See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/303401113

Gastroesophageal Reflux Disease: Review of Pathogenesis, Clinical Presentation,

Diagnosis and its Management in Infants and Children

Article · July 2014

CITATION READS

1 2,670

2 authors:

Huma Cheema Arit Parkash

The Children's Hospital and the Institute of Child Health Jinnah Sindh Medical University
71 PUBLICATIONS   405 CITATIONS    24 PUBLICATIONS   123 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Latent Tuberculosis in pediatrics View project

Celiac disease in children View project

All content following this page was uploaded by Arit Parkash on 21 May 2016.

The user has requested enhancement of the downloaded file.

www.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
Gastroesophageal Reflux Disease: Review
Pathogenesis, Clinical Presentation, Diagnosis and its
Management in Infants and Children
1
HUMA ARSHAD CHEEMA , ARIT PRAKASH2
1
Prof. of Pediatric Gastroenterology Hepatology Children’s Hospital and Institute of Child Health Lahore. 2Fellow
in Pediatric Gastroenterology Hepatology Children’s Hospital Lahore
E-mail: pedgilahore@gmail.com
------------------------------------------------------------------------------------
ABSTRACT
Gastroesophageal Reflux Disease (GERD) is a
common problem in the infants and children. It is
a common reason for visits to pediatrician. There
are variable clinical presentations, ranging from
typical to extra esophageal symptoms. The ability
to differentiate between Gastroesophageal reflux
(GER) and GERD and to identify the risk factors
in the pediatric patient is increasingly important
for proper management. Increasing numbers of
infants and children are receiving prescription
medications for symptoms associated with
Gastroesophageal reflux in our country. There is
need to describe diagnostic testing options for
GERD and their appropriate use in infants and
children with suspected GERD. There is also
need to describe age-appropriate strategies to
reduce the symptoms of GERD in children,
including lifestyle changes and pharmacologic
and surgical options. However, there has been
no systematic review regarding this disease in
pediatric population in Pakistan. Search was
conducted through Google and Pub Med, with
regard to epidemiology, clinical features,
investigation and management of GERD in
infants and children and guidelines has been
adapted for evaluation and management. It is
hoped that this review will be helpful to
implement best practices in the management of
acid reflux in infants and children.
Key words: Gastroesophageal Reflux,
Management guidelines, Pakistan
INTRODUCTION
Gastroesophageal Reflux: GER is the most
common esophageal disorder in infants, children,
and adolescents. It is defined as the passage of
127
of
Pak Ped Rev 2014; 2(3): 126-38
gastric contents into the esophagus and can
occur with and without regurgitation and
vomiting. It is a normal physiologic process that
occurs in healthy infants, children, and adults.
Regurgitation is the most common visible
symptom of GER and occurs daily in 50% of
infants less than 3 months of age resolving
spontaneously by the time baby is one year old.
Most reflux episodes are brief, physiologic and
do not causes symptom complex and duration
defined as <3 minutes, occur in the postprandial
period1.
Gastroesophageal Reflux Disease (GERD): Is
defined as a condition that develops when the
reflux of stomach contents causes troublesome
symptoms (child’s well-being is affected) and/or
complications2. Distinguishing between GER and
GERD, two Gastroesophageal reflux conditions,
is key to preventing unnecessary medical
treatments and guide appropriate therapy in
infants and children. Regurgitation is defined as
passage of refluxed gastric contents into ora-
pharynx.
Rumination syndrome is a distinct clinical entity
and not related to GER or GERD. It is an eating
disorder in which usually an infant or young child
regurgitates food back in mouth because of the
voluntary contraction of abdominal muscles and
re-chews partially digested food and then
swallows again3.
Symptoms or complications associated with
GERD are classified by the practice guidelines as
being either esophageal or extraesophageal1.
Esophageal symptoms are vomiting, poor weight
gain, esophagitis, dysphagia and abdominal or
sub sternal pain. Extra esophageal are mostly
respiratory disorders and some are established
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
like cough, wheezing in infancy and laryngitis and
others are proposed associations include
pharyngitis, sinusitis and recurrent otitis media4.
Reflux Esophagitis (RE): Apart from the
symptoms, patients can be described by the
endoscopic description of their esophageal
mucosa. That is characterized by visible breaks
of the mucosa in the distal esophagus. On
endoscopic examination, assessment can be
done regarding complications like presence and
severity of esophagitis, less commonly peptic
stricture, and rarely Barrett esophagus and
adenocarcinoma.
PATHOPHYSIOLOGY
GER occur during transient relaxations of the
lower esophageal sphincter (LES). LES is not a
true sphincter. The LES, supported by the crura
of the diaphragm at the Gastroesophageal
junction, together with valve like functions of the
esophagogastric junction anatomy, form the
antireflux barrier.(fig 1)
Fig 1 : In a healthy adult the LES is 3cms in
length at the level of the diaphragm while in
the neonate its only half of that.
Possible causes of GERD
Factors determining the esophageal
manifestations of reflux include the duration of
esophageal exposure (a product of the frequency
and duration of the reflux episode), the causticity
of the refluxate, and the susceptibility of the
esophagus to damage.
Normal function of lower esophageal stricture is
to act as a physical barrier between the
esophagus and the stomach, protecting the
esophagus from harmful gastric acid, and
preventing food from being regurgitated. During
128
swallowing, the LES relaxes and allows passage
of food and liquids into the stomach and
therefore when the refluxed stomach acid
touches the lining of esophagus, exposing
esophageal mucosa to direct acid and/or pepsin
injury. Although exact etiology is not known main
predisposing factors are transient relaxation of
the lower esophageal sphincter, the short infant
esophagus has limited volume, predominantly
recumbent position of infants, delayed emptying
and increased abdominal pressure. Current
understanding of LES functions suggest that LES
pressure of 5 to 10 mm Hg above intra gastric
pressure are sufficient to maintain
esophagogastric competence5. In some studies it
has found LES pressure is 6-15mmHg lower in
children with GERD6,7. Gravitational and
positional factors may exacerbate GER and
increase the risk of GERD by allowing reflux to
occur in a supine position8.
Fig 2: When does the GER become GERD?
• Aberrance in normal physiology
ƒ Insufficient clearance and buffering of
refluxate
ƒ Decreased rate of gastric emptying
ƒ Abnormalities in efficacy of epithelial
repair
ƒ Decreased neural protective reflexes
• Development of erosive esophagitis
causes esophageal shortening
ƒ May result in hiatal herniation
Gastroesophageal reflux has been associated
with significant respiratory symptoms in infants
and children. The infant's proximal airway and
esophagus are lined with receptors that are
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
activated by water, acid, or distention. Activation
of these receptors can increase airway
resistance, leading to the development of
reactive airway disease9. Vagal reflexes cause
bronchospasm, impaired airway protection and
laryngospasm. Laryngeal epithelium is more
susceptible to damage from refluxate than
esophageal epithelium and pepsin causes
depletion of laryngeal protective proteins and
carbonic anhydrase. Macro aspirations are
supposed to cause chronic laryngitis, recurrent
sinusitis, otitis media, recurrent pneumonia and
bronchiectasis. Micro aspirations are supposed
to cause chronic cough and bronchospasm,
laryngospasm and rarely infantile apnea.
PREVALENCE
Recurrent vomiting occurs in 50% of infants from
0 to 3 months, 67% in 4-month old and 5% in 10–
12-month old infants10. The natural history is not
clearly defined, by 12-18 months, most
symptomatic reflux will spontaneously resolve as
the sphincter matures, the infant adopts an
upright posture and begins having a more solid
diet. Persistence of regurgitation beyond 18
months of age is suggestive of pathological
condition. The prevalence of pathological GERD
in infants is between 2-10%10,11. However, the
second peak is seen in adult patients and
symptoms associated with GER are uncommon
in younger children. In a study from USA,
heartburn was reported in 1.8% of the 3-9 years
age group and 3.5% in the 10 to 17 years age
group compared to 22% in adults. Hence, the
prevalence of GERD is quite frequent in adult
patients and gradually increases with age during
childhood12.
Population-based studies suggest that GERD is
a common condition with a prevalence of 10 to
20% in Western Europe and North America13,14.
The prevalence in Asia is reportedly variable but
lower about 5%15. Based on the systematic
review by Jung, the prevalence of symptom-
based GERD in East Asia was found to be 2.5%-
4.8% before 2005 and 5.2%-8.5% from 2005 to
2010. In Southeast and Western Asia, it was
6.3%-18.3% after 2005, which was much higher
than East Asia16.
In certain families clustering of reflux cases have
been seen and complications like hiatal hernia,
129
erosive esophagitis, Barret esophagus and
esophageal adenocarcinoma have been noted
indicating genetic evidence. Cameron et al also
found increased concordance for reflux in
monozygotic compared with dizygotic twins
suggesting heritability of GERD1,4,17.
Several pediatric patients have certain
predisposing conditions and higher risk of GERD
and high frequency of its complications. Table1
TABLE 1: Pediatric Population at High Risk for
GERD and Its Complications
Low birth weight.
Obesity.
Cow's milk allergy.
Immaturity of the lower esophageal sphincter.
Chronic relaxation of the lower esophageal
sphincter.
Increased abdominal pressure.
Gastric distension.
Hiatus hernia.
Esophageal dysmotility.
Prematurity.
Cerebral palsy or other severe neurodevelopmental
problems.
Congenital esophageal anomalies.
CLINICAL FEATURES
Infants: Many newborn babies (in the first four
weeks of life) suffer from gastro-esophageal
reflux, especially if they are born premature.
Infants with uncomplicated GERD regurgitate
without any secondary signs or symptoms of
inadequate growth, esophagitis, or respiratory
disease. Infants with GER are thriving and
represent the majority of infants (“happy
spitters”). Patients with complicated GERD may
manifest persistent regurgitation with secondary
poor weight gain and failure to thrive18. Other
features are signs of esophagitis, including
persistent irritability, pain, feeding problems, and
iron deficiency anemia.
Pulmonary manifestations include apnea with
cyanotic episodes which may occur secondary to
upper airway stimulation by pharyngeal
regurgitation. Instead of a pure obstructive apnea
pattern, a mixed pattern of both obstructive and
central types generally predominates. A well-
defined relationship between apnea secondary to
GERD and an apparent life-threatening event
has not been established19. Lower airway
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan 130
 

symptoms secondary to bronchoconstriction and Older children: Older children can have
airway inflammation include wheezing and regurgitation during the preschool years;
chronic cough. Aspiration of refluxate may lead to complaints of abdominal and lower chest pain,
pneumonia, especially in infants with neurologic heartburn (pyrosis), odynophagia, dysphagia,
impairment. and signs of anemia and esophageal obstruction
TABLE 2: Symptoms and signs that may be
from stricture formation17. These manifestations
associated with Gastroesophageal reflux1 supervene in later childhood and adolescence.
Occasional children present with neck
Symptoms Signs contortions (arching, turning of head), designated
Recurrent regurgitation Esophagitis Sandifer syndrome20.
with/without vomiting
Weight loss or poor weight Esophageal stricture
gain
Irritability in infants Barrett esophagus
Ruminative behavior Laryngeal/pharyngeal
inflammation
Heartburn or chest pain Recurrent pneumonia
Hematemesis Anemia
Dysphagia, odynophagia Dental erosion
Wheezing Feeding refusal
Stridor Dystonic neck posturing
(Sandifer syndrome)
Cough Apnea spells
Hoarseness Apparent life-
threatening events

TABLE 3: Warning signals requiring investigation

in infants1
Bilious vomiting Fever
Gastrointestinal bleeding Lethargy
Hematemesis Hepatosplenomegaly Fig 3: Sandifer Syndrome
Hematochezia Bulging fontanel
Consistently forceful
DIAGNOSTIC APPROACH
Macro/microcephaly
vomiting Diagnostic approach in suspected GERD
Onset of vomiting after 6 depends on presenting symptoms and signs. A
Seizures
months of life thorough history in an infant is generally sufficient
Abdominal tenderness to differentiate between GER and GERD. Certain
Failure to thrive
or distension questionnaires have been developed based on
Documented or the facts elucidated in history. These
suspected questionnaires give high scores to red flags in
Diarrhea
genetic/metabolic history which point to a pathological reflux such
syndrome as history of failure to thrive, severe irritability
When warning signs are before and after feeds excessive and copious
presented then full work vomiting or any evidence of fresh or altered blood
up based on history and in the vomit. Any life-threatening event like apnea
Constipation
examination should be is taken very seriously. A commonly used
done to reach particular questionnaire the Modified Orenstein’s Infant
diagnosis.
GER Questionnaire has 11 based points with
maximum score of 25 to differentiate GER from

Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
GERD. Score of >7 have 74% sensitivity and
94% specificity in diagnosing GERD in infants21.
TABLE 4: GER vs. GERD in Infants. Modified
Orenstein’s Infant GER Questionnaire21
Question Points
1. How often does the baby usually spit
up?
¾ 1 to 3 times per day
¾ 3 to 5 times per day
¾ >5 times/day
2. How much does the baby usually
spit up?
¾ 1 teaspoonful to 1 tablespoonful
¾ 1 tablespoonful to 1 ounce
¾ >1 ounce
3. Does the spitting up seem to be
uncomfortable for the baby?
4. Does the baby refuse feeding even
when hungry?
5. Does the baby have trouble gaining
enough weight?
6. Does the baby cry a lot during or after
feeding?
7. Do you think the baby cries or fusses
more than normal?
8. How many hours does the baby cry or
fuss each day?
¾ 1 to 3 hours
¾ >3 hours
9. Do you think the baby hiccups more
than most babies?
10. Does the baby have spells of arching
back?
11. Has the baby ever stopped breathing
while awake and struggling to breathe
or turn blue or purple?
Maximum total score
• Score >7, sensitivity: 74% and specificity: 94%
for diagnosing GERD
Recent comprehensive guidelines developed by
the North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
have provided illustrations for diagnostic
approach in suspected GERD patients. These
guidelines focus on presence or absence of
failure to thrive mainly along with other red flags
suggestive of GERD. In the absence of these red
flags the recommendations is to reassure the
parents, in some cases thickened formula may
be used and the child commonly outgrows the
GER by 12 to 18 months of age. However the
131
presence of red flags the infant merits further
investigations.
• No one test can be used to diagnose
reflux, and instead must be matched to a
clinical question
• Reflux tests are useful
1 ƒ To document the presence of GER(D)
2
3 ƒ To detect complications
ƒ To establish a causal relationship
between GER and symptoms
1
2 ƒ To evaluate therapy
3
2 ƒ To exclude other conditions
Several other diseases have similar symptoms. It
1
is very important to get a correct diagnosis.
1 Further diagnostic studies like endoscopy, PH
study, barium upper gastrointestinal series are
3 useful when there is doubt in diagnosis and
1
symptoms are not classical, to look for
complications of GERD and when there is any
clue for anatomical abnormalities.
1 BARIUM CONTRAST RADIOGRAPH (fig 5)
2
1 This test is not useful for the diagnosis of GERD
but is useful to confirm or rule out anatomic
2 abnormalities of the upper gastrointestinal (GI)
tract that may cause symptoms similar to those
6 of GERD. It has poor sensitivity and specificity in
the diagnosis of GERD due to its limited duration
and the inability to differentiate physiologic GER
25 from GERD. The sensitivity of the upper GI
series varies from 31 to 86%, specificity 21 to
83% and positive predictive value 80 to 82%
when compared with pH monitoring22–24.
ADVANTAGE
Useful for detecting anatomic abnormalities.
LIMITATIONS
It does not differentiate between physiological
and nonphysiological reflux
ESOPHAGEAL PH MONITORING(fig 4)
A small wire with an acid sensor is placed
through the nose down to the bottom of the
esophagus, and usually left in place between 12-
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
24 hours. Recently, wireless sensors that can be
clipped to the esophageal mucosa during
endoscopy have allowed pH monitoring without a
nasal cannula for up to 48 hours. The sensor
detects when acid from the stomach is "refluxed"
into the esophagus. The conventional definition
of acid exposure in the esophagus is a pH <4.0,
the pH most associated with a complaint of
heartburn in adults. It can be done in any age
(neonates to adults).
Fig 4: Esophageal pH Probe
Fig 5: Barium swallow showing reflux
132
Advantages are it detects episodes of reflux,
determines temporal association between acid
GER and symptoms, determines effectiveness of
esophageal clearance mechanisms and
assesses adequacy of H2RA or PPI dosage in
unresponsive patients. But it 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.
The Reflux Index (RI) is the most commonly used
summary score, which is the percentage of time
esophageal pH is <4. A RI >10% in infants and
>5% in children are taken as suggestive of
GER1,25. In some studies, approximately 60% of
children with asthma had abnormal pH
monitoring studies26.
Combined Multiple Intraluminal Impedance
(MII) and pH Monitoring
Impedance testing depends upon measurement
of changes in resistance (in Ohms) to alternating
electrical current when a bolus passes by a pair
of metallic rings mounted on a catheter. This
technique can detect the movement of both
acidic and nonacidic fluids, solids, and air in the
esophagus. Hence it can detect acid, weakly acid
and nonacid reflux episodes. It is superior to pH
monitoring alone for evaluation of the temporal
relation between symptoms and GER. Whether
combined esophageal pH and impedance
monitoring will provide useful measurements that
vary directly with disease severity, prognosis,
and response to therapy in pediatric patients has
yet to be determined. Limitations are high cost,
limited availability, normal values in pediatric age
groups not yet defined and analyses of tracings
are time-consuming1,27.
UPPER GI ENDOSCOPY
This technique enables visualization and biopsy
of esophageal epithelium, determines presence
of esophagitis, other complications and
discriminates between reflux and non-reflux
esophagitis.
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
Fig 6: Endoscopic appearances of various grades of Esophagitis
But there is need for sedation or anesthesia.
Endoscopic grading systems have not yet
validated for pediatrics. There is poor correlation
between endoscopic appearance and
histopathology. Moreover it is not useful for extra-
esophageal GERD. Normal endoscopy (found in
60% to 80% cases of GERD in children) does not
rule out GERD and this type of GERD is called
Non-erosive reflux disease (NERD)27.
Endoscopic biopsy is important to identify or rule
out other causes of Esophagitis like Eosinophilic
Esophagitis, Crohn’s disease, infectious
esophagitis (Candida esophagitis or herpetic
esophagitis), and to diagnose and monitor Barrett
esophagus (BE) and its complications1,4. The
most important features of GERD on esophageal
histology are; basal zone hyperplasia (>20% of
total thickness) and elongation of papillae or rete
pegs (>50% of total thickness) 27.
BRONCHOSCOPY
This is an examination of the airways of the lungs
using an endoscope. Tissue biopsies may be
done as well to check for signs of reflux. This test
is usually only done when other tests haven't
shown reflux is present, but the baby still has
symptoms.
133
NUCLEAR MEDICINE SCAN
This test involves feeding the baby or child milk
that has a small amount of radioactive material in
it. A scanner is used to see what happens inside
the child's body. It can show how fast the milk
leaves the stomach, whether there are problems
with stomach movement or problems in the lower
part of the digestive tract and whether milk is
being inhaled into the lungs. It can detect acidic
and non-acidic GER, evaluates gastric emptying
and may demonstrate aspiration. Limitations are
lack of standardized techniques, absence of age-
specific normative data and period of observation
limited to early postprandial period. Nuclear
scintigraphy is not recommended for the routine
evaluation of pediatric patients with suspected
GERD1.
Empirical antireflux therapy, using a time-limited
trial of high-dose proton pump inhibitor (PPI), is a
cost-effective strategy for diagnosis in adults;
although not formally evaluated in older children,
it has also been applied to this age group. Failure
to respond to such empirical treatment, or a
requirement for the treatment for prolonged
periods, mandates formal diagnostic evaluation.
There is no evidence to support an empiric trial of
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
acid suppression as a diagnostic test in infants
and young children where symptoms suggestive
of GERD are less specific1.
MANAGEMENT
The main aims of treatment are to alleviate
symptoms, promote normal growth, and prevent
complications28.
CONSERVATIVE THERAPY OR
LIFESTYLE CHANGES
Conservative therapy, or lifestyle changes, is
recommended for all infants and children with
GER irrespective of disease severity. A complete
history can reveal provocative aspects of
lifestyle, such as huge feedings at infrequent
intervals in infants. It is important to normalize
feeding volume and frequency. Thickened
feedings may be beneficial when regurgitation
has resulted in poor weight gain. Pre-thickened
formula may be used, or infant formula may be
thickened by adding rice or cereal. In Cochrane
review 2009, there is no current evidence to
support or refute the use of feed thickeners in
treating newborn babies with gastro-esophageal
reflux29.Frequent, smaller feedings are
encouraged. There is evidence to support a 1- or
2-week trial of a hypoallergenic formula in
formula-fed infants with vomiting1.
Positioning therapy is a traditional part of
antireflux management. Supine positioning
confers the lowest risk for SIDS, and non-prone
positioning during sleep is recommended. In a
study of 24 infants younger than 5 months of
age30, the prone and left-side (left lateral)
positions were most effective in reducing the
reflux index (percent of time esophageal pH <4).
However, based on an analysis of data from a
population-based case reference study31, the
SIDS mortality rate associated with sleeping
prone was 4.4 per 1000 live births, compared
with 0.05 per 1000 live births for supine and
lateral sleeping positions combined.
For older children, conservative therapy is similar
to recommendations for adults: Avoid large
meals, and do not lie down immediately after
eating. Lose weight if obese; a recent study
confirmed that obesity is a strong risk factor for
reflux disease32. Avoid caffeine, chocolate, and
134
spicy foods that provoke symptoms. Eliminate
exposure to tobacco smoke.
Once the diagnosis of GER is established, the
parental education, reassurance, and anticipatory
guidance are recommended. 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, further
work up is recommended.
PHARMACOTHERAPY
According to the guidelines of the North
American Society for Pediatric Gastroenterology,
Hepatology, and Nutrition, infants with
uncomplicated physiologic GER should not be
treated with medication but with modest lifestyle
changes; medications should be reserved for
infants with GERD33.
The goals of antireflux pharmacotherapy are to
control symptoms, promote healing of
esophagitis if present, and prevent complications
by reducing exposure of the esophagus or
respiratory tract to acid refluxate. In addition,
pharmacotherapy aims to improve the patient’s
health-related quality of life and to avoid adverse
events of treatment.
Antacids are the most commonly used antireflux
therapy. They provide rapid relief of symptoms by
acid neutralization but effect is transient. The
long-term regular use of antacids cannot be
recommended because of side effects of
diarrhea (magnesium antacids) and constipation
(aluminum antacids) and rare reports of more
serious side effects of chronic use.
ACID SUPPRESSION THERAPIES
Therapeutic agents that decrease gastric acid
secretion are the most effective treatment for
management of GERD in children and adults.
Histamine-2 receptor antagonists (H2RAs) and
proton-pump inhibitors (PPIs) are recommended
for anti secretory therapy of GERD
HISTAMINE-2 RECEPTOR ANTAGONISTS
(H2RAS)
H2RAs exhibit tachyphylaxis or tolerance but
PPIs do not. Tachyphylaxis is a drawback to
chronic use. H2RAs have a rapid onset of action
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan
and, like buffering agents, are useful for on-
demand treatment1.
These agents are used in symptomatic GERD
and mild esophagitis.
PROTON PUMP INHIBITORS
For healing of erosive esophagitis and relief of
TABLE 5: Pharmacologic Agents with Pediatric Indications for Treatment of GERD
Medication
Histamine-2 Receptor Antagonists (H2RAs)
Cimetidine
Famotidine
Ranitidine
Proton Pump Inhibitors
Lansoprazole
Omeprazole
The most commonly reported adverse events
(headache, constipation, diarrhea, and
abdominal pain) occurred in less than 5% of
patients, which is similar to the incidence of
adverse events experienced with placebo in
studies in adults.35 on long term used side effects
reported are hypergastrinemia, and drug-induced
hypochlorhydria. Increasing evidence suggests
that hypochlorhydria, that is, acid suppression,
associated with H2RAs or PPIs may increase
rates of community-acquired pneumonia in adults
and children, gastroenteritis in children, and
candidemia and necrotizing enterocolitis in
preterm infants.1
PROKINETIC THERAPY
The rationale for prokinetic therapy in the
treatment of GERD is based on evidence that
such medications enhance esophageal
peristalsis and accelerates gastric emptying.1
Studies evaluating bethanechol, a direct
cholinergic agonist, and Domperidone, a
dopamine antagonist available in Canada, have
been few and have reported mixed results36.
Only one randomized controlled trial (RCT) has
evaluated bethanechol and no RCTs have
evaluated Domperidone in pediatric patients with
Gastroesophageal reflux.
Studies with erythromycin have suggested
prokinetic effects on the GI tract at doses lower
than antimicrobial doses 37. Erythromycin has
been evaluated in various pediatric populations,
135
GERD symptoms, PPIs are superior to H2RAs.
Both medications are superior to placebo1.
The recommended dosages of H2RAs and PPIs
with FDA-approved pediatric indications for
GERD34.
Dose Frequency
40 mg/kg/day Thrice daily or 4 times daily
1 mg/kg/day Twice daily
5–10 mg/kg/day Twice daily or thrice daily
0.4–2.8 mg/kg/day Once daily
0.7–3.3 mg/kg/day Once daily
but no RCT in children with GER has been
performed.
RCTs have evaluated the efficacy of
metoclopramide, an antidopaminergic agent, in
children with GER. Esophageal pH improvement
was reported in 1 of 6 RCTs; clinical
improvement in 1 of 4 RCTs. Use of
metoclopramide has been hampered by a high
incidence of adverse events, including central
nervous system (CNS) effects.
OTHER AGENTS
Buffering agents, alginate, and Sucralfate are
useful on demand for occasional heartburn.
Chronic use of buffering agents or sodium
alginate is not recommended for GERD because
some have absorbable components that may
have adverse effects with long-term use. Special
caution is required in infants.1
SURGICAL THERAPY
When medical therapy fails, anti-reflux surgery
(for example, fundoplication) may be considered
in selected patients but it carries a significant risk
of morbidity, including high failure rates38.
Surgery is effective therapy for intractable GERD
in children, particularly those with refractory
esophagitis or strictures and those at risk for
significant morbidity from chronic pulmonary
disease. The potential risks, benefits and costs of
successful prolonged medical therapy vs surgical
therapy have not been well studied in infants and
Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan 136
 

children with various GERD symptoms26. A cost- with preliminary methods, endoscopic and
analysis of initial medical or open surgical pathological confirmation of the disease is
therapy for complicated or chronic GORD has mandatory for a correct management.
found that in selected patients, surgery is
clinically more advantageous and cost-effective 1 Recurrent vomiting and/or regurgitation
than Omeperazole39. Some of the risks of
fundoplication include a wrap that is “too tight”
2 History and physical examination
(producing dysphagia or gas-bloat) or “too loose”
(and thus incompetent). Surgeons may choose to
perform a “tight” (360°, Nissen) or variations of a
“loose” (<360°, Thal, Toupet, Boix-Ochoa) wrap 3 Are there Evaluate
or to add a gastric drainage procedure (pyloro- warning signs? further
plasty) to improve gastric emptying, based on Yes
4
their experience and the patient’s disease. Long- No
term studies suggest that fundoplications often
become incompetent in children, as in adults,
with reflux recurrence rates of up to 14% for
Are there signs of
Nissen and up to 20% for loose wraps; this fact complicate GFR
Evaluate
currently combines with the potency of PPI disease?
further
therapy that is now available to shift practice 5 Yes
6
toward long-term pharmacotherapy in many
cases.
SUMMARY
As should be evident from the previous Uncomplicated infantile GER – “Happy spitter”
discussion, GERD is common in infants and
children. Uncomplicated GERD should give 7
conservative measures. There is no usage of
acid-suppressing or other drugs to treat infants
with uncomplicated reflux ("happy spitters").
Education and reassurance without any other
No tests signs. Reassurance
specific intervention usually is sufficient. Other Consider. Thickened Formula
treatment options include thickening of the
formula or expressed breast milk, or initiating a 8
brief trial of eliminating cow's milk and beef from
the diet. Identifying pediatric patients with
complications of GERD, such as erosive
esophagitis, is important because effective
treatment is available in this age group, as it is in
adults. Antisecretory therapy is the most effective Resolves by 18
months of age? Well child
pharmacologic treatment for GERD, H2 blocker
for mild esophagitis and PPIs in general provide 9 Yes
faster symptom relief and are effective in healing No
erosive esophagitis in patients unresponsive to
H2RAs. Surgical management of GERD is an 10
option for children in whom pharmacologic
therapy is unsuccessful, but the risks associated 11 Consultation with Pediatric GI
with surgical intervention must be considered Consider FDG & biopsy
against the relatively better prognosis in infants
without life-threatening complications of GERD. If Fig 7: Recommended Approach to the Infant
there is any doubt about the diagnosis of GERD with Recurrent Regurgitation and Vomiting1

Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan 137
 

 
Fig 9: Recommended Approach to the Older
Child or Adolescent with Heartburn 1

REFERENCES
 
1. Vandenplas Y, Rudolph CD, Di Lorenzo C,
Fig 8: Recommended Approach to the Infant with et al. Pediatric gastroesophageal reflux
Recurrent Regurgitation and Weight Loss1 clinical practice guidelines: joint
recommendations of the North American

Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan 138
 

Society for Pediatric Gastroenterology, pediatric practice-based survey. Pediatric

Hepatology, and Nutrition (NASPGHAN) Practice Research Group. Arch Pediatr
and the European Society for Pediatric Adolesc Med 1997; 151: 569–72.
Gastroenterology, Hepatology, and 11. De S, Rajeshwari K, Kalra KK, Gondal R,
Nutrition (ESPGHAN). J Pediatr Malhotra V, Mittal SK. Gastroesophageal
Gastroenterol Nutr 2009; 49: 498. reflux in infants and children in north India.
2. Vakil N, van Zanten SV, Kahrilas P, Dent J, Trop Gastroenterol, 2001; 22: 99-102.
Jones R. Global Consensus Group. The 12. Nelson P, Chen EH, Syniar GM, Christoffel
Montreal definition and classification of KK. Prevalence of symptomatic
gastroesophageal reflux disease: a global gastroesophageal reflux during childhood:
evidence-based consensus. Am J A pediatric practice-based survey, pediatric
Gastroenterol. 2006; 101: 1900–20. practice research group. Arch Pediatr
3. Fernandez S, Aspirot A, Kerzner B, Adolesc Med. 2000; 154: 150-54.
Friedlander J, Di Lorenzo C. Do some 13. Stanghellini V. Relationship between
adolescents with rumination syndrome upper gastrointestinal symptoms and
have “supragastric vomiting”? J Pediatr lifestyle, psychosocial factors and co-
Gastroenterol Nutr. 2010; 50(1): 103–05. morbidity in the general population: Results
4. [Guideline] Lightdale JR, Gremse DA. from the domestic/international
Gastroesophageal reflux: management gastroenterology surveillance study
guidance for the pediatrician. Pediatrics. [DIGEST]. Scand J Gastrenterol Suppl
Apr 29, 2013; e1684-96. 1999; 231: 29–37.
5. Jenson Geoffrey P. Davidson MD, 14. Dent J, El-Serag HB, Wallander MA,
FRACP, Taher I. Omari PhD. Johansson S. Epidemiology of gastro-
Pathophysiological mechanisms of oesophageal reflux disease: a systematic
Gastroesophageal reflux disease in review. Gut 2005; 54(5): 710–17.
children. Current Gastroenterology Reports. 15. Delavari A, Moradi G, Birjand i F, Elahi E,
2001; 3(3): 257-62. Saberifiroozi M. The Prevalence of
6. Moroz SP, Espinoza J, Cumming WA Gastroesophageal Reflux Disease (GERD)
Dinmant NE: Lower esophageal sphincter in the Islamic Republic of Iran: A
function in children with and without Systematic Review. Middle East Journal of
gastroesophageal reflux. Gastroenterology Digestive Diseases, January 2012; 4(1):
1976, 71: 236–41. 16 Jung HK. Epidemiology of
7. Staiano A, Cucchiara S, Del Giudice E, et gastroesophageal reflux disease in Asia: a
al.: Disorders of oesophageal motility in systematic review. J Neurogastroenterol
children with psychomotor retardation and Motil. 2011; 17: 14–27.
gastro-oesophageal reflux. Eur J Pediatr 17 Cameron AJ, Lagergren J, Henriksson C,
1991, 150: 638–41. et al. Gastroesophageal reflux disease in
8. Andrew D, Jung MD. Gastroesophageal monozygotic and dizygotic twins.
Reflux in Infants and Children. Am Fam Gastroenterology 2002; 122: 55–59.
Physician. 2001 Dec 1; 64(11): 1853-61. 18 Orenstein SR. Gastroesophageal reflux.
9. Rudolph CD. Supraesophageal Pediatr Rev. 1999; 20: 24–28.
complications of gastroesophageal reflux in 19 Glassman M, George D, Grill B.
children: challenges in diagnosis and Gastroesophageal reflux in children.
treatment. Am J Med. Aug 18, 2003; 115 Clinical manifestations, diagnosis, and
Suppl 3A:150S-56S. therapy. Gastroenterol Clin North Am.
10. Nelson SP, Chen EH, Syniar GM, 1995; 24: 71–98.
Christoffel KK. Prevalence of symptoms of 20 Theodoropoulos DS, Flockey RF, Boyce
gastroesophageal reflux during infancy. A HW Jr; Sandifer's syndrome and gastro-

Wwww.pakpedsreview.org.pk
 Gastroesophageal Reflux, Management guidelines, Pakistan 139
 

oesophageal reflux disease. J Neurol 31 Skadberg BT, Morild I, Markestad T.

Neurosurg Psychiatry. 1999 Jun; 66(6):
805-06.
21 Orenstein SR. Symptoms and reflux in
infants: Infant Gastroesophageal Reflux 32
Questionnaire Revised (I-GERQ-R)--utility
for symptom tracking and diagnosis. Curr
Gastroenterol Rep. 2010 Dec; 12(6): 431-
36. doi: 10.1007/s11894-010-0140-1.
22 Seibert JJ, Byrne WJ, Euler AR, Latture T, 33
Leach M, Campbell M. Gastroesophageal
reflux-the acid test: scintigraphy or the pH
probe? AJR Am J Roentgenol 1983; 140: 34
1087–90.
23 Meyers WF, Roberts CC, Johnson DG,
Herbst JJ. Value of tests for evaluation of
gastroesophageal reflux in children. J 35
Pediatr Surg 1985; 20: 515–20.
24 Chen MY, Ott DJ, Sinclair JW, Wu WC,
Gelfrand DW. Gastroesophageal reflux
disease: correlation of esophageal pH
testing and radiographic findings. Radiology
1992; 185(2): 483–86.
25 Wenzl TG. Role of diagnostic tests in
GERD. J Pediatr Gastroenterol Nutr. 2011; 36
53 (Suppl 2): S4-6.
26 Bhatia J, Parish A. GERD or not GERD:
the fussy infant. Journal of Perinatology 37
(2009); 29: S7–S11.
27 Poddar U. Diagnosis and Management of
Gastroesophageal Reflux Disease (GERD):
An Indian Perspective . Indian Pediatr 38
2013; 50: 119-26.
28 Managing gastro-oesophageal reflux in
infants; Managing gastro-oesophageal
reflux in infants. BMJ. 2010 Aug 27; 341:
c4420. doi: 10.1136/bmj.c4420.
29 Huang R-C, Forbes D, Davies MW.Feed
thickener for newborn infants with gastro- 39
oesophageal reflux.In Cochrane review:
January 21, 2009.
30 Tobin JM, McCloud P, Cameron DJS. 40
Posture and gastro-oesophageal reflux: a
case for left lateral positioning. Arch Dis
Child 1997; 76: 254-58.
Abandoning prone sleeping: effect on the
risk of sudden infant death syndrome. J
Pediatr 1998;132: 340-43.
Locke GR III, Talley NJ, Fett SL,
Zinsmeister AR, Melton LJ III. Risk factors
associated with symptoms of
gastroesophageal reflux. Am J Med 1999;
106: 642-49.
Gremse DA. GERD in the Pediatric Patient:
Management Considerations. MedGenMed.
2004; 6(2): 13.
Gremse DA. Lansoprazole:
pharmacokinetics, pharmacodynamics, and
clinical uses. Exp Opin Pharmacother.
2001; 2: 1663-70.
Rudolph C, Mazur LJ, Liptak GS, Baker R,
Boyle JT, Colletti RB, Gerson W, Werlin S.
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: S1-S31.
Euler AR. Use of bethanechol for the
treatment of gastroesophageal reflux. J
Pediatr 1980; 96: 321-24.
Curry JI, Lander TD, Stringer MD. Review
article: erythromycin as a prokinetic agent
in infants and children. Aliment Pharmacol
Ther 2001; 15: 595-603.
Mauritz FA, van Herwaarden-Lindeboom
MY, Stomp W, et al; The effects and
efficacy of antireflux surgery in children with
gastroesophageal reflux disease: a
systematic review. J Gastrointest Surg.
2011 Oct; 15(10): 1872-8. Epub 2011 Jul
29.
Shiwani MH. Scope of Laparoscopic Anti
Reflux Surgery in Pakistan. J Pak Med
Assoc. July 2006; 56(7):
Dallemagne B. Weerts J, Markiewicz S,
Dewandre J M, Wahlen C, Monami B, et al.
Clinical results of laparoscopic
fundoplication at ten years after surgery.
Surg Endosc 2006: 20: 159-65.

Wwww.pakpedsreview.org.pk

View publication stats