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CLINICAL REPORT
Gastroesophageal Reux: Management Guidance forthe
Pediatrician
abstractRecent comprehensive guidelines developed by the North
AmericanSociety for Pediatric Gastroenterology, Hepatology, and
Nutrition denethe common entities of gastroesophageal reux (GER) as
the physio-logic passage of gastric contents into the esophagus and
gastroesoph-ageal reux disease (GERD) as reux associated with
troublesomesymptoms or complications. The ability to distinguish
between GERand GERD is increasingly important to implement best
practices inthe management of acid reux in patients across all
pediatric agegroups, as children with GERD may benet from further
evaluationand treatment, whereas conservative recommendations are
the onlyindicated therapy in those with uncomplicated physiologic
reux. Thisclinical report endorses the rigorously developed,
well-referencedNorth American Society for Pediatric
Gastroenterology, Hepatology,and Nutrition guidelines and likewise
emphasizes important conceptsfor the general pediatrician. A key
issue is distinguishing between clin-ical manifestations of GER and
GERD in term infants, children, and ado-lescents to identify
patients who can be managed with conservativetreatment by the
pediatrician and to refer patients who require con-sultation with
the gastroenterologist. Accordingly, the evidence basispresented by
the guidelines for diagnostic approaches as well as treat-ments is
discussed. Lifestyle changes are emphasized as rst-line ther-apy in
both GER and GERD, whereas medications are explicitly indicatedonly
for patients with GERD. Surgical therapies are reserved for
chil-dren with intractable symptoms or who are at risk for
life-threateningcomplications of GERD. Recent black box warnings
from the US Foodand Drug Administration are discussed, and caution
is underlinedwhen using promoters of gastric emptying and motility.
Finally, atten-tion is paid to increasing evidence of inappropriate
prescriptions forproton pump inhibitors in the pediatric
population. Pediatrics2013;131:e1684e1695
INTRODUCTION
Gastroesophageal reux (GER) occurs in more than two-thirds
ofotherwise healthy infants and is the topic of discussion with
pedia-tricians at one-quarter of all routine 6-month infant
visits.1,2 In additionto seeking guidance from their pediatricians,
parents often requestevaluation by pediatric medical
subspecialists.3 It is, therefore, notsurprising that strongly
evidence-based guidelines incorporating
Jenifer R. Lightdale, MD, MPH, David A. Gremse, MD, andSECTION
ON GASTROENTEROLOGY, HEPATOLOGY, ANDNUTRITION
KEY WORDSgastroesophageal reux, gastroesophageal reux
disease,pediatrics, guidelines, review, global consensus,
reux-relateddisease, vomiting, regurgitation, rumination,
extraesophagealsymptoms, Barrett esophagus, proton pump
inhibitors,diagnostic imaging, impedance monitoring,
gastrointestinalendoscopy, lifestyle changes
ABBREVIATIONSGERgastroesophageal reuxGERDgastroesophageal reux
diseaseGIgastrointestinalH2RAhistamine-2 receptor
antagonistMIImultiple intraluminal impedancePPIproton pump
inhibitor
This document is copyrighted and is property of the
AmericanAcademy of Pediatrics and its Board of Directors. All
authorshave led conict of interest statements with the
AmericanAcademy of Pediatrics. Any conicts have been resolved
througha process approved by the Board of Directors. The
AmericanAcademy of Pediatrics has neither solicited nor accepted
anycommercial involvement in the development of the content ofthis
publication.
The guidance in this report does not indicate an exclusivecourse
of treatment or serve as a standard of medical care.Variations,
taking into account individual circumstances, may
beappropriate.
www.pediatrics.org/cgi/doi/10.1542/peds.2013-0421
doi:10.1542/peds.2013-0421
All clinical reports from the American Academy of
Pediatricsautomatically expire 5 years after publication unless
reafrmed,revised, or retired at or before that time.
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
Copyright 2013 by the American Academy of Pediatrics
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state-of-the-art approaches to theevaluation and management of
pedi-atric GER have been welcomed by bothgeneral pediatricians and
pediatricmedical subspecialists and surgicalspecialists. GER, dened
as the passageof gastric contents into the esophagus,is
distinguished from gastroesophagealreux disease (GERD), which
includestroublesome symptoms or complica-tions associated with
GER.4 Differen-tiating between GER and GERD lies atthe crux of the
guidelines jointly de-veloped by the North American Soci-ety for
Pediatric Gastroenterology,Hepatology, and Nutrition and
theEuropean Society for Pediatric Gas-troenterology, Hepatology,
and Nutri-tion.4 These denitions have furtherbeen recognized as
representing aglobal consensus.5 Therefore, it isimportant that all
practitioners whotreat children with reux-related dis-orders are
able to identify and dis-tinguish those children with GERD,who may
benet from further eval-uation and treatment, from thosewith simple
GER, in whom conser-vative recommendations are moreappropriate.
GER is considered a normal physio-logic process that occurs
severaltimes a day in healthy infants, children,and adults. GER is
generally associatedwith transient relaxations of the
loweresophageal sphincter independent ofswallowing, which permits
gastriccontents to enter the esophagus. Epi-sodes of GER in healthy
adults tend tooccur after meals, last less than 3minutes, and cause
few or no symp-toms.6 Less is known about the nor-mal physiology of
GER in infants andchildren, but regurgitation or spittingup, as the
most visible symptom, isreported to occur daily in 50% of
allinfants.7,8
In both infants and children, reux canalso be associated with
vomiting, de-ned as a forceful expulsion of gastric
contents via a coordinated autonomicand voluntary motor
response. Re-gurgitation and vomiting can be fur-ther
differentiated from rumination, inwhich recently ingested food is
ef-fortlessly regurgitated into the mouth,masticated, and
reswallowed. Rumi-nation syndrome has been identiedas a relatively
rare clinical entity thatinvolves the voluntary contraction
ofabdominal muscles.9 In contrast, bothregurgitation and vomiting
can beconsidered common and often non-pathologic manifestations of
GER.
Symptoms or conditions associatedwith GERD are classied by the
prac-tice guidelines as being eitheresophageal or extraesophageal.4
Bothclassications can be used to denethe disease, which can be
furthercharacterized by ndings of mucosalinjury on upper endoscopy.
Esopha-geal conditions include vomiting, poorweight gain,
dysphagia, abdominalor substernal/retrosternal pain,
andesophagitis. Extraesophageal con-ditions have been
subclassiedaccording to both established andproposed associations;
establishedextraesophageal manifestations of GERDcan include
respiratory symptoms, in-cluding cough and laryngitis, as wellas
wheezing in infancy.10,11 Althougholder studies from the 1990s
sug-gested that GERD may aggravateasthma, recent publications
havesuggested that the impact of GERD onasthma control is
considerably lessthan previously thought.10,1218
Otherextraesophageal manifestations in-clude dental erosions, and
proposedassociations include pharyngitis, si-nusitis, and recurrent
otitis media.Patients can be described clinically bytheir symptoms
or by the endoscopicdescription of their esophageal mu-cosa.
GERD-associated esophageal in-juries and complications found
onendoscopy include reux esophagitis,less commonly peptic
stricture, and
rarely Barrett esophagus and adeno-carcinoma.
Although the reported prevalence ofGERD in patients of all ages
world-wide is increasing,5 GERD is never-theless far less common
than GER.Population-based studies suggestreux disorders are not as
commonin Eastern Asia, where the prevalenceis 8.5%,19 compared with
WesternEurope and North America, where thecurrent prevalence of
GERD is esti-mated to be 10% to 20%.20 New epi-demiologic and
genetic evidencesuggests some heritability of GERDand its
complications, including ero-sive esophagitis, Barrett
esophagus,and esophageal adenocarcinoma.2123
A few pediatric populations at highrisk of GERD have also been
identi-ed, including children with neuro-logic impairment, certain
geneticdisorders, and esophageal atresia24,25
(Table 1). The prevalence of severe,chronic GERD is much higher
in pe-diatric patients with these GERD-promoting conditions. These
patientsmay be more prone to experienc-ing complications of severe
GERDthan patients who are otherwisehealthy.26
Population trends hypothesized tocontribute to a general
increase inthe prevalence of GERD include glo-bal epidemics of both
obesity andasthma. In some instances, GERD canbe implicated as
either the underlyingetiology (ie, recurrent pneumonia in
TABLE 1 Pediatric Populations at High Riskfor GERD and Its
Complications
Neurologic impairmentObeseHistory of esophageal atresia
(repaired)Hiatal herniaAchalasiaChronic respiratory disorders
Bronchopulmonary dysplasiaIdiopathic interstitial brosisCystic
brosis
History of lung transplantationPreterm infants
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the premature infant exacerbated byGERD) or a direct
repercussion (ie,obesity leading to GERD) of suchconditions. In the
great majority ofcases, however, GERD and comorbid-ities are known
to occur simulta-neously in patients without a clearcausal
relationship.
CLINICAL FEATURES OF GERD
Troublesome symptoms or complica-tions of pediatric GERD are
associatedwith a number of typical clinical pre-sentations in
infants and children,depending on patient age5 (Table 2).Reux may
occur commonly in pre-term newborn infants but is
generallynonacidic and improves with matura-tion. A full discussion
of reux inneonates and preterm infants is be-yond the scope of this
report.
Guidelines have distinguished betweenmanifestations of GERD in
full-terminfants (younger than 1 year) fromthose in children older
than 1 year andadolescents. Common symptoms ofGERD in infants
include regurgitationor vomiting associated with
irritability,anorexia or feeding refusal, poorweight gain,
dysphagia, presumablypainful swallowing, and arching ofthe back
during feedings. Relying ona symptom-based diagnosis of GERDcan be
difcult in the rst year of life,especially because symptoms of
GERDin infants do not always resolve withacid-suppression
therapy.5,27 GERD in
infants can also be associated withextraesophageal symptoms of
cough-ing, choking, wheezing, or upper re-spiratory symptoms.7 The
incidence ofGERD is reportedly lower in breastfedinfants than in
formula-fed infants.27
In line with the natural history ofregurgitation, GERD in
infants is con-sidered to have a peak incidence ofapproximately 50%
at 4 months ofage and then to decline to affect only5% to 10% of
infants at 12 months ofage.7,8
Common symptoms of GERD in chil-dren 1 to 5 years of age include
re-gurgitation, vomiting, abdominal pain,anorexia, and feeding
refusal.28 Gen-erally, GERD causes troublesomesymptoms without
necessarily in-terfering with growth; however, chil-dren with
clinically signicant GERDor endoscopically diagnosed esoph-agitis
may also develop an aversionto food, presumably because of
astimulus-response association of eatingwith pain. This aversion,
combined withfeeding difculties associated with re-peated episodes
of regurgitation, aswell as potential and substantial nu-trient
losses resulting from emesis,may lead to poor weight gain or
evenmalnutrition.
Older children and adolescents aremost likely to resemble adults
in theirclinical presentation with GERD and tocomplain of
heartburn, epigastricpain, chest pain, nocturnal pain, dys-phagia,
and sour burps. When elicitinga history in school-aged children
withsuspected GERD, it may be importantto directly ask patients
themselvesabout their symptoms rather thanrelying strongly on
parent report. In 1study, adolescents were signicantlymore likely
than their parents to re-port themselves to be experiencingsymptoms
of sour burps or nausea.1
Extraesophageal symptoms in olderchildren and adolescents can
includenocturnal cough, wheezing, recurrent
pneumonia, sore throat, hoarseness,chronic sinusitis,
laryngitis, or dentalerosions. In a pediatric patient withGERD and
dental erosions, the pro-gression of tooth structure loss maybe
indicative that existing therapy forGERD is not effective.
Conversely, sta-bility of dental erosions is 1 measureof adequacy
of GERD management.
DIAGNOSTIC STUDIES
For most pediatric patients, a historyand physical examination
in the ab-sence of warning signs are sufcientto reliably diagnose
uncomplicatedGER and initiate treatment strategies.Generally
speaking, diagnostic testingis not necessary. The reliability
ofsymptoms to make the clinical di-agnosis of GERD is particularly
high inadolescents, who often present withheartburn typical of
adults.2931 Nev-ertheless, dedicating at least part ofa clinical
visit to obtaining a clinicalhistory and performing a
physicalexamination are also essential to ex-clude more worrisome
diagnoses thatcan present with reux or vomiting(Table 3).
To date, no single symptom or clusterof symptoms can reliably be
usedto diagnose esophagitis or othercomplications of GERD in
children or topredict which patients are most likely
TABLE 2 Common Presenting Symptoms ofGERD in Pediatric
Patients
Infant Older Child/Adolescent
Feeding refusal Abdominal pain/heartburn
Recurrentvomiting
Recurrent vomiting
Poor weightgain
Dysphagia
Irritability AsthmaSleep
disturbanceRecurrent pneumonia
Respiratorysymptoms
Upper airway symptoms(chronic cough,hoarse voice)
TABLE 3 Concerning Symptoms and Signs(Warning Signs in Figures)
forPrimary Etiologies Presenting WithVomiting
Bilious vomitingGI tract bleeding
HematemesisHematochezia
Consistently forceful
vomitingFeverLethargyHepatosplenomegalyBulging
fontanelleMacro/microcephalySeizuresAbdominal tenderness or
distensionDocumented or suspected genetic/metabolic
syndromeAssociated chronic disease
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to respond to therapy.21 Nonetheless,a number of GERD symptom
ques-tionnaires have been validated andmay be useful in the
detection andsurveillance of GERD in affected chil-dren of all
ages. Kleinman et al de-veloped a questionnaire for infantsthat was
validated for documentationand monitoring of parent-reportedGERD
symptoms.30 Another question-naire by Strdal et al32 for
pediatricpatients 7 to 16 years of age com-pared favorably with
results of pHmonitoring. As yet another example,the GERD Symptom
Questionnaire de-veloped by Deal et al33 appears validfor
differentiating children with GERDfrom healthy controls but has
notbeen compared with objective stand-ards, such as pH monitoring
or en-doscopic ndings.
The strategy of using diagnostictesting to diagnose GERD may
alsobe fraught with complexity, becausethere is no single test that
can rule itin or out. Instead, diagnostic testsmust be used in a
thoughtful and serialmanner to document the presenceof reux of
gastric contents in theesophagus, to detect complications,
toestablish a causal relationship betweenreux and symptoms, to
evaluate theefcacy of therapies, and to excludeother conditions.
The diagnostic meth-ods most commonly used to evaluatepediatric
patients with GERD symptomsare upper gastrointestinal (GI)
tractcontrast radiography, esophageal pHand/or impedance
monitoring, and up-per endoscopy with esophageal biopsy.Upper GI
tract series are useful todelineate anatomy and to occasion-ally
document a motility disorder,whereas esophageal pH monitoringand
intraluminal esophageal impedancerepresent tools to quantify GER.
Up-per endoscopy with esophageal bi-opsy represents the primary
method toinvestigate the esophageal mucosa toboth exclude other
conditions that can
cause GERD-like symptoms and evaluatefor esophageal injury
attributable toGERD.4
Upper GI Tract Series
Upper GI tract contrast radiographygenerally involves obtaining
a series ofuoroscopic images of swallowedbarium until the ligament
of Treitz isvisualized. According to the newguidelines, the routine
performance ofupper GI tract radiographic imaging todiagnose GER or
GERD is not justied,4
because upper GI tract series are toobrief in duration to
adequately ruleout the occurrence of pathologic re-ux, and the high
frequency of non-pathologic reux during the examinationcan
encourage false-positive diagnoses.Additionally, observation of the
reuxof a barium column into the esoph-agus during GI tract contrast
studiesmay not correlate with the severityof GERD or the degree of
esophagealmucosal inammation in patients withreux esophagitis. It
is recognized thatupper GI tract series are useful in theevaluation
of vomiting to screen forpossible anatomic abnormalities of
theupper GI tract.4 For example, in infantswith bilious vomiting,
an upper GI tractseries may be useful for evaluating forpossible
malrotation or duodenal web.Persistent, forceful vomiting in the
rstfew months of life should be evaluatedwith pyloric
ultrasonography to evalu-ate for possible pyloric stenosis. Anupper
GI tract series should be re-served if the results of the pyloric
ul-trasound are equivocal.
Esophageal pH Monitoring
Continuous intraluminal esophagealpH monitoring can be used to
quan-tify the frequency and duration ofesophageal acid exposure
duringa study period. The conventionaldenition of acid exposure in
theesophagus is a pH
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material into the stomach. This nuclearscan evaluates
postprandial reux andcan also quantitate gastric emptying;however,
the lack of standardized tech-niques and age-specic normal
valueslimits the usefulness of this test.Therefore,
gastroesophageal scintigra-phy is not recommended in the
routineevaluation of pediatric patients withGER.4
Endoscopy and Esophageal Biopsy
It is certainly preferable to pursueconservative measures for
treatingGERD in children before consideringthe use of more invasive
testing. Inparticular, any diagnostic benets ofpursuing upper
endoscopy in pediatricpatients suspected of having GERDmust also be
weighed against minimal,but not entirely negligible, proceduraland
sedation risks.36 Nevertheless, theperformance of upper endoscopy
al-lows direct visualization of the esoph-ageal mucosa to determine
the presenceand severity of injury from the reux ofgastric contents
into the esophagus.26
Esophageal biopsies allow evaluationof the microscopic
anatomy.24 Upperendoscopy with esophageal biopsy maybe useful to
evaluate inammation inthe esophageal mucosa attributable toGERD and
to exclude other associatedconditions with symptoms that canmimic
GERD, such as eosinophilicesophagitis. Recent data conrm
thatapproximately 25% of infants youngerthan 1 year will have
histologic evi-dence of esophageal inammation.37
This test is indicated in patients withGERD who fail to respond
to pharma-cologic therapy or as part of the ini-tial management if
symptoms of poorweight gain, unexplained anemia orfecal occult
blood, recurrent pneumo-nia, or hematemesis exist.
Upper endoscopy may also be helpfulin the assessment of other
causes ofabdominal pain and vomiting in pe-diatric patients, such
as esophageal
or antral webs, Crohn esophagitis,peptic ulcer, Helicobacter
pylori in-fection, and infectious esophagitis.Erosive esophagitis
is reported lessoften in infants and children withGERD than in
adults with GERD; how-ever, a normal endoscopic appear-ance of the
esophageal mucosa inpediatric patients does not excludehistologic
evidence of reux esoph-agitis.5,8 Esophageal biopsy is benecialin
evaluating for conditions that maymimic symptoms of GERD, such as
eo-sinophilic esophagitis, infectious esoph-agitis (Candida
esophagitis or herpeticesophagitis), Crohn disease, or
Barrettesophagus.24 Because endoscopic nd-ings correlate poorly
with histologictesting in infants and children, per-forming
esophageal biopsies duringendoscopy is recommended for
theevaluation of GERD in children.4
MANAGEMENT
The new guidelines describe severaltreatment options for
treating childrenwith GER and GERD. In particular, life-style
changes are emphasized, becausethey can effectively minimize
symptomsof both in infants and children. Forpatients who require
medication, op-tions include buffering agents, acidsecretion
suppressants, and promotersof gastric emptying and motility.
Finally,surgical approaches are reserved forchildren who have
intractable symp-toms unresponsive to medical therapyor who are at
risk for life-threateningcomplications of GERD.
LIFESTYLE CHANGES
Lifestyle Modications for Infants
Lifestyle changes to treat GERD ininfants may involve a
combinationof feeding changes and positioningtherapy. Modifying
maternal diet if in-fants are breastfed, changing formulas,and
reducing the feeding volume whileincreasing the frequency of
feedings
may be effective strategies to addressGERD in many patients. In
particular,the guidelines emphasize that milkprotein allergy can
cause a clinicalpresentation that mimics GERD ininfants. Therefore,
a 2- to 4-week trialof a maternal exclusion diet that re-stricts at
least milk and egg is rec-ommended in breastfeeding infantswith
GERD symptoms, whereas an ex-tensively hydrolyzed protein or
aminoacidbased formula may be appro-priate in formula-fed
infants.4,30 It isimportant to note that this recom-mendation
applies to the subset ofinfants with complications of GER, andnot
happy spitters.
In 1 study of formula-fed infants, GERDsymptoms resolved in 24%
of infantsafter a 2-week trial of changing toa protein hydrolysate
formula thick-ened with 1 tablespoon rice cereal perounce, avoiding
overfeeding, avoidingseated and supine positions, and
avoidingenvironmental tobacco smoke.3 Feedingchanges can also be
recommendedin breastfed infants, because it iswell known that small
amounts ofcow milk protein ingested by themother may be expressed
in humanmilk. Indeed, several studies havefound that breastfed
infants maybenet from a maternal diet thatrestricts cow milk and
eggs.38,39
The feeding management strategy thatinvolves the use of
thickened feedings,either by adding up to 1 tablespoon ofdry rice
cereal per 1 oz of formula30 orchanging to commercially
thickened(added rice) formulas for full-terminfants who are not cow
milk proteinintolerant, is recognized as a reason-able management
strategy for other-wise healthy infants with both GER andGERD.4 On
the other hand, all pediatricclinicians should be aware of a
possibleassociation between thickened feedingsand necrotizing
enterocolitis in preterminfants.40 The Food and Drug
Adminis-tration issued a warning regarding a
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common commercially available thick-ening agent in 2011,
suggesting thatparents, caregivers and health careproviders
not...feed SimplyThick toinfants born before 37 weeks gestationwho
are currently receiving hospitalcare or have been discharged from
thehospital in the past 30 days.
Thickened feedings appear to de-crease observed regurgitation
ratherthan the actual number of reux epi-sodes. Little is known
about the effectof thickening formula on the naturalhistory of
infantile reux or the po-tential allergenicity of
commercialthickening agents. Excessive energyintake may occur with
long-term use offeedings thickened with rice cereal orcorn. To this
point, it is important torealize that thickening a 20-kcal/ozinfant
formula with 1 tablespoon ofrice cereal per ounce increases
theenergy density to 34 kcal/oz. Com-mercially available
antiregurgitantformulae contain processed rice, corn,or potato
starch; guar gum; or locustbean gum and may present an optionthat
does not involve excess energyintake by infants when consumed
innormal volumes. To date, there hasbeen little investigation into
any re-lationship between use of added ricecereal or
antiregurgitant formulae andchildhood obesity.
Lifestyle changes that may also benetinfants with GERD include
keepingthem in the completely upright posi-tion or even placing
them prone. In-deed, a number of recent studies thatused impedance
and pH monitoringhave conrmed older studies that usedpH monitoring
to demonstrate signif-icantly less GER in infants in the atprone
position compared with theat supine position.41,42 However,
theguidelines are unequivocal that therisk of sudden infant death
syndromein sleeping infants outweighs thebenets of prone
positioning in themanagement of GERD and, therefore,
that prone positioning should beconsidered acceptable only if
the in-fant is observed and awake.4 Pronepositioning is suggested
to be bene-cial in children older than 1 year witheither GER or
GERD, because the riskof sudden infant death syndrome isgreatly
decreased in older age groups.
Perceived and actual benets of seatedor semisupine positioning
are alsoexplored in the new guidelines.Semisupine positioning,
particularlyin an infant carrier or car seat, mayexacerbate GER and
should beavoided when possible, especiallyafter feeding.43 More
recent dataobtained with esophageal imped-ancepH monitoring have
conrmedthat postprandial reux occurssimilarly when infants are in
carseats as when they are supine butalso suggests that being in a
carseat for 2 hours after a feedingreduces reux-related
respiratoryevents.44
Lifestyle Modications for Childrenand Adolescents
Lifestyle changes that may benetGERD in older children and
adoles-cents are more akin to recommen-dations made for adult
patients,including the importance of weightloss in overweight
patients, cessationof smoking, and avoiding alcohol
use.Recommendations for conservativelymanaging GERD in older
children andadolescents, likewise, may involve di-etary modication
and positioningchanges, although the effectiveness ofthe latter as
a treatment of GERD inolder children has not been as wellstudied as
in infants. In terms of di-etary changes, older children
andadolescents are advised to avoid caf-feine, chocolate, alcohol,
and spicyfoods as potential symptom triggers.The guidelines also
point out that 3independent studies have demonstrateddecreased reux
episodes with
postprandial chewing of sugarlessgum.4547
PHARMACOTHERAPEUTIC AGENTSFOR PEDIATRIC GERD
Several medications may be used totreat GERD in infants and
children. The2 major classes of pharmacologicagents for treatment
of GERD are acidsuppressants and prokinetic agents(Table 4).
Growing evidence that de-monstrates the former to be moreeffective
than the latter has led to anincreased use of acid suppressants
tomanage suspected GERD in pediatricpatients4,39; however, there is
also sig-nicant concern for the overprescriptionof acid
suppressants, particularly protonpump inhibitors (PPIs), and it is
im-portant to understand the new guide-lines for medication
indications.
Acid Suppressants
The main classes of acid suppressantsare antacids, histamine-2
receptorantagonists (H2RAs), and PPIs. Theprinciples of using these
medicationsin the treatment of pediatric GERD aresimilar to those
in adults, other thanthe need to prescribe weight-adjusteddoses and
the need to consider theform of the drug prescribed (ie, forease of
ingestion in infants and chil-dren). Dosage ranges for drugs
com-monly prescribed for pediatric patientswith GERD are listed in
Table 4.
Antacids
Antacids are a class of medicationsthat can be used to directly
buffergastric acid in the esophagus or stom-ach to reduce heartburn
and ideallyallow mucosal healing of esophagitis.There is limited
historical evidencethat on-demand use of antacids canlead to
symptom relief in infants andchildren.48 Instead, although
antacidsare generally seen as a relatively be-nign approach to
treating pediatric
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GERD, it is important to recognize thatthey are not entirely
without risk. In-deed, several studies link aluminum-containing
preparations with alumi-num toxicity and its complications
inchildren.4951 Similarly, milk-alkali syn-drome, a triad of
hypercalcemia, al-kalosis, and renal failure, has beendescribed in
children receiving calcium-containing preparations and adds toa
note of caution. According to thenew guidelines, chronic antacid
ther-apy is generally not recommended inpediatrics for the
treatment of GERD.4
In addition, the safety and efcacy ofsurface protective agents,
such asalginates or sucralfate, an aluminum-containing preparation,
have not beenadequately studied in the pediatricpopulation. As
such, no surface agentis currently recommended as indepen-dent
treatment of severe symptomsof GERD or erosive esophagitis
inchildren.4
H2RAs
H2RAs represent a major class ofmedications that has completely
rev-olutionized the treatment of GERD inchildren. H2RAs decrease
the secretionof acid by inhibiting the histamine-2receptor on the
gastric parietal cell.Expert opinion suggests little clinical
difference between the various for-mulations of H2RAs.
Randomized placebo-controlled pediatric clinical trials haveshown
that cimetidine and nizatidineare superior to placebo for the
treat-ment of erosive esophagitis in chil-dren.52,53
Pharmacokinetic studies inschool-aged children suggest thatgastric
pH begins to increase within 30minutes of administration of an
H2RAand reaches peak plasma concen-trations 2.5 hours after dosing.
Theacid-inhibiting effects of H2RAs lastfor approximately 6 hours,
so H2RAsare quite effective if administered 2or 3 times a day.
However, H2RAs inherently have somelimitations. In particular, a
fairly rapidtachyphylaxis can develop within 6weeks of initiation
of treatment, lim-iting its potential for long-term use.
Inaddition, H2RAs have been shown to beless effective than PPIs in
symptomrelief and healing rates of erosiveesophagitis. Although
most of thesedownsides have been demonstratedmost clearly in
adults, they are alsobelieved to affect children. It is
alsoimportant to recognize that cimetidinehas specically been
linked to an in-creased risk of liver disease and gy-necomastia,
and that these associationsmay be generalizable to other H2RAs.
PPIs
Most recently, PPIs have emerged asthe most potent class of acid
sup-pressants by repeatedly demonstrat-ing superior efcacy compared
withH2RAs. PPIs decrease acid secretion byinhibition of H+,
K+-ATPase in the gas-tric parietal cell canaliculus. PPIs
areuniquely able to inhibit meal-inducedacid secretion and have a
capacity tomaintain gastric pH >4 for a longerperiod of time
than H2RAs. Theseproperties contribute to higher andfaster healing
rates for erosiveesophagitis with PPI therapy com-pared with H2RA
therapy. Finally,unlike H2RAs, the acid suppressionability of PPIs
has not been observedto diminish with chronic use.
The timing of dosing most PPIs isimportant for maximum
efcacy.Both pediatricians and pediatricmedical subspecialists must
be dili-gent at educating their patients toadminister PPIs,
ideally, approxi-mately 30 minutes before meals.7
All clinicians should also recognizethat the metabolism of PPIs
isknown to differ in children com-pared with adults, with a
trendtoward a shorter half-life, necessi-tating a higher
per-kilogram dose toachieve a peak serum concentration
TABLE 4 Pediatric Doses of Medications Prescribed for GERD
Medications Doses Formulations Ages Indicated by the Foodand
Drug Administration
Cimetidine 3040 mg/kg/d, divided in 4 doses Syrup 16 yRanitidine
510 mg/kg/d, divided in 2 to 3 doses Peppermint-avored syrup;
Effervescent tablet 1 mo16 yFamotidine 1 mg/kg/d, divided in 2
doses Cherry-banana-mintavored oral suspension 116 yNizatidine 10
mg/kg/d, divided in 2 doses Bubble gumavored solution 12
yOmeprazole 0.73.3 mg/kg/d Sprinkle contents of capsule onto soft
foods 216 yLansoprazole 0.73 mg/kg/d Sprinkle contents of capsule
onto soft foods or select juices 117 y
Administer capsule contents in juice through nasogastric
tubeStrawberry-avored disintegrating tabletOrally disintegrating
tablet via oral syringe or nasogastric
tube (8 French)Esomeprazole 0.73.3 mg/kg/d Sprinkle contents of
capsule onto soft foods 117 y
Administer capsule contents in juice through nasogastric
tubeRabeprazole 20 mg daily Oral tablet 1217 yDexlansoprazole 3060
mg daily Oral tablet No pediatric indicationPantoprazole 40 mg
daily (adult dose) Oral tablet No pediatric indication
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and area under the curve similar tothose in adults.45 A fairly
wide rangeof effective doses is evident in chil-dren. For example,
an open-labelstudy of omeprazole in children re-vealed an effective
dosage range of0.7 to 3.3 mg/kg daily, on the basis ofimprovement
in clinical symptomsand the results of esophageal pHmonitoring.47
Lansoprazole, 0.7 to3.0 mg/kg daily, improved GERDsymptoms and
healed all cases oferosive esophagitis in the treat-ment of 1- to
12-year-old childrenwith GERD.48 Other trials of PPItherapy support
the efcacy of treat-ment of severe esophagitis and esoph-agitis
refractory to H2RAs in children.4,45
As in adults, PPIs are considered safeand generally well
tolerated with rel-atively few adverse effects. In terms oftheir
long-term use, published studieshave reported PPI use for up to
11years in small numbers of children.16
The Food and Drug Administration hasapproved a number of PPIs
for use inpediatric patients in recent years, in-cluding
omeprazole, lansoprazole, andesomeprazole for people 1 year
andolder and rabeprazole for people 12years and older. Nonetheless,
the newguidelines strike a note of cautionwhen discussing the
dramatic in-crease in past years in the number ofPPI prescriptions
written for pediatricpatients, particularly infants, who maybe at
increased risk of lower re-spiratory tract infections.5456
Overuse or misuse of PPIs in infantswith reux is a matter for
greatconcern. Placebo-controlled trials ininfants have not
demonstrated supe-riority of PPIs over placebo forreduction in
irritability.57 Headaches,diarrhea, constipation, and nauseahave
been described as occurring inup to 14% of older children andadults
prescribed PPIs.25,58 Althoughconsidered a benign histologic
change,enterochromafn cell hyperplasia has
FIGURE 1Approach to the infant with recurrent regurgitation and
vomiting.
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recently been demonstrated in up to50% of children receiving
PPIs for morethan 2.5 years.25 Finally, a growing bodyof evidence
suggests that acid sup-pression, in general, with either H2RAsor
PPIs, may be a risk factor for pedi-atric community-acquired
pneumonia,gastroenteritis, candidemia, and necro-tizing
enterocolitis in preterm infants.59,60
Prokinetic Agents
Desired pharmacologic effects ofprokinetic agents include
improvingcontractility of the body of theesophagus, increasing
lower esoph-ageal sphincter pressure, and in-creasing the rate of
gastric emptying.To date, efforts to design a prokineticagent with
benets that outweighadverse effects has proven difcult.Even
metoclopramide, the most com-mon prokinetic agent still
available,recently received a black box warningregarding its
adverse effects. Indeed,adverse effects have been reported in11% to
34% of patients treated withmetoclopramide, including
drowsiness,restlessness, and extrapyramidal reac-tions. Although a
meta-analysis of 7randomized controlled trials of meto-clopramide
in patients younger than 2years with GERD conrmed a decreasein GERD
symptoms, it was clearly at thecost of such signicant adverse
ef-fects.61 Other drugs in this categoryinclude bethanechol,
cisapride (nolonger available commercially in theUnited States),
baclofen, and eryth-romycin. Each works as a prokineticby using a
different mechanism. Nev-ertheless, after careful review,
guide-lines unequivocally state that there isinsufcient evidence to
support theroutine use of any prokinetic agent forthe treatment of
GERD in infants orolder children.4
Surgery for Pediatric GERD
Several surgical procedures can beused to decrease GER disorders
in
children. Fundoplication, whereby thegastric fundus is wrapped
around thedistal esophagus, is most commonand can be performed to
prevent reuxby increasing baseline pressure of thelower esophageal
sphincter, decreasingthe number of transient lower esoph-ageal
sphincter relaxations, and in-creasing the length of the
esophagusthat is intra-abdominal to accentuatethe angle of His and
reduce a hiatalhernia, if indicated.17,56,57 Total esoph-agogastric
dissociation is another op-erative procedure that is rarely
usedafter failed fundoplication. Both pro-cedures are associated
with signicant
morbidity and do not reduce the riskof direct aspiration of oral
contents.Careful patient selection is one of thekeys to successful
outcome.17 Childrenwho have failed pharmacologic treat-ment may be
candidates for surgicaltherapy, as are children at severe riskof
aspiration of their gastric contents.In most patients, if acid
suppressionwith PPIs is ineffective, the accuracy ofthe diagnosis
of GERD should be reas-sessed, because fundoplication maynot
produce optimum clinical results.Clinical conditions, such as
cyclicvomiting, rumination, gastroparesis,and eosinophilic
esophagitis, should
FIGURE 2Approach to the infant with recurrent regurgitation and
weight loss.
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be carefully ruled out before surgery,because they are likely to
still causesymptoms after surgery. If antireuxsurgery is pursued,
the new guide-lines also stress the importance ofproviding families
with adequatecounseling and education before theprocedure so that
they have a re-alistic understanding of the
potentialcomplicationsincluding symptomrecurrence.4
SUMMARY
The updated guidelines published in2009 are particularly rich
with de-scriptions of typical presentations ofGERD across all
pediatric age groups.4
With an emphasis on evidence-based,best practice, they present a
numberof algorithms that can be of great useto both general
pediatricians and pe-diatric medical subspecialists. Theguidelines
discuss the evaluation andmanagement of recurrent regurgitationand
vomiting in both infants and olderchildren and the importance of
dis-tinguishing GERD from numerous otherdisorders. The gures shown
demon-strate the recommended approachesfor commonly encountered
presenta-tions of GERD in pediatric patients andare summarized
here.
In the infant with uncomplicated re-current regurgitation, it
may be im-portant to recognize physiologic GERthat is effortless,
painless, and notaffecting growth (Fig 1). In this situa-tion,
pediatricians should focus onminimal testing and
conservativemanagement. Overuse of medicationsin the so-called
happy spitter shouldbe avoided by all pediatric physicians.Instead,
pediatricians are well servedto diagnose GER and provide
signif-icant parental education, anticipa-tory guidance, and
reassurance. Inturn, they will provide high-value,high-quality care
without risk totheir patients or unnecessary directand indirect
costs.
Pediatricians must also be able torecognize infants with
recurrent re-gurgitation and troublesome symp-toms of GERD (Fig 2).
The newguidelines emphasize weight loss asa crucial warning sign
that shouldalter clinical management. Older chil-dren with
heartburn may benet fromempirical treatment with PPIs (Fig 3).In
general, there is a paucity of stud-ies in pediatrics that
demonstrate theeffectiveness of this approach. In-stead, it is
essential to carefully followall patients empirically treated
forGERD to ensure that they are improv-ing, because there are many
clinicalconditions that may mimic its symp-toms. It cannot be
overemphasizedthat pediatric best practice involvesboth identifying
children at risk forcomplications of GERD and reassuringparents of
patients with physiologic GER
who are not at risk for complicationsto avoid unnecessary
diagnostic proce-dures or pharmacologic therapy.6264
LEAD AUTHORSJenifer R. Lightdale, MD, MPHDavid A. Gremse, MD
SECTION ON GASTROENTEROLOGY,HEPATOLOGY, AND NUTRITIONEXECUTIVE
COMMITTEE, 20112012Leo A. Heitlinger, MD, ChairpersonMichael
Cabana, MDMark A. Gilger, MDRoberto Gugig, MDJenifer R. Lightdale,
MD, MPHIvor D. Hill, MB, ChB, MD
FORMER EXECUTIVE COMMITTEEMEMBERSRobert D. Baker, MD, PhDDavid
A. Gremse, MDMelvin B. Heyman, MD
STAFFDebra L. Burrowes, MHA
FIGURE 3Approach to the older child or adolescent with
heartburn.
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HEPATOLOGY, AND NUTRITIONJenifer R. Lightdale, David A. Gremse
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Gastroesophageal Reflux: Management Guidance for the
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