nical Guideline

Section: 1.1 Name of Guideline

ProlongedNeonatalJaundice
Title of Guideline (must include the word Guideline (not
protocol, policy, procedure etc)
Contact Name and Job Title (author)

Directorate & Speciality

Guideline for the assessment and

management of prolonged neonatal
jaundice
Dr Louise Wells
Consultant Paediatrician Dr Damian
Wood
Consultant Paediatrician
Family Health
Paediatrics
18/02/2013

Date of submission
Date on which guideline must be reviewed (this should be
one to three years)

18/02/2018

Explicit definition of patient group to which it applies (e.g.

inclusion and exclusion criteria, diagnosis)

Infants with prolonged jaundice arising

in the neonatal period
Excludes Management in first 14 days
of life which is covered by neonatal
guideline 1752
Detection and Management of
Jaundice in Newborn Infants
This guideline describes the
assessment, investigation and
management of prolonged neonatal
jaundice in infants.

Abstract

Key Words

Jaundice, neonatal,
hyperbilirubinaemia, biliary atresia

Statement of the evidence base of the guideline has the

guideline been peer reviewed by colleagues?

The evidence base is drawn from the

research evidence included in the
recent NICE guidance. The majority of
the research pertaining to prolonged
neonatal jaundice is level 3 evidence.

Evidence base: (1-5)

1a
meta analysis of randomised controlled trials
1b
at least one randomised controlled trial
2a
at least one well-designed controlled study without
randomisation
2b
at least one other type of well-designed quasiexperimental study
3
well designed non-experimental descriptive studies
(i.e. comparative / correlation and case studies)
4
expert committee reports or opinions and / or clinical
experiences of respected authorities
5
recommended best practise based on the clinical
experience of the guideline developer
Consultation Process

Target audience

Departmental Clinical Guidelines

Meeting
Neonatal Unit Clinical Guidelines
Medical and nursing staff caring for
infants with prolonged neonatal
jaundice

This guideline has been registered with the trust. However, clinical guidelines are
guidelines only. The interpretation and application of clinical guidelines will remain the
responsibility of the individual clinician. If in doubt contact a senior colleague or
expert. Caution is advised when using guidelines after the review date.

Dr Louise Wells

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nical Guideline
Section: 1.1 Name of Guideline

1.ProlongedNeonatalJaundice
Introduction
Prolongedneonataljaundice(hyperbilirubinaemia)isdefinedas:

visiblejaundicepersistingbeyondday14intermneonates
visiblejaundicepersistingbeyondday21inpreterminfants

(bornatlessthan37completedweeksgestation).
CausesofProlongedJaundice
Therearemanycausesofprolongedjaundiceinneonates.Thecommonestisbreast
milkjaundicewhichresolvesspontaneouslyovertime.Themainreasonfor
prolongedjaundicescreeningistopickupbiliaryatresiaasearlyaspossible.Belowis
alistofsomeoftheothercauses.
Unconjugated/Mixed
Conjugated
Breastmilkjaundice
Decreasedexcretion(conjugated)
Haemolysis
Obstruction
Coombspositive
Biliaryatresia
Rhesusincompatibility
Choledochalcyst
AntiKell,antiDuffy
Spontaneousbileduct
ABOincompatibility
perforation
Coombsnegative
Hepatoblastoma,
Redcellmembrane
haemangioma,neuroblastoma
defectse.g.
Infection
sphero/elliptocytosis
Septicaemia,UTI
Redcellenzyme
TORCHinfections,syphilis
defectse.g.G6PD,
Hepatitis,Varicellazoster,HIV
andotherviral
pyruvatekinase
Inherited/metabolic/endocrine
deficiency
a1antitrypsindeficiency
Haemoglobinopathy
Alagille'ssyndrome
Sepsis
Cysticfibrosis
Disseminated
Galactosaemia,fructosaemia
intravascular
Glycogenstoragediseases
coagulation
Tyrosinosis
Increasedenterohepaticcirculation
Pyloricstenosis
Hypermethioninaemia
Intestinalobstruction
Hypopituitarism/
Decreasedconjugation(unconjugated)
hypoadrenalism
CriglerNajjarsyndrome
Mytochondrialcytopathies
Gilbert'sdisease
PFICsyndromes
Hypothyroidism
Chromosomaldisorders
Prematurity
Turner'ssyndrome

Trisomy13,18,21
Toxic/drugs
Fetalalcoholsyndrome
Idiopathicneonatalhepatitis
TPN/PN

Dr Louise Wells

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Section: 1.1 Name of Guideline

2.ReferralsfromPrimaryCare
Infantswithprolongedjaundiceshouldbeseeninthenextprolongedjaundiceclinic
(withinaweek)unless:

Theyareunwell(fever,difficultybreathing,pallor,vomiting)
Theyhavepalestoolsordarkurine
Theyhavebleedingorbruising

Communitymidwivesand/orhealthvisitorsshouldcontacttheoncallSpecialist
Registrarorconsultanttodiscussthebaby.Iftheyarewell,havenormalstoolsand
urineandnobleedingorbruisingtheyshouldbebookedintothenextprolonged
jaundiceclinicbycontactingthewardclerkonD33atNottinghamChildrensHospital
(01159249924X69033).

Thebabiesname,dateofbirthandNHSnumberalongwithmothersnameanda
telephonecontactnumbershouldrecordedatthetimeofreferralandadateand
timeforajaundiceclinicappointmentprovidedbythewardclerkonD33at
NottinghamChildrensHospital.

3.InitialAssessmentattheprolongedjaundiceclinic.
IdentifyLifeThreateningFeatures

Rememberprolongedjaundicecanbecausedbyconditionswhichcanbeassociated
with severe infection (galactosaemia) and cardiac problems (haemolytic anaemia,
Alagillessyndrome).AssessAirway,Breathing,CirculationandDisabilitytoidentify
potential lifethreatening features. If you are concerned that the baby has
immediatelylifethreateningfeaturescallforseniormedicalandnursingassistance
andinstituteinitialmanagementaspertheCardiopulmonaryresuscitationguideline.
History
Foreverybabywithprolongedjaundicethefollowinginformationshouldbe
obtained:
Methodoffeedingandweightgain(includebirthweightandcurrentweight)
Urinecolour/recentwetnappies
Colourofstool/delayedpassage
Lethargyandsleep/wake/feedbehaviour
Seizuresandabnormalmovements
Bleeding/bruising
Familyhistory
o Blood/liverandmetabolicdisorders
o Cysticfibrosis
Antenatalhistory
o Maternaldrughistory/infection/USSandbloodgroup

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Examination
Checkthenursingobservations(temp,HR,CRT,BP)andtheinformationintheChild
HealthRecord(redbook).Plotavailableweightsonagrowthchart(themajorityof
healthyinfantshaveregainedtheirbirthweightby14daysofage).Examinefor
Jaundice
Pallor
Hydrationstatus
Dysmorphicfeatures
Cataracts
Hepatosplenomegaly
Hypotoniaandencephalopathy
Petechia/purpura
Lookinthenappycolourofstoolandurine
Examineforfeaturessuggestiveofcongenitalheartdisease

Investigations
Carryoutthefollowinginvestigationinbabieswithprolongedjaundice(thatis,
persistingmorethan14daysintermbabiesandmorethan21daysinpreterm
babies):
visualinspectionofstoolandurinelookforpalechalkystoolsand/ordark
urinewhichstainsthenappy
totalandconjugatedbilirubin
fullbloodcount

bloodgroupdetermination(motherandbaby)andDAT(Coombstest)
ensurethatroutinemetabolic(heelprick)screening(includingscreeningfor
congenitalhypothyroidism)hasbeenperformed.

Results

Conjugatedbilirubinabove25 mol/Lorgreaterthan20%ofthetotal
bilirubinshouldbereferredimmediatelyforfurthermanagementbythe
paediatricgastroenterologyteam.(seesection5)
Totalbilirubingreaterthan350mol/L(Conjugatedbilirubinbelow25
mol/L)shouldberepeatedinoneweekifthebabyiswellandothertests
normal
Haemoglobin:Ifthehaemoglobininlessthan10g/dlthenrepeatthe
haemoglobinin1weektoensurethelevelsarenotdroppingrapidly.
Considerironandfolicacidsupplementation
Neutrophilcount:Iftheneutrophilcountis
>1.0
itdoesnotneedrepeating
0.51.0
repeatinchildrenschildrensoutpatientsin4weeks

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Section: 1.1 Name of Guideline

<0.5

repeatinchildrenschildrensoutpatientsin2weeks

Parentsshouldbesentaform,dateandtimetocometochildrenschildrens
outpatientsforrepeatbloods.Theformshouldhavethehotweekconsultants
codeonitandbelabelledforCOPD.Theresultwillthencomebacktothe
relevantconsultant.

Otherabnormalresultsshouldbediscussedwiththehotweek
consultant
Inthosewhohave
o Totalbilirubinlessthan350,
o conjugatedbilirubinlessthan25micromol/l
o NormalHb
o Normalneutrophilcount
o
nofurtherassessmentisneededunlessnewconcerns.Theparentaladvice
sheetshouldbegiven,andlettersenttoprimarycareteam

5.InvestigationandManagementofConjugatedHyperbilirubinaemia

ReferimmediatelyforfurthermanagementbytheConsultantPaediatric
Gastroenterologist.

Thisisdefinedasaconjugatedbilirubinabove25mol/L.Percentagevaluesmaybe
falselyreassuringincasesofhightotalvalues.Inbabieswithconjugated
hyperbilirubinaemiatheprioritiesareto:
establishthediagnosis(particularlyearlydiagnosisofbiliaryatresia)
preventintracranialhaemorrhagebyidentifyingandcorrectingclotting
abnormalitieswhichreflectunderlyingimpairedsyntheticliverfunction
Nochildwithconjugatedhyperbilirubinemiashouldbeathomewithout
havinghadacoagulationscreenandcortisoldone)

Investigation

Askparent/carerandnursingstafftokeepasamplefromeverystooltoshow
gastroenterologyteam

Incasesofconjugatedhyperbilirubinaemiaperformthefollowinginvestigations
Liverfunctiontests
Coagulationscreen
Bloodglucose
Fullbloodcount
TORCHscreen/Hepatitisserology

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Alpha1Antitrypsinlevel(Li.Hep.)andgenotype(EDTA)
Gal1PutdiscusswithClinicalChemsitryChemistryifthechildreceived
priorbloodtransfusion
ThyroidFunctionTests(XTFT
Cortisol(<420isabnormalandneedsd/wendocrineteam)
Plasmaaminoacids
SerumironandferritinorZPP
Urinemetabolicscreen
Abdominalultrasound(lookingforevidenceofacholedochalcystandthe
presenceofavisiblegallbladder)
DiscussfurthermanagementwiththePaediatricGastroenterologist.

PrescribeoralPhenobarbital5mg/kgoncedaily(immediatelyifstools
acholic)tomaximisehepaticexcretioninpreparationforaHIDAscan.
Morespecializedinvestigationswillinclude:
HIDAScanafterenzymeinductionforfivedayswithPhenobarbital(5mg/kg
oncedailybeforescanandstoppedafterscan)
AbdominalUltrasound(beforenextfeedbutdonotstarveduetoriskof
hypoglycaemia)
CXR(butterflyvertebrae)
Eyeexamination(posteriorembryotoxin)viareferraltotheconsultant
paediatricophthalmologist
Liverbiopsy(aftercorrectionofcoagulopathy)
Echocardiography(pulmonarystenosis)
Sweattest

BiliaryAtresia
Biliary atresia occurs in 1:14,000 live births and is characterised by progressive
obliteration of extrahepatic bile ducts. Affected infants have a conjugated
hyperbilirubinaemia.Theaetiologyofbiliaryatresiaisunknown.Insome,itmaybea
developmental anomaly although meconium is of normal colour in nearly all cases
indicatingatleastinitialpatencyofthebiliarytree,butthereisahigherincidenceof
associatedcardiovascular,gastrointestinalandgenitourinaryanomaly(1020%)for
example:
situsinversus
polysplenia
absentinferiorvenacava
malrotation

Affectedinfantsmaygrownormallyforfirstmonthsand1/3rdhavenormalstools.

Dr Louise Wells

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IdiopathicNeonatalHepatitisSyndrome
NeonatalHepatitisSyndromeisthecollectivenamegiventoavariedgroupof
disordersthatresultinacombinationof:
conjugatedhyperbilirubinaemia
decreasedorabsentbileflow
darkurine
paleacholicstools

Neonatalhepatitissyndromeoccursinonein25003000livebirthsandwhilstthere
isaparticularemphasisplacedonearlydiagnosisofbiliaryatresiainasmanyasone
thirdofcasesnospecificcauseisidentified,thusleavingagroupcollectivelyknown
as idiopathic neonatal hepatitis. These idiopathic cases generally have a good
prognosiswith90%showingfullrecoverywithinthefirstyearoflife.

6.InvestigationandManagementofsignificantUnconjugatedHyperbilirubinaemia
(greaterthen350mol/L)
HaemolyticJaundice
There are number of haemolytic disorders which may result in jaundice and
anaemia. They often cause early onset jaundice (jaundice visible before 24hrs of
age).Thehyperbilirubinaemiaisunconjugatedandtheremaybeotherevidenceof
haemolysis including hepatosplenomegaly. In cases of haemolytic jaundice the
haemoglobinlevelandreticulocyteshouldbemonitoredtodetectanaemiaandthe
bloodfilmexaminedalongwithtestingforbloodgroupincompatibilityandredcell
disorders. If a haemolytic disorder is the likely cause of the prolonged neonatal
jaundice then further discussion with the paediatric haematology team is
recommended.

BreastMilkJaundice

Themajorityofinfantswithprolongedjaundicewillturnouttohavebreastmilk
jaundiceadiagnosisofexclusion.Thejaundiceismoremarkedandprolonged
jaundicethaninthosebabieswhoarepurelyformulafedandisthoughttobedueto
anumberoffactors:

Lowerbreastmilkvolume
Slowerguttransit
Enhancedenterohepaticcirculationofbilirubin
Breastmilkofbglucuronidaseunconjugatesbilirubinenablingittoreenter
thecirculation
Alteredbacterialcolonisationresultsinadecreaseintheconversionof
bilirubinglucuronidestourobilinoids

Breastmilkjaundiceoccursinupto1/3rdofbreastfedbabiesandpeaksat23
weeks.Resolutioncantake23months.

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Amixedpictureofraisedunconjugatedandconjugatedbilirubinseeninthe
followingandappropriateinvestigationsdoneinthiscase:

Neonatalhepatitis(LFTs)
intrauterineinfections(TORCHscreen)
bacterialsepsis(urinecultureandbloodcultureifunwell)
Galactosaemia(gal1PUT)
Aminoacidaemias(plasmaaminoacids)
congenitalhypopituitarism(TFTS)
Haemolyticanaemia(DCT)
BreastMilkJaundice
PhysiologicalJaundice

AdviceforParents
Forwellinfantswhoseinvestigationshavebeencompleted:

ProvidetheparentswithacopyoftheParentInformationSheet
InformthePrimarycareteamandparentsofnormalscreeningresultsby
letter

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References
NICEClinicalGuidelineCG98NeonatalJaundiceMay2010

MillarAJW,SharifK.SurgeryforBiliaryTractProblemsinChildren.Paediatricsand
ChildHealth.2008:18(6):278282

GupteG.ConjugatedHyperbilirubinaemia.PaediatricsandChild
Health.2008:18(10):474476

Dr Louise Wells

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