nical Guideline

Section: 1.1 Name of Guideline

Dr Louise Wells Page 1 of 9 Feb 2013
ProlongedNeonatalJaundice
Title of Guideline (must include the word Guideline (not
protocol, policy, procedure etc)
Guideline for the assessment and
management of prolonged neonatal
jaundice
Contact Name and Job Title (author)
Dr Louise Wells
Consultant Paediatrician Dr Damian
Wood
Consultant Paediatrician

Directorate & Speciality
Family Health
Paediatrics
Date of submission
18/02/2013

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
J aundice in Newborn Infants
Abstract
This guideline describes the
assessment, investigation and
management of prolonged neonatal
jaundice in infants.

Key Words
J aundice, neonatal,
hyperbilirubinaemia, biliary atresia

Statement of the evidence base of the guideline has the
guideline been peer reviewed by colleagues?

Evidence base: (1-5)
1a meta anal ysis 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 quasi-
experimental 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
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.
Consultation Process
Departmental Clinical Guidelines
Meeting
Neonatal Unit Clinical Guidelines

Target audience
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.
nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 2 of 9 Feb 2013
1.ProlongedNeonatalJaundice
Introduction
Prolongedneonataljaundice(hyperbilirubinaemia)isdefinedas:

visiblejaundicepersistingbeyondday14intermneonates
visiblejaundicepersistingbeyondday21inpreterminfants
(bornatlessthan37completedweeksgestation).
CausesofProlongedJaundice
Therearemanycausesofprolongedjaundiceinneonates.Thecommonestisbreast
milkjaundicewhichresolvesspontaneouslyovertime.Themainreasonfor
prolongedjaundicescreeningistopickupbiliaryatresiaasearlyaspossible.Belowis
alistofsomeoftheothercauses.

Unconjugated/Mixed Conjugated
Breastmilkjaundice
Haemolysis
Coombspositive
Rhesusincompatibility
AntiKell,antiDuffy
ABOincompatibility
Coombsnegative
Redcellmembrane
defectse.g.
sphero/elliptocytosis
Redcellenzyme
defectse.g.G6PD,
pyruvatekinase
deficiency
Haemoglobinopathy
Sepsis
Disseminated
intravascular
coagulation
Increasedenterohepaticcirculation
Pyloricstenosis
Intestinalobstruction
Decreasedconjugation(unconjugated)
CriglerNajjarsyndrome
Gilbert'sdisease
Hypothyroidism
Prematurity

Decreasedexcretion(conjugated)
Obstruction
Biliaryatresia
Choledochalcyst
Spontaneousbileduct
perforation
Hepatoblastoma,
haemangioma,neuroblastoma
Infection
Septicaemia,UTI
TORCHinfections,syphilis
Hepatitis,Varicellazoster,HIV
andotherviral
Inherited/metabolic/endocrine
a1antitrypsindeficiency
Alagille'ssyndrome
Cysticfibrosis
Galactosaemia,fructosaemia
Glycogenstoragediseases
Tyrosinosis
Hypermethioninaemia
Hypopituitarism/
hypoadrenalism
Mytochondrialcytopathies
PFICsyndromes
Chromosomaldisorders
Turner'ssyndrome
Trisomy13,18,21
Toxic/drugs
Fetalalcoholsyndrome
Idiopathicneonatalhepatitis
TPN/PN

nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 3 of 9 Feb 2013

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,
Alagilles syndrome). Assess Airway, Breathing, Circulation and Disability to identify
potential lifethreatening features. If you are concerned that the baby has
immediately life threatening features call for senior medical and nursing assistance
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
nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 4 of 9 Feb 2013

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
nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 5 of 9 Feb 2013
<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
nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 6 of 9 Feb 2013
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.

nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 7 of 9 Feb 2013
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). The hyperbilirubinaemia is unconjugated and there may be other evidence of
haemolysis including hepatosplenomegaly. In cases of haemolytic jaundice the
haemoglobinlevelandreticulocyteshouldbemonitoredtodetectanaemiaandthe
blood film examined along with testing for blood group incompatibility and red cell
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.
nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 8 of 9 Feb 2013

Amixedpictureofraisedunconjugatedandconjugatedbilirubinseeninthe
followingandappropriateinvestigationsdoneinthiscase:

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


AdviceforParents

Forwellinfantswhoseinvestigationshavebeencompleted:

ProvidetheparentswithacopyoftheParentInformationSheet
InformthePrimarycareteamandparentsofnormalscreeningresultsby
letter




nical Guideline
Section: 1.1 Name of Guideline
Dr Louise Wells Page 9 of 9 Feb 2013
References

NICEClinicalGuidelineCG98NeonatalJaundiceMay2010

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

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