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Gastroesophagealrefluxininfants

OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Gastroesophagealrefluxininfants
Author
HarlandSWinter,MD

SectionEditors
StevenAAbrams,MD
BUKLi,MD

DeputyEditor
AlisonGHoppin,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2016.|Thistopiclastupdated:Apr04,2016.
INTRODUCTIONThepassageofgastriccontentsintotheesophagus(gastroesophagealreflux,orGER)isa
normalphysiologicprocessthatoccursinhealthyinfants,children,andadults.Mostepisodesarebriefanddonot
causesymptoms,esophagealinjury,orresultinothercomplications.Incontrast,gastroesophagealrefluxdisease
(GERD)occurswhentherefluxepisodesareassociatedwithcomplicationssuchasesophagitisorpoorweight
gain.TherangeofsymptomsandcomplicationsofGERDinchildrenvarywiththeageofthechild.
ThediagnosisandmanagementofGERininfantswillbereviewedhere.Refluxinprematureinfants,andthe
clinicalmanifestations,diagnosis,andpathophysiologyofGERDinolderchildrenarediscussedseparately.(See
"Clinicalmanifestationsanddiagnosisofgastroesophagealrefluxdiseaseinchildrenandadolescents"and
"Gastroesophagealrefluxinprematureinfants"and"Managementofgastroesophagealrefluxdiseaseinchildren
andadolescents".)
Theseissuesarealsodiscussedinanofficialconsensusstatementandmanagementguidelinesissuedbythe
NorthAmericanSocietyofPediatricGastroenterology,HepatologyandNutrition(NASPGHAN),theEuropean
SocietyofPediatricGastroenterology,HepatologyandNutrition(ESPGHAN)[1],andtheAmericanAcademyof
Pediatrics(AAP)[2].ThefulltextoftheseguidelinesisavailableattheNASPGHANwebsite
(www.naspghan.org).
DEFINITIONSInthefollowingdiscussion,theterm"uncomplicated"gastroesophagealreflux(GER)isusedto
describethenormalphysiologicprocessoffrequentregurgitationintheabsenceofpathologicalconsequences.
Theterm,"gastroesophagealrefluxdisease"orGERD,isusedwhentherefluxhaspathologicalconsequences,
suchasesophagitis,nutritionalcompromise,orrespiratorycomplications.
Strictlyspeaking,theterm"regurgitate"describeseffortlessrefluxuptotheoropharynxorabove,and"vomit"
describesforcefulexpulsion(engagingabdominalandrespiratorymuscles)oftherefluxateoutofthemouth,but
notnecessarilyrepetitively.Thetermsarenotclearlydistinguishedandoftenusedinterchangeablyinclinical
practice.Inthisreview,wewillusetheterm"regurgitate"todescribeobviousGER,whetherornottherefluxate
comesoutsideofthemouthothercommonlyusedtermsare"spittingup"or"spilling."
EPIDEMIOLOGY
NaturalhistoryGastroesophagealreflux(GER)isextremelycommoninhealthyinfants,inwhomgastricfluids
mayrefluxintotheesophagus30ormoretimesdaily[3].Many,butnotalloftheserefluxepisodesresultin
regurgitationintotheoralcavity.Thefrequencyofreflux,aswellastheproportionofrefluxepisodesthatresultin
regurgitation,declineswithincreasingage,suchthatphysiologicregurgitationorvomitingdecreasestowardthe
endofthefirstyearoflife,andisunusualinchildrenolderthan18monthsold[46].
Inonestudyofhealthyinfantsyoungerthan13monthsofage,regurgitationatleastonceperdaywasreportedin
approximatelyonehalfof0to3montholdinfants,comparedwithonly5percentof10to12montholdinfants
[5].Regurgitationwasmostcommonaroundfourmonths(61percent),decreasingto21percentbetweensixand
sevenmonths.Thedescriptionofregurgitationasbeinga"problem"wasgivenby23percentofparentsofchildren
agedsixmonths,anddecreasedthereafter.Achangeinformula,thickeningoffeedings,terminationofbreast
feeding,anduseofmedicationtotreatregurgitationwerereportedbyparentstobebeneficialinsomechildren.In
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almostallchildrenwithregurgitationthatisconsideredtobeaproblembytheirparents,theconditionimproves
andusuallyresolvesbytheendofthefirstyearoflife[6].
AssociationofrefluxwithGERDAlthoughtherelationshipbetweenregurgitationduringchildhoodandthe
subsequentdevelopmentofGERDhasnotbeenwellstudied,onereportsuggestedthatfrequentepisodesof
regurgitationduringinfancymaybeassociatedwithanincreasedlikelihoodofhavingGERDsymptomsinlater
childhood[7].Thestudyincluded693childrenwhowerefollowedforthefirsttwoyearsoflifeandwerethen
recontacted8to11yearslater.Childrenwhohadahistoryoffrequentregurgitation(definedas>90daysof
"spilling"duringthefirsttwoyearsoflife)weresignificantlymorelikelytoreportGERDsymptomsduringfollowup
atnineyearsofage(relativerisk2.3,95%CI1.34.0).
GERDoccasionallyleadstoesophagealstricturesorBarrett'sesophagus.Thesecomplicationsoccurprimarilyin
childrenwithesophagealdysmotilitysecondarytorepairedesophagealatresia.Childrenwithcysticfibrosisare
alsomorelikelytohavetheseproblemsbecausetheyhavechroniccoughwhichinducesrefluxand,when
combinedwithimpairedbufferingcapacityoftheirsaliva,resultsinprolongedacidexposureinthedistal
esophagus.(See"Clinicalmanifestationsanddiagnosisofgastroesophagealrefluxdiseaseinchildrenand
adolescents",sectionon'Clinicalmanifestations'.)
TheprevalenceandclinicalriskfactorsforGERDinchildrenarediscussedinaseparatetopicreview.(See
"Clinicalmanifestationsanddiagnosisofgastroesophagealrefluxdiseaseinchildrenandadolescents",sectionon
'Prevalence'.)
CLINICALAPPROACHTheevaluationofaninfantwithfrequentregurgitationfocusesondeterminingifthe
symptomiscausedbyunderlyingpathologicaldisease,andiftherefluxiscausingsecondarycomplications.In
themajorityofinfants,afocusedhistoryandphysicalexaminationwillconfirmthattherefluxisuncomplicated,
andlittlefurtherevaluationorinterventionisrequired.
Thefirststepintheevaluationistodetermineiftheinfanthasanywarningsignsthatwouldsuggestanunderlying
disorderotherthangastroesophagealrefluxdisease(GERD),asoutlinedbelow.Thesecondstepistodetermineif
theinfanthassecondarycomplicationsofthereflux,suchasesophagitisorfailuretothrive.Thisstepisguidedby
whethertheinfanthasassociatedproblemswithweightgain,feedingrefusal,irritability,and/orgrossbloodinthe
emesisoroccultbloodinthestool.
WarningsignalsofunderlyingpathologyThepresenceofwarningsignalssuggeststhataninfant'sreflux
mayberelatedtoanunderlyinggastrointestinalorsystemicdiseasethatmaybeassociatedwithregurgitationor
vomiting(table1)[1,8].Thesefindingsshouldpromptfurtherevaluation.Warningsignalsinclude:
Symptomsofgastrointestinalobstructionordisease

Biliousvomiting
Gastrointestinalbleeding:hematemesis,hematochezia*
Consistentlyforcefulvomiting
Onsetofvomitingaftersixmonthsoflife*
Constipation
Diarrhea
Abdominaltenderness,distension
Recurrentpneumonia(raisespossibilityoftracheoesophagealfistula)

Symptomsorsignssuggestingsystemicorneurologicdisease

Hepatosplenomegaly
Bulgingfontanelle
Macrocephalyormicrocephaly
Seizures

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Hypotoniaorhypertonia(eg,cerebralpalsy)
Stigmataofgeneticdisorders(eg,Trisomy21)
Chronicinfections(eg,HIV)
Nonspecificsymptoms

Fever
Pneumonia*
Lethargy
Failuretothrive*

*mayalsobeaconsequenceofGERD
ManagementbypresentingsymptomsIfwarningsignsareabsent,theevaluationandmanagementofthe
infantdependsonthetypeandseverityofassociatedsymptoms,asshowninthealgorithm(algorithm1)and
detailedbelow.
UncomplicatedgastroesophagealrefluxInmostinfantspresentingwithfrequentregurgitation,warning
signalswillbeabsent.Iftheinfantalsohasgoodweightgain,feedswell,andisnotunusuallyirritable,heorshe
canbeconsideredtohave"uncomplicated"gastroesophagealreflux(GER)andnotGERD[2,9].Suchinfantsare
sometimesreferredtoas"happyspitters."Thehistoryandphysicalexaminationusuallyaresufficientfor
establishingthediagnosis,andspecificlaboratorytestingisnotrequired.
Educationandreassuranceoftheinfant'sparentsareappropriate(see'Informationforpatients'below).Theinfant
shouldbereevaluatedperiodicallyfortheappearanceofothernewsymptomsorwarningsignals.Theregurgitation
usuallyresolvesbyoneyearofage.Ifthesymptomsworsenordonotimprovebythetimethechildis18to24
monthsofage,thechildshouldbereevaluatedifpossible,apediatricgastroenterologistshouldbeconsulted.
(See"Clinicalmanifestationsanddiagnosisofgastroesophagealrefluxdiseaseinchildrenandadolescents".)
Ifthefamily'squalityoflifeisaffectedbytheinfant'sregurgitation,oriftheinfanthasnasalcongestionordifficulty
sleepingbecauseofregurgitationwhilesupine,conservativemeasurestoimprovethesymptomsmaybe
worthwhile.Theseincludeatrialofthickenedfeeds,uprightpositioningafterfeeds,oralimitedtwoweektrialofa
hypoallergenicdiet(becauseintoleranceofcow'smilkorotherdietaryproteinmayhavesimilarsymptoms).Even
ininfantswithfrequentregurgitation,pronepositioningforsleepisnotrecommendedbecauseofanincreasedrisk
forsuddeninfantdeathsyndrome(SIDS).(See'Lifestylechanges'below.)
RefluxandpoorweightgainPoorweightgainisoccasionallycausedbyGERD,butmaybeasymptom
ofavarietyofotherphysiologicorpsychosocialdisorders.Suchinfantsshouldfirstbeevaluatedforadequacyof
caloricintakeandproblemswithswallowing(algorithm1).Ifthecaloricintakeisadequate,theinfantshouldbe
evaluatedforcausesofregurgitationandweightlossotherthanGERD.Anuppergastrointestinalseriesshouldbe
performedtoexcludeanatomicabnormalitiesnotethatthisstudyisintendedtoexcludeanatomicabnormalities,
andisnotusefultoexcludeorconfirmthediagnosisofGERD.Ifthereisaclinicalsuspicionofpyloricstenosis
(eg,persistentforcefulvomitingdevelopingduringthefirstfewmonthsoflife),pyloricultrasonographyisthe
preferredinitialtest(see'Radiographicstudies'below).Laboratorytestingshouldincludestooltestingforoccult
blood,completebloodcount,electrolytes,andareviewofnewbornscreeningtests.Inolderinfantswhohave
beenexposedtowheat,rye,orbarley,serologicscreeningforceliacdiseaseshouldbeperformed(preferably
immunoglobulinAantibodiesagainsttissuetransglutaminase[IgAtTG],whichisoftendonewithatotalIgAtorule
outfalsenegativetestingduetoIgAdeficiency).Otherserologicaltestsmaybeusefulwhenevaluatingchildren
whoareIgAdeficientoryoungerthantwoyearsofage.(See"Diagnosisofceliacdiseaseinchildren".)
Inselectedcaseswithseverefailuretothriveorotherconcerningsymptoms,additionalevaluationtoscreenfor
metabolicdiseasesmayincludeserumelectrolytes,glucose,ammonia,liverfunctiontests,urinalysis,urine
ketones,andurinereducingsubstances.(See"Inbornerrorsofmetabolism:Metabolicemergencies",sectionon
'Initialevaluation'.)
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GERandpoorweightgainalsomaybecausedbyfoodproteininducedgastrointestinaldisease.Thishasbeen
calledcowsmilkproteinintolerancebecausecowsmilkproteinisthemostcommontrigger.Inmostcasesonly
therectumorcolonareaffected(proctocolitis),andthisisnotassociatedwithGERorpoorweightgain.However,
insomecasesthesmallintestineisinvolved,withmoreextensivesymptoms(foodproteininducedenteropathy,or
foodproteininducedenterocolitissyndrome[FPIES]).Toinvestigatethispossibility,wesuggestanempirictwo
weektrialofamilkfreedietinmostinfantswithGER,andparticularlyinthosewithpoorweightgain,grossor
occultrectalbleeding,eczema,orastrongfamilyhistoryofatopicdisease.Ifthereisnotaclearresponsetothe
dietchangeduringthetrial,otherdiagnosesandtreatmentsshouldbeexplored.About30percentofchildrenwho
areintolerantofcow'smilkalsodonottoleratesoyprotein.(See'Milkfreediet'belowand"Foodproteininduced
proctocolitisofinfancy"and"Foodproteininducedenterocolitissyndrome(FPIES)",sectionon'Allergicfood
proteininducedproctocolitisandenteropathy'.)
IfGERDisstillsuspectedaftertheaboveevaluation,treatmentoptionsincludethickeningtheformulaorof
expressedbreastmilk,anincreaseinthecaloricdensityoftheformula,oralimitedtrialofsuppressionofgastric
acidity[10].(See'Lifestylechanges'below.)
Ifaninfantfailstorespondtothesetreatmenttrialsorisillappearing,evaluationwithupperendoscopymaybe
appropriate.Treatmentdependsonthegrossandhistologicalfindings.(See"Clinicalmanifestationsanddiagnosis
ofgastroesophagealrefluxdiseaseinchildrenandadolescents",sectionon'Endoscopyandhistology'and
'Indicationsforpharmacotherapy'below.)
Occasionally,patientsmayrequirehospitalizationorenteralfeedings.Antirefluxsurgeryisrarelyindicatedpriorto
oneyearofage.
RefluxandfeedingrefusalFeedingrefusalisoccasionallybutnotcommonlycausedbyGERD.Avariety
ofotherdisorders,includingeosinophilicesophagitis,cancausefeedingrefusal,anddiagnostictestingshould
dependonassociatedsymptomsandevaluationofpossiblepsychosocialcontributors.Ifastrongsuspicionof
GERDremains,theevaluationandtreatmentissimilartothatofaninfantwithrefluxandpoorweightgain,andan
empirictrialofamilkfreedietoralimitedtrialofdrugtherapycanbeconsidered(algorithm1).
RefluxandirritabilityIrritabilityanddisturbedsleepininfantsusuallyarenotcausedbyacidrefluxthese
symptomsarenonspecificandcanbecausedbyavarietyofnonpathologicalandpathologicalconditions.Evenin
aninfantwithfrequentregurgitation,thereislittleevidencesuggestingthattherefluxcausesesophagealpainthe
commonbeliefthatrefluxcausespainininfantsislargelyextrapolatedfromstudiesinadults.Afewstudieshave
shownanassociationbetweenrefluxasdocumentedbyesophagealpHmonitoringoresophagitisandmeasures
ofapparentdiscomfort[11].However,multipleotherstudieshavefailedtodemonstrateanassociationbetween
irritabilityandGERDininfants[1,12].Inseveralplacebocontrolledtrialsofinfantspresentingwithirritability,acid
suppressionhadnoeffectonsymptoms[10,1315].(See'Argumentsagainstpharmacotherapy'below.)
IrritabilityismorelikelytobecausedbyGERDifthesymptomoccurswhentheinfantisregurgitating.Particularly
suggestiveisthesymptomcomplexofarchingoftheback,torsionoftheneck,andliftingupofthechin,known
asSandifersyndromethisposturingcanbeconfusedwithtorticollisorseizures.Ininfantspresentingwiththese
symptoms,acarefulhistoryshouldbetakentoexcludecausesotherthanreflux.Ifwarningsignsareabsentand
thesymptomsseemtoberelatedtoreflux,thefirststepinmanagementincludeslifestylechanges(changingtoa
hypoallergenicformula,thickeningfeeds,andpositioningtherapy)oralimitedempirictwoweektrialofacid
suppressiontherapy(algorithm1)(see'Lifestylechanges'below).Forthoseinfantswithsevereorpersistent
symptoms,itmaybeappropriatetoinvestigatewithendoscopyand/oresophagealpHmonitoringbeforeempiric
intervention.
Ifsleepdisturbanceisaprominentcomplaint,thefamilymaybenefitfromcounselingaboutestablishinghealthy
sleeppatternsintheinfant.
RefluxandrectalbleedingAsdiscussedabove,afoodproteininducedproctocolitis(or"intolerance")can
haveaclinicalpresentationthatmimicsGERD.Thisdisordertypicallypresentswithrectalbleeding(causedby
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proctocolitis),withbothGERandrectalbleeding,orlesscommonlywithisolatedGER.Therectalbleeding
associatedwithfoodproteininducedproctocolitisisoftenassociatedwithmucousandhasa"stringlike"
appearance,unlikethebrightredbloodthatisseenwithafissureorulceration.Forthisreason,theclinician
shouldinspecttheinfant'sstoolforgrossandoccultblood.Tolookforananalfissure,carefulinspectionofthe
analcanalwithgoodlightingisnecessary.Foodproteininducedproctocolitisissomewhatmorelikelyininfants
witheczemaorastrongfamilyhistoryofatopicdisease.FormostinfantswithproblematicGER,anempirictrial
ofamilkandsoyfreedietisanappropriatestep,regardlessofwhetherthereisrectalbleeding.(See'Milkfree
diet'belowand"Foodproteininducedproctocolitisofinfancy".)
SymptomsrarelycausedbyGERD
ApneaorapparentlifethreateningeventsWhenaninfantpresentswithanapparentlifethreatening
event(ALTE),anassociationwithGERisfrequentlyconsidered,butrarelyestablishedwithcertainty[8].An
associationbetweenrefluxandapneaorbradycardiahasnotbeendemonstratedconvincingly.Evenwhenan
episodeofGERappearstohaveimmediatelyprecededtheALTE,thedirectcauseoftherespiratoryeventismost
likelylaryngospasm.Althoughrefluxmayhavetriggeredlaryngospasm,thisdoesnotmeanthattreatmentofreflux
willpreventsimilarepisodesinthefuture.OthercausesofALTE,apnea,orcyanosisincludeneurologicorcardiac
disorders.(See"Apparentlifethreateningeventininfants",sectionon'Gastroesophagealreflux'.)
PersistentwheezingAlthoughrefluxmaybeassociatedwithrespiratorydisordersininfants,including
recurrentstridor,chroniccough,recurrentpneumonia,andreactiveairwaydisease,thepresenceofsuch
symptomsshouldpromptanevaluationforcausesotherthanGERD.AssociationsbetweenwheezingandGERD
havebeendemonstratedinadultsandinsomegroupsofchildren,butthereislittleevidenceforthisassociationin
infantsexceptforafewnonrandomizedstudies[16,17].Beforeconsideringatrialofempirictreatmentforreflux,
infantswithpersistentwheezingshouldbecarefullyevaluatedforothercausesoftheserespiratorysymptoms,
includingareactiontodietaryprotein(cow'smilkorsoysensitivity),congenitalairwayanomalies,
hypogammaglobulinemia,andcysticfibrosis(CF).(See"Approachtowheezinginchildren"and"Assessmentof
stridorinchildren"and"Approachtochroniccoughinchildren".)
DIAGNOSTICTESTS
EsophagealpHandimpedancemonitoringEsophagealrefluxcanbequantifiedbymonitoringesophageal
pH(pHprobe)and/orimpedance(multichannelintraluminalimpedanceMII).However,thesestudiesrarelyare
usefulinevaluatinggastroesophagealreflux(GER)orestablishingthediagnosisofgastroesophagealreflux
disease(GERD)ininfants.ManyhealthyinfantshavefrequentepisodesofGERwithoutpathological
consequences,andthereisonlyaweakassociationbetweenabnormalresultsofesophagealmonitoringandthe
presenceofrefluxcomplications(ie,GERD)inthisagegroup[1820].However,inspecialsituations,suchas
infantswithseverediscreteepisodesofsymptoms(suchasapnea,bradycardia,cough,oroxygendesaturation),
esophagealpHand/orMIImonitoringmaybeusedinconjunctionwithmonitoringofrespirations,heartrate,or
oxygensaturationtoestablishwhetherthereisatemporalrelationshipbetweenepisodesofrefluxandthese
discreteevents[21](see'Apneaorapparentlifethreateningevents'aboveand'Refluxandirritability'above).
EsophagealpHmonitoringcanalsobeusedtoassesstheadequacyofacidsuppressiontherapy.
Whenmonitoringofesophagealrefluxisundertaken,theidealtechniqueistomeasurebothesophagealpHand
MIIonasingledevice,andrecordingfor24hours[2].MIIdetectsrefluxeventsregardlessofpH,whereaspH
monitoringdetectsonlyacidreflux.Infantsandchildrenwithwheezingorcoughingthatoccursduringsleepor
whenlyingdown,mayhavenonacidrefluxthatcanbeidentifiedbyMII.(See"Clinicalmanifestationsand
diagnosisofgastroesophagealrefluxdiseaseinchildrenandadolescents",sectionon'EsophagealpHmonitoring
orimpedancemonitoring'.)
RadiographicstudiesAnuppergastrointestinalseries(UGI)isnotnecessaryfortheroutineevaluationof
infantswithGER[1,8].Thisisbecausethestudydoesnotreflectthefrequencyofrefluxunderphysiologic
conditions,andinfantswithandwithoutGERDmayhaverefluxepisodesobservedduringthestudy.Inselected
cases,suchasinfantswithbiliousvomitingorpoorweightgain,anUGIseriesmaybehelpfultoexclude
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anatomicabnormalitiessuchasmalrotation,antralweb,annularpancreas,orectopicpancreatictissue(whichis
typicallyfoundinthedistalstomach).Infantswithpersistentforcefulvomitingdevelopingduringthefirstfew
monthsoflifeshouldbeevaluatedfirstwithpyloricultrasonographytoassessforthepossibilityofpyloric
stenosis.(See"Infantilehypertrophicpyloricstenosis".)
EndoscopicstudiesUpperendoscopyisofdiagnosticbenefitininfantswhohavenotrespondedtoempiric
clinicaltrialsand/orthosechildrenwhoaresuspectedofhavingdietaryproteinintolerancethatremains
problematicdespitedietaryelimination.Whenendoscopyisperformed,biopsiesoftheesophagus,stomach,or
duodenumshouldbetakenbecausetheycanrevealclinicallysignificantdiseasesevenwhenthegross
appearanceofthemucosaisnormal.InadditiontoprovidingevidenceaboutGERD,biopsiesalsomayreveal
inflammationcharacteristicofdietaryproteinintolerance(oftentermed"allergy")orothersystemicdisorders.
Theresultsofthebiopsiesmustbeinterpretedinthecontextoftheinfant'sclinicalpresentation,andmild
histologicalabnormalitiesmaynotbeclinicallysignificant.Approximately25percentofinfantsundergoing
endoscopyhavesomeevidenceofesophagealinflammation[22],andthehistologicfindingsarepoorlycorrelated
withsymptoms.Asanexample,inastudyof19infantswithhistologicalabnormalitiesincludingbasalcelllayer
hyperplasiawhoweretreatedwithplaceboforoneyearaspartofarandomizedtrial,overhalfdisplayed
improvementorresolutionofsymptomsduringtheplacebotreatment,despitethelackofimprovementinthe
histology[23].
TREATMENTOPTIONS
LifestylechangesSeveraltypesoflifestylechangesaresuggestedforinfantswithgastroesophagealreflux
disease(GERD),orforthosewithuncomplicatedrefluxifthesymptomsaredistressingtothefamily.Althoughthe
efficacyoflifestylechangesvarieswiththeinterventionandamongpatients,therisksarelow,soempirictrialsare
appropriate.Inonestudyof50infantswithproblematicreflux,atwoweektrialofcombinedlifestylechanges
(milkfreediet,thickenedfeeds,antirefluxpositioning,andtobaccosmokeavoidance),symptomsimproved
substantiallyinnearly60percent,andresolvedinnearly25percent[24].
ExposuretotobaccosmokeTheclinicianshouldcounselallfamiliestoavoidexposingtheinfantto
tobaccosmoke.Theextenttowhichtobaccosmokepromotesrefluxininfantsisnotwellestablished,butitis
wellestablishedthatnicotineislowerstheloweresophagealsphincterpressure.Irrespectiveofreflux,thereare
manyotherbenefitstotheinfant'shealthbyavoidingexposuretotobaccosmoke.Importantmeasurestoavoid
smokeexposureincludesmokingbansinthehomeandcar,andifpossible,cessationofparentalsmoking.(See
"Secondhandsmokeexposure:Effectsinchildren"and"Controlofsecondhandsmokeexposure".)
FeedingsizeBecausesimplerefluxispromotedbygastricdistention,providingsmallerfeedingsoften
reducesthefrequencyorquantityofreflux.Theclinicianshouldprovideadvicetoensurethattheinfantisnot
overfed.Ingeneral,thisismostrelevantforinfantswhoarebottlefed.Forinfantswithsuboptimalweightgain,it
maybehelpfultoprovidesmallerbutmorefrequentfeedings,and/ortoconcentratetheformula.
MilkfreedietWesuggestanempirictrialofremovingallcow'smilkfromthedietforinfantswith
problematicgastroesophagealreflux(GER),andespeciallyforthosewithgrossoroccultbloodintheirstool,
eczema,orastrongfamilyhistoryofatopy.Thisisbecausefoodproteinintolerance(typicallytocow'smilk)can
haveaclinicalpresentationthatmimicsGERD[1,2].Asanexample,somestudiesreportthatupto40percentof
infantswithproblematicGERhaveafoodproteinintolerance[2527].Themajorityoftheseinfantswillbe
sensitivetocow'smilkproteinalone,butasubstantialnumberarealsosensitivetosoyproteins.BecauseGERD
isgenerallyaclinicaldiagnosis,initiatingatwoweektrialofamilkandsoyfreedietisappropriate,particularlyif
theconditioniscomplicatedbypoorweightgain,irritability,orfeedingrefusal[2831].
Breastfedinfantscanbetreatedwithcarefuleliminationofallcow'smilkproteinsandbeeffromthemother'sdiet.
Majorsourcesofsoyproteinmayneedtobeeliminatedaswell.Theresponsetothischangeisoftenmore
delayedthaninformulafedinfantsbecauseittakessometimetoeliminatetheoffendingproteinfrombreastmilk,
andsmallamountsofmilkorbeefproteinmaybefoundinfoods.Thesedietsaredifficultandadherencetothe
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dietmaybecomeanissueovertime.Somefamiliesmayhaveimprovedcomplianceifbothparentscommitto
takingthesamediet,forconvenienceandtoprovidesupport.(See"Foodproteininducedproctocolitisofinfancy",
sectionon'Management'.)
Informulafedinfants,wesuggestswitchingtoanextensivelyhydrolyzedformula(oftenmarketedas
"hypoallergenic")(table2).Becauseasignificantnumberofaffectedinfantsaresensitivetosoyinsteadoforin
additiontocow'smilk,substitutionofsoybasedformulasisnotrecommended.Similarly,lactosefreecow'smilk
basedformulasarenotlikelytobehelpful[32].Ifthereisastrongsuspicionofafoodproteinintolerance(because
ofbloodystoolsoratopicsymptoms)andtheinfantdoesnotrespondtoahydrolyzedformula,atrialofanamino
acidbased("elemental")formulaoreliminationofotherdietaryproteinsmaybenecessary.
Infantswhorespondtothedietarychangearegenerallymaintainedonamilkfreedietuntiloneyearofage,at
whichtimemany(althoughnotall)infantswillhavebecometoleranttotheprotein.Infantswhodonotrespondto
dietaryrestrictioninitiallymayrespondtoatrialofotherlifestylechangesasoutlinedbelow.
BreastversusformulafeedingForinfantswithGERwhoarebreastfed,continuationofbreastfeeding
shouldbeencouragedifpracticable.Thisisbecausebreastfeedingmayhaveaprotectiveeffectonregurgitation
ininfants,basedonlimiteddata.Asanexample,breastfedneonates(agetwotoeightdays)experienceless
nocturnalesophagealacidexposurecomparedwithformulafedneonates[33].Mechanismsforthisprotective
effectofbreastfeedingmightincludedifferencesingastricemptyingordifferentialexposureofinfantswitha
cow'smilkproteinintolerance,butthesepossibilitieshavenotbeenformallyevaluated.
ThickeningfeedsAtrialofthickeningfeedsisworthwhileformostinfantswithproblematicreflux,except
perhapsininfantswhoarepretermoroverweight.Thebenefitofthickeningfeedsismodestatbest,andfor
motherswhoarebreastfeeding,thepotentialbenefitmaynotwarranttheinconvenienceofexpressingbreastmilk.
Breastfeedingshouldnotbestoppedforthepurposesofthickeningfeeds.
Thickeningfeedsappeartomodestlyimprovesomeofthesymptomsandobjectivemeasuresofrefluxfrequency
[3439].Inametaanalysisofeightstudies,thickenedfeedssignificantlyreducedtheregurgitationseverityscore
andthefrequencyofemesis,althoughnottherefluxindex[37].Thereisnodirectevidencetosuggestthatthis
symptomaticimprovementcorrespondstoadecreasedincidenceofrefluxrelatedpathology,suchasesophagitis
[1].
Standardformulasorexpressedbreastmilkusuallyarethickenedbyaddingoatinfantcereal,uptoonetablespoon
ofdrycerealperounceofformula.Althoughricecerealhastraditionallybeenusedforthispurpose,oatcerealis
nowpreferredbecauseofconcernsaboutpossiblecontaminationofricecerealwitharsenic[4042].Itmaybe
necessarytoadjustthenippleofthebottletopermitadequateflowofthethickenedformula.Premixedformulas
thickenedwithricestarchareavailableinsomecountriesincludingtheUnitedStates,andformulasthickenedwith
carobflourorlocustbeangumalsoareavailableinsomecountries.Theefficacyofsuchprethickenedformulasto
decreaseregurgitationandesophagealacidexposurehasnotbeenextensivelyevaluated[4345].
Thickeningoffeedswithcerealcanincreasethecaloricdensityoftheformula,whichmayhelpinfantswhoare
underweightasaresultofhavingGERD,butisnotdesirableinthosewhoareoverweight.Thecaloricdensityof
oneounceofformulathickenedwithonetablespoonfulofoatcerealisapproximately34Kcalperounce(1
tablespoonper2ounceformulaprovidesacaloricdensityof27Kcalperounce).Thecaloricdensityofformulas
thickenedwithothersubstancesvaries.Providersandfamiliesshouldbealertforsignsofexcessiveweightgain
ininfantsfedthickenedformulas,andshoulddiscontinueformulathickeningassoonasitisnolongerneededto
controlrefluxsymptoms.
Thickeningformulaswithcerealappearstobesafe,althoughonestudysuggestedthatthesechildrenmay
experienceincreasedcoughingduringfeedings[46].Inaddition,concernshavebeenraisedabouttheuseofa
thickeningagentthatcontainsxanthangum("SimplyThick")becauseofapossibleassociationwithnecrotizing
enterocolitisbothprematureandterminfantsappeartobeatrisk.TheUnitedStatesFoodandDrug
Administration(FDA)hasissuedawarningabouttheuseofthisthickeningagent[47].(See"Gastroesophageal
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refluxinprematureinfants",sectionon'Diet'.)
PositioningtherapyKeepinganinfantupright(eg,onaparent'sshoulder)for20to30minutesafterafeed
seemstoreducethelikelihoodofregurgitation,andcanbeattemptedwhenpracticable.Semisupinepositioning
(inaninfantseat)isnothelpful,asitincreasesreflux[48].
Allinfantsyoungerthan12monthsofageshouldbeplacedinthesupinepositionforsleep,eveniftheyhave
reflux.Althoughthepronepositiontendstoreducereflux[4852],itisalsoassociatedwithahigherriskforsudden
infantdeathsyndrome(SIDS),andthisriskoutweighsthepotentialbeneficialeffectofpronesleepingonreflux
[1,2,8,53].(See"Suddeninfantdeathsyndrome:Riskfactorsandriskreductionstrategies".)
Lateralpositioningisnotrecommendedtotreatrefluxininfants.Inadults,theleftlateraldecubitusposition
improvedrefluxascomparedwiththerightlateraldecubitusposition[54].However,resultsofstudiesinyoung
infantsareinconsistentabouttheeffectofsidepositioningonreflux[50,51].Moreover,sidepositioningis
associatedwithanincreasedriskforSIDS[53,55].Similarly,elevationoftheheadofthecribisnotrecommended
becauseithasnoeffectonrefluxforinfantsplacedinthesupineposition[37].
InafewinfantswithsevereGERD(eg,thoseathighriskofaspiration,suchastheneurologicallyimpaired),the
risksassociatedwithpersistentGERDmayoutweightherisksassociatedwithpronepositioning.Thisdecision
canbemadeonacasebycasebasis.
PharmacotherapyAcidsuppressingmedicationshavealimitedroleinthetreatmentofinfantswith
regurgitation.TheyarenotvaluableintreatingchildrenlessthanoneyearofagewithuncomplicatedGER("happy
spitters")[1,8].
ArgumentsagainstpharmacotherapyPharmacotherapyisnotindicatedforinfantswithuncomplicated
reflux,becauseoflackofefficacyandmodestsafetyconcerns,andbecausethesymptomsresolvewithout
treatmentinmanyinfants.
Inmostinfantswithrefluxmanagedwithconservativemeasuresalone,symptomswillimproveovertimewith
advancingageandgrowth.ThisisthecaseformanyinfantswithsymptomssuggestiveofGERD,including
parentreporteddiscomfortandirritabilityduringepisodesofrefluxorfeeding.Inanobservationalstudy,over50
percentofsuchinfantsdemonstratedclinicallysignificantimprovementorresolutionofsymptomswith
conservativemeasuresalone,includingthickenedfeeds,avoidanceexposuretotobaccosmoke,and/or
eliminationofcow'smilkproteinsfromtheirdiet(byswitchingtoahypoallergenicformula,orrestrictionofmilk
frommother'sdietiftheinfantisbreastfed)[24].(See'Lifestylechanges'above.)
Apreponderanceofevidencesuggeststhatacidsuppressingmedicationsarenoteffectiveininfantsfortreatment
ofsymptomssuchasregurgitationandirritability,asillustratedbythefollowingstudies:
InarandomizedtrialofinfantsdiagnosedwithGERDusingastandardizedquestionnaireofsymptomsas
reportedbytheirparents,therewasnodifferenceinsymptomsamonginfantstreatedwithaprotonpump
inhibitor(PPI)ascomparedwiththosetreatedwithplacebo[13].
ArandomizedtrialfoundnodifferenceinrefluxsymptomsininfantstreatedwithaPPIascomparedwith
placebo[14].ThisstudyalsoreportedthatGERDsymptomsworsenedwheninfantswereswitchedfromthe
PPItoplacebo,butthismayhavebeenduetoacidreboundwhichhasbeendescribedinotherpopulations
afterwithdrawalfromPPItherapy.
Basedontheseandotherfindings,asystematicreviewalsoconcludedthatPPIsarenoteffectivein
reducingsymptomsofirritabilityorregurgitationininfants[56].
Inastudyofinfantsreferredtoapediatricgastroenterologist,mostweretreatedwithacidsuppressivedrugs
beforetheconsultationanddiscontinuationofthemedicationsdidnotcauseworseningofsymptoms[57].
Thissuggeststhatacidsuppressingmedicationsareprobablyoverprescribed.
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SafetyconcernsaboutPPIsandotherdrugsareoutlinedbelow.(See'Drugselection'below.)
IndicationsforpharmacotherapyAcidsuppressingmedicationsareindicatedinthefollowingsituations:
Wesuggestalimitedtrialofacidsuppression(eg,twoweeks)forpatientswiththefollowing
characteristics:
Infantswithmildesophagitisonendoscopicbiopsies.Thisisbecausemildmorphometricabnormalities
seenonbiopsymaynotbeclinicallysignificant(see'Endoscopicstudies'above).Ifthepatienthasa
clearclinicalresponsetotreatment,thecoursemaybeextended.Infantswithesophagealatresia,
chronicneuromusculardiseases(eg,developmentaldelay),chronicrespiratorydisease,suchascystic
fibrosis,ordiaphragmatichiataldefectsaremorelikelytodeveloperosiveesophagealdiseaseover
timeandmaybenefitfromearlytreatmentifclinicallyindicated[58,59].
InfantswithsignificantsymptomssuspectedtobecausedbyGERDsuchasmarkedirritability,feeding
refusalorpoorweightgain,andinwhomconservativemeasuresincludingmilkfreediethavefailed.If
theseinfantshaveaclearimprovementinsymptoms,acidsuppressionmaybecontinuedforthreeto
sixmonths,thenreevaluated.
Werecommendathreetosixmonthcourseofacidsuppressionforinfantswithmoderateorsevere
esophagitisdocumentedbyendoscopicbiopsies,inadditiontothelifestylechangesdescribedabove[1,8].
Thosewitherosiveesophagitisshouldundergoarepeatendoscopytodemonstratehealingafterthreetosix
months.
AllpatientstreatedwithchronicPPIsshouldbeperiodicallyevaluatedtodeterminewhetherongoingtreatmentis
necessary.(See'Monitoringandfollowup'below.)
DrugselectionWhenpharmacotherapyischosenasatreatment,orforalimitedtrial,aPPIisgenerally
preferredoverhistaminetype2receptorantagonists(H2RA).RandomizedtrialsinadultsshowthatPPIsleadto
morerapidhealingofesophagitisthanH2RAs[60].Therearenosimilarcomparative,randomizedtrialsinchildren,
butseveralcaseseriesreportthatPPIshavehealedsevereesophagitisthathadbeenunresponsivetoH2RA
therapy[61,62].InfantsandyoungerchildrenmetabolizePPIsmorerapidlythanolderchildrenandrequirehigher
perkilogramdosingthanolderindividuals[6365].Tobemosteffective,theyshouldbetaken30minutespriorto
thefirstmeal/feedingoftheday.UnlikeH2RAs,PPIsdonotloseefficacywithprolongeduse.ThePPIs
omeprazole,lansoprazole,esomeprazole,andpantoprazolehaveallbeenstudiedinyoungchildren,andsome
haveformulationsthatfacilitateadministrationtoinfantsandyoungchildren.OfthesePPIs,onlyomeprazoleand
esomeprazolearecurrentlyapprovedbytheUnitedStatesFDAforuseininfantsolderthanonemonthofagewith
erosiveesophagitis[1,66,67].
TherearealsosafetyconcernsabouttheuseofPPIs,includingshorttermacidrebound,andincreasedrisksfor
pneumoniaanddiarrhea[6870].TherearetheoreticalreasonstoconsidervitaminB12andirondeficiencyin
childrenchronicallytakingPPIs.Inaddition,studiesinadultshaveraisedtheoreticalconcernsthatlongtermuse
ofPPIsmaybeassociatedwithincreasedriskforosteoporosis.(See"Overviewandcomparisonoftheproton
pumpinhibitorsforthetreatmentofacidrelateddisorders",sectionon'Safety'.)
H2RAsareareasonablealternativetoPPIsforashorttermtrialofacidsuppression.Theyarelesseffectivethan
PPIsinreducinggastricacidity,butmoreeffectivethanplacebo[71].Theirlongtermuseislimitedby
tachyphylaxis(tolerance),whichusuallydevelopswithinafewweeksofchronicuse.(See"Physiologyofgastric
acidsecretion",sectionon'Toleranceandacidrebound'.)
AntacidsarenotgenerallyusefulinthetreatmentofGERininfants.Thesedrugsdirectlybuffergastricacidinthe
esophagusorstomachandmayprovideshorttermreliefofacidrelatedsymptomsinolderchildrenandadults.
However,inmostinfantswithfrequentregurgitation,thereislittleevidencesuggestingthattherefluxcauses
esophagealinjuryorpain.Thosefewinfantswithesophagitisshouldbetreatedwithlongeractingagents(PPIsor
H2RAs).Moreover,chronicuseofantacidsininfantscanbeassociatedwithaluminumtoxicity,milkalkali
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syndrome,orrickets,andshouldbeavoided[2].Similarconsiderationsapplytosurfaceprotectiveagentssuchas
sucralfate,whichhasnotbeenadequatelystudiedininfants.
ProkineticagentscurrentlyhaveaminimalroleinthetreatmentofGERinthisagegroup.BecauseGERis
essentiallyamotilitydisorder,useofprokineticsshouldtheoreticallyenhancegastricemptyingandincrease
restingloweresophagealsphincterpressure.However,thefewprokineticagentswithanyestablishedefficacy
alsohavesignificantsafetyconcerns,includingcentralnervoussystemsideeffectsformetoclopramide,and
cardiacarrhythmiasforcisapride,whichresultedinitsremovalfromthemarketintheUnitedStatesandCanada.
Thus,prokineticagentsshouldbeconsideredforuseonlyincarefullyselectedandfullyinformedpatients,and
withappropriatemonitoringforconcernsanddruginteractions[1].
Amoredetaileddiscussionofpharmacologicaltherapyforthepediatricagegroup,includingsafetyconsiderations,
isprovidedseparately.Specificissuesrelatedtoprematureinfantsarediscussedinaseparatetopicreview.(See
"Managementofgastroesophagealrefluxdiseaseinchildrenandadolescents",sectionon'Pharmacotherapy'and
"Gastroesophagealrefluxinprematureinfants",sectionon'Pharmacologictherapy'.)
MonitoringandfollowupBecauseofsafetyconcerns,patientstreatedwithPPIsshouldbereevaluated
onaregularbasistodetermineifongoinguseisnecessary.Inourpractice,weattempttoweanpatientsfrom
PPIsaftersixmonthsoftreatment,andthenperiodicallythereafter,dependingonsymptomcontrol.When
stoppingtherapyaftersixmonths,onemightconsidertransitioningtoanH2RAfortwoweeks,followedby
tapering,toavoidacidrebound.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Acidreflux(gastroesophagealreflux)inbabies(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Acidreflux(gastroesophagealreflux)ininfants(Beyond
theBasics)")
SUMMARYANDRECOMMENDATIONS
Gastroesophagealreflux(GER)andregurgitationareextremelycommonduringinfancyandtypicallyresolve
ontheirownbyoneyearofage.Mostinfantswithfrequent,uncomplicatedregurgitationdonotrequire
interventionorevaluationbeyondacarefulhistoryandphysicalexamination.Thetermgastroesophageal
refluxdisease(GERD)isusedwhentherefluxhaspathologicalconsequences,suchasesophagitis,
nutritionalcompromise,orrespiratorycomplications.
Infantspresentingwithfrequentregurgitationshouldbeevaluatedforthepresenceofwarningsigns
suggestiveofunderlyingpathologicaldisease(table1).Warningsignsincludeconsistentforcefulvomiting
(especially,priorto12weeksofage),biliousvomiting,markedhematemesis,constipationordiarrhea,
symptomsorsignsofneurologicdisease(macrocephaly,microcephaly,seizures,hypoorhypertonia),
abdominaltendernessordistension,hepatosplenomegaly,fever,failuretothrive,orothersystemic
symptoms.Inmostcases,acarefulhistoryandphysicalexaminationwillbeadequatetoidentifythese
warningsigns.(See'Warningsignalsofunderlyingpathology'above.)
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Infantswithoutwarningsignsandwhofeedwellandarenotunusuallyirritable,haveuncomplicatedGER
ratherthanGERD.Wesuggestnotusingacidsuppressingorotherdrugsfortheseinfants(Grade2B).
Educationandreassurancewithoutanyotherspecificinterventionusuallyissufficient.Ifthesymptomis
problematicforthefamily,treatmentoptionsincludethickeningoftheformulaorexpressedbreastmilk,ora
brieftrialofeliminatingcow'smilkfromthediet.(See'Uncomplicatedgastroesophagealreflux'aboveand
'Lifestylechanges'above.)
Infantswithoutwarningsignsbutwithothersymptomssuchaspoorweightgain,feedingrefusal,or
irritability,usuallycanbemanagedwithoneormorelifestylechanges,includingavoidanceoftobacco
smoke,changesinfeedingpatterns,thickeningoffeeds,positioningtherapy,andatrialofacow'smilkfree
diet(algorithm1).Therationaleforthemilkfreedietisthatasubstantialpercentageofinfantswith
problematicrefluxhaveanunderlyingfoodproteinintolerance(typicallycow'smilk).Thetrialisparticularly
importantfor(butnotlimitedto)infantswithgrossoroccultbloodinthestool,eczema,orastrongfamily
historyofatopicdisease.Otherdiagnosesandtreatmentsshouldbeexploredifthereisnotaclearresponse
tothedietchangewithinafewweeks.(See'Lifestylechanges'aboveand'Milkfreediet'above.)
Werecommendthatallinfants,includingthosewithreflux,bepositionedsupineforsleep(Grade1C).
Althoughpronepositioningtendstodecreasereflux,italsoisasignificantriskfactorforsuddeninfantdeath
syndrome(SIDS).Semisupinepositioning(eg,inaninfantseat)isnothelpfulandevenexacerbatesreflux.
Lateralpositioningmayormaynotimprovereflux,andisalsoassociatedwithanincreasedriskforSIDS.
(See"Suddeninfantdeathsyndrome:Riskfactorsandriskreductionstrategies"and'Positioningtherapy'
above.)
Therearemanycausesofirritabilityininfants.Ifthehistorysuggestsastrongtemporalassociationbetween
episodesofirritabilityandreflux,alimitedempirictrialofacidsuppressionand/orevaluationforreflux(using
esophagealimpedanceand/orpHmonitoring)orendoscopyisappropriate.(See'Refluxandirritability'
above.)
Acidsuppressingmedicationsareindicatedinthefollowingsituations(see'Indicationsforpharmacotherapy'
above):
Forinfantswithmoderateorsevereesophagitisdocumentedbyendoscopicbiopsies,werecommend
treatmentwithanacidsuppressingmedicationforthreetosixmonths(Grade1B),inconjunctionwith
lifestylechanges.Forinitialtreatment,wesuggestchoosingaprotonpumpinhibitor(PPI)(Grade2B).
Forinfantswithmildesophagitisonendoscopicbiopsies,orthosewithsignificantsymptoms
suspectedtobecausedbyGERDsuchaspoorweightgain,feedingrefusal,ormarkedirritabilitythat
istemporallyassociatedwithrefluxepisodes,andinwhomconservativemeasuresincludingmilkfree
diethavefailed,wesuggestalimitedtrialofacidsuppression(eg,twoweeks)(Grade2C).Eithera
PPIorahistaminetype2receptorantagonist(H2RA)isanappropriatechoiceforthisshorttermtrialof
acidsuppressioninthisgroup.Iftheseinfantshaveanunequivocalimprovementinsymptoms,acid
suppressionmaybecontinuedforthreetosixmonths,thenreevaluated.(See'Drugselection'above.)
AllpatientstreatedwithchronicPPIsshouldbeperiodicallyevaluatedtodeterminewhetherongoing
treatmentisnecessary.(See'Monitoringandfollowup'above.)
Surgicalprocedurestotreatreflux,suchasfundoplication,arerarelyindicatedininfantsyoungerthanone
yearofage.However,somechildrenwhopresentwithrefluxduringinfancymayultimatelyrequiresurgical
managementlaterinchildhood.(See"Managementofgastroesophagealrefluxdiseaseinchildrenand
adolescents",sectionon'Surgery'.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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GRAPHICS
Differentialdiagnosisofvomitingininfants
Gastrointestinalobstruction

Infectious

Pyloricstenosis

Sepsis

Malrotationwithvolvulus

Meningitis

Intussusception(maybeintermittent)

Urinarytractinfection

Intestinalduplication,stenosis,oratresia

Pneumonia

Hirschsprungdisease

Otitismedia

Antral/duodenalweb

Hepatitis

Foreignbody

Metabolic/endocrine

Incarceratedhernia

Galactosemia

Othergastrointestinalcauses

Hereditaryfructoseintolerance

PhysiologicalgastroesophagealrefluxorGERD

Ureacycledefects

Foodproteininduced(eg,anaphylaxis,foodproteininduced
enteropathy,orFPIES)

Aminoandorganicacidemias

Gastroenteritis
Pepticulcerdisease

Fattyacidoxidationdisorders
Metabolicacidosis

Eosinophilicesophagitis/gastroenteritis

Congenitaladrenal
hyperplasia/adrenalcrisis

Gastroparesis

Renal

Pancreatitis

Obstructiveuropathy

Neurologic

Renalinsufficiency

Hydrocephalus

Toxic

Subduralhematoma

Lead

Intracranialhemorrhage

Iron

Masslesion

VitaminAorD
Medications(ipecac,digoxin,
theophylline,etc)
Othertoxins

Cardiac
Heartfailure
GERD:gastroesophagealrefluxdiseaseFPIES:foodproteininducedenterocolitissyndrome.
Modifiedwithpermissionfrom:RudolphCD,MazurLJ,LiptakGS,etal.Guidelinesforevaluationand
treatmentofgastroesophagealrefluxininfantsandchildren:recommendationsoftheNorthAmerican
SocietyforPediatricGastroenterologyandNutrition.JPediatrGastroenterolNutr200132:S1.Copyright
2001LippincottWilliams&Wilkins.

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Graphic61133Version11.0

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Algorithmforevaluatinganinfantwithfrequentregurgitation

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Dottedlinedenotesalternatepathway,dependingonresultsofclinicalassessment.
GERD:gastroesophagealrefluxdiseaseCBC:completebloodcountBUN:bloodureanitrogentTGIgA:
immunoglobulinAantibodiestotissuetransglutaminasePPI:protonpumpinhibitor.
*Warningsignalsincludebiliousvomiting,consistentlyforcefulvomiting,abdominaltendernessor
distension,fever,orothersystemicsigns(seetext).
Trialsofboththickenedfeedsandacow'smilkandsoyfreedietshouldgenerallybeperformedbeforea
trialofacidsuppression.Ifneitherofthesetrialsissuccessful,thenextstepisatrialofacidsuppression.
Graphic62732Version7.0

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Formulaoptionsforinfantswithdietaryproteininducedconditions

Manufacturer

Extensivelyhydrolyzedcaseinbasedformulas
EnfamilNutramigen

MeadJohnsonNutrition

EnfamilNutramigenwithEnfloraLGG

MeadJohnsonNutrition

PregestimilDHAandARA

MeadJohnsonNutrition

SimilacExpertCareAlimentum*

AbbottNutrition

Extensivelyhydrolyzedwheybasedformulas
GerberExtensiveHA

Gerber

Aminoacidbasedformulas
Elecareforinfants

AbbottNutrition

NeocateinfantDHAandARA

Nutricia

NeocateNutra

Nutricia

PurAminoDHAandARA

MeadJohnsonNutrition

LGG:LactobacillusrhamnosusGGDHA:docosahexaenoicacidARA:arachidonicacid.
*ThereadytofeedformofSimilacExpertCareAlimentumiscornfree.Thepowderformincludescorn
maltodextrin.
Graphic79377Version18.0

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ContributorDisclosures
HarlandSWinter,MDGrant/Research/ClinicalTrialSupport:Shire[IBD(Mesalamine)]UCB[IBD
(Certolizumab)]Janssen[IBD(Infliximab)]Nutricia[Autism]Nestle[IBD]Abbvie[IBD(Adalimumab)]Pediatric
IBDFoundation[IBD]AutismResearchInstitute[Autism].Consultant/AdvisoryBoards:Salix[IBD
(Mesalamine)]Janssen[IBD(Infliximab)]Avaxia[IBD(antiTNF)].StevenAAbrams,MD
Grant/Research/ClinicalTrialSupport:MeadJohnson,Nutrition[PediatricNutrition(Infantformulas)].
Consultant/AdvisoryBoards:MilkPrep[dairyproducts(fluidmilk)].BUKLi,MDNothingtodisclose.AlisonG
Hoppin,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovided
tosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDate
standardsofevidence.
Conflictofinterestpolicy

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