Transcript Neonatal Hyperbilirubinemia

Neonatal
Hyperbilirubinemia
Topic Sections
General
Information
Screening Techniques
Treatment
Follow-up Care
Systematic Prevention of Kernicterus
Presentation Objectives
Following the presentation, discussion and reading, the participant will be able to:
 Describe the most common causes of neonatal hyperbilirubinemia;
 Differentiate between physiologic and pathologic jaundice;
 List 5 factors which increase an infants risk of excessive hyperbilirubinemia;
 Discuss the differences between breast milk jaundice and breastfeeding
jaundice;
 Demonstrate accurate lactation assistance to mothers exclusively
breastfeeding;
 Identify signs of worsening Acute Bilirubin Encephalopathy;
 Describe the components of a systematic evaluation, universal screening and
assessment;
 Implement hyperbilirubinemia decision making nomogram with infants 35 weeks
gestation or more;
 Describe nursing responsibilities when caring for an infant receiving
phototherapy;
 Provide discharge teaching regarding the risk of excessive hyperbilirubinemia;
 Describe appropriate follow-up for infants discharged at less than 72 hours of
age; and
 List 5 root causes of excessive hyperbilirubinemia and 2 interventions to
prevent each.
General Information
Overview
Most newborn infants experience some degree of
jaundice
 Most jaundice is benign, but because of the
potential for bilirubin toxicity, newborn infants
must be monitored to identify those at risk for
excessive hyperbilirubinemia, treated
appropriately and followed-up by experienced
perinatal health care professionals.
 125 case reports have been filed since 1982. This
represents an under-reporting since Acute
Bilirubin Encephalopathy and Kernicterus are not
mandatory reporting diagnosis and many
providers do not diagnose these problems.

Neonatal Intensive Care Vol3,June 2000
Definitions
 Hyperbilirubinemia is an increase in the serum bilirubin
characterized by jaundice
 Bilirubin
 Unconjugated (indirect acting)
 Conjugated (direct acting)
 Jaundice is an yellowish
discoloration of the skin,
sclera and mucous membranes which is rarely
perceptible until the serum
bilirubin level exceeds 7.0 mg/dl
 Acute Bilirubin Encephalopathy: clinical nervous
system findings caused by bilirubin toxicity
 Kernicterus: chronic, permanent clinical sequelae of
bilirubin toxicity
Hyperbilirubinemia
Types of Hyperbilirubinemia
 Physiologic
 Pathologic
 Hemolytic Disease
– Rhesus Incompatibilities
– ABO Incompatibilities
 Neonatal Sepsis
 “Breast Milk” Jaundice
Hyperbilirubinemia
Physiologic Jaundice
 increase
in bilirubin by the second day of
life
 declines by the fifth day of life
 onset and resolution maybe delayed in
premature infants (5 and 14 days,
respectively)
Hyperbilirubinemia
Pathologic Jaundice
Apparent jaundice in the first 24 hours of life
 Total serum bilirubin levels increasing by more than
5 mg/dl per day
 Total bilirubin levels > 12.5 to 15 mg/dl
 Direct (conjugated) levels >1.5 - 2.0 mg/dl
 Persistent jaundice (beyond the first week of life in
the full term infant or second week in the preterm
infant)

 Hepatitis, biliary atresia, Down syndrome,
hypothuroidism, breast milk inhibitors, etc.
Neonatal Jaundice
Predominant Factors
Gestation, Feeding, Weight loss, Race
Increase Unconjugated (Indirect) Bilirubin
Increased formation / synthesis
Decreased uptake
Decreased conjugation
Decreased elimination
Increase Conjugated (Direct) Bilirubin
Decreased excretion of bilirubin Mono/Diglucuronide
Unconjugated Hyperbilirubinemia

Synthesis
 Overload
– Polycythemia
– Organ hemorrhage
– Swallowed maternal blood
 Hemolysis
–
–
–
–
Rh, ABO, others
Abnormal RBC morphology
RBC enzyme deficiencies
Sepsis
Abnormal hepatic conjugation and secretion
 Conjugation: Type I, II Crigler-Najar
 Secretion
- Hypothyroidism
- Galactosemia
- Rare metabolic causes
Unconjugated Hyperbilirubinemia
Increased Enterohepatic Circulation
 Pyloric stenosis
 Small/Large Bowel Obstruction
Prematurity
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Decreased glucoronyl transferase in liver
Decreased serum albumin
Hemolysis
Sepsis
Hypoxemia
Hypothermia
Drug therapy
Hyperbilirubinemia
Bilirubin - Albumin Binding: Conjugation
 conjugated bilirubin can not pass the
blood-brain barrier
 factors preventing conjugation
 prematurity
 hypoproteinemia
 acidosis (respiratory or metabolic)
 neonatal depression
 medications: oxytocin, sulfa, diazepam
 exchange transfusion
Bone marrow
RBCs
Hgb
RETICULOENDOTHELIAL
SYSTEM (RES)
Hgb
heme
oxygenase
Globin
+
Heme
Globin
Biliverdin
Heme precursors
Myoglobulin
Non-hgb heme proteins
Biliverdin
reductase
Kidney
Bilirubin
Fe
+
Por phogens
Liver
Fe
SHUNT PATHWAY
Bilirubin-Albumin Complex
uptake
ENTEROHEPATIC CIRC
Cytoplasmic
protein
binding
Smooth
endoplasmic
retic ulum
Conj ugated
bilirubin
Urine
urobilinogen
excretion
Hydrolysis
Bilirubin
Intestine
Urobilinogen
Stercobilin
Breast Feeding and Jaundice
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Breastfeeding is considered one of the most important risk
factors for hyperbilirubinemia. Exclusive breastfeeding is
most strongly associated with increased risk of jaundice
Breast fed infants are 3 times more likely to have
TSB >12mg/dL than formula fed infants
Bilirubin levels peak later in breastfed infants
1/3 of all breastfed infants are clinically jaundiced beyond
2 weeks of age
Despite the increased risk, exclusive breastfeeding is still the
recommended feeding choice of the AAP
Goal is to optimize breastfeeding, hydration and nutrition
while observing for signs of excessive hyperbilirubinemia
Breast Feeding and Jaundice
 Breast Feeding Jaundice (physiologic)
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Early onset
Significant institutional variation
Frequency and effectiveness of nursing
“Starvation/Dehydration”
Breast Milk Jaundice (dysfunctional)
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Later onset (10-14 days)
Universal
Familial
Gaining weight, thriving
Prolonged (~ 2-3 months)
Gradual Decline
Differences in Total Serum Bilirubin Levels by Feeding Method
Number of Infants
140
Breast
Bottle
120
100
80
60
40
20
0
0
2
4
6
8 10 12 14 16 18
Maximum Total Bilirubin Concentration mg/dl
Is Breastfeeding Really Favoring Early Neonatal Jaundice?
n= 2174,  37wks
 TSB in jaundiced infants during first days of life
 Type of feeding, method of delivery,Wt loss,
maternal and neonatal risk factors assessed
 5.1% of infants exceeded bilirubin levels of
12.9mg/dL
 Average Bilirubin Peak Levels

 Breastfed exclusively: 10.3 mg/dL +/- 2.5
 Mixed feedings: 10.8 mg/dL +/- 2.2
 Bottle-fed exclusively: 11.0 mg/dL +/- 4.5
G. Bertini,MD; C.Dani,MD; M. Tronchin,PhD;F. Rubalteli,MD
PEDIATRICS Vol.107 March 2001
Is Breastfeeding
Really Favoring
Early Neonatal
Jaundice?
G. Bertini,MD; C.Dani,MD; M. Tronchin,PhD;F. Rubalteli,MD
PEDIATRICS Vol.107 March 2001
Support for Breastfed Infants

Support optimal breastfeeding
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Infant to breast immediately after birth
Infant and mothers remain physically together 24 hours a day
Breastfeeding 8-12 times per day
Avoid supplementation unless medically indicated, ordered by physician and
consented to by mother
 Educate mother on signs of effective breastfeeding: good latch, audible
swallows, changes in breast after feeding, appropriate voiding and stooling
for age in days, appropriate weight changes (total weight loss < 7%, regain
birthweight by 5-7 days of life, gaining 20-30 grams/day after return to
birthweight)
 Provide lactation consultation, referrals and support


Observe for signs of hyperbilirubinemia and screen appropriately
If clinical course requires supplementation or interruption of
breastfeeding ensure maintenance of mothers milk by regular emptying
of the breast. Do not supplement with water or dextrose water. Consider
supplementation with expressed breast milk or formula.
Conjugated Hyperbilirubinemia
Cause
 Hepatocellular disturbance
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Primary Hepatitis
Toxic Hepatitis
Hematologic Disorders
Metabolic disorders
Ductal disturbance
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Extra/Intra Hepatic Biliary Atresia
Alagille Syndrome
Cystic Disease
Bile plug syndrome
Tumors of the liver and biliary tract
Conjugated Hyperbilirubinemia
Evaluation
Consider transfer to NICU and consultation with
Neonatologist, Gastrenterologist, Hematologist
 Liver function tests
 Hematologic tests
 Tests for infectious Disease
 Urine tests
 Liver Biopsy
 Ultrasound

Acute Bilirubin Encephalopathy (ABE)

Acute clinical nervous system manifestations of bilirubin toxicity
Early
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
Intermediate (anecdotal evidence suggests emergent exchange
transfusion at this stage may reverse the CNS changes)
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
Severe jaundice
Lethargy
Hypotonia
Poor suck
Moderate stupor
Irritability
Hypertonia: backward arching the neck (retrocollis) or the truck (opisthotonus)
Fever
High-pitched cry
Hypertonia alternating with drowsiness and hypotonia
Advanced (CNS damage is most likely irreversible at this point)
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Pronounced retrocollis-opisthotonus
Shrill cry
No feeding
Apnea, deep stupor to coma
Fever
Seizures, Death
Kernicterus
Chronic, permanent clinical sequelae of bilirubin toxicity
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Resulting from deposits of unconjugated bilirubin within the
brain.
Visualized as yellow staining of basal ganglia,
hippocampus, geniculate bodies, brain stem nuclei and
cerebellum
Causing neuronal necrosis
Bilirubin levels at which kernicterus occurs vary depending
on the presence of hemolytic disease and gestational age
No “safe” levels of bilirubin have been identified
Thought to be highly preventable in most cases
Kernicterus
Full-Term: associated with severe hyperbilirubinemia
 Preterm: may occur at low bili levels
 Risk Factors

 Peak bilirubin level
 Duration of hyperbilirubinemia
 Bilirubin: Albumin ratio

Signs and symptoms
 Early signs as seen in Advanced ABE are possible
 Late Signs
–
–
–
–
–
Athetoid cerebral palsy
Auditory dysfunction
Dental enamel dysplasia
Paralysis of the upward gaze
Less frequently: Intellectual and other handicaps
Screening & Evaluation
Risk Factors for Severe Hyperbilirubinemia
Jaundice in first 24 hrs of life
 Previous jaundiced sibling with phototherapy
 Visible jaundice before discharge
 35-38 weeks gestation
 Exclusive breastfeeding
 East Asian race
 Cephalhematoma, Bruising
 Maternal age  25y
 Male sex

Assessment
 Suggest
hemolytic disease
 Family history
 Jaundice < 24hrs
 Bilirubin > 0.5mg/dL/hr
 Pallor, hepatosplenomegaly
 Rapid  after 24-48hrs (G6PD)
 Ethnicity (G6PD)
 Phototherapy failure
Differential Diagnosis

Clinical signs suggesting the possibility of other
diseases such as Sepsis, Galactosemia

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Vomiting
Lethargy
Poor feeding
Hepatosplenomegaly
Excessive wt. loss
Apnea
Tachypnea
Temperature instability
Signs of cholestatic jaundice, biliary atresia, others
 Dark urine, or positive for Bilirubin
 Light-colored stools
 Persistent jaundice for > 3wks
Hyperbilirubinemia
Laboratory Evaluation
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Prenatal maternal blood
type
Rh negative or Type
unknown: Neonatal blood
type, Direct Coombs
Save cord blood (Type O
mothers or Rh negative)
Serum bilirubin levels
(direct and indirect)
CBC
 differential
 platelets
 reticulocyte count
Further Evaluation

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Cord blood serology
Smear morphology
Sepsis work-up
 blood cultures
 CSF evaluation
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G6PD
Hemoglobin
electrophoresis
Hematology
consultation
The Value of First-Day Bilirubin Measurement in Predicting the Development
of Significant Hyperbilirubinemia in Healthy Term Newborns
SBL in the First 24hrs
of life
Cases with Peak SBL
<20mg/dLafter72hrs of
age(n)
< 6mg/dL(n=292)
292
 6mg/dL(n=206)
192
Cases Requiring
Phototherapy
Treatment with a
Peak SBL
20mg/dL after
72hrs of age(n)
0
Sensitivity
(%)
Specificity
(%)
Positive
Predictive
Value (%)
Negative
Predictive
Value
100
60
6.7
100
14
F. Alpay,MD;U. Sarici,MD; H. Tosuncuk,MD, N. Inanc,phD,E. Gokcay,MD
PEDIATRICS Vol.106, August 2000
Predictive Ability of Predischarge Hour-specific Serum Bilirubin for Subsequent
Significant Hyperbilirubinemia in Healthy Term and Near Term Newborns
n=13,003, Coombs negative, 60% breastfeeding
 TSB with newborn screening
 Percentile-based bilirubin nomogram

 6.1% High-Risk Zone
 32.1% Intermediate-Risk Zones
 61.8% Low-Risk Zone
V. Bhutani,MD; L.Johnson,MD; E.Sivieri,MS
PEDIATRICS Vol.103 January 1999
Predictive Ability of Predischarge Hour-specific Serum Bilirubin for Subsequent
Significant Hyperbilirubinemia in Healthy Term and Near Term Newborns
PEDIATRICS Vol.103 January 1999
Noninvasive Measurement of Total Serum Bilirubin in a Multiracial Predischarge
Newborn Population to Assess the Risk of Severe Hyperbilirubinemia
n
= 490 (59%W, 29%B, 3.5%H, 4.5A, 3.5% others)
12-98 hrs, BW 2000-5665gms, 35-42wks
 TSB range = 0.2 - 18.2mg/dL
 TcB in 2 institutions, 11 devices

 BiliCheck device (spectRx Inc, Norcross,GA)
V. Bhutani,MD; G.Gourley,MD; S. Adler,MD; B. Kreamer,BS, L. Johnson,MD
PEDIATRICS Vol.106 No.2 August 2000
Transcutaneous Bilirubin Measurement:
A Multicenter Evaluation of a New Device
n = 210 infants (140W, 31A, 14H, 9 B, 16 other)
 6 European hospitals
 Less than 28 days old , greater than 30 weeks
gestation
 Co. Coefficient 0.89 (95% C.I.)
 Analysis covariance: transcutaneous bilirubin
measurement accurate independent of race,
birthweight, gestational age, chronological age
 TCB reliable substitute of TSB (better in higher level)

BiliCheck (BC SpectRx Inc, Norcross,GA)
F. Rubaltella,MD;G. Gourley,MD;N. Loskamp,MD,N. Modi,MD;P. Vert,MD
PEDIATRICS Vol..107, June2001
1
Indirect Serum Bilirubin Concentration
and Its Relation To The Progression
of Dermal Icterus in Full-Term Infants*
2
Bilirubin (mg/100 mL)
Dermal
Zone
5
3
5
1
2
3
4
5
Mean ± SD
5.9 ± 0.3
8.9 ± 1.7
11.8 ± 1.8
15 ± 1.7
Range
4.3 ± 7.9
5.4 ± 12.2
8.1 ± 16.5
11.1 ± 18.37
>15
Observations
13
49
52
45
29
4
*Includes all infants whose rate of serum bilirubin rise was 0.7
mg/dL /h or less.
5
Dermal Zones of J aundice
Evaluation
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Assess risk factors first
Assess for jaundice every
8-12 hours
Standing orders for RN to
perform TCB or order
TSB if jaundice noted on
first day, is more severe
than expected for age in hours or increasing rapidly
Plot TCB of TSB findings on nomogram
Assess risk zone, or change in risk zones
BIND Score
Treatment
Treatment

Goals
 Prevention of kernicterus
 Treatment of underlying conditions
 Maintenance of hydration and nutrition

Interventions
 Intensive Phototherapy
 Adjuct therapies
– Albumin
– Hydration
– Other Medications
 Exchange transfusion
Phototherapy
 Indication for early phototherapy
 Bilirubin rising faster than 0.5mg/dL/hr or 5mg/dL/d
 Persistent, severe metabolic or respiratory acidosis
 Sepsis
 Sick VLBW infants

Indication for photherapy in infants >35 weeks gestation
AAP: Clinical Practice
Guideline: Management
of Hyperbilirubinemia in
the Newborn Infant 35 or
More Weeks Gestation,
July 2004
Phototherapy

Mechanism of action
 Skin exposure to lights causing geometric photoisomerization and
bilirubin photooxidation allowing diffusion and albumin binding
 Not useful in neonates with elevated conjugated bilirubin

Technique
 Light source
–
–
–
–
banks, spotlights, fiber optic blankets, LED
white, blue, green
wave length: 420-500nm
irradiance > 5 uW/sq cm/nm or change bulbs every 2000 hours
 Positioned 15-20cm above infant
 Largest surface area possible exposed
 Intermittent vs. Continuous: current evidence does not allow
recommendations
Special Blue
Vita Lite
550
600
350
400
450
500
400
450
500
550
600
350
350
400
450
500
550
600
Blue
350
400
450
500
550
600
400
450
500
550
600
350
350
400
450
500
550
600
Daylight
Tungsten-halogen
Wavelength (nm)
Gr een
Phototherapy Precautions
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Ensure patent airway
Maintain constant body temperature by using incubator and Neutral Thermal
Environment. Assess temperature every 4-8 hours
Maintain fluid balance by increasing intake and minimizing loss (insensible,
respiratory, GI)
Cover eyes and genitalia
Assure skin integrity
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frequent diaper changes
water baths
no lotions or oils on skin
position to avoid skin irritation
Careful technique when repeatedly drawing labs
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Consider use of automatic lancet
Warm foot before procedure
Avoid areas of previous puncture
Provide comfort measures before and during procedure (swaddling, sucrose)
Complications of Phototherapy

Dehydration
 increased insensible water loss
 loose stools
Irritability or lethargy
 Skin rashes
 Overheating
 Retinal injury
 Adverse effect on cell growth
 Oxidize essential fatty acids, decreases vitamins
and calcium in premature infants
 Tanning/Bronze Baby Syndrome

Home Phototherapy
AAP Guidelines
Healthy full term infant
 Greater than 48 hrs. old
 TSB between 14 and 20mg/dL
 No direct hyperbilirubinemia.
 No history or signs of hemolysis
 Rate of bili increase <1mg/dL in 3-4hrs

Pharmacologic Treatments
 Phenobarbital
 Accelerates metabolic pathways for bilirubin
clearance
 Tin-mesoporphyrin
 inhibits heme oxygenase
 IV
gamma globulin
 inhibits hemolysis
 Act.
Charcoal
 binds bili in the intestine
Exchange Transfusion
 Procedure
 Transfer care to Neonatologist and NICU
 Complications
 Thrombocytopenia
 Portal vein thrombosis/perforation
 Necrotizing Enterocolitis
 Cardiac arrythmias
 Hypo- Calcemia, magnesemia, glycemia
 Respiratory & metabolic accidosis
 HIV, Hepatitis B & C infection
Exchange Transfusion

Indication in infants 35 weeks gestation or more
AAP: Clinical Practice Guideline: Management of Hyperbilirubinemia in the Newborn
Infant 35 or More Weeks Gestation, July 2004
Future Issues and Therapies
 Predicting
Hyperbilirubinemia using
transcutaneous bilimeters, ETCO (exhales
carbon monoxide)
 Registry to report cases of excessive
hyperbilirubinemia ( 20mg/dL) and poor
neurologic outcome
 Metalloporphyrin for high producers
 Gene therapy for conjugation defect
Follow-up Care
Follow-up Care

Plan based on
 Age in hours at discharge
 Risk of excessive hyperbilirubinemia
 Availability and reliability of follow-up

Components
 Written discharge instructions regarding
hyperbilirubinemia, breastfeeding, dehydration
 Time specific appointment based on age in hours at
discharge and risk factors
–
–
–
–
Infant < 24 hours old: should be seen by 72 hours of age
Infant between 24-47.9 hours old: seen at 96 hours of age
Infant between 48-72 hours old: seen at 120 hours of age
Infant >72 hours old at discharge: physician’s discretion
 Follow-up resources for lactation support
Systematic Prevention
Overview
 System
failures associated with identifying
and treating severe hyperbilirubinemia
 Root causes related to four patient care
processes:
 Patient Assessment
 Continuum of Care
 Patient & Family Education
 Treatment
Root Causes Identified

Patient Care Related
 The unreliability of the visual assessment of jaundice in newborns with dark
skin.
 Failure to recognize jaundice in the infant –or its severity– based on visual
assessment, and measure a bilirubin level before the infant’s discharge from
the hospital or during a follow-up visit.
 Failure to measure the bilirubin level in an infant who is jaundiced in the first
24 hours.

Continuum of Care
 Early discharge (<48 hours) with no follow-up within one to two days of
discharge.
 Failure to provide early follow-up with physical assessment for infants who
are jaundiced before discharge.
 Failure to provide ongoing lactation support to ensure adequacy of intake for
breast-fed newborns.

Patient Education
 Failure to provide appropriate information to parents about jaundice and
failure to respond appropriately to parental concerns about a jaundiced
newborn, poor feeding, lactation difficulties and change in newborn behavior
and activity.
Sentinel Alerts 18/31, JCAHO, 2001
Risk Reduction Strategies
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Predischarge TCB/TSB with use of a percentile based on nomogram to
predict the risk and guide follow-up
Policies and procedures or standing orders allowing nurses to order
TCB/TSB for jaundiced newborns, proper documentation of bilirubin
values and a report
Policies for assessing the risk of severe hyperbilirubinemia in all infants by
history, clinical evaluation and, if necessary, by laboratory measurement.
Procedures for follow-up of all newborns within 24-48 hours by a physician
or pediatric nurse. If this cannot be achieved, decisions regarding timing of
discharge or other follow-up must be based on risk assessment.
Policies and procedures on jaundice management that specifically cover the
nurse’s role, documentation, charting requirements, and monitoring of jaundice
predischarge. Policies should also cover the ER and Newborn NICU.
Provide parents with adequate educational materials about newborn infants that
includes information about jaundice.
Provide adequate equipment – bilirubin lights and blankets, and non-invasive
TcB measurement device or lab services for timely TSB test.