborn Infant 35 or More Weeks of
Gestation
PEDIATRICS Vol. 114 No. 1 July 2004
Prevention of Kernicterus:
Identifying infants at risk for Hyperbilirubinemia
• Prenatal maternal blood type and antibody screen
• Blood type and direct coombs on the baby
– Or type only babies of:
• Rh negative mothers (necessary for Rhogam eval)
• Other antibody screen positive
• O mothers (for ABO incompatibility), or hold cord blood 5-7
days for testing
• Good follow up and check bilirubin levels
Risk Factors Without Hemolysis*
•
•
•
•
•
•
•
•
•
Jaundice in first 24 hours
Visible jaundice before discharge
Previous jaundiced sibling
Gestation 35-38 weeks
Exclusive breastfeeding
East Asian Race
Bruising/cephalohematoma
Maternal age >25 years
Male sex
*AAP subcommittee on Neonatal Hyperbili, Pediatrics,
September 2001
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;114:297-316
Copyright ©2004 American Academy of Pediatrics
4 Newborn Hyperbilirubinemias
• Exaggerated physiologic?
– By exclusion
• Lack of Breast Milk Jaundice
– Feeding History
• Prematurity
– Assess maturity, review dating
• Hemolytic jaundice (ABO, DCcEe, et al)
– Review prenatal and newborn labs
Evaluation of Hyperbilirubinemia
• Feeding history critical
• Assess breastfeeding
– Sucking, swallowing, satisfaction, decrease in
breast size
– Stools (color and frequency)
– Urine output
– Weight loss (<10% at 5-7 days)
– 3-5 day office visit
Evaluation of Hyperbilirubinemia
•
•
•
•
Mother’s blood type and antibody screen
Baby’s blood type and Direct Coombs
CBC, reticulocyte count (hemolysis)
Total and Direct Bilirubin
– Remember: “One bilirubin leads to another”
• Head to toe progression
• Transcutaneous bilirubin meter
Evaluation of Hyperbilirubinemia
• Head to Toe progression: Is it reliable?
LI Kramer. AJDC. 1969;118:454-458
Breast Feeding (lack of) Jaundice
• Gradual increase in bilirubin
– Presentation toward end of first week of life
• Clues are all in the feeding history
• No reported case of kernicterus(?) in
healthy term infants
– Even with levels of up to 30
– However, you must treat!?
Breast Feeding (lack of) Jaundice
No reported case of kernicterus?*
– Kernicterus in Otherwise Healthy, Breast-fed
Term Newborns. Maisels & Newman.
Pediatrics 1995;96:730-733
• 6 patients
• 4-10 days of age
• Bilirubin levels 39-50
Jaundice of Prematurity
• Jaundice appears at a level of 6-8
• No relationship between kernicterus at
autopsy and bilirubin level
• So if they are jaundiced treat them with
phototherapy until it resolves
ABO Incompatibility: “UCLA Protocol”
Age(h)
Bilirubin Level
Treatment
<12
<10
>10
<12
>12
<14
>14
>15
Observe
Phototherapy
Observe
Phototherapy
Observe
Phototherapy
Phototherapy
<18
<24
>24
Rapid rise, then a plateau
Osborn, et al. Pediatrics 1984;74:371-4
Non-ABO Hemolytic Jaundice
• Rho is the same as “D”
• Don’t ignore: C, c, E, e, Duffy, Kell, Lewis…
• Rapid rate of rise:
– Jaundice in the first 24 hours is abnormal
– Bilirubin level >10 in first 24 hours is abnormal
– Rate of rise >0.5 mg/dL/h
• Coombs test
– Detects IgG antibodies on the baby’s RBCs
• Must keep bilirubin <20
Management of Hyperbilirubinemia
• Improve feeding
• Phototherapy
• Exchange Transfusion
Management of Hyperbilirubinemia
• Deal with feeding issues
– Reverse catabolism and decrease
enterohepatic circulation
– Lactation consultation
– Don’t supplement with water or
dextrose water
– For Non-preterm and non-hemolytic
jaundice
Guidelines for phototherapy in hospitalized infants of 35 or more weeks'
gestation
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Copyright ©2004 American Academy of Pediatrics
Phototherapy
• Fast application, available
everywhere
• Use “blue light” 420-475
nm with spectral irradiance
of at least 20 uW/cm2/nm
• All that is needed for most
preemies, physiologic/
breast feeding jaundice,
most ABO incompatibility
• Assess effectiveness of
therapy
Phototherapy
• Intensive Phototherapy
– Multiple lights for surface coverage
– With a light blanket
– Put lights close to baby for high radiance
• Intensive phototherapy failing to lower the
bilirubin level suggests:
– Hemolytic disease
– Some other pathologic process
– Weak lights, baby out from under too often
Management of Hyperbilirubinemia
• Exchange Transfusion
– Reserve for hemolytic disease
with bilirubin >20
– Those unresponsive to intensive
phototherapy with bilirubin >25
Guidelines for exchange transfusion in infants 35 or more weeks' gestation
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Copyright ©2004 American Academy of Pediatrics
Case 2
• 6 day old term male born at home to a G6P5->6
woman. Noted to be jaundiced on 3rd day of life.
On day of admit had apneic/cyanotic episode. At
local ED, total bili was 42.9 with direct of 4.4 and
was coombs +. Baby was opisthotonic with
tongue thrusting. 2 exchange transfusions and
aggressive phototherapy performed. Total bili
down to 16 after first exchange. Baby died of
kernicterus several months later.
Case 3
• 8 day old former 36 week female born to a
G4P2->3 woman with gestational diabetes.
Brought to clinic with 22% wt loss. Total
bili 28.5 with direct of 0.9. Na 178.
Coombs -. Hydrated and aggressive
phototherapy. 4 hours after admit bili down
to 22. Feeding issues addressed and baby
discharged home doing well.
Case 4
• 19 day old former term male recovering
from extensive subgaleal hematoma. Has
Total bilirubin level of 53.8. Treated with
phototherapy only.
• Does he develop kernicterus?
• No, he has a direct bilirubin fraction of
37.0. (so, unconjugated fraction is only
16.2)