©2005 AWHONN

Hyperbilirubinemia in the Hyperbilirubinemia in the Neonate: Risk Assessment, Neonate: Risk Assessment, Screening and ManagementScreening and Management

Second EditionSecond Edition

©2005 AWHONN

ObjectivesObjectives

Summarize the mechanisms of bilirubin production and clearanceSummarize the mechanisms of bilirubin production and clearance

Describe a systematic process to assess and monitor neonatal Describe a systematic process to assess and monitor neonatal hyperbilirubinemiahyperbilirubinemia

Identify infants at risk for severe hyperbilirubinemiaIdentify infants at risk for severe hyperbilirubinemia

Identify prevention strategies for atIdentify prevention strategies for at--risk infantsrisk infants

Describe the recommended treatment modalities for severe Describe the recommended treatment modalities for severe hyperbilirubinemiahyperbilirubinemia

Summarize the current consensus guidelines for early interventioSummarize the current consensus guidelines for early intervention, treatment, n, treatment, and followand follow--up of neonates at risk for severe hyperbilirubinemiaup of neonates at risk for severe hyperbilirubinemia

Identify resources for staff and family education related to neoIdentify resources for staff and family education related to neonatal jaundice natal jaundice and hyperbilirubinemiaand hyperbilirubinemia

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HyperbilirubinemiaHyperbilirubinemia

©2005 AWHONN

Bilirubin ProductionBilirubin Production Erythrocyte

Hemoglobin Tissue Heme Globin - amino acid pool Heme Proteins Heme for recycle (20%) (80%) Iron - (iron pool for recycling) Heme Oxygenase

CO - Carbon Monoxide ---- pulmonary excretion Biliverdin Bilirubin Reductase Reticulo-endothelial System Unconjugated Bilirubin + Serum albumin

LIVER

©2005 AWHONN

Types of BilirubinTypes of Bilirubin

Conjugated Conjugated -- directdirectWaterWater--solublesoluble

Easily excreted in urine Easily excreted in urine and stooland stool

Less toxic formLess toxic form

Requires ORequires O22 and glucoseand glucose

UnconjugatedUnconjugated -- indirectindirectFat or nonFat or non--water water soluble soluble

Potentially more toxic Potentially more toxic

Bound vs. unbound to Bound vs. unbound to albuminalbumin

Clinical management decisions are based on total serum bilirubin levels (by heel-stick sampling).

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Bilirubin ClearanceBilirubin ClearanceUnconjugated Bilirubin

Liver Bilirubin glucuronide (conjugated bilirubin) β-glucuronidase Unconjugated Bilirubin Enterohepatic Circulation Bilirubin in Stools Gastro-intestinal tract

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Development of Severe HyperbilirubinemiaDevelopment of Severe Hyperbilirubinemia

Increase in Increase in bilirubinbilirubin productionproductionSuch as Rh, ABO incompatibility, G6PD deficiency, Such as Rh, ABO incompatibility, G6PD deficiency, septicemia, extravascular blood, polycythemiasepticemia, extravascular blood, polycythemia

Decrease in Decrease in bilirubinbilirubin excretion excretion Bowel obstructions, hereditary defects, Bowel obstructions, hereditary defects, hypothyroidismhypothyroidism

Combination of both Combination of both Seen in prematurity, infectionSeen in prematurity, infection, G6PD deficiency, G6PD deficiency

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Increases in Bilirubin Production: Increases in Bilirubin Production: HemolysisHemolysis

Genetic factorsGenetic factors

G6PD deficiencyG6PD deficiency

Erythrocyte enzymatic Erythrocyte enzymatic defectsdefects

Antibody mediatedAntibody mediated

Rh/ABO incompatibilityRh/ABO incompatibility

Acquired hemolytic Acquired hemolytic disordersdisorders

InfectionInfection

Drugs Drugs

Additional causeAdditional cause

PolycythemiaPolycythemia

Maternal diabetesMaternal diabetes

Extravasation of bloodExtravasation of blood

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Decrease in Bilirubin ExcretionDecrease in Bilirubin Excretion

Increased Increased enterohepaticenterohepatic circulationcirculationBowel obstructionsBowel obstructions

Maternal liver diseaseMaternal liver disease

Hereditary defect Hereditary defect CriglerCrigler--Najjar, LuceyNajjar, Lucey--DriscollDriscoll

HypothyroidismHypothyroidism

HypopituitarismHypopituitarism

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Combination of Combination of ↑↑ Production & Production & ↓↓ ExcretionExcretion

PrematurityPrematurity

InfectionInfectionBacterial sepsis, viral, protozoalBacterial sepsis, viral, protozoal

G6PD deficiencyG6PD deficiency

©2005 AWHONN

Major Risk Factors for Severe Major Risk Factors for Severe HyperbilirubinemiaHyperbilirubinemia

PrePre--discharge TSB/TcB in the highdischarge TSB/TcB in the high--risk zonerisk zone

Jaundice observed in the first 24 hoursJaundice observed in the first 24 hours

Blood group incompatibility, other known hemolytic disease Blood group incompatibility, other known hemolytic disease

Gestational age 35Gestational age 35--36 weeks36 weeks

Previous sibling received phototherapyPrevious sibling received phototherapy

Exclusive breastfeedingExclusive breastfeeding

Bruising/Bruising/cephalohematomacephalohematoma

Asian raceAsian race

©2005 AWHONN

Risk Factors for Risk Factors for Severe Severe HyperbilirubinemiaHyperbilirubinemia ((concon’’tt))

Minor risk factorsMinor risk factors

PrePre--discharge TSB/TcB in the highdischarge TSB/TcB in the high--intermediate risk zoneintermediate risk zoneGestational age 37Gestational age 37--38 weeks38 weeksJaundice observed before dischargeJaundice observed before dischargeMale genderMale genderMaternal age Maternal age >>25 years25 years

Decreased riskDecreased risk

TSB/TcB in the lowTSB/TcB in the low--risk zonerisk zoneGestational age Gestational age >>41 weeks41 weeksExclusive bottle feedingExclusive bottle feedingBlack raceBlack raceDischarged from hospital after 72 hoursDischarged from hospital after 72 hours

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BreastfeedingBreastfeeding

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Causes of Lactation FailureCauses of Lactation Failure

Lack of clinicianLack of clinician--initiated educationinitiated education

Lack of on site certified consultantsLack of on site certified consultants

Lack of documentation of infant latchingLack of documentation of infant latching

Inadequate measure of milk transferInadequate measure of milk transfer

Inappropriate followInappropriate follow--up and record of urine and stool pattern up and record of urine and stool pattern changeschanges

©2005 AWHONN

Hour-Specific Bilirubin Nomogram

95th %ile

75th %ile

40th %ile

©2005 AWHONN

Early Onset of Severe HyperbilirubinemiaEarly Onset of Severe Hyperbilirubinemia

Early OnsetEarly Onset

TSB/TcB values are >75TSB/TcB values are >75th th percentile prior to percentile prior to 72 hours of age72 hours of age

Acute/rapid rise in TSB/TcBAcute/rapid rise in TSB/TcB

↑↑ risk for potential adverse eventsrisk for potential adverse events

Frequent causes: ABO, Frequent causes: ABO, RhRh incompatibilityincompatibility

©2005 AWHONN

Late Onset Late Onset HyperbilirubinemiaHyperbilirubinemia

Late OnsetLate Onset

TSB/TcB values >95th percentile beyond TSB/TcB values >95th percentile beyond 72 hours of age72 hours of age

Frequent causes: BreastFrequent causes: Breast--fed infants with G6PD fed infants with G6PD deficiency, familial, or ethnic risk factorsdeficiency, familial, or ethnic risk factors

Need followNeed follow--up monitoring at the time of dischargeup monitoring at the time of discharge

©2005 AWHONN

Potential Neurotoxicity of BilirubinPotential Neurotoxicity of Bilirubin

Postnatal Age

Bilirubin levels* Why this level can be dangerous

Any age

Any jaundiced baby with any neurological signs suspicious for bilirubin induced neuro -dysfunction (BIND)

Any baby with signs suspicious for BIND must be assumed to have severe hype rbilirubinemia until proven otherwise

TSB >99.9 th percentile (correlates to TSB > 25 mg/dl)

These TSB levels may exceed the binding ability of serum albumin and the neur otoxicity risk increases exponentially

Over 72 hours

age

TSB >95 th and <99.9 th

percentile (correlates to TSB of 17 and 25 mg/dl)

Low levels of albumin (<3.4 g/dl) can be seen in term newborns and, more commonly near -term or bruised infants

TSB >95 th percentile and postnatal age

During the first 72 hours, the binding ability of albumin is compromised and lower TSB levels may be potentially neurotoxic

Less than 72 hours

age TSB >75 th percentile and a rate of rise > 0.20 mg/dl/hour

An increase in bilirubin load at > 1 mg per 5 hours or ~ 5 mg/day is likely to result in a TSB >95 th percentile and may reach neurotoxic levels

©2005 AWHONN

Risk of Bilirubin EntryRisk of Bilirubin Entry

These conditions These conditions ↑↑neurotoxicityneurotoxicity by:by:

↓↓ BilirubinBilirubin--albumin albumin bindingbinding

↓↓ Brain blood flowBrain blood flow

Disrupting the bloodDisrupting the blood--brain barrierbrain barrier

AsphyxiaAsphyxia

PrematurityPrematurityHypoalbuminemiaHypoalbuminemiaBilirubinBilirubin--displacing displacing drugsdrugsHyperosmolalityHyperosmolalityHypercarbiaHypercarbiaAcidosisAcidosisHypoxic injuryHypoxic injury

©2005 AWHONN

Clinical Progression of Clinical Progression of Bilirubin EncephalopathyBilirubin Encephalopathy

Clinical Evaluation

Non-specific, Subtle

Progressive Toxicity

Advanced Toxicity

Mental StatusSleepy

+ poor feedLethargy

+ irritabilitySemi-coma or

seizures

Muscle ToneSlight

Decrease

Hyper- or hypotonia

depending on arousal state orMild Nuchal

/Truncal arching

Markedlyincreased

(oposthotonus) or, decreased

tone or,bicycling

movements

Cry High-pitched Shrill Inconsolable

©2005 AWHONN

Reasons for ReReasons for Re--emergence of Kernicterusemergence of Kernicterus

Early dischargeEarly discharge

Lack of concern about Lack of concern about jaundicejaundice

OverOver--reliance on visual reliance on visual assessmentassessment

Birubin test considered as Birubin test considered as a healthcare costa healthcare cost

Limited experience with Limited experience with severe jaundicesevere jaundice

Clinicians were not Clinicians were not consistently using the AAP consistently using the AAP practice guidelines practice guidelines

©2005 AWHONN

Case Presentation, CalCase Presentation, Cal

BW: 2863gBW: 2863g

Gestation:Gestation: 37 wks37 wks

D.O.B.:D.O.B.: 3/23 @ 23523/23 @ 2352

Discharge: 36 hrs of ageDischarge: 36 hrs of age

Breastfeeding Breastfeeding

Blood typeBlood type--mom: O Rh+mom: O Rh+

Blood typeBlood type--infant: A Rh+ infant: A Rh+

©2005 AWHONN

Case Presentation, CalCase Presentation, Cal

Age 4 daysAge 4 days: very sleepy, poor : very sleepy, poor feeding, feeding, ““yellow to toes,yellow to toes,”” seen seen by MDby MD

7% wt loss, No TSB done7% wt loss, No TSB done

2 calls to MD overnight2 calls to MD overnight

Age 5 daysAge 5 days: seen in office and : seen in office and admitted for signs of admitted for signs of lethargy, poor feedinglethargy, poor feeding

TSB=34.6 mg/dlTSB=34.6 mg/dl

Double phototherapy X 3 daysDouble phototherapy X 3 days

No exchange transfusionNo exchange transfusion

©2005 AWHONN

JCAHO Sentinel Alert on KernicterusJCAHO Sentinel Alert on Kernicterus

11st st issued May of 2001issued May of 2001 to hospitals in the United to hospitals in the United StatesStates

Prompted by an increase in number of reported Prompted by an increase in number of reported casescasesCited risk factors, root causes, risk reduction Cited risk factors, root causes, risk reduction strategies, and followstrategies, and follow--up recommendationsup recommendations

ReRe--issued July 2004 to hospitals in the United issued July 2004 to hospitals in the United StatesStates

Recommended updated AAP guidelines be followed Recommended updated AAP guidelines be followed

©2005 AWHONN

Key Recommendations to Reduce Key Recommendations to Reduce Severe HyperbilirubinemiaSevere Hyperbilirubinemia

Promote & support Promote & support breastfeedingbreastfeedingEstablish institutional Establish institutional protocols to identify & protocols to identify & evaluate all infants evaluate all infants Obtain TSB/TcB levels on Obtain TSB/TcB levels on jaundiced infants in the 1st jaundiced infants in the 1st 24 hrs24 hrsVisual estimations can lead to Visual estimations can lead to errorserrorsUse age in hours to interpret Use age in hours to interpret TSB/TcB levelsTSB/TcB levels

Infants <38 weeks & Infants <38 weeks & breastfeeding are at higher risk breastfeeding are at higher risk Perform systematic risk Perform systematic risk assessment at time of dischargeassessment at time of dischargeGive written and verbal Give written and verbal information to parents about information to parents about jaundice jaundice Utilize phototherapy and Utilize phototherapy and exchange transfusion when exchange transfusion when indicated indicated Provide appropriate followProvide appropriate follow--up up based on risk assessmentbased on risk assessment

©2005 AWHONN

Assessment TechniquesAssessment Techniques

Visual Visual

Most widely used methodMost widely used method

Cephalocaudal Cephalocaudal progressionprogression

BUTBUT

Not reliableNot reliable

Not accurateNot accurate

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Assessment TechniquesAssessment Techniques

Total Serum Bilirubin Levels (TSB)Total Serum Bilirubin Levels (TSB)

Primary test and monitoring methodPrimary test and monitoring method

Unrestricted ability to obtain the testUnrestricted ability to obtain the test

Universal bilirubin testingUniversal bilirubin testing

Evaluate by infantEvaluate by infant’’s age in hourss age in hours

©2005 AWHONN

Assessment TechniquesAssessment Techniques

Transcutaneous Bilirubin Transcutaneous Bilirubin Measurement (TcB)Measurement (TcB)

NonNon--invasiveinvasive

More accurate than visual More accurate than visual assessmentassessment

Facilitates home and Facilitates home and clinic followclinic follow--upup

©2005 AWHONN

Assessment TechniquesAssessment Techniques

TSB monitoring remains the primary diagnostic TSB monitoring remains the primary diagnostic test to accurately identify bilirubin levels, and test to accurately identify bilirubin levels, and TSB levels must be determined prior to TSB levels must be determined prior to beginning any treatment.beginning any treatment.

©2005 AWHONN

Assessment TechniquesAssessment Techniques

EndEnd--Tidal Carbon Monoxide Measurement Tidal Carbon Monoxide Measurement ((ETCOcETCOc))

RapidRapid

NonNon--invasiveinvasive

Rules out hemolysis as a contributor to jaundiceRules out hemolysis as a contributor to jaundice

The only clinical test that provides information The only clinical test that provides information about the rates of about the rates of hemeheme catabolism and bilirubin catabolism and bilirubin productionproduction

©2005 AWHONN

Clinical Vigilance Can Clinical Vigilance Can Prevent the WorstPrevent the Worst

Consider these factors when Consider these factors when assessing for dischargeassessing for discharge

1.1. Visual assessment of Visual assessment of jaundice jaundice

2.2. Evaluation of clinical risk Evaluation of clinical risk factorsfactors

3.3. Universal TSB/TcB Universal TSB/TcB evaluationevaluation

4.4. HourHour--specific bilirubin specific bilirubin designation of riskdesignation of risk

5.5. Evaluation of hemolysis if Evaluation of hemolysis if TSB >75TSB >75thth percentilepercentile

©2005 AWHONN

Management TechniquesManagement TechniquesSupporting LactationSupporting Lactation

Prenatal breastfeeding educationPrenatal breastfeeding education

Supportive hospital routinesSupportive hospital routines

Evaluation of breastfeeding techniqueEvaluation of breastfeeding technique

Identification of lactation risk factorsIdentification of lactation risk factors

Intervention for breastfeeding problemsIntervention for breastfeeding problems

Early followEarly follow--up assessment of lactation and up assessment of lactation and infant weightinfant weight

©2005 AWHONN

Management TechniquesManagement TechniquesPhototherapyPhototherapy

©2005 AWHONN

Management TechniquesManagement TechniquesPhototherapyPhototherapy (con(con’’t)t)

Phototherapy units should allow for Phototherapy units should allow for maximum adsorption of bilirubinmaximum adsorption of bilirubin in a in a range fromrange from 420420--480 nm.480 nm.

©2005 AWHONN

Management TechniquesManagement TechniquesPhototherapy Phototherapy ((concon’’tt))

Adverse EffectsAdverse EffectsDehydration Dehydration

Lack of visualLack of visual--sensory input sensory input in animalsin animals

Watery diarrhea Watery diarrhea

Skin rashesSkin rashes

HyperthermiaHyperthermia

↓↓ maternalmaternal--infant infant interactioninteraction

SyndromesSyndromesBronze Baby Syndrome Bronze Baby Syndrome (in case of direct (in case of direct hyperbilirubinemia)hyperbilirubinemia)

Vulnerable Child SyndromeVulnerable Child Syndrome

©2005 AWHONN

Management TechniquesManagement TechniquesExchange TransfusionsExchange Transfusions

Absolute indications:Absolute indications:Signs of Acute Bilirubin Encephalopathy (intermediate or Signs of Acute Bilirubin Encephalopathy (intermediate or advanced)advanced)

Hazardous TSB levels >30 mg/dl (in infants with no risk Hazardous TSB levels >30 mg/dl (in infants with no risk factors) or >23 mg/dl (with higher risk factors)factors) or >23 mg/dl (with higher risk factors)

Failure of intensive phototherapy for infants with severe Failure of intensive phototherapy for infants with severe hyperbilirubinemia (substantial decline in bilirubin after hyperbilirubinemia (substantial decline in bilirubin after 33--4 hours, such as >2 mg/dl in 4 hours)4 hours, such as >2 mg/dl in 4 hours)

Onset of any clinical neurologic signs in infants with Onset of any clinical neurologic signs in infants with excessive hyperbilirubinemiaexcessive hyperbilirubinemia

©2005 AWHONN

Emerging Research: Emerging Research: Bilirubin as Natural AntioxidantBilirubin as Natural Antioxidant

Potent antioxidant when bound to albuminPotent antioxidant when bound to albumin

Protective component for the bodyProtective component for the body

May provide primary protection from ischemiaMay provide primary protection from ischemia--related injuries and retinopathy of prematurityrelated injuries and retinopathy of prematurity

Antioxidant effect not fully understoodAntioxidant effect not fully understood

©2005 AWHONN

Therapies Under InvestigationTherapies Under Investigation

Agent Agent Metabolic ProcessMetabolic Process MechanismMechanism

Tin protoporphyrin Tin protoporphyrin HemeHeme degradation degradation HemeHeme--oxygenaseoxygenaseinhibitorinhibitor

Zinc or TinZinc or Tin Alternate heme catabolism Alternate heme catabolism HemeHeme excretedexcretedmesoporphyrinmesoporphyrin in bile (currently in bile (currently

in US studies)in US studies)

Agar, Charcoal Agar, Charcoal ↓↓ EEnterohepatic nterohepatic Sequester Sequester bilirubin bilirubin circulation in circulation in bowel (used bowel (used outside the US)outside the US)

©2005 AWHONN

Therapies Under Investigation (Therapies Under Investigation (concon’’tt) )

Homeopathic Homeopathic Metabolic Process Metabolic Process MechanismMechanismAgentAgent

Bilirubin Bilirubin OxidaseOxidase ↓↓EEnterohepatic circulationnterohepatic circulation DegradeDegradebilirubinbilirubin in in gutgut

Herbal products Usually cathartics Herbal products Usually cathartics IncreaseIncreasestoolstoolexcretionexcretion

©2005 AWHONN

Follow-up Care MapRisk Assessment

Evaluation:Bili workup

Bili Follow-up 24hrs

Bili Follow-up 48hrs

Visual follow-up

95th %ile75th %ile

40th %ile

©2005 AWHONN

Use a System ApproachUse a System Approach

Prenatal educationPrenatal education through through post discharge evaluationpost discharge evaluation

InpatientInpatient

Evaluate jaundice with vital Evaluate jaundice with vital signssigns

Corroborate with TcB/TSBCorroborate with TcB/TSB

PeerPeer--review of cases with review of cases with TSB >25 mg/dlTSB >25 mg/dl

Post discharge followPost discharge follow--upup

RiskRisk--based and/or TSB/based and/or TSB/TcBTcB

Inpatient

PostDischargeFollow-Up

PrenatalEducation

©2005 AWHONN

Your Role as the Nurse IncludesYour Role as the Nurse Includes

Supporting and teaching breastfeeding Supporting and teaching breastfeeding

Identifying and monitoring jaundiceIdentifying and monitoring jaundice

Coordinating discharge planning for atCoordinating discharge planning for at--risk infantsrisk infants

Assuring proper treatmentAssuring proper treatment

Educating parentsEducating parents

Partnering with other healthcare professionals Partnering with other healthcare professionals through a multidisciplinary teamthrough a multidisciplinary team

©2005 AWHONN

Further Information Available FromFurther Information Available From

AWHONNAWHONNCDCCDCJCAHOJCAHOAAPAAPPICKPICKCochrane LibraryCochrane LibraryAHRQAHRQ

©2005 AWHONN

Make a Difference by Using Evidence in Make a Difference by Using Evidence in Your Nursing PracticeYour Nursing Practice