neonatal hyperbilirubinemia. jaundice yellowish discoloration of skin +/- sclera of newborns due to...

Neonatal Neonatal HyperbilirubinemiaHyperbilirubinemia

JaundiceJaundice

Yellowish discoloration of skin +/- Yellowish discoloration of skin +/- sclera of newborns due to bilirubinsclera of newborns due to bilirubin

Affects nearly all newbornsAffects nearly all newborns Peak: 48-120 hours, typically 5-6 Peak: 48-120 hours, typically 5-6

mg/dL, usually does not exceed 17-18 mg/dL, usually does not exceed 17-18 mg/dLmg/dL

Pathologic: TSB exceeds age (in hours) Pathologic: TSB exceeds age (in hours) specific 95specific 95thth percentile according to percentile according to Bhutani nomogramBhutani nomogram

Effects of Effects of hyperbilirubinemiahyperbilirubinemia Bilirubin toxicityBilirubin toxicity

– Toxicity due to unbound (free) formToxicity due to unbound (free) form– Focal necrosis of neurons and gliaFocal necrosis of neurons and glia

Acute bilirubin encephalopathyAcute bilirubin encephalopathy Chronic= kernicterusChronic= kernicterus Most often affects basal ganglia and Most often affects basal ganglia and

brainstem nucleibrainstem nuclei– Movement disordersMovement disorders– Impaired upward gazeImpaired upward gaze– Auditory abnormalitiesAuditory abnormalities

EffectsEffects

Bilirubin toxicityBilirubin toxicity– At risk when TSB > 25-30 mg/dLAt risk when TSB > 25-30 mg/dL

Premature and sick infantsPremature and sick infants Albumin levelAlbumin level Drugs- silfisoxazole, moxalactam, ceftriaxoneDrugs- silfisoxazole, moxalactam, ceftriaxone AcidosisAcidosis

– Near term (35-37) weeksNear term (35-37) weeks– Breast fedBreast fed– Hemolytic diseaseHemolytic disease– Discharge before 48 hoursDischarge before 48 hours

ManifestationsManifestations

Phase one- 1Phase one- 1stst few days few days– Lethargy, hypotonia, poor suck, high Lethargy, hypotonia, poor suck, high

pitched crypitched cry Phase two- end of 1Phase two- end of 1stst week week

– Irritable, hypertonia, retrocollis, Irritable, hypertonia, retrocollis, opisthotonusopisthotonus

Phase three- after 1Phase three- after 1stst week week– Stupor, coma, shrill cryStupor, coma, shrill cry

EvaluationEvaluation

Transcutaneous bilirubinTranscutaneous bilirubin Total serum bilirubinTotal serum bilirubin End-tidal carbon monoxideEnd-tidal carbon monoxide Blood type, direct Coombs testBlood type, direct Coombs test CBC, peripheral blood smearCBC, peripheral blood smear Reticulocytes, G6PD screenReticulocytes, G6PD screen Serum albuminSerum albumin

Special circumstancesSpecial circumstances

Jaundice in 1Jaundice in 1stst 24 hours 24 hours– Frequently due to hemolysisFrequently due to hemolysis– Require immediate evaluation and Require immediate evaluation and

close surveillanceclose surveillance Other reasons for increased Other reasons for increased

bilirubin productionbilirubin production– Cephalohematoma, extensive Cephalohematoma, extensive

bruising, conjugation disordersbruising, conjugation disorders

ManagementManagement

PhototherapyPhototherapy– MechanismsMechanisms

Structural isomerizationStructural isomerization PhotoisomerizationPhotoisomerization Photo-oxidationPhoto-oxidation

– IrradianceIrradiance– Initiation if bilirubin exceeds the 95Initiation if bilirubin exceeds the 95thth

percentile for hour-specific TSB percentile for hour-specific TSB concentration and risk categoryconcentration and risk category

Risk categories-Risk categories-phototherapyphototherapy Lower risk: at least 38 weeks gestation, no Lower risk: at least 38 weeks gestation, no

risk factorsrisk factors– >12 mg/dL at 24 hours, >15 mg/dL at 48 hours, >12 mg/dL at 24 hours, >15 mg/dL at 48 hours,

>18 mg/dL at 72 hours>18 mg/dL at 72 hours

Medium risk: at least 38 weeks with risk Medium risk: at least 38 weeks with risk factors or 35-38 weeks without risk factorsfactors or 35-38 weeks without risk factors– >10 mg/dL at 24 hours, >13 mg/dL at 48 hours, >10 mg/dL at 24 hours, >13 mg/dL at 48 hours,

>15 mg/dL at 72 hours>15 mg/dL at 72 hours

Higher risk: 35-38 weeks with risk factorsHigher risk: 35-38 weeks with risk factors– >8 at 24 hours, >11 at 48 hours, >13.5 at 72 hours>8 at 24 hours, >11 at 48 hours, >13.5 at 72 hours


Rate of decline of TSBRate of decline of TSB– IrradianceIrradiance– Surface areaSurface area– Initial TSBInitial TSB

DiscontinuationDiscontinuation– TSB level below 95TSB level below 95thth percentile for percentile for

ageage– Is less than 13 mg/dLIs less than 13 mg/dL


Exchange transfusionExchange transfusion– Hyperbilirubinemia unresponsive to Hyperbilirubinemia unresponsive to

phototherapyphototherapy– Especially useful with immune-Especially useful with immune-

mediated hemolysismediated hemolysis Removal of circulating antibodies and Removal of circulating antibodies and

sensitized RBCssensitized RBCs

– For TSB > 25 mg/dLFor TSB > 25 mg/dL– Presence of bilirubin neurotoxicityPresence of bilirubin neurotoxicity

Risk categories- Risk categories- exchange transfusionexchange transfusion Lower risk: at least 38 weeks gestation, no risk Lower risk: at least 38 weeks gestation, no risk

factorsfactors– >19 mg/dL at 24 hours, >22 mg/dL at 48 hours, >24 >19 mg/dL at 24 hours, >22 mg/dL at 48 hours, >24

mg/dL at 72 hoursmg/dL at 72 hours– TSB/Albumin>8.0TSB/Albumin>8.0

Medium risk: at least 38 weeks with risk factors or 35-Medium risk: at least 38 weeks with risk factors or 35-38 weeks without risk factors38 weeks without risk factors– >16.5 mg/dL at 24 hours, >19 mg/dL at 48 hours, >21 >16.5 mg/dL at 24 hours, >19 mg/dL at 48 hours, >21

mg/dL at 72 hoursmg/dL at 72 hours– TSB/Albumin>7.2TSB/Albumin>7.2

Higher risk: 35-38 weeks with risk factorsHigher risk: 35-38 weeks with risk factors– >15 at 24 hours, >17 at 48 hours, >18.5 at 72 hours>15 at 24 hours, >17 at 48 hours, >18.5 at 72 hours– TSB/Albumin>6.8TSB/Albumin>6.8

SummarySummary

Assess for jaundice every 8-12 Assess for jaundice every 8-12 hourshours

Assess risk factorsAssess risk factors If discharging, appropriate follow-If discharging, appropriate follow-

up is necessaryup is necessary Treatment should be initiated Treatment should be initiated

immediately upon identifying immediately upon identifying significant hyperbilirubinemiasignificant hyperbilirubinemia

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

2004 AAP 2004 AAP GuidelinesGuidelines

Management of Hyperbilirubinemia in Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks the Newborn Infant 35 or More Weeks of Gestationof Gestation

Subcommittee on HyperbilirubinemiaPediatrics 2004; 114;297-316

PreventionPrevention

BreastfeedingBreastfeeding– Should be encouraged for most Should be encouraged for most

womenwomen Separate AAP guidelinesSeparate AAP guidelines

– 8-12 times/day for 1st several days8-12 times/day for 1st several days– Assistance and educationAssistance and education– Avoid supplements in non-Avoid supplements in non-

dehydrated infantsdehydrated infants Do not decrease level & severity of Do not decrease level & severity of

hyperbilihyperbili

PreventionPrevention Ongoing assessments for risk of Ongoing assessments for risk of

developing severe hyperbilirubinemiadeveloping severe hyperbilirubinemia– Monitor at least every 8-12 hoursMonitor at least every 8-12 hours– Don’t rely on clinical examDon’t rely on clinical exam– Blood testingBlood testing

Prenatal (Mom): ABO & Rh type, antibodyPrenatal (Mom): ABO & Rh type, antibody Infant cord bloodInfant cord blood

– Mom not tested, Rh (-): Coomb’s, ABO, RhMom not tested, Rh (-): Coomb’s, ABO, Rh– Mom O or Rh (+): optional to test cord bloodMom O or Rh (+): optional to test cord blood

Laboratory investigationLaboratory investigation

Indicated (if bilirubin concentrations reach Indicated (if bilirubin concentrations reach phototherapy levels) phototherapy levels) – Serum total or unconjugated bilirubin concentration Serum total or unconjugated bilirubin concentration

Serum conjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test Blood group with direct antibody test

(Coombs’ test) (Coombs’ test) Hemoglobin and hematocrit determinations Hemoglobin and hematocrit determinations

Optional (in specific clinical circumstances)Optional (in specific clinical circumstances) Complete blood count including manual Complete blood count including manual differential white cell count differential white cell count – Blood smear for red cell morphology Blood smear for red cell morphology – Reticulocyte count Reticulocyte count – Glucose-6-phosphate dehydrogenase screenGlucose-6-phosphate dehydrogenase screen

Serum electrolytes and albumin or protein Serum electrolytes and albumin or protein concentrationsconcentrations

Copyright ©2004 American Academy of Pediatrics

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

Risk Factors for Severe Risk Factors for Severe HyperbilirubinemiaHyperbilirubinemia

Major risk factorsMajor risk factors – Predischarge bili in high-Predischarge bili in high-

risk zone risk zone – Jaundice in 1st 24 hrsJaundice in 1st 24 hrs– Blood group incomp with + Blood group incomp with +

direct antiglobulin test, direct antiglobulin test, other known hemolytic other known hemolytic disease (eg, G6PD disease (eg, G6PD deficiency)deficiency)

– Gestational age 35–36 wkGestational age 35–36 wk– Previous sibling received Previous sibling received

phototherapyphototherapy– Cephalohematoma or Cephalohematoma or

significant bruisingsignificant bruising– Exclusive breastfeedingExclusive breastfeeding– East Asian raceEast Asian race

Minor risk factorsMinor risk factors

– Bili in high intermed-risk Bili in high intermed-risk zonezone

– Gestational age 37–38 wkGestational age 37–38 wk– Jaundice before dischargeJaundice before discharge– Previous sibling with Previous sibling with

jaundicejaundice– Macrosomia infant with Macrosomia infant with

diabetic motherdiabetic mother– Maternal age ≥ 25Maternal age ≥ 25– Male Male

Decreased RiskDecreased Risk– Bili in low-risk zoneBili in low-risk zone– ≥ ≥ 41 wks gestation41 wks gestation– Exclusive bottle feedExclusive bottle feed– Black raceBlack race– D/c from hospital > 72hrsD/c from hospital > 72hrs

DischargeDischarge Assess riskAssess risk

– Predischarge biliPredischarge bili Use nomogram to determine risk zoneUse nomogram to determine risk zone

– And/or Assessment of risk factorsAnd/or Assessment of risk factors

TSB ZoneTSB Zone Newborns Newborns (%)(%)

% with TSB % with TSB >95>95thth % %

High riskHigh risk 66 39.539.5

High intermedHigh intermed 12.512.5 12.912.9

Low intermedLow intermed 19.619.6 2.262.26

LowLow 61.861.8 00

DischargeDischarge

Close follow-up necessaryClose follow-up necessary– Individualize based on riskIndividualize based on risk– Weight, % change from BW, intake, Weight, % change from BW, intake,

voiding habits, jaundicevoiding habits, jaundice

Infant Infant DischargeDischarge

Should be Should be Seen bySeen by

< 24 hours< 24 hours 72 hours72 hours

24-48 hours24-48 hours 96 hours96 hours

48-72 hours48-72 hours 120 hours120 hours



Algorithm for the management of jaundice in the newborn nursery

PhototherapyPhototherapy

Mechanism: converts bilirubin to Mechanism: converts bilirubin to water soluble form that is easily water soluble form that is easily excretedexcreted

FormsForms– Fluorescent lightingFluorescent lighting– Fiberoptic blanketsFiberoptic blankets

Goal is to decrease TSB by 4-5 mg/dL Goal is to decrease TSB by 4-5 mg/dL or < 15 mg/dL totalor < 15 mg/dL total

Breastfed infants are slower to recoverBreastfed infants are slower to recover

PhototherapyPhototherapy

Severe rebound Severe rebound hyperbilirubinemia is rarehyperbilirubinemia is rare– Average increase is 1 mg/dLAverage increase is 1 mg/dL

IntensiveIntensive– Special blue tube with light in blue-Special blue tube with light in blue-

green spectrumgreen spectrum– Close to infantClose to infant– Expose maximum surface areaExpose maximum surface area



Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

Exchange Exchange TransfusionTransfusion

Mechanism: removes bilirubin and Mechanism: removes bilirubin and antibodies from circulation and antibodies from circulation and correct anemiacorrect anemia

Most beneficial to infants with Most beneficial to infants with hemolysishemolysis

Generally neverGenerally never used until after used until after intensive phototherapy attemptedintensive phototherapy attempted

Risk of KirnicterusRisk of Kirnicterus

TSB level > 25-30 mg/dlTSB level > 25-30 mg/dl AcidosisAcidosis Increased free bilirubinIncreased free bilirubin low albumin, drug displacementlow albumin, drug displacement Blood-brain barrier disruptionBlood-brain barrier disruption prematurity, sepsis, ischemia prematurity, sepsis, ischemia

Kernicterus cases Kernicterus cases potentially correctable potentially correctable causescauses Early discharge (<48hrs) without f/u Early discharge (<48hrs) without f/u

within 48 hrswithin 48 hrs Failure to check bilirubin level if onset in Failure to check bilirubin level if onset in

first 24 hoursfirst 24 hours Failure to note risk factorsFailure to note risk factors Visual assessment underestimate of Visual assessment underestimate of

severityseverity Delay in testing jaundiced newborns or Delay in testing jaundiced newborns or

treating elevated levelstreating elevated levels Lack of concern for presence of Lack of concern for presence of jaundicejaundice

or parental concernor parental concern Pediatrics 2001; 108:763-765Pediatrics 2001; 108:763-765

Common Clinical Risk Common Clinical Risk Factors Factors for Severe Hyper-for Severe Hyper-bilirubinemia bilirubinemia JaundiceJaundice in the first 24 hours in the first 24 hours Visible Visible jaundicejaundice at discharge at discharge Previous jaundiced siblingPrevious jaundiced sibling Near term gestation 35-38 weeksNear term gestation 35-38 weeks Exclusive breastfeedingExclusive breastfeeding East Asian (4), Mediterranean (1), African East Asian (4), Mediterranean (1), African

origin (12) (G6PD deficiency), 19/61 origin (12) (G6PD deficiency), 19/61 kernicterus cases = G6PDkernicterus cases = G6PD

Bruising, cephalohematoma, birth traumaBruising, cephalohematoma, birth trauma Hemolysis risk, O + maternal blood type, Hemolysis risk, O + maternal blood type,

sepsis sepsis

Medications Medications increasing increasing bilirubin bilirubin toxicity toxicity

Sulfisoxazole (displacement or Sulfisoxazole (displacement or G6PD hemolysis)G6PD hemolysis)

Ceftriaxone (displacement from Ceftriaxone (displacement from albumin)albumin)

Trans cutaneous Trans cutaneous bilirubinbilirubin

Older devices affected by skin pigmentationOlder devices affected by skin pigmentation Newer multi-wavelength spectral reflectance Newer multi-wavelength spectral reflectance

correlate 0.88 with the serum value, correlate 0.88 with the serum value, example SpectRx, ± 3 mg/dlexample SpectRx, ± 3 mg/dl ? Confirm values > 40% per age? Confirm values > 40% per age Carbon monoxide exhaledCarbon monoxide exhaled

Direct Coombs TestingDirect Coombs Testing

Strongly positive:Strongly positive:– RhRh– KellKell– KiddKidd– Duffy Duffy

Negative or “weakly positive:Negative or “weakly positive:– Anti-A Anti-A

Hemolysis consider Hemolysis consider present present

Hct < 45%Hct < 45% Abnormal blood smear with 3-4+ Abnormal blood smear with 3-4+

spherocytesspherocytes Reticulocyte count is 4.5% in the Reticulocyte count is 4.5% in the

first 72 hrs, orfirst 72 hrs, or Reticulocyte count is >1-2% in Reticulocyte count is >1-2% in

the first 1-2 wksthe first 1-2 wks

ReferencesReferences American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia. American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia.

Management of hyperbilirubinemia in the newborn infant 35 or more weeks Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. of gestation. PediatricsPediatrics. 2004;114:297-316. 2004;114:297-316

Johnson LH, Bhutani VK, Brown AK. System-based approach to management Johnson LH, Bhutani VK, Brown AK. System-based approach to management of neonatal jaundice and prevention of kernicterus. of neonatal jaundice and prevention of kernicterus. J PediatrJ Pediatr. 2002;140:396-. 2002;140:396-403403

American Academy of Pediatrics, Steering Committee on Quality American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Classification of recommendations for Improvement and Management. Classification of recommendations for clinical practice guidelines. clinical practice guidelines. PediatricsPediatrics. 2004;114:874-877. 2004;114:874-877

Gartner LM, Herschel M. Jaundice and breastfeeding. Gartner LM, Herschel M. Jaundice and breastfeeding. Pediatr Clin North AmPediatr Clin North Am. . 2001;48:389-3992001;48:389-399

Moyer VA, Ahn C, Sneed S. Accuracy of clinical judgment in neonatal Moyer VA, Ahn C, Sneed S. Accuracy of clinical judgment in neonatal jaundice. jaundice. Arch Pediatr Adolesc MedArch Pediatr Adolesc Med. 2000;154:391-394. 2000;154:391-394

Ip S, Glicken S, Kulig J, Obrien R, Sege R, Lau J. Ip S, Glicken S, Kulig J, Obrien R, Sege R, Lau J. Management of Neonatal Management of Neonatal HyperbilirubinemiaHyperbilirubinemia. Rockville, MD: US Department of Health and Human . Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Research and Quality; 2003. AHRQ Services, Agency for Healthcare Research and Quality; 2003. AHRQ Publication 03-E011Publication 03-E011

Bhutani VK, Johnson LH, Sivieri EH. Predictive ability of a predischarge hour-Bhutani VK, Johnson LH, Sivieri EH. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent hyperbilirubinemia in healthy term specific serum bilirubin for subsequent hyperbilirubinemia in healthy term and near-term newborns. and near-term newborns. PediatricsPediatrics. 1999;103:6-14.. 1999;103:6-14.

American Academy of Pediatrics, Subcommittee on Neonatal American Academy of Pediatrics, Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Hyperbilirubinemia. Neonatal jaundice and kernicterus. PediatricsPediatrics. . 2001;108:763-7652001;108:763-765

Mohammadh Khassawneh MD accessed online 2009Mohammadh Khassawneh MD accessed online 2009

neonatal hyperbilirubinemia. jaundice yellowish discoloration of skin +/- sclera of newborns due to...

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