Gastro esophageal reflux disease (GERD) in children

2. GERD in ChildrenGERD in Children
Definition
Pathophysiology
Prevalence and Incidence
Symptoms and Complications
Impact on Life
Diagnosis
Management

3. Gastroesophageal reflux disease (GERD)
Gastroesophageal reflux disease (GERD) is the most common
esophageal disorder in children of all ages.

4. Pathophysiology
Factors determining the esophageal manifestations of
reflux include
the duration of esophageal exposure (a product of the frequency
and duration of reflux episodes),
the causticity of the refluxate, and
the susceptibility of the esophagus to damage.
Note: The LES, supported by the crura of the diaphragm at the
gastroesophageal junction, together with valvelike functions of
the esophagogastric junction anatomy, form the antireflux
barrier.

5. In the context of even the normal intra-abdominal pressure
augmentations that occur during daily life, the frequency of
reflux episodes is increased :
 by insufficient LES tone,
 by abnormal frequency of LES relaxations, and
 by hiatal herniation that prevents the LES pressure from being
proportionately augmented by the crura during abdominal
straining.
 Normal intra-abdominal pressure augmentations may be further
exacerbated by straining or respiratory efforts.
Pathophysiology

6. The duration of reflux episodes is increased by lack of
swallowing (e.g., during sleep) and by defective esophageal
peristalsis.
Vicious cycles ensue because chronic esophagitis produces
esophageal peristaltic dysfunction (low-amplitude waves,
propagation disturbances), decreased LES tone, and
inflammatory esophageal shortening that induces hiatal
herniation, all worsening reflux.
Pathophysiology

7. Transient LES relaxation (TLESR) is the primary mechanism
allowing reflux to occur.
Whether GERD is caused by a higher frequency of TLESRs or
by a greater incidence of reflux during TLESRs is debated; each
is likely in different persons.
Straining during a TLESR makes reflux more likely, as do
positions that place the gastroesophageal junction below the air-
fluid interface in the stomach.
Pathophysiology

8. Other factors influencing gastric pressure-volume
dynamics, such as
increased movement,
straining,
obesity,
large-volume or hyperosmolar meals, and
increased respiratory effort (coughing, wheezing) can have the
same effect.
Pathophysiology

9. Epidemiology and Natural History
Infant reflux becomes evident in the 1st few months of life,
peaks at 4 mo, and resolves in up to 88% by 12 mo and nearly∼
all by 24 mo.
Symptoms in older children tend to be chronic, waxing and
waning, but completely resolving in no more than half, which
resembles adult patterns.

10. As a continuously variable and common disorder, complex
inheritance involving multiple genes and environmental
factors is likely.
GERD likely has genetic predispositions: family clustering of
GERD symptoms, endoscopic esophagitis, hiatal hernia, Barrett
esophagus, and adenocarcinoma have been identified.
A pediatric autosomal dominant form with otolaryngologic and
respiratory manifestations has been located to chromosome
13q14, and the locus is termed GERD1.
Epidemiology and Natural History

11. Prevalence of GERD diagnosed in UK primary care
during 2000-2005
Rodriguez G et al. Scand J Gastroenterol 2010;45:139–46.

12. GERD in children
Symptoms and
complications

13. The Montréal definition of GERD
“GERD is a condition which develops when the reflux
of stomach content causes troublesome symptoms
and/or complications”
Esophageal
Syndromes
Extra-esophageal
Syndromes
Symptomatic
Syndromes
 Typical Reflux
Syndrome
 Reflux Chest
Pain Syndrome
Syndromes with
Esophageal Injury
 Reflux Esophagitis
 Reflux Stricture
 Barrett’s Esophagus
 Adenocarcinoma
Established
Associations
 Reflux Cough
 Reflux Laryngitis
 Reflux Asthma
 Reflux Dental Eros.
Proposed
Associations
 Pharyngitis
 Sinusitis
 Idiopathic
Pulmonary Fibrosis
 Recurrent Otitis
Media
Vakil et al. Am J Gastroenterol 2006;101:1900–20
Clinical Manifestations

14. Sherman PM et al. Am J Gasroenterol 2009;104:1278–95
• Excessive regurgitation
• Feeding refusal/
anorexia
• Unexplained crying
• Choking/gagging/
coughing
• Sleep disturbance
• Abdominal pain
Symptomatic
syndromes
Older child or
adolescent with
cognitive ability
to reliably report
symptoms
Symptoms purported
to be due to GERD*
Infant or younger child
(0–8 years), or older
without cognitive ability
to reliably
report symptoms
Definite
associations
• Typical Reflux
Syndrome
Bronchopulmonary
• Asthma
• Pulmonary fibrosis
• Bronchopulmonary dysplasia
Laryngotracheal and pharyngeal
• Chronic cough
• Chronic laryngitis
• Hoarseness
• Pharyngitis
Rhinological and otological
• Sinusitis
• Serious otitis media
Infants
• Pathological apnea
• Bradycardia
• Apparent life-
threatening events
• Reflux esophagitis
• Reflux stricture
• Barrett’s esophagus
• Adenocarcinoma
• Sandifer’s
syndrome
• Dental erosion
Esophageal Extraesophageal
GERD is present in pediatric patients when reflux of gastric contents
is the cause of troublesome symptoms and/or complications
*For cases in which other causes have been ruled out
(e.g. food allergy, especially in infants)
Syndromes with
esophageal injury
Possible
associations
Global definition of GERD in children

15. Clinical Manifestations
Infantile reflux manifests more often with regurgitation
(especially postprandially), signs of esophagitis (irritability,
arching, choking, gagging, feeding aversion), and resulting
failure to thrive;
symptoms resolve spontaneously in the majority by 12–24 mo.

16. Older children can have regurgitation during the preschool
years; complaints of abdominal and chest pain supervene in
later childhood and adolescence.
Occasional children present with neck contortions (arching,
turning of head), designated Sandifer syndrome.
Clinical Manifestations

17. The respiratory presentations are also age dependent:
GERD in infants can manifest as obstructive apnea or as
stridor or lower airway disease in which reflux complicates
primary airway disease such as laryngomalacia or
bronchopulmonary dysplasia.
Otitis media, sinusitis, lymphoid hyperplasia, hoarseness, vocal
cord nodules, and laryngeal edema have all been associated
with GERD.
Clinical Manifestations

18. Airway manifestations in older children are more commonly
related to asthma or to otolaryngologic disease such as
laryngitis or sinusitis.
Despite the high prevalence of GERD symptoms in
asthmatic children, data showing direction of causality are
conflicting.
Clinical Manifestations

19. Prevalence of GERD symptoms in a pediatric
practice-based survey in Chicago
Suffered symptom
during previous week (%)
0
2
4
6
8
10
Heartburn†
Regurgitation‡ Epigastric
pain§
age: 3–9 years (Parent) n=566
age: 10–17 years (Parent) n=584
age: 10-17 years (Child) n=615
†
Burning/painful feeling in
middle of chest
‡
Sour taste or taste
of throw-up
§
Stomach ache above the
belly button
Nelson SP et al. Arch Pediatr Adolesc Med 2000;154:150–4
1.8
2.3
7.2
3.5
1.4
3.0
5.2
8.2
5.0

20. Heartburn/
retrosternal pain
0
10
20
30
40
50
60
70
80
Children (%)
Nausea
n=99
Størdal K et al. Scand J Gastroenterol 2005;40:636–40
Abdominal
pain
Regurgitation/
vomiting
Epigastric
pain
Dysphagia
Symptoms among 7–16 year-olds with
suspected GERD referred for pH-monitoring

21. Prevalence of reflux esophagitis in children
increases with age
Prevalence of reflux esophagitis
(%)
0
20
40
60
80
100
Age range (years)
0–2 3–5 6–12 13–17
8303 children aged 0–18 years who
underwent endoscopy (for any reason)
between 1999 and 2002
Gilger MA et al. J Pediatr Gastroenterol Nutr 2004;39 Suppl 1:S383–4
9.9
6.8
25
40

22. Risk of extraesophageal conditions
Ruiguomez A et al. Scan J Gastroenterol, 2010; 45: 814–821

23. GERD affects many aspects of
children’s lives
Sleeping habits in 69% of children
Eating habits in 72% of children
School performance in 53% of children
Social activities in 48% of children
StrategyOne survey. Parents’ Perspective on GERD
A survey among 205 parents of 1–17-year-old children with GERD
showed that, in the past year, the condition affected:

24. Childhood GERD impacts on the life of the
caregiver
Caring for a child with GERD may affect many aspects of the
caregiver’s life, including :
Mealtimes
Housework and household expenses
Emotional well-being
Physical health
Social life
Relationships
Employment
Kim J et al. Health Qual Life Outcomes 2005;3:5

25. GERD in children
Diagnosis

26. Diagnostic approaches in suspected GERD
History and physical examination
Diagnostic tests
– Barium contrast radiography
– Esophageal pH monitoring
– Endoscopy and biopsy
1- Vandenplas Y et al. JPGN 2009; 49:498-547*MII=Multiple Intraluminal Impedance

27. Diagnosis
For most of the typical GERD presentations, particularly in older
children, a thorough history and physical examination suffice
initially to reach the diagnosis.
This initial evaluation aims to identify the pertinent positives in
support of GERD and its complications and the negatives that
make other diagnoses unlikely.

28. milk and other food allergies,
eosinophilic esophagitis,
pyloric stenosis,
intestinal obstruction
(especially malrotation with
intermittent volvulus),
nonesophageal inflammatory
diseases,
infections,
inborn errors of metabolism,
hydronephrosis, increased
intracranial pressure,
rumination, and bulimia.
Important other diagnoses to consider in the evaluation of
an infant or a child with chronic vomiting are:
Diagnosis

29. History and physical examination
Aim to exclude worrisome
disorders and to identify
complications of GERD.
Symptoms and signs
associated with reflux are
nonspecific.
Regurgitation, vomiting
irritability and heartburn can
be caused by other
conditions.
1- Vandenplas Y et al. JPGN 2009; 49:498-547

30. History of the child with suspected GERD
Feeding and dietary history
Pattern of vomiting
Medical history
Medications
Family psychosocial history
Family medical history
Growth Chart
1- Vandenplas Y et al. JPGN 2009; 49:498-547

31. Diagnostic approaches in suspected GERD
History and physical examination
Diagnostic tests
– Barium contrast radiography
– Esophageal pH monitoring
– Endoscopy and biopsy
1- Vandenplas Y et al. JPGN 2009; 49:498-547*MII=Multiple Intraluminal Impedance

32. Diagnostic tests
Aim:
– To document the presence of pathologic reflux or its complications.
– To evaluate therapy.
– To exclude other conditions.
1- Vandenplas Y et al. JPGN 2009; 49:498-547

33. Most of the esophageal tests are of some use in particular
patients with suspected GERD.
Contrast (usually barium) radiographic study of the
esophagus and upper gastrointestinal tract is performed in
children with vomiting and dysphagia to evaluate for achalasia,
esophageal strictures and stenosis, hiatal hernia, and gastric
outlet or intestinal obstruction .
It has poor sensitivity and specificity in the diagnosis of GERD
due to its limited duration and the inability to differentiate
physiologic GER from GERD.
Barium contrast radiography

34. Barium contrast radiography
Advantages
– Useful for detecting anatomic
abnormalities.
Limitations
– Cannot discriminate between
physiologic and non-physiologic
GER episodes.
1- Vandenplas Y et al. JPGN 2009; 49:498-547

35. Endoscopy allows diagnosis of erosive esophagitis and
complications such as strictures or Barrett esophagus;
esophageal biopsies can diagnose histologic reflux esophagitis
in the absence of erosions while simultaneously eliminating
allergic and infectious causes.
Endoscopy is also used therapeutically to dilate reflux-
induced strictures. Radionucleotide scintigraphy using
technetium can demonstrate aspiration and delayed gastric
emptying when these are suspected.
Endoscopy and biopsy

36. Endoscopy and biopsy
Advantages
– Enables visualization and biopsy
of esophageal epithelium.
– Determines presence of
esophagitis and other
complications.
Limitations
– Need for sedation or anesthesia.
– Generally not useful for extra
esophageal GERD.
1- Vandenplas Y et al. JPGN 2009; 49:498-547

37. Normal values of distal esophageal acid exposure (pH <4) are
generally established as <5-8% of the total monitored time, but
these quantitative normals are insufficient to establish or
disprove a diagnosis of pathologic GERD.
The most important indications for esophageal pH
monitoring are for assessing efficacy of acid suppression
during treatment, evaluating apneic episodes in conjunction with
a pneumogram and perhaps impedance, and evaluating atypical
GERD presentations such as chronic cough, stridor, and
asthma.
Esophageal pH monitoring

38. Esophageal pH monitoring
Advantages
– Detects episodes of reflux.
– Determines temporal association
between acid GER and
symptoms.
– Determines effectiveness of
esophageal clearance
mechanisms.
– Assesses adequacy of H2RA or
PPI dosage in unresponsive
patients.
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.
1- Vandenplas Y et al. JPGN 2009; 49:498-547

39. 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.
Diagnostic tests

40. GERD in children
Management

41. Treatment goals in childhood GERD
Relieve symptoms
Heal esophagitis
Manage and prevent complications
Maintain remission
Rudolph CD et al. J Pediatr Gastroenterol Nutr 2001;32 Suppl 2:S1–31
“Optimal treatment was defined as improvement or
resolution of the presenting symptoms and complications
of gastroesophageal reflux, with interventions that have
few or no adverse effects, and with resultant resumption
of functional health.”

42. Treatment
Lifestyle and dietary changes
Pharmacologic therapies
Surgical therapy
1- Vandenplas Y et al. JPGN 2009; 49:498-547

43. Lifestyle and dietary changes
Avoid alcohol
Lose weight, if obese
Positioning changes
Cessation of smoking
Avoid large meals
Avoid chocolate, caffeine and
spicy food
Normalize feeding volume and
frequency
Consider thickened formula
Positioning
Trial of hypoallergenic formula
Keep things loose around the
waist
1- Vandenplas Y et al. JPGN 2009; 49:498-547
“Current evidence generally does not support (or refute)
the use of specific dietary changes to treat reflux beyond
infancy. “

44. Management
Conservative therapy and lifestyle modification form the
foundation of GERD therapy.
Dietary measures for infants include normalization of any
abnormal feeding techniques, volumes, and frequencies.
Thickening of feeds or use of commercially prethickened
formulas increases the percentage of infants with no
regurgitation, decreases the frequency of daily regurgitation and
emesis, and increases the infant's weight gain.

45. The evidence does not clearly favor one type of thickener over
another; the addition of a Tbsp of rice cereal per oz of formula
results in a greater caloric density (30 kcal/oz), and reduced
crying time, although it might not modify the number of
nonregurgitant reflux episodes.
A short trial of a hypoallergenic diet may be used to exclude
milk or soy protein allergy before pharmacotherapy.
Older children should be counseled to avoid acidic or reflux-
inducing foods (tomatoes, chocolate, mint) and beverages
(juices, carbonated and caffeinated drinks, alcohol).
Weight reduction for obese patients and elimination of smoke
exposure are other crucial measures at all ages.
Management

46. Positioning measures are particularly important for infants,
who cannot control their positions independently.
Seated position worsens infant reflux and should be avoided in
infants with GERD.
Esophageal pH monitoring demonstrates more reflux episodes
in infants in supine and side positions compared with the prone
position, but evidence that the supine position reduces the risk
of sudden infant death syndrome has led the American
Academy of Pediatrics and the North American Society of
Pediatric Gastroenterology and Nutrition to recommend supine
positioning during sleep.
Management

47. When the infant is awake and observed, prone position and
upright carried position can be used to minimize reflux. The
efficacy of positioning for older children is unclear, but some
evidence suggests a benefit to left side position and head
elevation during sleep.
The head should be elevated by elevating the head of the bed,
rather than using excess pillows, to avoid abdominal flexion and
compression that might worsen reflux.
Management

48. The available controlled trials have not demonstrated much
efficacy for GERD.
In 2009, the FDA announced a black box warning for
metoclopramide, linking its chronic use (>3 mo) with tardive
dyskinesia, the rarely reversible movement disorder.
Baclofen is a centrally acting γ-aminobutyric acid (GABA)
agonist that has been shown to decrease reflux by decreasing
TLESRs in healthy adults and in a small number of
neurologically impaired children with GERD.
New agents of great interest include peripherally acting GABA
agonists devoid of central side effects, and metabotropic
glutamate receptor 5 (mGluR5) antagonists that are reported to
reduce TLESRs, but are as yet inadequately studied for this
indication in children.
Management

49. Pharmacologic therapy
Antacids and other agents
Prokinetic therapy
– Cisapride, domperidone, metocolpramide,
bethanecol, erythromycin and baclofen
H2RAs
– Cimetidine, ranitidine, nizatidine and
famotidine
PPIs
1- Vandenplas Y et al. JPGN 2009; 49:498-547

50. Antacids and other agents
1- Vandenplas Y et al. JPGN 2009; 49:498-547
“Buffering agents, alginate, and sucralfate are useful on
demand for occasional heartburn.”
“Because more effective alternatives (H2RAs and PPIs) are
available, chronic therapy with buffering agents, alginates, and
sucralfate is not recommended for GERD.”

51. Pharmacotherapy is directed at ameliorating the acidity of the
gastric contents or at promoting their aboral movement.
Antacids are the most commonly used antireflux therapy and
are readily available over the counter.
They provide rapid but transient relief of symptoms by acid
neutralization.
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.
Management - Antacids

52. Prokinetics therapy
1- Vandenplas Y et al. JPGN 2009; 49:498-547
“Potential side effects of each currently available prokinetic
agent outweigh the potential benefits.”
“There is insufficient support to justify the routine use of
metoclopramide, erythromycin, bethanechol, or domperidone
for GERD”

53. Prokinetic agents include metoclopramide (dopamine-2 and 5-
HT3 antagonist), bethanechol (cholinergic agonist), and
erythromycin (motilin receptor agonist).
Most of these increase LES pressure; some improve gastric
emptying or esophageal clearance.
None affects the frequency of TLESRs.
Management - Prokinetics

54. Histamine-2 Receptors antagonists
1- Vandenplas Y et al. JPGN 2009; 49:498-547
“H2RAs exhibit tachyphylaxis or tolerance and tachyphylaxis is
a drawback to chronic use.”
“H2RAs have a rapid onset of action and are useful for on-
demand treatment.”

55. Histamine-2 receptor antagonists (H2RAs: cimetidine,
famotidine, nizatidine, and ranitidine) are widely used
antisecretory agents that act by selective inhibition of histamine
receptors on gastric parietal cells.
There is a definite benefit of H2RAs in treatment of mild-to-
moderate reflux esophagitis.
H2RAs have been recommended as first-line therapy because
of their excellent overall safety profile, but they are being
superseded by PPIs in this role, as increased experience with
pediatric use and safety, US Food and Drug Administration
(FDA) approval, and pediatric formulations and dosing are
acquired.
Management- Histamine-2 R antagonists

56. Proton Pump Inhibitors
1- Vandenplas Y et al. JPGN 2009; 49:498-547
“PPIs are superior to H2RAs in relieving symptoms and healing
esophagitis.”

57. PPIs (omeprazole, lansoprazole, pantoprazole, rabeprazole,
and esomeprazole) provide the most potent antireflux effect by
blocking the hydrogen-potassium ATPase channels of the final
common pathway in gastric acid secretion.
PPIs are superior to H2RAs in the treatment of severe and
erosive esophagitis.
Pharmacodynamic studies have indicated that children require
higher doses of PPIs than adults on a per-weight basis.
The use of PPIs to treat infants and children deemed to have
GERD on the basis of symptoms has considerably increased in
recent years.
Controlled trials in infants with GERD diagnosed on the basis of
symptoms alone have suggested an efficacy similar to placebo
and have raised a safety concern.
Management - Proton Pump Inhibitors

58. Surgery
1- Vandenplas Y et al. JPGN 2009; 49:498-547
“Antireflux surgery may be
of benefit in selected children with chronic-relapsing
GERD.”
“Indications include failure of optimized
medical therapy, dependence on long-term medical
therapy, significant nonadherence to medical therapy,
or pulmonary aspiration of refluxate.”

59. Surgery, usually fundoplication, 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.
It may be combined with a gastrostomy for feeding or venting.
Management - Surgery

60. Chronic Heartburn
History and physical examination
Education;
Life-style change;
PPI for 2-4 weeks
Improves
Consultation with
pediatric GI
Continue PPI
For 8-16 weeks
Discontinue PPI
Relapse
Observation
Yes
Yes No
No
Management approach to the older child or
adolescent with heartburn
1- Vandenplas Y et al. JPGN 2009; 49:498-547

61. Management approach to children with
erosive esophagitis
“In pediatric patients with
endoscopically diagnosed reflux esophagitis or established
nonerosive reflux disease, PPIs for 3 months constitute
initial therapy.”
“Not all reflux esophagitis are
chronic or relapsing, and therefore trials of tapering
the dose and then withdrawal of PPI therapy should be
performed.”
1- Vandenplas Y et al. JPGN 2009; 49:498-547

62. Approved indications of PPIs for GERD in
children in the EU and the USA
Drug EU indication US indication
Omeprazole GERD≥ 1 year GERD 1-16 years
Esomeprazole GERD≥ 1 year GERD 1-17 years
Lansoprazole Not approved GERD 1-17 years
Pantoprazole Not approved Not approved
Rabeprazole Not approved Not approved
Vandenplas Y et al. JPGN 2009; 49:498-547
G.Tafuri et al. Eur J Clin pharmacol 2009;65:209-216
Losec SmPC 2008
Nexium SmPC 2008

63. Approved dosage and formulations of PPIs
for GERD in children in the EU and USA
Drug Dosage Formulations
Omeprazole
•10-20Kg: 10mg
•>20Kg: 20 mg
•Capsules
•MUPS
•Sachet (USA)
Esomeprazole
•10<20Kg: 10 mg
•>20Kg: 10-20 mg
•Sachet
•Capsule
Lansoprazole
•<30 kg: 15 mg
•>30 kg: 30 mg
•Capsule
•Oral suspension (USA)
•SoluTab
Pantoprazole No Tablet
Rabeprazole No Tablet
Vandenplas Y et al. JPGN 2009; 49:498-547
G.Tafuri et al. Eur J Clin pharmacol 2009;65:209-216
Losec SmPC 2008
Nexium SmPC 2008

64. THANKS FOR
YOUR Attention