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Constipationininfantsandchildren:Evaluation
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Constipationininfantsandchildren:Evaluation
Author
ManuRSood,FRCPCH,MD
SectionEditor
BUKLi,MD
DeputyEditor
AlisonGHoppin,MD
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jan2016.|Thistopiclastupdated:Apr01,2015.
INTRODUCTIONConstipationaffectsupto30percentofchildrenandaccountingforanestimated3to5
percentofallvisitstopediatricians[1].Thepeakprevalenceisduringthepreschoolyearsinmostreports.
Thereisnoconsistenteffectofgenderontheprevalenceofchildhoodconstipation.
Complaintsrangefrominfrequentbowelevacuation,hardsmallfeces,difficultorpainfulevacuationoflarge
diameterstools,andfecalincontinence(voluntaryorinvoluntaryevacuationoffecesintotheunderwear,also
knownasencopresis)[2,3].Mostbutnotallchildrenwithfecalincontinencehaveunderlyingconstipation.
Functionalconstipationisresponsibleformorethan95percentofcasesofconstipationinhealthychildrenone
yearandolder,andisparticularlycommonamongpreschoolagedchildren[4].Althoughitiscommon,itis
importanttoevaluateaffectedchildrentoidentifythefewthathaveorganiccausesofconstipation.Moreover,
childrenwithfunctionalconstipationwillbenefitfrompromptandthoroughtreatmentinterventions.Delayedor
inadequateinterventionmayresultinstoolwithholdingbehaviorwithworseningconstipationandpsychosocial
consequences.
Theevaluationofaninfantorchildwithconstipationinchildrenwillbereviewedhere.Relatedinformationis
availableinthefollowingtopicreviews:
(See"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis".)
(See"Functionalfecalincontinenceininfantsandchildren:Definition,clinicalmanifestationsand
evaluation".)
(See"Chronicfunctionalconstipationandfecalincontinenceininfantsandchildren:Treatment".)
(See"Preventionandtreatmentofacuteconstipationininfantsandchildren".)
EVALUATIONEvaluationofachildwithconstipationreliesprimarilyonafocusedhistoryandphysical
examinationfurthertestingisperformediftheinitialevaluationraisesconcernforanorganiccauseof
constipation.
HistoryThehistoryshouldfocusonfeaturesthatsuggestfunctionalconstipation(table1)andalsoassess
forfeaturesthatraiseconcernforsomerarebutseriousorganiccausesofthesymptom(table2).Thehistory
shouldbeobtainedfromtheparentsorcaretakers,andalsofromthechild,ifthisisappropriateforhisorher
age.Thepartnershipestablishedwiththefamilyshouldcontinueuntiltheconstipationisresolved,toensure
thatsymptomsdonotprogressandbecomemoreproblematic[5].
Inaninfant,apparentstrainingduringdefecationdoesnotnecessarilyindicateconstipation.Ifaccompaniedby
thepassageofsoftstoolsinanotherwisehealthyinfant,thissymptomisknownas"infantdyschezia"(see
"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Infant
dyschezia').Organiccausesofconstipationshouldbeconsideredifthestrainingbehaviorisaccompaniedby
hardstoolsorifwarningsignsarepresent.Themostimportantorganiccausesofconstipationininfantsare
Hirschsprungdiseaseandcysticfibrosis.Inparticular,ahistoryofdelayedpassageofmeconiumshouldraise
concernsaboutthepossibilityofHirschsprungdisease,asmorethan90percentofnormalnewbornsbutonly
10percentofinfantswithHirschsprungdiseasepassmeconiumwithinthefirst24hoursoflife.(See
"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon
'Differentialdiagnosis'and'Alarmsigns'below.)
AlarmsignsAlarmsignsfromthehistorythatsuggestthepossibilityoforganiccausesinclude(table3)
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[6,7]:
Acutesigns
Delayedpassageofmeconium(firstmeconiumpassedafter48hoursoflife)(table4)
Fever,vomiting,ordiarrhea
Rectalbleeding(unlessattributabletoananalfissure)
Severeabdominaldistension
Chronicsigns
Constipationpresentfrombirthorearlyinfancy
Ribbonstools(verynarrowindiameter)
Urinaryincontinenceorbladderdisease
Weightlossorpoorweightgain
Delayedgrowth(eg,decreasingheightpercentiles)
Extraintestinalsymptoms(especiallyneurologicdeficits)
CongenitalanomaliesorsyndromesassociatedwithHirschsprungdisease(eg,Downsyndrome)
FamilyhistoryofHirschsprungdisease
PsychosocialandenvironmentalfactorsWhenfunctionalconstipationissuspected,particular
attentionshouldbegiventopsychosocialorenvironmentalfactorsthatmayhaveinfluencedthechild'sbowel
activities.Thesefactorsincludeahistoryofpainfulevacuation,difficultieswithtoilettraining,stoolwithholding,
introductionofcow'smilk,anddiet.Dietaryfactorsthatsometimescontributetoconstipationincludelowfiber
content(fewfruitsorvegetables)andlowfluidintake,althoughtheseassociationsareweak.(See"Functional
constipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Etiology'.)
Findingssupportingafunctionaletiologyinclude:
Onsetofconstipationcoincideswithdietarychange(eg,introductionofcow'smilk),toilettraining,or
painfulbowelmovement
Stoolwithholdingbehavior(table5)
Goodresponsetoconventionallaxatives
Iffeasible,parentsshouldprepareafivetosevendaysymptomanddietaryhistorybeforebringingthechildfor
theevaluation[8],takingcaretorecordstoolfrequency,appearance,andanypaininvolved.Thepointatwhich
theconstipationwasfirstnoted,andanypotentialrelationshipwithacoincidentevent,shouldbesought.
ConstipationandbladderdysfunctionAnorectalandlowerurinarytractfunctionareinterrelated.Asa
result,constipationisoftenassociatedwithbladderdysfunction,includingbladderoveractivity(urge),increased
ordecreasedvoidingfrequency,andbladderunderactivity[9].Thisrelationshipbetweenabnormalboweland
bladderfunctionisreferredtoasthebowelbladderdysfunction,alsoknownasdysfunctionalelimination
syndrome.Althoughbladderdysfunctioniscommonlyassociatedwithfunctionalconstipation,neurogenic
disordersmustalsobeexcluded.Successfultreatmentoftheconstipationisanimportantcomponentof
treatingthebladderdysfunction[10].(See"Etiologyandclinicalfeaturesofbladderdysfunctioninchildren",
sectionon'Constipationandbowelbladderdysfunction'.)
PhysicalexaminationThephysicalexaminationshouldincludeanevaluationoftheperianalarea,including
theappearanceandlocationoftheanus,andsensoryandmotorfunction.Adigitalrectalexaminationis
includedforselectedcases(table1andtable3)[7]:
ExternalexaminationThegeneralphysicalexaminationshouldincludeassessmentofgrowthand
abdominaldistension,andabdominalorpelvicmasses.Findingssuggestiveofspinaldysraphisminclude
sensoryandmotordeficits,apatulousanus,urinaryincontinence,anabsentcremastericreflex,increased
pigmentation,vascularnevi,orhairtuftsinthesacrococcygealarea[11].(See"Closedspinaldysraphism:
Clinicalmanifestations,diagnosis,andmanagement",sectionon'Cutaneous'and"Functionalconstipationin
infantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Differentialdiagnosis'and
"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Other
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causes'.)
Onneurologicexamination,findingssuggestingneurologicdysfunction(duetospinaldysraphismorother
cause)includeapatulousanus,absentanalwink,absentcremastericreflex,decreasedlowerextremitytoneor
strength,andabsenceofadelayintherelaxationphaseofthelowerextremitydeeptendonreflexes(which
suggestshypertonia).
Theperineumshouldbeinspectedforabnormalitiesofanorectaldevelopment,whichrepresentaspectrum
fromhighimperforateanustoanteriorlydisplacedanus(figure1)[12].Whenthecommunicationisabnormally
closetothefourchetteorscrotum,theanusisconsidered"anteriorlydisplaced"or"ectopic".Ananteriorly
displacedanusiseasilyoverlooked.Theabnormalityissuggestedbynotingthattheanalopeningisnot
locatedinthecenterofthepigmentedareaoftheperineum(picture1AB).Thediagnosisissupportedby
measuringtheAnalPositionIndex(API),whichisdefinedastheratiooftheanusfourchette/scrotumdistance
tothecoccyxfourchette/scrotumdistance.Measurementsaremosteasilymadebyplacingastripofclear
tapeonthelongitudinalaxisoftheperineum,markingthepositionsofthecoccyx,anus,and
fourchette/scrotum,thenremovingthetapeformeasurementagainstastandardruler.Normalratiosare
discussedelsewhere.(See"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferential
diagnosis",sectionon'Anorectalanomalies'.)
DigitalanorectalexaminationAdigitalanorectalexaminationisnotroutinelynecessaryforthe
evaluationofpatientswithatypicalhistoryandsymptomsoffunctionalconstipation.Thisisbecausethe
digitalanorectalexaminationisunpleasantforthechildandhasonlymoderatesensitivityandspecificityfor
detectingorconfirmingconstipationinthisgroupofpatients[7].However,someprovidersperformadigital
examinationinselectedcasesofsuspectedfunctionalconstipationbecauseitmayrevealafecalimpaction
thatrequiresacleanoutapproach(initiationoftreatmentwithhighdosesoflaxativesand/orenemas),orthe
presenceofoccultbloodthatrequiresfurtherdiagnostictesting.
Adigitalexaminationissuggestedforthefollowinggroupsofpatients[7]:
Infantswithconstipation
Childrenwithsymptomssinceearlyinfancy
Infantsorchildrenwithotheralarmsignsthatsuggestorganicdisease(table3)
Childreninwhomthepresenceordegreeofconstipationisunclear(eg,meetingonlyoneRomeIII
criterion)
FindingssuggestiveofHirschsprungdiseaseincludeatightanalcanalwithanemptyampulla.Theremaybe
anexplosivereleaseofgasandstoolafterthedigitalrectalexamination(squirtsignorblastsign),whichmay
relievetheobstructiontemporarily.Inaddition,infantswithHirschsprungdiseaseoftenhavegrossdistentionof
theabdomenandfailuretothrive.(See"Congenitalaganglionicmegacolon(Hirschsprungdisease)"and
"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon
'Hirschsprungdisease'.)
Findingssuggestiveoffunctionalconstipationareadistendedrectumthatisfullofstool.However,lackof
stooldoesnotexcludethepossibilityoffunctionalconstipation.
Testingofthestoolforoccultblood(guaiactesting,eg,Hemoccult),shouldbeperformedinmostcasesifstool
isavailablefromthedigitalrectalexaminationordiaper.Thisisparticularlyimportantininfantswith
constipation,inwhomsubclinicalmilkproteinintolerance(orotherfoodproteinintolerance)maypresentas
constipation(see"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",
sectionon'Cow'smilkintolerance').Ininfantsandchildrenwithmarkedabdominaldistensionorwhoareill
appearing,stoolswithvisibleoroccultbloodmayindicateenterocolitis,andthepatientrequiresurgentfurther
evaluation.(See"EmergencycomplicationsofHirschsprungdisease",sectionon'Enterocolitis'and
"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon
'Hirschsprungdisease'.)
DIAGNOSISOFFUNCTIONALCONSTIPATION
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DiagnosticcriteriaAMultinationalWorkingTeamdevelopedcriteriaforfunctionalgastrointestinaldisorders
knownastheRomeIIIcriteria[13,14].Forchildrenwithdevelopmentalageoffouryearsorolder,functional
constipationisdefinedbythepresenceofatleasttwoofthefollowingsymptomsoccurringforatleasttwo
months(table6):
Twoorfewerdefecationsperweek
Atleastoneepisodeoffecalincontinenceperweek
Historyofretentiveposturingorexcessivevolitionalstoolretention(stoolwithholding)
Historyofpainfulorhardbowelmovements
Presenceofalargefecalmassintherectum
Historyoflargediameterstoolsthatmayobstructthetoilet
Forinfantsandtoddlers,thecriteriaaremodifiedtoonemonthdurationofsymptomsandtoreflectage
appropriatetoiletingskills.
ExclusionoforganiccausesThediagnosisoffunctionalconstipationalsorequiresexclusionoforganic
causesofthesymptom.Organiccausesareresponsibleforfewerthan5percentofchildrenwithconstipation
[11,15],butaremorecommonamongyounginfants,andamonginfantsandchildrenpresentingwithatypical
featuresoralarmsigns(table3)(see'Alarmsigns'above).Themaincausesarelistedinthetable(table2)
anddetailedinaseparatetopicreview.(See"Functionalconstipationininfantsandchildren:Clinicalfeatures
anddifferentialdiagnosis",sectionon'Differentialdiagnosis'.)
Particularattentionshouldbepaidtothefollowingcauses,whicharerelativelycommonorrequireurgent
diagnosis:
CommonorganiccausesCowsmilk(orotherdietaryprotein)intoleranceceliacdisease
Urgentcauses
InfantsHirschsprungdisease,spinaldysraphism,sacralteratoma,infantilebotulism
AllagesCysticfibrosis,leadpoisoning,intestinalobstruction
FURTHERTESTINGInmostcases,organiccausesofconstipationcanbeexcludedonthebasisofa
carefulhistoryandphysicalexamination.Ifwarningsignsofpossibleorganicconstipationarepresent,focused
laboratoryandradiographictestingshouldbeperformed.Inaddition,thesetestsmaybeappropriateforpatients
whofailtorespondtoawellconceivedandcarefullyadministeredinterventionprogram,includingdisimpaction,
frequentandeffectiveuseoflaxatives,andbehavioralmanagement.(See"Chronicfunctionalconstipationand
fecalincontinenceininfantsandchildren:Treatment".)
Imaging
AbdominalradiographAplainabdominalradiographisnotindicatedfortheroutineevaluationof
functionalconstipation[7].However,itcanbehelpfultodocumentretainedstoolwhenthereis
inadequatehistoricalinformationtodetermineifthepatienthasconstipationorifthephysicalexamination
islimitedbypatientcooperation,obesity,orisdeferredforpsychologicalconsiderations.Itshouldbe
recognizedthatabdominalradiographsareinconsistentlyinterpretedbydifferentobservers,arenot
particularlyspecificforconstipation,andrarelyaddtothediagnosisiftherectalexaminationrevealsa
largeamountofretainedstool[7,16,17].Thus,theyarenotanessentialpartoftheevaluationof
constipationandshouldnotbeusedasasubstituteforathoroughhistoryandphysicalexamination.
BariumenemaAbariumenemaprovidessupportiveevidenceforHirschsprungdiseaseinchildrenwith
featuressuggestiveofthisdisorder,suchasearlyonsetconstipationfromtheneonatalperiod,especially
withdelayedpassageofmeconium,orsuggestivefindingsonanorectalexamination.Thestudyshould
beperformed"unprepped",ie,withoutmeasurestoremovestoolfromtherectum(image1AB).Some
providersuseanorectalmanometryastheinitialinvestigationorproceeddirectlytorectalbiopsy.Invery
younginfants,thebariumenemamaybenormalandthediagnosismustbeestablishedbyrectalbiopsy.
(See"Congenitalaganglionicmegacolon(Hirschsprungdisease)"and"Functionalconstipationininfants
andchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Hirschsprungdisease'.)
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SpineradiographsPlainfilmsofthelumbosacralspineshouldbeperformedforchildrenwithevidence
ofspinaldysraphismorneurologicalimpairmentoftheperianalareaorlowerextremities.Ifthereisahigh
suspicionofneurologicdysfunction,magneticresonanceimaging(MRI)shouldbeconsideredto
investigatethepossibilityoftetheredcordandspinalcordtumors[7,18,19].(See"Closedspinal
dysraphism:Clinicalmanifestations,diagnosis,andmanagement".)
LaboratorytestsWesuggestlaboratorytestingatthetimeoftheinitialevaluationinpatientswithsignsor
symptomssuggestiveofanorganiccauseofconstipation,suchasthefollowingclinicalsituations:
CeliacscreeningForchildrenwithfailuretothriveorrecurrentabdominalpain,performacomplete
bloodcountandserologicscreeningforceliacdisease(usuallyIgAantibodiestotissue
transglutaminase).Thesymptomsofceliacdiseasemaybesubtle.Therefore,wehavealowthreshold
forperformingceliacscreeninginchildrenwithconstipation,despitelimitedinformationaboutitsclinical
utilityinthispopulation.(See"Epidemiology,pathogenesis,andclinicalmanifestationsofceliacdisease
inchildren"and"Diagnosisofceliacdiseaseinchildren".)
UrineanalysisandcultureForchildrenwithahistoryofrectosigmoidimpaction,especiallyin
associationwithencopresis[2022],performaurineanalysisandurineculture.Thisisbecausefecal
impactionmaypredisposetourinarytractinfectionsduetothemechanicaleffectsofthedistended
rectumcompressingthebladder.
ThyroidstimulatinghormoneForchildrenwithimpairedlineargrowthanddepressedreflexes,or
thosewithahistoryofcentralnervoussystemdisease,wesuggestscreeningforhypothyroidism.A
growthvelocitylessthan5cm/year(1.6inches/year)suggeststhepossibilityofgrowthfailurein
prepubertalchildren.Ifcentralhypothyroidismissuspected,thescreenshouldincludemeasurementof
freethyroxine(T4)aswellasthyroidstimulatinghormone(TSH).(See"Acquiredhypothyroidismin
childhoodandadolescence".)
ElectrolytesandcalciumForchildrenatriskforelectrolytedisturbances(eg,thosewithmetabolic
abnormalitiesorinabilitytotolerateadequatefluids),wesuggestmeasuringserumconcentrationsof
electrolytesandcalcium.
BloodleadlevelScreeningforleadtoxicityshouldbeperformedinchildrenwithriskfactors.
Screeningrecommendationsvarybycommunity.Childrenatparticularriskincludethosewithpica,
developmentaldisabilities,orafamilyhistoryofleadpoisoninginasibling,orthoselivinginhousingbuilt
before1950orhousingthatrecentlyhasbeenrenovated.(See"Childhoodleadpoisoning:Clinical
manifestationsanddiagnosis"and"Screeningtestsinchildrenandadolescents",sectionon'Lead
poisoning'.)
Thislistisnotexhaustiveandspecificlaboratorytestingmaybeconsideredinanypatientwithanatypical
presentation.
MotilitytestingMotilitytestingistypicallyconsideredinpatientswhohavenoobviousorganiccauseof
constipationandwhofailtorespondtovigoroustreatmentoffunctionalconstipation.
ColontransitstudiesAcolonictransitstudyisnothelpfulfortheroutineevaluationofachildwith
constipationbecausetheresultsrarelyaltermanagement[7].Thesestudieshelptoidentifysubsetofchildren
withintractableconstipationthathasabnormallyslowmovementoffoodresiduethroughthecolon,acondition
referredtoas"slowtransit"constipation.Slowtransitconstipationisaclinicaldescriptionratherthanadisease
becauseitremainsunclearwhetherthisgroupofchildrenisdistinctfromthosewithfunctionalconstipation,
manyofwhomhaverelativelydelayedcolonictransit.Acolonictransitstudyisgenerallyreservedforthe
secondaryevaluationofselectedpatientsinwhomthediagnosisisuncleardespiteathoroughinitialevaluation
andtrialsoftreatment.Inparticular,itmaybeusefultohelpdistinguishbetweenretentive(constipation
associated)fecalincontinenceandnonretentivefecalincontinence[7].Onesmallstudyreportedthatchildren
withnormalcolontransitalsohaveanormalcolonmanometrystudy[23].Therefore,acolontransitstudy(eg,
Sitzmarkstudy)mayhelptoscreenforpatientswhomayrequirefurtherevaluationwithcolonmanometry.
Somechildrenwithconstipationandslowcolontransitdevelopchronicintractablediseaseandhaveapoor
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outcome.Thisismorelikelyinchildrenwithonsetofsymptomsbeforethreeyearsofage,severesymptoms
(passinglessthanonestoolaweek),andlackofresponsetooptimalstandardtherapywithlaxativesand
behavioralintervention.Wesuggestearlyreferraltoagastroenterologistforpatientswiththisprofile.These
patientscanbenefitfromevaluationofcolontransittimeandmotilitystudiestoassessforacolon
neuromuscularabnormality.(See"Chronicfunctionalconstipationandfecalincontinenceininfantsand
children:Treatment",sectionon'Treatmentfailure'.)
Colonictransitstudiescanbeperformedusingavarietyofprotocols[24,25].Oneoftheeasiesttechniquesis
tohavethechildswallowacapsulecontaining24radiopaquemarkers(Sitzmarkcapsules)onceadayforthree
days.Plainradiographsaretakenonthefourthday(andsometimesalsoontheseventhday),andanalyzedfor
thenumberandlocationofretainedmarkers[25].Ideally,anyfecalimpactionshouldberelieved,andlaxatives
shouldbediscontinuedseveraldayspriortoperformingthestudy.
Thecolonictransittime(CTT)canthenbecalculatedwiththefollowingformula:
Fortheday4films:
Colonictransittime(hours)=#markersremainingx1.0
(where1.0=72hours/72markersingested)
Fortheday7films:
Colonictransittime(hours)=#markersremainingx2.3
(where2.3=168hours/72markersingested)
Ifcapsulescontaining20(ratherthan24)radiopaquemarkersareused,theconstant1.2isusedfortheday4
calculation,and2.8fortheday7calculation.Ifthecapsulescontainingradiopaquemarkersarenotavailable,
segmentsofnumber10radiopaquenasogastrictubecutinto1cmlengthscanbeusedasmarkers,andthe
constantadjustedaccordingtothenumberofmarkersingested.Transittimealsomaybeanalyzedbycolonic
segment,usingsimilarcalculations.
Inonestudyofadolescents,CTTwas58.3forthosewithconstipationand30.2hoursforthosewithout
constipation[25].PediatricslowtransitconstipationisgenerallydefinedasCTT>100hours[26].Mostchildren
withslowtransitconstipationhavenoidentifiableunderlyingdisease.Typicalfeaturesofchildrenwithslow
transitconstipationaredelayedpassageofthefirstmeconiumstoolbeyond24hoursofage,symptomsof
severeconstipationwithinayear,ortreatmentresistantencopresisattwotothreeyearsofage,andsoft
stoolsdespiteinfrequentbowelactions[26,27].Theyaremanagedinthesamewayasotherchildrenwith
functionalconstipation,buttheyhaveaworseprognosisforpromptrecovery[28].Suchchildrenmayrequire
furtherevaluationandmayrespondtostimulantlaxatives.Afewhavedisordersassociatedwithcolonic
dysmotility,whichincludeintestinalneuronaldysplasiaandintestinalneuronaldysplasiatypeB.(See
"Functionalconstipationininfantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Other
causes'.)
Thisstudyalsomayhelptoidentifypatientswithoutletobstruction,manifestedbyaccumulationofmarkersin
therectosigmoidarea.PatientswithoutletobstructionmayrequireabiopsytoevaluateforHirschsprung
diseaseorotherneuromusculardisorders[11].However,thispatternalsomaybeseeninpatientswithfecal
impactionandinthosewithabnormalresponsesofthepelvicfloormusclesduringdefecation.(See"Etiology
andevaluationofchronicconstipationinadults",sectionon'Outletdelay'and"Functionalconstipationin
infantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Differentialdiagnosis'.)
AnorectalmanometryAnorectalmanometryinvolvesplacementofacathetercontainingpressure
transducingsensorsintotherectum,therebypermittingmeasurementofneuromuscularfunctionofthe
anorectum.Theprocedureincludesmeasurementsoftherectoanalinhibitoryreflex(whichisabsentin
Hirschsprungdisease),rectalsensationandcompliance,andsqueezepressures.Thetestisperformedmainly
inchildrenwithintractableconstipationthatrestrictstheirlifestyle,orwhenthereissuspicionofinternalanal
sphincterachalasia,orHirschsprungdisease[11,20,2931].Anorectalmanometryalsocanidentifypatients
withdyssynergicdefecation,whichisafunctionaldisordercharacterizedbytheincompleteevacuationoffecal
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materialfromtherectumduetoparadoxicalcontractionorfailuretorelaxpelvicfloormuscleswhenstrainingto
defecate.Thechancesofartifactduetocathetermovement(whichcanmimicrectoanalinhibitoryresponse)
arehigherinchildrenlessthansixmonthsofage.DefinitivediagnosisofHirschsprungdiseaseismadeby
rectalbiopsy.(See"Congenitalaganglionicmegacolon(Hirschsprungdisease)"and"Functionalconstipationin
infantsandchildren:Clinicalfeaturesanddifferentialdiagnosis",sectionon'Differentialdiagnosis'.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasics
andBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoread
materials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.
Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepth
informationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Constipationinchildren(TheBasics)"and"Patientinformation:
Hirschsprungdisease(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Constipationininfantsandchildren(Beyondthe
Basics)")
SUMMARYANDRECOMMENDATIONSThefollowingrecommendationsareconsistentwithguidelines
developedbytheNorthAmericanSocietyforPediatricGastroenterology,Hepatology,andNutrition
(NASPGHAN)andendorsedbytheAmericanAcademyofPediatrics(AAP)(availableat:www.naspghan.org)
[7].
Functionalconstipationisresponsibleformorethan95percentofcasesofconstipationinhealthy
childrenoneyearandolder,Itisdefinedbythepresenceofatleasttwoofsixcriteriadescribingstool
frequency,hardness,size,fecalincontinence,orvolitionalstoolretention(table6).Thesymptomsmust
bepresentforonemonthininfantsandtoddlers,andtwomonthsinolderchildren.Thediagnosisalso
requiresexclusionoforganiccausesofthesymptoms.Functionalconstipationusuallycanbediagnosed
baseduponthehistoryandphysicalexamination.Keyelementsofthehistoryandphysicalexamination
areoutlinedinthetable(table1).(See'Diagnosisoffunctionalconstipation'above.)
Organiccausesareresponsibleforfewerthan5percentofchildrenwithconstipation(table2),butare
morecommonamongyounginfants.Particularattentionshouldbegiventopatientswithalarmsigns
(table3)orotherelementsofthehistoryandphysicalexaminationthatraisesuspicionforanorganic
cause(table3).(See'Alarmsigns'above.)
SignsandsymptomssuggestiveofHirschsprungdiseaseincludedelayedpassageofmeconium
(after48hoursoflife),failuretothriveordelayedgrowth,vomiting,abdominaldistension,atight
analcanalwithanemptyampulla,oranexplosiveexpulsionofstoolafterthedigitalexamination
(squirtsign).Hirschsprungdiseaseshouldbeparticularlyconsideredforinfantspresentingwith
constipationduringtheneonatalperiod.Othercausesofconstipationordelayedpassageof
meconiumintheearlyneonatalperiodarelistedinthetable(table4).(See"Congenitalaganglionic
megacolon(Hirschsprungdisease)".)
Cow'smilkmaycauseconstipationininfantsandyoungchildren.Thediagnosisissuggestedby
onsetofsymptomsthatcoincidewithanincreaseincow'smilkinthedietandisgenerally
confirmedandtreatedbysubstitutionofsoyorhydrolyzedproteinintheformula.(See
'Psychosocialandenvironmentalfactors'aboveand"Functionalconstipationininfantsandchildren:
Clinicalfeaturesanddifferentialdiagnosis",sectionon'Cow'smilkintolerance'.)
Celiacdiseaseiscommonandoccasionallyisassociatedwithconstipation.Asaresult,wehavea
lowthresholdforperformingceliacscreeninginchildrenwithconstipation,bymeasuringceliac
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specificantibodies(usuallyIgAantibodiestotissuetransglutaminase).(See'Laboratorytests'
above.)
Laboratoryandradiographictestingshouldbeselectivelyperformedbaseduponthehistoryandphysical
examination.Forthemajorityofchildrenwhosepresentationistypicaloffunctionalconstipation,
laboratorytestingispursuedonlyifthepatientfailstorespondtoawellconceivedandcarefully
administeredinterventionprogram,includingdisimpaction,frequentandeffectiveuseoflaxatives,and
behavioralmanagement.Incontrast,laboratorytestingshouldbeperformedearlyinpatientswithsignsor
symptomssuggestiveofanorganiccauseofconstipation.(See'Furthertesting'above.)
ACKNOWLEDGMENTTheeditorialstaffatUpToDatewouldliketoacknowledgeGeorgeDFerry,MD,
whocontributedtoanearlierversionofthistopicreview.
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1.vandenBergMM,BenningaMA,DiLorenzoC.Epidemiologyofchildhoodconstipation:asystematic
review.AmJGastroenterol2006101:2401.
2.RubinGP.Childhoodconstipation.AmFamPhysician200367:1041.
3.LoeningBauckeV.Chronicconstipationinchildren.Gastroenterology1993105:1557.
4.LoeningBauckeV.Prevalence,symptomsandoutcomeofconstipationininfantsandtoddlers.JPediatr
2005146:359.
5.ProcterE,LoaderP.A6yearfollowupstudyofchronicconstipationandsoilinginaspecialistpaediatric
service.ChildCareHealthDev200329:103.
6.LeungAK,ChanPY,ChoHY.Constipationinchildren.AmFamPhysician199654:611.
7.TabbersMM,DiLorenzoC,BergerMY,etal.Evaluationandtreatmentoffunctionalconstipationin
infantsandchildren:evidencebasedrecommendationsfromESPGHANandNASPGHAN.JPediatr
GastroenterolNutr201458:258.
8.ArceDA,ErmocillaCA,CostaH.Evaluationofconstipation.AmFamPhysician200265:2283.
9.BurgersRE,MugieSM,ChaseJ,etal.Managementoffunctionalconstipationinchildrenwithlower
urinarytractsymptoms:reportfromtheStandardizationCommitteeoftheInternationalChildren's
ContinenceSociety.JUrol2013190:29.
10.FengWC,ChurchillBM.Dysfunctionaleliminationsyndromeinchildrenwithoutobviousspinalcord
diseases.PediatrClinNorthAm200148:1489.
11.DiLorenzoC.Pediatricanorectaldisorders.GastroenterolClinNorthAm200130:269.
12.HendrenWH.Pediatricrectalandperinealproblems.PediatrClinNorthAm199845:1353.
13.RasquinA,DiLorenzoC,ForbesD,etal.Childhoodfunctionalgastrointestinaldisorders:
child/adolescent.Gastroenterology2006130:1527.
14.HymanPE,MillaPJ,BenningaMA,etal.Childhoodfunctionalgastrointestinaldisorders:
neonate/toddler.Gastroenterology2006130:1519.
15.ThiessenPN.Recurrentabdominalpain.PediatrRev200223:39.
16.PensabeneL,BuonomoC,FishmanL,etal.Lackofutilityofabdominalxraysintheevaluationof
childrenwithconstipation:comparisonofdifferentscoringmethods.JPediatrGastroenterolNutr2010
51:155.
17.BergerMY,TabbersMM,KurverMJ,etal.Valueofabdominalradiography,colonictransittime,and
rectalultrasoundscanninginthediagnosisofidiopathicconstipationinchildren:asystematicreview.J
Pediatr2012161:44.
18.RosenR,BuonomoC,AndradeR,NurkoS.Incidenceofspinalcordlesionsinpatientswithintractable
constipation.JPediatr2004145:409.
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20.AbiHannaA,LakeAM.Constipationandencopresisinchildhood.PediatrRev199819:23.
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22.LoeningBauckeV.Urinaryincontinenceandurinarytractinfectionandtheirresolutionwithtreatmentof
chronicconstipationofchildhood.Pediatrics1997100:228.
23.TipnisNA,ElChammasKI,RudolphCD,etal.Dooroanaltransitmarkerspredictwhichchildrenwould
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24.LoeningBaucke,V.Constipationandencopresis.In:PediatricGastroenterologyandNutritioninClinical
Practice.LifschitzCH(Ed),MarcelDekker,NewYork2001.p.551.
25.ZaslavskyC,daSilveiraTR,MaguilnikI.Totalandsegmentalcolonictransittimewithradioopaque
markersinadolescentswithfunctionalconstipation.JPediatrGastroenterolNutr199827:138.
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GRAPHICS
Evaluationofaninfantorchildwithconstipation
History
Implications
Wastheredelayed
SuggestsHirschsprungdisease
passageofmeconium
(ie,firstmeconiumafter
48hoursoflife)?
Onsetofconstipation:
Wasconstipation
Morelikelytobeanorganiccause(eg,Hirschsprungdisease)
presentfrombirthor
earlyinfancy?
Wastherea
Suggestsfunctionalconstipation
precedingchangein
dietordiarrheal
illness?
Wastheonset
Suggestsfunctionalconstipation
aroundthetimeof
toilettraining,or
aroundaprecipitating
event?
Werethereproblems
withtoilettraining?
(eg,childresistance,
Suggestsfunctionalconstipation
fearorlatemastery)
Stoolqualityand
appearance:
Isdefecationpainful?
Suggestsfunctionalconstipation
Arethestoolshardor
soft?
Softstoolssuggestscauseotherthanconstipation(eg,dyscheziain
aninfant)
Doesthestoolform
Supportsdiagnosisoffunctionalconstipation
pelletsinthediaper
ortoilet?Dothey
clogthetoilet?
Istherebloodonthe
stool?
Possibleanalfissure,whichcancauseorresultfromfunctional
constipation
Ifthechildistoilet
Indicatesfecalincontinence,whichisusuallyduetofunctional
trained,doesheorshe
have"accidents"inthe
constipationandwithholding,leadingtofecalimpaction
underwear?
Doesthechildhave
stoolwithholding
behavior?("dance",hide
Suggestsfunctionalconstipation,withstoolwithholding
orappeartobetrying
nottohaveabowel
movement)
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Dietaryissues:
Isthedietunusual?
Lowfluidintakeoccasionallycontributestoconstipation
Aretheresourcesof
fiber?Isthere
adequatefluid?
Didtheconstipation
coincidewitha
changeindiet?(eg,
Suggestsfunctionalconstipation,possiblycow'smilkprotein
intolerance
transitiontosolid
foodsininfants,orto
milk)
Arethereunderlying
Considerneurogeniccausesofconstipationsomecongenital
medicalproblems,
congenitalanomalies,
abnormalgrowth,or
syndromesareassociatedwithHirschsprungdisease(eg,
Downsyndrome).Congenitalmalformations,suchaskidneyand
urinarytractanomalies,alsoraiseconcernsforanorectal,sacraland
developmentaldelay?
spinalabnormalities,whichcaninterferewithdefecation.
Whattreatmentshave
beentried,andwhat
Informsclinicalmanagement
wastheresponse?
Isthereafamilyhistory
offunctional
constipation,
Eachofthesecauseshassomefamilialpatterns
Hirschsprungdisease,or
celiacdisease?
Physical
examination
Abdominaldistension
Severedistensionraisesconcernfororganicdisease
Palpablestoolmass
Consistentwithconstipationfromanycause,butlackofpalpable
stooldoesnotruleoutconstipation
Massinsuprapubicarea
Commonfindinginpatientswithrectalstoolimpaction,butcanalso
suggestsacralteratoma
Cutaneouschangesin
thelumbosacralarea
(dimple,hairtuft,
lipoma,ordeviationof
theglutealcleft)
Suggestsspinaldysraphism
Soiledunderwear(fecal
incontinence)
Inthepresenceofrectalstoolimpaction,suggestsoverflow
incontinenceandfunctionalconstipation
Absentanalwinkor
Suggestsneurologicdysfunction
cremastericreflex,
decreasedlower
extremitytoneor
strength
Analfissureorscarring
Analfissuresmaybeacauseoraconsequenceoffunctional
constipation
Anteriorlydisplaced
Suggestsanorectalanomaly
anus,orperianal
fistula
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Digitalrectal
examination:
Analsphinctertone
IncreasedtonesuggestsHirschsprungdisease,lowtonesuggest
neurogenicconstipation
Sizeofrectalvault
Largevaultisconsistentwithchronicfunctionalconstipation
Impactedstool(hard
orsoft)
Softstoolsuggestspossibilityofanorectaldysfunction,including
Hirschsprungdisease
Explosiveexpulsionof
stoolafterthe
examination(squirt
sign)
SuggestsHirschsprungdisease
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Causesofconstipationinchildren
Physiologiccausesofconstipation
Functionalconstipation*(mayhavedietaryorbehavioraltriggers,exacerbatedbypainful
defecationandstoolwithholding)
Cow'smilkorotherdietaryproteinintolerance*
Lowdietaryfiber*
Inadequatefluidintake(fever,hotweather)
Immobility
Anorexianervosa
Starvation
Neurogeniccauses
Hirschsprungdisease
Cerebralpalsy
Myelomeningocele
Spinalcordinjury
Closedspinaldysraphism (eg,tetheredcord,sacralagenesis,splitspinalcord
malformation[diastematomyelia])
Sacralteratoma
Neurofibromatosis
Muscularweakness(maybegeneralized,asinDownsyndrome,orduetoabnormal
abdominalmusculature, asinprunebellysyndromeorgastroschisis)
Infantilebotulism (constipationanearlycomplaint,facialandocularpalsies,poorsuck
andhypotoniaareotherfeatures)
Pseudoobstruction(eg,visceralneuropathies,myopathies,mitochondrialdisorders)
Intestinalneuronaldysplasia
Familialoracquireddysautonomia
Endocrineandmetaboliccauses
Cysticfibrosis (withmeconiumileusinneonates, ordistalintestinalobstructionsyndrome
inolderchildren)
Hypokalemia
Leadpoisoning
VitaminDintoxication
Hypoorhypercalcemia
Hypothyroidism
Diabetesmellitus
Pheochromocytoma
Multipleendocrineneoplasiatype2B(MEN2B)
Polyuria(leadingtodehydration)
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Juvenilesystemicsclerosis(scleroderma)ormixedconnectivetissuedisease
Acuteintermittentporphyria
Anatomiccauses
Anorectalanomalies(imperforateanus, anteriorlydisplacedanus)
Intestinalobstruction (inneonates,consideratresia,websorvolvulus)
Smallleftcolonsyndrome
Othercauses
Celiacdisease*
Drugs(opiates,anticholinergics,antidepressants,chemotherapy,aluminumcontaining
antacids)
*Relativelycommoncause.
Promptdiagnosisisimportanttotheoutcome.
Generallypresentsduringinfancy.
RefertoUpToDatetopicreviewsonclosedspinaldysraphism(spinabifidaocculta).
SimilarfindingsmayoccurininfantswithHirschsprungdisease.
Datafrom:
1.TunnessenWJ.Constipationandfecalretention.In:SignsandSymptomsinPediatrics,3rded,
Lippincott,Williams&Wilkins,Philadelphia1999.p.518.
2.TabbersMM,DilorenzoC,BergerMY,etal.EvaluationandTreatmentofFunctional
ConstipationinInfantsandChildren:EvidenceBasedRecommendationsFromESPGHANand
NASPGHAN.JPediatrGastroenterolNutr201458:265.
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Alarmsignsorphysicalfindingsthatsuggestanorganiccauseof
constipationinchildren
Symptomsorhistory
Acutesigns
Physicalfindings
Severeabdominaldistension
Delayedpassageofmeconium(after48
hoursoflife)
Pelvicmass(eg,sacralteratoma)
Fever,vomiting,ordiarrhea
Lumbosacraldimple,hairtuftorlipoma,or
deviationoftheglutealcleft
Rectalbleeding(unlessattributabletoan
analfissure)
Severeabdominaldistension
Chronicsigns
Constipationpresentfrombirthorearly
infancy
Ribbonstools(verynarrowindiameter)
Lowerspineabnormalities
Analscars
Anteriorlydisplacedanus
Patulousanus
Perianalfistula
Tightanalcanalwithemptyrectum
Urinaryincontinenceorbladderdisease
Explosiveexpulsionofstoolafterdigital
examinationoftherectum
Weightlossorpoorweightgain
Absentanalwink
Delayedgrowth(eg,decreasingheight
percentiles)
Absentcremastericreflex
Extraintestinalsymptoms(especially
neurologicdeficits)
Congenitalanomaliesorsyndrome
associatedwithHirschsprungdisease(eg,
Downsyndrome)
FamilyhistoryofHirschsprungdisease
Decreasedlowerextremitytoneor
strength
Abnormallowerextremitydeeptendon
reflex:absenceofdelayinrelaxation
phase
Abnormalthyroidgland
Extremefearduringtheanalinspection
BasedoninformationinTabbersMM,DilorenzoC,BergerMY,etal.EvaluationandTreatmentof
FunctionalConstipationinInfantsandChildren:EvidenceBasedRecommendationsFromESPGHAN
andNASPGHAN.JPediatrGastroenterolNutr201458:265.
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Diagnosestoconsiderininfantsandchildrenwithdelayed
passageofmeconium
Condition
Comments
Hirschsprung
Abdominaldistensionandvomitingarecommon.Ondigitalexamination,
disease
typicalfindingsareatightanalcanalwithemptyrectum,oftenwithan
explosive"squirt"ofsoftstoolwhenthefingeriswithdrawn.Oncontrast
enema,atransitionzonemaybeseen,butoftenisnotvisibleinnewborns.
Intestinal
Consideratresia,webs,orvolvulus.Obstructionmaybepresentevenin
obstruction
infantswhopassmeconium.
Meconiumileus
Symptomsoftenbeginonseconddayoflife.Mostpatientswithmeconium
ileushavecysticfibrosis.
Meconiumplug
syndrome
Causedbycolonicdysmotilityorabnormalmeconiumconsistency,
Functionalileus
Occursinsettingofprematurity,sepsis,respiratorydistress,pneumonia,or
leadingtoobstipationinthenewborn.Acontrastenemaisboth
diagnosticandtherapeutic.Somepatientswithmeconiumplug
syndromehaveHirschsprungdisease.
electrolytedisturbances.
Smallleft
colon*
Bariumenemashowssmallcaliberleftcolon.Increasedincidencewith
maternaldiabetes.
Drugs
administeredto
motherbefore
delivery
Magnesiumsulfate(MgSO4),opiates,organglionicblockingagents.
Hypothyroidism
Infantswithhypothyroidismalsomayhaveprolongedjaundice,lethargy,and
lowbodytemperature.
*SimilarfindingsmayoccurininfantswithHirschsprungdisease(HD),soaffectedinfantsshouldbe
observedcloselyandevaluatedforHDifappropriate.
Datafrom:TunnessenWJ.Constipationandfecalretention.In:SignsandSymptomsinPediatrics,
3rded,Lippincott,Williams&Wilkins,Philadelphia1999.p.518.
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Causesofvoluntarystoolwithholdingininfantsandchildren
Painfuldefecation
Analfissure
Perianalirritation
Sexualabuse
Hemorrhoids
Changeofenviroment
Newschool,traveling,orotherchangeinroutine
Familystress
Impropertoilettraining
Emotionaldisturbance
Severementalretardation
Depression
Datafrom:TunnessenWJ.Constipationandfecalretention.In:SignsandSymptomsinPediatrics,
3rded,Lippincott,Williams&Wilkins,Philadelphia1999.p.518.
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Spectrumofanorectalanatomyinthefemale
A)Normalanatomywithanusinnormallocationandperinealbodybetween
anusandvagina.B)Severeanomalywithrectumendinghighinthevagina.
Arrowheadsmarknormalanallocation.C)Lowanomalywithrectoperineal
fistula(fourchetteectopicanus),anteriortonormalanallocation.D)
Intermediatepositionofanalopeningintheperineum.
Reproducedwithpermissionfrom:HendrenWH.Pediatricrectalandperineal
problems.PediatrClinNorthAm199845:1353.Copyright1998Elsevier.
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Rectalshelfinathreemontholdgirlwithan
intermediateanorectalanomaly
A)Theanalopeningisexcentricallylocatedinpigmentedskinof
perineum.Theopeningisnotstenotic.B)Todemonstratethe
posteriorshelf,asurgicalclampisinsertedintotheanalopening,
pullingoutwardontheposteriorlipofanorectalcanal.
Reproducedwithpermissionfrom:HendrenWH.Pediatricrectalandperineal
problems.PediatrClinNorthAm199845:1353.Copyright1998Elsevier.
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Nineteenyearoldwomanwithlifelonghistoryof
severeconstipation
A)Inthis19yearoldwomanwithalifelonghistoryofconstipation,
theanusisclearlyanteriorlylocated,withashortperinealbody.
Normally,theanusshouldbelocatedintheshinypigmentedskin,
whichisposteriortoanalopeninginthispatient.B)Bariumenemain
thesamepatient.Thereismarkeddilatationofrectum,extendingto
theanus.Thisisthetypicalappearanceofsocalled"habit
constipation"or"psychogenic"constipation.However,someofthese
casesareprobablycausedbyunrecognizedslightanorectal
malformation,asinthiscase.Afteranoplasty,thispatientdeveloped
normaldefecationpatterns.
Reproducedwithpermissionfrom:HendrenWH.Pediatricrectalandperineal
problems.PediatrClinNorthAm199845:1353.Copyright1998Elsevier.
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RomeIIIcriteriaforthediagnosisoffunctionalconstipationin
children
Infantsandtoddlers
Atleasttwoofthefollowingpresentforatleast
onemonth
Twoorfewerdefecationsperweek
Atleastoneepisodeofincontinenceafterthe
acquisitionoftoiletingskills
Historyofexcessivestoolretention
Historyofpainfulorhardbowelmovements
Presenceofalargefecalmassintherectum
Historyoflargediameterstoolsthatmay
obstructthetoilet
Childrenwithdevelopmental
age4to18years
Atleasttwoofthefollowingpresentforat
leasttwomonths*
Twoorfewerdefecationsperweek
Atleastoneepisodeoffecalincontinence
perweek
Historyofretentiveposturingorexcessive
volitionalstoolretention
Historyofpainfulorhardbowelmovements
Presenceofalargefecalmassintherectum
Historyoflargediameterstoolsthatmay
obstructthetoilet
*Inaddition,thesymptomsareinsufficienttofulfillthediagnosticcriteriaofirritablebowel
syndrome.
Datafrom:
1.HymanPE,MillaPJ,BenningaMA,etal.Childhoodfunctionalgastrointestinaldisorders:
Neonate/toddler.Gastroenterology2006130:1519
2.RasquinA,DiLorenzoC,ForbesD,etal.Childhoodfunctionalgastrointestinaldisorders:
child/adolescent.Gastroenterology2006130:1527
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BariumenemainHirschsprungdisease
BariumenemaofaninfantwithHirschsprungdisease,showingthe
transitionzone(arrow)betweentheloweraganglionicbowelandthe
normalcolonabove.
CourtesyofGeorgeDFerry,MD.
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Functionalconstipation
Thisunpreppedbariumenemaiscompatiblewithfunctional
constipation.Therectumismildlydilatedwithstoolandthereisno
evidenceofobstruction.
CourtesyofGeorgeDFerry,MD.
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Disclosures
Disclosures:ManuRSood,FRCPCH,MDConsultant/AdvisoryBoards[Malabsorption(Sacrosidase)].EquityOwnership/Stock
Options(spouse/partner):AbbVieAbbott.Employment(spouse/partner):AbbVieNorelevantconflictontopic.BUKLi,MDNothing
todisclose.AlisonGHoppin,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvetting
throughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriately
referencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy
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