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Differentiating GER from


GERD:
To "D" or not to "D"
Jenifer R. Lightdale, MD, MPH
Gastroenterology and Nutrition
Boston Childrens Hospital
Harvard Medical School
Childrens Hospital Boston

TM

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Statements and opinions expressed are those of the authors and not
necessarily those of the American Academy of Pediatrics.
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the planning and content of the presentation, and is not receiving any
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the event that the presentation contains statements about uses of
drugs that are not within the drugs' approved indications,Mead
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the FDA-approved product label.

AAP PCO Webinar Objectives


Clarify terms related to reflux disease in
children
Review options for testing and treating
reflux disorders
Discuss guidelines for appropriately
managing children with reflux disease

Practice Change
As a result of participating in this webinar,
attendees will be aware of a guideline based
approach for identifying which patients will
benefit from treatment for gastroesophgeal
reflux disease (GERD), as well as which
patients should be reassured their
gastroesophgeal reflux (GER) is physiologic
and not harmful.

Jenifer R. Lightdale, MD, MPH


o Pediatric Gastroenterologist
o Childrens Hospital Boston
o Endoscopy
o Colic/fussy babies
o Quality of care

Lay Reports on GERD in Infants


Increased in past decade
Describe inconsolable newborns who
improved dramatically on proton pump
inhibitors (PPIs)
o Discussed colic as poorly understood

Have contributed to 750% rise in use of PPIs


in infants
o 1999-2004

Evokes questions of previous misdiagnosis


vs. current overuse

WSJ Provocative Health Reporting:


Even the terminology is confusingmost
babies have reflux [and] it usually doesnt
hurt
GER becomes more-serious GERD if the
infant wont eat and stops gaining weight,
vomits blood and is extremely irritable

GOOD NEWS!
There is a pediatric global definition of
GER vs. GERD
o To define reflux disease and its manifestations
in infants, toddlers, children, and adolescents

A primary objective of the definition is to


clarify terms related to reflux-related
symptoms and signs in children
Sherman PM, Hassall E, Fagundes-Neto U, et al. A global, evidence-based consensus on the definition of gastroesophageal
reflux disease in the pediatric population. Am J Gastroenterol. 2009;104(5):12781295

More Good News!


There are Pediatric Gastroesophageal
Reflux Clinical Practice Guidelines
o Endorsed by the North American and European
Societies for Pediatric Gastroenterology,
Hepatology, and Nutrition
o Basis of a 2013 Clinical Report from the
American Academy of Pediatrics (AAP)

Intended to be used in daily practice of all


practitioners when evaluating and
managing children with reflux disease

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557. Lightdale JR, Gremse DA. Section on Gastroenterology, Hepatology and Nutrition. Gastroenterology
Reflux: Management Guidance for the Pediatriatrician. Pediatrics. 2013: 131(5): e1684-1695.

Global consensus especially useful because


physiologic GER is now recognized to be relatively
common in babies and kids

(Mean upper limit of normal)

Infants
(N=50
9)

Childre
n
(N=48)

Adults
(N=43
2)

# daily reflux episodes

73

25

45

# reflux episodes lasting


> 5 min

9.7

6.8

3.2

11.7%

5.4%

6%

Reflux index (% of time


pH < 4)*
*over approx 24 hours

Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and
children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr
Gastroenterol Nutr. 2001;32(supplement 2):S1S31

Clarification via Global


Consensus
GERD is defined to be present when reflux of
gastric contents causes either troublesome
symptoms or complications

Troublesome symptoms or
complications of reflux
Recurrent vomiting
and
poor weight gain in
infant
Recurrent vomiting
and
irritability in infant
Recurrent vomiting in
older child
Heartburn in
child/adolescent
Esophagitis

Dysphagia or feeding
refusal
Apnea or ALTE
Asthma
Recurrent pneumonia
Upper airway
symptoms
Unusual arching or
seizure-like
movements (Sandifer
syndrome)

Example of Sandifer Syndrome

Photos courtesy of Harland Winter, MD.


Werlin SL, D'Souza BJ, Hogan WJ, et al. Sandifer syndrome: an
unappreciated clinical entity. Dev Med Child Neurol. 1980;22(3):374378

What about complications


of GERD?
e.g. Is there a danger to not
recognizing and treating it?

Complications of Reflux
Normal midand
distal
esophagus
Z-line

Erosive esophagitis:
grade 2 and grade 4
Erosions

Complications of Reflux
Esophageal stricture
secondary to GERD:
radiography and
endoscopy
Stricture

Barretts
esophagus:
endoscopy and
histology
Barretts
Normal

Barretts

Normal

Endoscopic Biopsies
Useful to evaluate for a variety conditions,
but are not required for diagnosis of GERD
Possible findings on biopsy:
o
o
o
o
o

Gastroesophageal reflux
Food allergy or intolerance
Primary eosinophilic esophagitis
Drug induced
Infection
Candida
Herpes simplex
Cytomegalovirus

Pathologic esophagitis

EH
EH
PL

PL

BL

BL

Normal
Esophagitis
EH, epithelial height; PL, papillary layer; BL, basal layer
Normal: PL ~ 40% of epithelial height; BL ~ 15%
GERD: PL ~ 90% of epithelial height; BL ~ 30%

Normal esophagus

Peptic esophagitis

Eosinophilic esophagitis

Eosinophilic
Esophagitis

Clinical Cases
5 month old who effortlessly spits-up 6
10x/day, but seems comfortable and is
growing well
4 month old who is losing weight is
reported to vomit 23x/day, and seems
increasingly fussy with feeds
15 year old who presents complaining of
heartburn

So What is GER??? And What is GERD???

Understanding the difference


o May help to avoid overclassifying patients
with GERD vs. physiologic GER
o May avoid overtesting
o May avoid overtreatment
o May help identify when to refer patients to
specialists

GER
Gastroesophageal Reflux
o The passage of gastric contents into the
esophagus
o Occurs with/without regurgitation and vomiting

GER is a normal physiologic process


o Several times/day in healthy infants, children,
and adults

Most Episodes of GER

Last < 3 minutes


Occur in the postprandial period
Cause few or no symptoms
GER can cause vomiting
o A coordinated autonomic and voluntary motor
response with forceful expulsion of gastric contents

Regurgitation (spitting up) is the most visible


symptom of GER
o Occurs daily in 50% of infants < 3 months of age
o Resolves spontaneously in most by 1214 months

Prevalence of Regurgitation in Infancy


1 time a day
4 times a day

% of
Infant
s

Age (months)

n=948

0-3

4-6

7-9

10-12

Adapted from Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastroesophageal reflux
during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr
Adolesc Med. 1997;151(6):569572

Physiology of GER
GER occurs during transient relaxations of
the lower esophageal sphincter (LES)
o Relaxation of the LES that is unaccompanied
by swallowing permits gastric contents into the
esophagus

LES is not a true sphincter


o Comprised of crural support, an
intraabdominal segment, and the angle of
His

Composition of the LES

Healthy adult LES 3cm in length, at level of


diaphragm
Neonate LES 1.5cm in length, above the

Esophageal Capacity

Shorter esophagus
Smaller capacity

Gravit
y

Adu
lt

Infa
nt

WHEN DOES GER become GERD


Aberrance in normal physiology
o Insufficient clearance and buffering of
refluxate
o Decreased rate of gastric emptying
o Abnormalities in efficacy of epithelial repair
o Decreased neural protective reflexes

Development of erosive esophagitis


causes esophageal shortening
o May result in hiatal herniation

Esophagitis can cause shortening of the


stomach, leading to hiatal hernia.

Copyright 2003 New England Minimally Invasive Surgeons

Genetics of Reflux
Cluster studies suggest inheritability of
GER/GERD and their complications
o
o
o
o

Hiatal hernia
Erosive esophagitis
Barretts esophagus
Esophageal adenocarcinoma

Swedish Twin Registry


o Increased concordance in monozygotic vs.
dizygotic
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and
the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal
Nutr. 2009;49(4):548557

High Risk Populations


Several pediatric patient populations
appear to be at higher risk of GERD
o
o
o
o
o
o

Neurologically impaired
Obese infants, children, and adolescents
Certain genetic syndromes
Esophageal atresia
Chronic lung diseases
History of prematurity

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and
the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557

Testing for Reflux Disorders


No one test can be used to diagnose reflux,
and instead must be matched to a clinical
question
Reflux tests are useful
o To document the presence of GER(D)
o To detect complications
o To establish a causal relationship between GER
and symptoms
o To evaluate therapy
Vandenplas
Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
o Y,To
exclude other conditions
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557

Diagnostic Approach
Depends on symptoms and signs
History and physical examination
Upper gastrointestinal (GI) series
Esophageal pH monitoring
Esophagogastroduodenoscopy and biopsy
Empirical medical therapy

Upper GI Radiography
Advantage
Useful for detecting
anatomic abnormalities

Limitation
Cannot discriminate
between physiologic and
nonphysiologic GER
episodes

Pyloric stenosis

Malrotation

Esophagogastroduodenoscopy
(EGD)
Advantages

Enables visualization and


biopsy of esophageal
epithelium
Determines presence of
esophagitis, other
complications
Discriminates between reflux
and non-reflux esophagitis
Limitations

Need for sedation or anesthesia


Endoscopic grading systems not
yet validated for pediatrics
Poor correlation between
endoscopic appearance and
histopathology
Generally not useful for extraesophageal GERD

Esophageal pH Monitoring
Advantages

Detects episodes of reflux

Determines temporal association


between acid GER and
symptoms

Limitations

Cannot detect nonacidic reflux

Cannot detect GER


complications associated with
normal range of GER

Not useful in detecting


association between GER and
apnea unless combined with
other techniques

Multiple Intraluminal Electrical


Impedance Measurement
Advantages
pH channel
pH 4

Z1

Impedance
channels

Limitations

Z4

Detects nonacidic GER episodes


Detects brief (< 15 s) acidic GER
episodes
Useful for studying respiratory
symptoms and GER in infants

Normal values in pediatric age


groups not yet defined
Analysis of tracings timeconsuming
Portable device unavailable for
outpatient studies

Impedance
Sensors
Pediatric
Catheter

pH
Sensors
Infant
Catheter

Non-Acid
Reflux

History and Physical Exam


Symptoms and signs associated with GER
are non-specific

o i.e. Not all children with GER have heartburn or


irritability
o Conversely, heartburn and irritability can be
caused by conditions other than GER

Major roles of History/Physical Exam when


evaluating GERD
o To exclude other worrisome disorders that
present with vomiting
o To recognize complications of GERD

Symptoms and Signs of GER/GERD


Symptoms
Recurrent regurgitation
with/without vomiting
Weight loss or poor weight
gain
Irritability in infants
Heartburn or chest pain
Hematemesis
Dysphagia, Odynophagia,
Feeding refusal
Apnea spells
Wheezing
Stridor
Cough
Hoarseness
Dystonic neck posturing
(Sandifer syndrome)

Signs
Esophagitis
Esophageal stricture
Barrett Esophagus
Laryngeal/pharyngeal
inflammation
Recurrent pneumonia
Anemia
Dental erosion

Indications for Further Evaluation in


Infants With Vomiting
Bilious vomiting
GI bleeding
Hematemesis
Hematochezia

Consistently forceful
vomiting
Onset of vomiting after
6 months of life
Severe failure to thrive
Diarrhea
Constipation
Fever

Lethargy
Hepatosplenomegaly
Bulging fontanelle
Macro/microcephaly
Seizures
Abdominal tenderness
or distension
Documented or
suspected
genetic/metabolic
syndrome
Associated chronic
disease

Differential Diagnosis of Vomiting in Infants and Children


GI

Gastrointestinal
obstruction
Pyloric stenosis
Malrotation with
intermittent volvulus
Intestinal duplication
Hirschsprung disease
Antral/duodenal web
Foreign body
Incarcerated hernia

Other GI disorders
Achalasia
Gastroparesis
Gastroenteritis
Peptic ulcer
Eosinophilic
esophagitis/gastroenter
itis
Food allergy
Inflammatory bowel
disease
Pancreatitis
Appendicitis

Differential Diagnosis of Vomiting


in Infants and Children Non-GI
Neurologic
Hydrocephalus
Subdural
hematoma
Intracranial
hemorrhage
Intracranial
mass
Infant migraine
Infectious
Sepsis
Meningitis
Urinary tract
infection
Pneumonia
Otitis media
Hepatitis

Metabolic/endocrine
Galactosemia
Hereditary
fructose
intolerance
Urea cycle defects
Amino and organic
acidemias
Congenital adrenal
hyperplasia
Renal
Obstructive
uropathy
Renal insufficiency

Toxic
Lead
Iron
Vitamin A and D
Medications: ipecac,
digoxin,
theophylline, etc.
Cardiac
Congestive heart
failure
Vascular ring
Psychiatric
Munchausen
syndrome
by proxy
Child neglect or

Important to Obtain a
Feeding and Vomiting History
Feeding and dietary
history
Amount/frequency
(overfeeding)
Preparation of formula
Recent changes in feeding
type or technique
Position during feeding
Burping
Behavior during feeding:
choking, gagging, cough,
arching, discomfort, refusal

Pattern of vomiting
Frequency/amount
Pain
Forceful or not
Blood or bile
Associated fever,
lethargy, diarrhea

Other Histories in the Infant/Child


With Suspected GERD
Past medical history
Prematurity
Growth and
development
Past surgery and
hospitalizations
Newborn screen
results
Recurrent illnesses
(croup, pneumonia,
asthma)
Symptoms of
hoarseness,
fussiness, hiccups
Apnea
Previous weight and
height gain

Medications
Current vs. Recent
Prescription
Non-prescription
Family psychosocial history
Sources of stress
Maternal or paternal
drug use
Post partum
depression

Family medical
history
Significant
illnesses
Family history of
GI disorders
Family history of
atopy
Growth chart
Height
Weight
Head
circumference

History/Physical Examination
Severity of reflux or esophagitis found on
diagnostic testing does not directly
correlate with symptom severity
In infants and toddlers, there is no
symptom or group of symptoms that can
reliably diagnose GERD or predict
treatment response
In older children and adolescents, history
and physical examination are generally
sufficient to reliably diagnose GERD and
initiate management

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and
the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal
Nutr. 2009;49(4):548557

Conservative Therapy for GER


For Infants

For Older Children

Normalize feeding
volume
and frequency

Avoid large meals

Consider thickened
formula

Lose weight, if obese

Do not lie down


immediately after eating

Consider non-prone
positioning during sleep

Avoid caffeine, chocolate,


and spicy foods that
provoke symptoms

Consider trial of
hypoallergenic formula

Eliminate exposure to
tobacco smoke

Treating physiologic GER in infants


Once the diagnosis of GER is established
o Parental education, reassurance, and anticipatory
guidance are recommended
o Dietary changes and thickening of formula can be
considered

In general no other intervention is necessary


If symptoms worsen or do not resolve by 12 to 18
months of age or warning signs develop,
referral to a pediatric gastroenterologist is
recommended
Vandenplas
Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint

recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557

Treatment of GER in infants


Evidence supports
o 24 week trial of an extensive protein
hydrolysate in formula fed infants with
vomiting
o Thickening of formula which may decrease
visible reflux (regurgitation)
o Supine position for sleeping

If no improvement, referral to a pediatric


gastroenterologist may be appropriate
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and
the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557

Effect of Thickening Milk Formula


Feedings With Rice Cereal
Unthickened
Thickened
p=.015

Caloric Density
(cal/cc)

n=20

Emesis
(episodes/90 min)

p=.026

Sleep Time
(min asleep/90 min)

p=.042

Crying Time
(min crying/90 min)

Adapted from Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr.
1987;110(2):181186

Thickened formula

Unthickened formula

Pre-thickened Formulas Change


Viscosity With Acidification

Formula +
rice cereal
Enfamil AR

Reprinted with permission from Mead Johnson Nutrition

Unthickened
formula

Positioning and GER

60

Sitting
Supine

Adapted from Ramenofsky ML, Leape LL. Continuous upper esophageal pH monitoring in
infants and children with gastroesophageal reflux, pneumonia, and apneic spells. J
Pediatr Surg. 1981;16(3):374378

Prone

Effect of Sleep Position on GER in Infants and


Sudden Infant Death Syndrome (SIDS) Mortality

Supine

Reflux
Index1
(% time pH
15.3
<4)

Left side
Right side
Prone

SIDS Mortality2 Reflux Index


SIDS
(per 1000 live Odds Ratio
Mortality
births)
Odds Ratio3

0.05*

2.3

1.0

7.7

0.05*

1.1

3.5

12.0

0.05*

1.8

3.5

6.7

4.4

1.0

13.9

*Mortality rate for all non-prone positions combined

Combined odds ratio


Tobin JM, McCloud P, Cameron DJ. Posture and gastro-oesophageal reflux: a case for left lateral positioning. Arch Dis Child.
1997;76(3):254358
2
Skadberg BT, Morild I, Markestad T. Abandoning prone sleeping: Effect on the risk of sudden infant death syndrome. J
Pediatr. 1998;132(2):340343
3
Oyen N, Markestad T, Skaerven R, et al. Combined effects of sleeping position and prenatal risk factors in sudden infant
death syndrome: the Nordic Epidemiological SIDS Study. Pediatrics. 1997;100(4):613621
1

Positioning Therapy for GERD


For Infants
Non-prone positioning during
sleep is recommended
Supine positioning confers lowest
risk for SIDS and is preferred

Prone positioning may be


considered in cases where risk
of death from GER
complications outweighs
potential increased risk of SIDS

For Older Children


Left side positioning during
sleep may be beneficial
Elevate head of bed
Avoid lying down
immediately after eating

If prone positioning is
recommended, discuss
rationale with parents
Avoid
soft bedding,
pillows,
loose
American Academy
of Pediatrics, Task
Force on Infant
Sleep Position and Sudden Infant Death Syndrome. Changing concepts
of sudden infant death syndrome: implications for infant sleeping environment and sleep position. Pediatrics. 2000;105(3 Pt
sheets near infant
1):650656; Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in
infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr
Gastroenterol Nutr. 2001;32(supplement 2):S1S31

Treatment of GERD in Older Children


A left sided sleeping position with
elevation of the head of the bed may
decrease symptoms and GER
In adults, obesity and late night eating are
associated with increased reflux
o To date, no evidence to support specific
dietary restrictions to decrease symptoms of
GER in pediatric populations

Appropriate to trial acid suppression

Goals of Pharmacotherapy
Control symptoms
Promote healing
Prevent complications
Improve health-related quality of life
Avoid adverse effects of treatment

Medical Treatment of GERD


Both Histamine-2 receptor antagonists
(H2RAs) and PPIs

o Produce relief of symptoms and mucosal


healing of GERD
o Are superior to buffering agents, alginates,
and sucralfate

PPIs are superior to H2RAs in relieving


symptoms and healing esophagitis.
Potential side effects of each currently
available prokinetic agent outweigh the
potential benefits

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557

o No evidence for routine use of


metoclopramide, erythromycin, bethanechol,
or domperidone for GERD

Inhibition of Acid Secretion in Gastric Parietal Cell

Copyright 1996 by Excerpta Medica Inc.


Adapted from Sanders SW. Pathogenesis and treatment of acid peptic
disorders: comparison of proton pump inhibitors with other antiulcer agents.
Clin Ther. 1996;18(1):234

Effect of H2RAs on Healing of


Esophagitis
N = 32 children with esophagitis treated with cimetidine 30-40 mg/kg/d or placebo for 12 weeks

Cimetidine
Placebo

71%

Esophagitis Healing

20%
Significant symptom improvement with cimetidine, not placebo

Cucchiara S, Gobio-Casali L, Balli F, et al. Cimetidine treatment of reflux esophagitis in children: an Italian multicentric study. J
Pediatr Gastroenterol Nutr. 1989;8(2):150156

N = 26 children with esophagitis treated with nizatidine 10 mg/kg/d or placebo for 8 weeks

69%

Nizatidine
Placebo

Esophagitis Healing

15%
Vomiting reduced in both treatment arms; significant improvement in other
GERD symptoms only with nizatidine

Simeone D, Caria MC, Miele E, et al. Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of
nizatidine. J Pediatr Gastroenterol Nutr. 1997;25(1):5155

Proton Pump Inhibition

Copyright 1996 by Excerpta Medica Inc.


Adapted from Sanders SW. Pathogenesis and treatment of acid peptic
disorders: comparison of proton pump inhibitors with other antiulcer
agents. Clin Ther. 1996;18(1):234

PPIs in Adults With GERD


Most potent inhibitors of acid secretion
Both pharmacolic and numerous
randomized controlled trials
Superior to H2RAs in relieving reflux
symptoms and healing esophagitis
Effective in patients unresponsive to highdose H2RA
Superior to H2RAs in maintaining remission of
esophagitis

Demonstrated safety in patients treated


for 1.4 to 11.2 years (N=230 patients)

PPIs in Infants and Children With GERD


Pharmacologic studies with omeprazole
and lansoprazole
No randomized placebo-controlled trials
have demonstrated improvement of GERD
in children

Case Series of Esophagitis Patients


Treated With Omeprazole
Authors

Results

Gunasekaran, et
al, 1993

15 children
< 3.3 mg/kg/day x 12.2 mo
(mean)

Symptoms and endoscopic


assessment improved in all

De Giacomo, et al,
1997

10 children
20 or 40 mg QD x 3 mo

Clinical, endoscopic, and pH


improvements in all; no
change
in biopsy findings

Alliet, et al, 1998

12 infants
0.5 mg/kg/day x 6 wk

Endoscopic and histologic


improvement or resolution in
all

Strauss, et al,
1999

18 children
0.3-1.4 mg/kg/day x 812
wk

13/17 asymptomatic

Hassall, et al,
2000

57 children
0.7-3.5 mg/kg/day x 3 mo

Esophagitis healed in 54/57;


symptomatic improvement in
93%

Effect of Omeprazole on Esophagitis


100 80
60
40
20
% of
Patient
0

95%
72%

N = 65
children
with erosive
esophagitis

44%

Healed with
0.7 mg/kg/day

Healed with
< 1.4 mg/kg/day

Healed with
< 3.5 mg/kg/day

Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter
study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group. J Pediatr.
2000;137(6):800807

Optimal Timing of PPI Dose


Single PPI dose:
Administer half-hour
before breakfast
If second PPI dose:
Administer half-hour
before evening meal

Available Prokinetic Agents Are


Unproven or Ineffective
Cisapride: withdrawn
Bethanechol: only 1 randomized controlled
trial (RCT)
Erythromycin: no RCT
Domperidone: available in Canada, no RCT
Metoclopramide:
Esophageal pH improvement in 1 of 6 RCT
Clinical improvement in 1 of 4 RCT
High
incidence
(~30%
prevalence)
of joint
Vandenplas Y,
Rudolph CD,
Di Lorenzo C, et al. Pediatric
gastroesophageal
reflux clinical practice guidelines:
recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the
European Society
for Pediatric Gastroenterology,
adverse
eventsHepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr.
2009;49(4):548557

Increasing Concern about Safety


of Prokinetics
Prokinetic
Adverse Events
Bethanechol

Malaise, abdominal cramps, colicky, pain, nausea and


belching, diarrhea, urinary urgency; contraindicated

in
hyperthyroidism, bronchial asthma, and other
conditions
Domperidone

Hyperprolactinemia, dry mouth, rash, headache,


diarrhea, nervousness

Erythromycin

Abdominal pain, nausea, vomiting, diarrhea, pyloric


stenosis

Metoclopramide

Restlessness, drowsiness, fatigue and lassitude


(10%); insomnia, headache, confusion, dizziness,
mental depression; extrapyramidal reactions

including
parkinsonian-like symptoms, tardive dyskinesia, and
motor restlessness; galactorrhea, gynecomastia,
Prescribing Information for Reglan and Urecholine; Curry JI, Lander TD, Stringer MD. Erythromycin as a
cardiovascular
effects,
nausea, diarrhea
prokinetic agent in infants and children.
Aliment Pharmacol Ther
2001;15(5):595603;
Ramirez B, Richter JE.
Review article: promotility drugs in the treatment of gastro-oesophageal reflux disease Aliment Pharmacol
Ther. 1993;7(1):520

Treatment of GERD in Older Children


Lifestyle changes with a 4-week PPI trial
are recommended.
If symptoms resolve, continue PPI for 3
months
If symptoms persist or recur after
treatment, child should be referred to a
pediatric gastroenterologist

Conclusions
It is important to clarify whether a
pediatric patient has physiologic GER or
pathologic GERD
There are guidelines for appropriate
testing and treating of children with reflux
disease
o Also useful for deciding when to refer to
subspecialists

Recommended
Approach to the
Infant With
Recurrent
Regurgitation and
Vomiting

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric


gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the
European Society for Pediatric Gastroenterology, Hepatology, and

Recommended
Approach to the
Infant With
Recurrent
Regurgitation and
Weight Loss

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric


gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for
Pediatric Gastroenterology, Hepatology, and Nutrition
(NASPHAN) and the European Society for Pediatric
Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J

Recommended
Approach to the
Older Child or
Adolescent With
Heartburn

Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric


gastroesophageal reflux clinical practice guidelines: joint
recommendations of the North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition (NASPHAN) and
the European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition (ESPGHAN). J Pediatr

THANK YOU!

Acknowledgements
AAP
EQIPP Staff and CoFaculty
NASPGHAN
NASPGHAN
Foundation (CDHNF)

References
Lightdale JR, Gremse DA. Section on Gastroenterology, Hepatology and
Nutrition. Gastroenterology Reflux: Management Guidance for the
Pediatriatrician. Pediatrics. 2013;131(5):e16841695
Sherman PM, Hassall E, Fagundes-Neto U, Gold BD, Kato S, Koletzko S,
Orenstein S, Rudolph C, Vakil N, Vandenplas Y. A global, evidence-based
consensus on the definition of gastroesophageal reflux disease in the pediatric
population. Am J Gastroenterol. 2009;104(5):12781295
Orenstein SR, McGowan JD. Efficacy of conservative therapy as taught in the
primary care setting for symptoms suggesting infant gastroesophageal reflux. J
Pediatr. 2008;152:310314
Nelson SP, Chen EH, Syniar GM, Christoffel KK. Prevalence of symptoms of
gastroesophageal reflux during childhood: a pediatric practice-based survey.
Pediatric Practice Research Group. Arch Pediatr Adolesc Med. 2000;154:150
154
Vandenplas Y, Rudolph C, Di Lorenzo C, Hassall E, Liptak G, Mazur L,
Sondheimer J, Staiano A, Thomson M, Veereman-Wauters G, Wenz T. Pediatric
Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations
of the North American Society of Pediatric Gastroenterology Hepatology and
Nutrition (NASPGHAN) and the European Society of Pediatric Gastroenterology

TM

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