Gastroesophageal reflux
in children
浙江大学医学院附属儿童医院
江米足
Definition of GER or GERD
GER: means involuntary passage of
gastric contents into the esophagus and is
often physiological.
 GERD: means symptoms or complications
associated with pathological GER.
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Hassall E. Arch Dis Child 2005
Prevalence
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USA:
3-9 y:566 cases, 1.8%
 10-17 y:615 cases, 3.5%
 Adults (＞18 y):22%
The prevalence of GERD slowly increases with
age during childhood and becomes quite frequent
among young adults.
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Nelson SP, et al. Arch Pediatr Adolesc Med 2000
Prevalence
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Australia:863
infants
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India:602 infants
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3-4m(41%)
13-14m(＜5%)
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1-6m(55%)
7-12m(15%)
12-24m(10%)
Italy:2642 infants
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0-12m (12%)
Martin AJ, et al. Pediatrics 2002
Campanozzi A et al. Pediatrics 2009
De S, et al. Trop Gastroenterol 2001
Prevalence
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GER is frequently seen in early infancy and it
almost disappears by one year of age.
Persistence or appearance of regurgitation
beyond 18 months of age is suggestive of
pathological condition.
The prevalence of GERD in infancy is 5%-9%
of all infants with regurgitation.
Poddar U. Indian Pediatr 2013
Risk factors of GER
Poor function of LES (pressure and length)
 Esophageal dysmotility resulting in
reduced clearance
 Abnormal anatomy-including congenital
malformation (short intra-abdominal
esophagus) or acquired disease
(esophageal atresia repair)
 Higher intra-gastric pressure and delayed
gastric emptying
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Liu XL, et al. Hong Kong Med J 2012
Mechanisms
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Closing mechanisms
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The diaphragm creates a pinch cork action and
functions to increase the pressure
The intra-abdominal portion of the esophagus
The angle of His between the stomach and the
esophagus
Opening mechanisms
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Increased intra-abdominal pressure (from
abdominal tumours, coughing, and
constipation) increases intra-gastric pressure
Liu XL, et al. Hong Kong Med J 2012
TLESR
TLESR is the predominant mechanism of
GER triggering, accounting for 50-100%
(median 91.5%) of all GER episodes.
Omari TI, et al. Gut 2002
Clinical symptoms of GER
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Clinical features of GER vary in children of
different ages.
Typical symptoms
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Regurgitation
Vomiting
Heartburn
Chest pain
Atypical symptoms
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Feeding difficulties/anorexia
Failure to thrive
Postural defect
Stridor
Chronic cough
Laryngitis, otitis
Asthma
Martigne L, et al. Eur J Pediatr 2012
sinusitis
Yuksel ES, et al. Eur J Med Sci 2010
Presenting symptoms
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Regurgitation or vomiting
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Healthy: no failure to thrive or other
associated symptoms
Infants with GERD
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Growth failure or indirect symptoms of pain due to
esophagitis like irritability, feeding difficulty, sleeping
difficulties, crying episodes, anemia
Rarely apnea or ALTE
Chronic respiratory diseases and upper airway
problems like sinusitis, otitis media, laryngitis, dental
erosion
In children and adolescents, symptoms and
complications of GERD are heartburn or
substernal pain
Diagnostic test
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Esophageal pH monitoring
Multichannel intraluminal impedance (MII)
measurement
High resolution manometry (HRM)
Endoscopy
Confocal laser endomicroscopy
Barium UGI series
Nuclear scintigraphy
GER questionnaire
Rome III criteria
Esophageal pH monitoring
To establish the presence of acidic reflux
(pH<4)
 To quantify reflux in patients with mainly
extra-esophageal symptoms
 To assess the efficacy of medical therapy
 To measure GER in patients not
responding to antireflux treatment and in
research
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24 hr ambularoty pH-metry
Parameters of pH monitoring
Percent total time with a pH<4.0 (reflux
index, RI)
 Percent upright time with a pH<4.0
 Percent supine time with a pH<4.0
 Number of reflux episodes
 Number of reflux episodes lasting≥5 min
 Longest reflux episode (min)
 The scoring system
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Boix-Ochoa score
Demeester score
Diagnostic criteria of pathological GER
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RI is the main parameter in diagnosing GERD.
RI 10%（<1 year）, 5% （>1 year ）
RI 10%（<1 year), 4.2%（>1 year）
USA: RI≥12% (<1 year)，≥6% (>1 year)
RI>7% as abnormal, <3% as normal, 3-7% as
indeterminate (ESPGHN, NASPGHN)
Boix-Ochoa score >11.99
Demeester score >14.72
Van der Pol RJ, et al. J Pediatrics 2012
Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009
Mattioli G, et al. Dig Dis Sci 2006
Aggarwal S, et al.Trop Gastroenterol 2004
Wenzl TG. J Pediatr Gastroenterol Nutr 2011
Esophageal pH monitoring
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Advantages
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Be done in any age
Be relatively non-invasive
Disadvantage
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Does not measure non-acid or weakly acidic
reflux
Multichannel intraluminalimpedance (MII) measurement
To detect the change in electrical
resistance (or impedance) when
substances pass through the esophagus
using a series of impedance sensors lying
1 cm apart on a probe
 Impedance is inversely proportional to
electrical conductivity
 Since the conductivity of liquid (high) and
air (low) is different, MII can easily
differentiate liquid from gas reflux

Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012
Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012
Advantages of MII-pH monitoring
Be superior to pH-study alone for
evaluation of GER-related symptom
association
 Picking up acid, non-acid or weakly acid
reflux,
 the direction of reflux
 To distinguish between liquid, solid and
gas reflux in all age groups
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Limitations of MII-pH study
High cost
 Limited availability
 Limited therapeutic implications (clinical
relevance of measuring non-acidic reflux
remains doubtful)
 The lack of evidence-based parameters for
assessment of GER
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High resolution manometry (HRM)
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Conventional manometry assemblies detect
pressure using a catheter with several waterperfused sideholes by gaps between the pressure
sensors which are several centimeters long.
HRM catheters are equipped with intraluminal
pressure transducers
Simultaneously measure from hypopharynx to
stomach
Assign color to specific pressure levels which are
than presented in a spatiotemporal plot
Pressure topography plots are more intuitive and
easier learned by clinicians
Kessing BF, et al. Curr Gastroenterol Rep 2012
Clinical application of HRM
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HRM is superior to other diagnostic tools
for the evaluation of achalasia and
contributes to a more specific classification
of esophageal disorders in patients with
non-obstructive dysphagia
Kessing BF, et al. Curr Gastroenterol Rep 2012
Endoscopy
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Upper gastrointestinal endoscopy is the best
method of detecting esophagitis as a
consequence of GERD.
Normal endoscopy (found in 60%-80% cases of
GERD in children) does not rule out GERD and
this type of GERD is called Non-erosive reflux
disease (NERD).
Endoscopy needs to be combined with a biopsy to
increase the diagnostic yield (especially in NERD)
and to rule out other causes of esophagitis (like
eosinophilic esophagitis, Crohn’s disease).
Indications of endoscopy
Persistence of symptoms despite therapy
 Dysphagia or odynophagia
 Evidence of GI bleeding or iron deficiency
anemia
 Stricture or ulcer on barium study
 Long duration GERD to detect Barrett’s
esophagus.
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Advantages of endoscopy
Gives a direct information about the
presence and severity of esophagitis
 Detects complications like ulcer, stricture,
Barrett’s esophagus
 Documents healing of erosive esophagitis
after therapy.
 Exclude other causes of esophagits by
endoscopic esophageal biopsy.
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Los Angeles classification
A One or more mucosal breaks, each ≤ 5
mm in length
 B At least one mucosal break > 5 mm long,
but not continuous between the tops of
adjacent mucosal folds
 C At least one mucosal break that is
continuous between the tops of adjacent
mucosal folds, but which is not
circumferential (< 75% of luminal
circumference)
 D Mucosal break that involves at least
75% of the luminal circumference
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Kamal A, et al. Best Practice Res Clin Gastroenterol 2010
The evidence of histology
Histology is more sensitive than
endoscopy in the early stage (non-erosive
stage).
 Erosive esophagitis is the most definite
evidence of GERD on endoscopy.
 Biopsy (2 cm proximal to
gastroesophageal junction) helps to
establish the diagnosis of GERD if there is
no erosion or mucosal break on endoscopy.
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Esophageal histological features of GERD
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Basal zone hyperplasia (>20% of total thickness)
Elongation of papillae (>50% of total thickness)
Infiltration with neutrophils or eosinophils
(<15/high power field)
The presence of dilated intercellular spaces
Growing of blood vessels in papilla
Histological changes are neither sensitive nor
specific for reflux disease in NERD cases and
should not be used alone to diagnose or exclude
GERD
Poddar U. Indian Pediatr 2013
Tobey NA, et al. Gastroenterology 1996
Boccia G, et al. Am J Gastroenterol 2007
Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009
Barium UGI series
Be useful to detect anatomical anomalies
such as the angle of His, esophageal
dysmotility, mucosal irregularity, stricture,
and hiatus hernia, but not useful in
diagnosing GERD.
 The sensitivity and specificity to diagnose
GERD is less than 50%.
 Cannot differentiate physiological from
pathological reflux.
 Most useful in ruling out underlying
obstruction such as that due to achalasia
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Nuclear scintigraphy
Be a non-invasive test but has poor
sensitivity and specificity.
 To confirm silent aspiration in patients
with recurrent pneumonia due to
aspiration of gastric contents.
 Be a useful tool in evaluation of delayed
gastric emptying
 Not recommended for the routine
evaluation of pediatric patients with
suspected GERD.
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Infant GER questionnaire (I-GERQ)
Orenstein SR, et al. Clin Pediatr 1996
I-GERQ
Maximum total score:25
 Score＞7, for diagnosing GERD in infants
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Sensitivity 74%
Specificity 94%
Can be used to segregate those infants
who needs empirical therapy or further
investigation because of its simplicity
(take just 20 minutes to complete) and
reproducibility.
Rome III criteria
Must include all of the following in
otherwise healthy infants 3 weeks to 12
months of age
 Regurgitation 2 or more times per day for
3 or more weeks
 No retching, hematemesis, aspiration,
apnea, failure to thrive, feeding or
swallowing difficulties, or abnormal
posturing
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Diagnostic test
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When symptoms are not classical and in cases
with complicated GERD
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In a patient with classical symptoms of GERD
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pH study is required to document reflux
When esophagitis is suspected (pain or blood loss)
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No need to confirm the presence of GER by pH study or
by endoscopy
In patients with extra-esophageal symptoms like
respiratory symptoms without any GER
symptoms
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Endoscopy,pH study, barium upper GI series
Upper gastrointestinal endoscopy with esophageal
biopsy is recommended
Any suggestion of an anatomical abnormality like
intestinal obstruction or dysphagia
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Barium upper GI series is indicated
Diagnostic approach to GERD
There is no gold standard for the diagnosis
of GERD.
 The choice of investigation depends on the
clinical situation for which the
investigation is asked for.
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Management---GER in infants
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Counseling-the most important part
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Explain the natural history of GER in infants to parents
or care-givers
Other measures
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Feeding advice
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positioning
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Avoid overfeeding, forceful feeding
Try to give small but frequent feeds
Prone position-not recommended (the risk of SIDS)
Left lateral position (age>13m)-the best in preventing
reflux
feed thickening
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Adding rice, corn or potato starch
 decrease the number regurgitation of vomiting
 does not decreases the acid exposure of esophagus
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Feed thickener has only cosmetic value but no therapeutic
benefit.
Proton pump inhibitors (PPIs)
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PPIs are not recommended in this subset
of patient
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Only a few of the infants are likely to have
acid-related cause for their symptoms
The largest randomized, controlled trial in
infants showed that for symptoms, presumably
to be related to reflux disease, a PPI was not
better than placebo.
Orenstein SR, et al. J Pediatr 2009
Management---GERD in children
Besides medication, life-style modification
in terms of weight reduction, avoiding
caffeine, chocolate, abstinence from
alcohol, tobacco helps in children.
 Adolescents, like in adults, may benefit
from the left lateral decubitus sleeping
position with head-end elevation
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Pharmacological therapy
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Acid suppressants
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Histamin-2 receptor antagonists (H2RA)
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Ranitidine: 6-8mg/kg/day, bid or tid
Famotidine:1mg/kg/day, bid
PPIs
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Omeprazole:0.7 to 3.5 mg/kg/day, qd
Neutralizing or surface protective agents
(antacids or sucralfate)
 Prokinetics
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H2RA
Rapid onset of action (in 30 min)
 Short acting (6 hr) acid suppressants
 used for on-demand therapy (SOS therapy)
 A lack of post-prandial acid suppressant
effect
 Develop tachyphylaxis on long-term use
(in 6 weeks)
 Cannot be used for long term therapy
 H2RA are less effective than PPI
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PPIs
Inhibit acid secretion by irreversibly
blocking Na+-K+-ATPase in the apical
membrane of parietal cells
 Be taken 30 min before breakfast as
parietal cells get activated in response to
a meal.
 Require a higher per kilogram dose than
adults to obtain a similar degree of acid
suppression due to higher metabolism of
the drug.
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Omeprazole, 2-2.5mg/kg/day
Lansoprazole, 1.4mg/kg/day
Side effect of PPIs
Mild side effects have been reported in up
to 14% of children
 Most common side effects
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headache
diarrhea
constipation
nausea
Prokinetics
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metoclopramide, domperidone,
erythromycin, baclofen or itopride in the
management of GERD
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prokinetics may be of some use is GERD
with associated gastroparesis
Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009
Poddar U. Indian Pediatr 2013
Duration of medical therapy
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GERD needs profound acid suppression for a
longer duration of time
PPI therapy is recommended for at least 12
weeks and then to taper over 2 to 3 months as
rebound hyperacidity after sudden stoppage of
PPI
No symptomatic improvement in 4 weeks then
the dose of PPI needs to be increased
A relapse on withdrawal of PPI, medication needs
to be restarted
Frequent relapses or continuous symptoms are
indications for prolonged PPI therapy or surgery
Repeat endoscopy to document healing is
indicated at the end of 12 weeks course in
erosive esophagitis
 Prolonged PPI therapy (median 3 years
and up to 12 years) is safe
 Full healing dose is superior to half dose in
PPI maintenance therapy
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Surgery
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Nissen fundoplication (open or laparoscopic) may
be of benefit in children with confirmed GERD
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Who
Who
Who
Who
have failed optimal medical therapy
are dependent on medical therapy for a long time
are significantly noncompliant to medical therapy
have life threatening complication of GERD
Point: who need surgery most, develop surgery
related complications and surgical failure most
Fundoplication in early infancy has a higher
failure rate than in late childhood
Hassall E. Arch Dis Child 2005
Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009
Poddar U. Indian Pediatr 2013
Conclusion
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GER is common in infants but GERD is not so common in
early childhood
Most infants have physiological reflux and need minimal
intervention as their symptoms resolve by 18 months of
age
There is no gold standard diagnostic test for GERD and
investigation should be tailored to the clinical concern for a
given child
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For extraesophageal manifestations, pH-metry with or without
impedance is the best investigations
For esophagitis, endoscopy is the best investigations
Empirical PPI therapy for 4 weeks is justified in older
children and adolescents with classical symptoms
Medical therapy with PPI is very effective and safe.
Surgical therapy is not a panacea as it carries significant
morbidity and often fails in those who need it most.