This document discusses Gastro Esophageal Reflux Disease (GERD) in infants. It provides definitions of key terms like GER and GERD. It reviews the epidemiology and natural history of GER in infants, noting that the prevalence of daily regurgitation peaks between 1-6 months of age in around 70% of infants. It discusses the anatomy and physiology involved in GER and reviews approaches to diagnosing GERD in infants, including history, physical exam, upper GI imaging, endoscopy, and pH monitoring. Non-pharmacological and pharmacological treatment options are also covered.

1. Gastro Esophageal Reflux Disease (GERD)
in Infants
DR GABY FALAKHA
PEDIATRICIAN & NEONATOLOGIST

2. Learning Objectives
 To review the definitions, natural history and mechanisms of GER and
GERD
 To discuss the diagnosis of GERD in infants
 To discuss the management options for physiologic GER and GERD

3. Outline
1. Introduction
2. Epidemiology and natural history
3. Evaluation & Diagnosis
4. Non-Pharmacological treatment
5. Medication and surgery
6. Take home messages

4. DEFINITIONS
 Gastroesophageal reflux (GER): passage of gastric contents into the
esophagus
 Gastroesophageal reflux disease (GERD): Refers to reflux that has
pathologic consequences, such as esophagitis, nutritional compromise
with weight loss, or respiratory complications
 Regurgitation: Describes effortless reflux up to the oropharynx or above.
 Vomiting: Describes forceful emptying of the stomach
 Refractory GERD: Unresponsive to medical treatment
The New Rome IV Criteria for Functional Gastrointestinal Disorders in Infants and Toddlers. Zeevenhooven J, Koppen IJ, Benninga MA Pediatr Gastroenterol Hepatol Nutr. 2017;20(1):1.

5. Introduction
 The GI tract is a one-way passage, food and
water enter through the mouth and exist, after
multiple digestion processes, through the
anus.
 The digestive system is equipped with a series
of sphincters and valves to prevent backward
circulation
 The only exception is the lower esophageal
sphincter (LES) which through relaxation allows
the exist of air that inadvertently went in, with
food through swallowing (17-30 x/day)

6. Epidemiology

7. Prevalence of Regurgitation in Infancy
0
10
20
30
40
50
60
70
0-3 4-6 7-9 10-12
Age (months)
% of
Infants
 1 time a day
 4 times a day
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):569–572
n=948

8. Natural history of gastroesophageal reflux in infancy:
new data from a prospective cohort
 Methods: a prospective cohort study including all full-term
living neonates born at Besançon Teaching Hospital, France.
 Regurgitation was based on the answer to the first question
of the I-GERQ-R as anything coming out of the mouth daily.
 157/347 births were included
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152

9. Natural history of gastroesophageal reflux in infancy:
new data from a prospective cohort
 Methods: a prospective cohort study including all full-term
living neonates born at Besançon Teaching Hospital, France.
 Regurgitation was based on the answer to the first question
of the I-GERQ-R as anything coming out of the mouth daily.
 157/347 births were included
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152

10. Natural history of gastroesophageal reflux in infancy:
new data from a prospective cohort
 Results: The prevalence of regurgitation
at least once a day was 45.7% overall.
 In total: 72, 69, 56, 18, and 13% of
infants regurgitated at least once a day
at 1, 3, 6, 10, and 12 months of age,
respectively.
 Two risk factors were identified: family
history of GER and exposure to passive
smoking.
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152

11. Incidence of GER and GERD between one and
twelve months of age
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152

12. The estimated prevalence of GERD
Age Incidence (%)
Low risk High Risk
0-23 months 2.2 12.3
2-11 years 0.6 4.1
12-17 years 0.8 7.6
Martigne L, Delaage PH, Thomas-Delecourt F, et al. Prevalence and management of gastroesophageal reflux disease in children and adolescents: a
nationwide cross-sectional observational study. Eur J Pediatr 2012;171(12):1767–73.

13. High Risk Populations
1. Neurologically impaired
2. Neuromuscular diseases
3. Obese infants and children
4. Certain genetic syndromes
5. Esophageal atresia
6. Chronic lung diseases
7. 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):548–557

14. • Pulmonologists were most likely to report that respiratory
symptoms are caused by GERD
• Neonatologists were least likely to report that a
therapeutic trial of pharmacologic agents would be useful
for diagnosing GERD or that lansoprazole, ranitidine, or
cimetidine are safe or effective
• No pharmacologic therapy had 50% of respondents
supporting its effectiveness.
Pediatric Specialists’ Beliefs About Gastroesophageal
Reflux Disease in Premature Infants
Catherine A. Golski et al. www.pediatrics.org/cgi/doi/10.1542/peds.2008-3841
RESULTS : A total of 1021 neonatologists, 232 pediatric pulmonologists, and
222 pediatric gastroenterologists participated in the study

15. Anatomy & Physiology

16. Anatomy of the esophagus
Pandolfino, J. E. and A. J. Gawron (2015). "Achalasia: a systematic review." JAMA 313(18): 1841-1852.

17. A) Pandolfino, J. E. and A. J. Gawron (2015). "Achalasia: a systematic review." JAMA 313(18): 1841-1852.
Anatomy of the Lower Esophageal Sphincter
Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med. 1997 Mar 27;336(13):924-32.
• Healthy adult – LES 3cm in
length, at level of diaphragm
• Neonate – LES 1.5cm in
length, above the diaphragm

19. 1. Esophageal peristalsis and relaxation of the
lower esophageal sphincter induced by
swallowing result from the excitation of
receptors in the pharynx.
2. The afferent stimulus travels to the sensory
nucleus, the nucleus solitarius (small inset).
3. A programmed set of events from the dorsal
vagal nucleus and the nucleus ambiguus
mediates esophageal peristalsis and
sphincter relaxation.
4. The vagal efferent fibers communicate with
myenteric neurons that mediate relaxation
(large inset).
5. The postganglionic transmitters are nitric
oxide (NO) and vasoactive intestinal peptide
(VIP).
Ach: acetylcholine
(+) signs: excitatory effects
(-) signs: inhibitory effects
RAVINDERK. MITTAL, M.D., NEJM; March 27, 1997
Neurologic control

20. 6. Transient relaxation of the lower
esophageal sphincter, appears to use the
same pathway.
7. The afferent signals for such relaxation
may originate in the pharynx, the larynx,
or the stomach.
8. The efferent pathway is in the vagus
nerve, and nitric oxide is the
postganglionic neurotransmitter.
9. Contraction of the crural diaphragm is
controlled by the inspiratory center in
the brain stem and the nucleus of the
phrenic nerve.
10.The crural diaphragm is innervated by
the right and left phrenic nerves through
nicotinic cholinergic receptors.
Ach: acetylcholine
(+) signs: excitatory effects
(-) signs: inhibitory effects
RAVINDERK. MITTAL, M.D., NEJM; March 27, 1997

21. Why do Infants regurgitate?
 Supine position
 Fed frequently (6-8 meals per day)
 Limited capacity of their stomach
 Parents want to be sure they’re giving maximum amount of milk
 Crying is interpreted as a sign of hunger
 Questionable immaturity of LES especially in preterm babies

22. Adult
Esophageal Capacity
Infant
Weaver TL. Anatomy and embryology. In: Walker WA, Durie PR, Hamilton JR, et al, eds. Pediatric Gastrointestinal Disease, 1st ed. Philadelphia: BC Decker; 1991:195-216.
11 cm at birth, with a diameter of 5 mm
24-30 cm long, with lateral and anteroposterior
diameters of 30 and 19 mm

23. Colo-Gastric Break
 Background & aims: Patients with constipation frequently complain of dyspeptic
symptoms that may be explained by reflex inhibition of upper-gastrointestinal motor
activity by colonic stimuli (Colo-Gastric break).
 Methods: 42 children (mean age, 80.5 month) affected by FD (Rome II criteria).
 All subjects underwent ultrasonographic measurement of the total gastric emptying time
(TGEt) at baseline (T0) and after 3 months (T3).
 Children's bowel habits and the dyspeptic symptomatic score were evaluated at entry and
after 1 (T1), 2 (T2), and 3(T3) months.
 Constipated patients were treated with osmotic laxatives for 3 months.
 Dyspeptic children without constipation represented the comparison group.
Gabriella Bocia et al,Clin Gastroenterol Hepatol. 2008 May;6(5):556-60.
TGEt: Total gastric emptying time
FC: Functional constipation
FD: Functional dyspepsia

24. Colo-Gastric Break
 Results:
1. FC was present in 28 of 42 (66.6%) patients.
2. Constipated dyspeptic children had significantly more prolonged total gastric emptying
time (TGEt) than subjects without constipation
3. Patients on osmotic laxatives had a significant decrease in TGEt at 3 months (P < .001).
4. The median dyspeptic symptomatic score as well as the number and consistency of
evacuations per week significantly improved at T1 in comparison with T0 and even more
at T2 and T3 (P < .001, for each).
 Conclusions: FC was associated with delayed gastric emptying. Normalization of bowel
habit may improve gastric emptying as well as dyspeptic symptoms.
Gabriella Bocia et al,Clin Gastroenterol Hepatol. 2008 May;6(5):556-60.
TGEt: Total gastric emptying time
FC: Functional constipation
FD: Functional dyspepsia

25. Diagnostic Approach

26. History and Physical Exam
 Symptoms and signs associated with GER are non-specific
 Exclude other worrisome disorders that present with vomiting
 Recognize complications of GERD
 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
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):548–557

27. 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
 Timing of smpx
 Refluxate quality
Pattern of vomiting
 Frequency/amount
 Pain
 Forceful or not
 Blood or bile
 Associated fever, lethargy,
diarrhea

28. 1. Bilious vomiting
2. Hematemesis, hematochezia
3. Consistently forceful vomiting
4. Onset of vomiting after six months of life
5. Constipation and/or Diarrhea
6. Abdominal tenderness, distension
7. Poor weight gain or weight loss
Red Flags

29. The challenging clinical overlap
1. Functional gastrointestinal disorders (FGID)
2. Gastrointestinal reflux disease (GERD)
3. Cow’s milk allergy (CMA)
4. Eosinophilic esophagitis (EoE)
PPI: proton pump inhibitor
AAF: amino acid-based formula
CM: cow’s milk
GI: gastrointestinal tract
eHF: extensively hydrolyzed formula
Salvatore S, Agosti M, Baldassarre ME, et al. Cow's milk allergy or gastroesophageal reflux disease- Can
we solve the dilemma in infants? Nutrients 2021; 13:297.

30. The challenging clinical overlap
1. Functional gastrointestinal disorders (FGID)
2. Gastrointestinal reflux disease (GERD)
3. Cow’s milk allergy (CMA)
4. Eosinophilic esophagitis (EoE)
PPI: proton pump inhibitor
AAF: amino acid-based formula
CM: cow’s milk
GI: gastrointestinal tract
eHF: extensively hydrolyzed formula
Salvatore S, Agosti M, Baldassarre ME, et al. Cow's milk allergy or gastroesophageal reflux disease- Can
we solve the dilemma in infants? Nutrients 2021; 13:297.

31. Upper GI Radiography
Advantage
Useful for detecting anatomic
abnormalities
Limitation
Cannot discriminate between
physiologic and non-physiologic
GER episodes
Pyloric stenosis
Malrotation
Reflux

32. Upper GI Radiography
Advantage
Useful for detecting anatomic
abnormalities
Limitation
Cannot discriminate between
physiologic and non-physiologic
GER episodes
Pyloric stenosis
Malrotation
Reflux
Not
recommended

33. 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
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999;45:172-80.

34. 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
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999;45:172-80.
Not
recommended

35. Esophageal pH probe
Assessment of three methods of pH probe positioning in preterm infants. Emmerson AJ, Chant T, May J, Vales P ;J Pediatr Gastroenterol Nutr. 2002;35(1):69.
• Advantages
• Detects episodes of reflux
• Determines temporal association between acid GER and symptoms
• Limitations
• Cannot detect nonacidic reflux
• Not useful in detecting association between GER and apnea unless
combined with other techniques
• The wide spectrum of size of infants makes placement of the
catheter challenging, as misplacement may result in under- or
overestimation of acid reflux
• Placement is confirmed radiographically.

36. Esophageal pH probe
Assessment of three methods of pH probe positioning in preterm infants. Emmerson AJ, Chant T, May J, Vales P ;J Pediatr Gastroenterol Nutr. 2002;35(1):69.
• Advantages
• Detects episodes of reflux
• Determines temporal association between acid GER and symptoms
• Limitations
• Cannot detect nonacidic reflux
• Not useful in detecting association between GER and apnea unless
combined with other techniques
• The wide spectrum of size of infants makes placement of the
catheter challenging, as misplacement may result in under- or
overestimation of acid reflux
• Placement is confirmed radiographically.
Not
recommended

37. Multiple Intraluminal Impedance
Advantages
• Detects nonacidic GER episodes
• Detects brief (< 15 s) acidic GER episodes
• Useful for studying respiratory symptoms and GER in infants
Limitations
• Normal values in pediatric age groups not yet defined
• Analysis of tracings time-consuming
• Portable device unavailable for outpatient studies
Wenzl TG. Investigating esophageal reflux with the intraluminal impedance technique. J Pediatr Gastroenterol Nutr 2002;34:261-8.

38. Pediatric
Catheter
Infant
Catheter
pH Sensors
Impedance
Sensors

39. Characterization of GER events during pH-impedance
A. Liquid acid characterized by retrograde drop in
impedance and pH drop below 4. Note this is not full-
column GER (does not reach Z1). Bolus clearance time
(BCT) determines bolus contact and clearance efficiency.
B. Gas nonacid characterized by rapid rise in impedance
reaching the most proximal impedance channel (Z1) and
pH > 4. Crying is associated with this GER event
C. Mixed acid characterized by liquid and gas components
with pH < 4. Acid clearance time (ACT) measures
esophageal acid contact time. As numerous iterations are
possible, it is important to discern the true cause of
symptoms for effective diagnosis and therapies.
Sudarshan R. Jadcherla Clin Perinatol 47 (2020) 243–263

40. Characterization of GER events during pH-impedance
A. Liquid acid characterized by retrograde drop in
impedance and pH drop below 4. Note this is not full-
column GER (does not reach Z1). Bolus clearance time
(BCT) determines bolus contact and clearance efficiency.
B. Gas nonacid characterized by rapid rise in impedance
reaching the most proximal impedance channel (Z1) and
pH > 4. Crying is associated with this GER event
C. Mixed acid characterized by liquid and gas components
with pH < 4. Acid clearance time (ACT) measures
esophageal acid contact time. As numerous iterations are
possible, it is important to discern the true cause of
symptoms for effective diagnosis and therapies.
Sudarshan R. Jadcherla Clin Perinatol 47 (2020) 243–263
Useful in severe
GERD
but not available

41. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines. JPGN 2018;66: 516–554
Other diagnostic interventions for GERD
Salivary pepsin • Not to be used for the diagnosis of GERD in infants and children
Manometry • To consider only when a motility disorder is suspected.
Scintigraphy • Not to be used for the diagnosis of GERD in infants and children

42. Testing for Reflux Disorders
 No one test can be used to diagnose reflux
 Reflux tests are useful
 To document the presence of GER(D)
 To detect complications
 To establish a causal relationship between GER and symptoms
 To evaluate therapy
 To exclude other conditions
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):548–557

43. Non-Pharmacologic treatment

44. AR Formulas
 Pre-thickened infant milks, so-called “anti-regurgitation‘ (AR) milks, have
been proposed for several years.
 These AR formulations already contain a thickener, selected from rice,
starch and carob gum, at the origin of the viscosity of the reconstituted
milk and thus having an anti-regurgitation effect.
 However, these milks have drawbacks: they very often have secondary
effects like constipation or diarrhea

45. Thickeners
 The preparations based on carob flour are known to cause abdominal pain,
colic and diarrhea Subsequent to the fermentation of carob in the colon
(Cane et al., Arch Dis Child 1985, 60: 71-75).
 Carob induces frequent, liquid and gelatinous stools. Although rare, serious
complications such as acute intestinal obstruction or necrotizing
enterocolitis have been reported in premature and newly born infants
(Vandenplas et al., “The Diagnosis and management of gastro-esophageal
reflux in infants. Early Hum Dev 2005, 81: 1011-24).

46. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines. JPGN 2018;66: 516–554
 Rice readily absorbs arsenic from the environment, about 10 times more
than other grains.
 Safety concerns were raised because of elevated levels of inorganic arsenic
in all forms of rice including infant cereals.
Arsenic exposure
Neurotoxicity
Long-term cancer
Rice Based Thickeners

47. At a pH between 6 and 3.5, viscosity is comprised
between 150 and 1,600 mPas*
*Mpas: Milli Pascals per second
Cold-soluble carob
The so-called “cold-soluble' carob is distinguished
from native carob, notably in that it has a lower
average molecular weight of carob than that of
native carob.
This particular weight average molecular weight may
for example be obtained by breaking the glycoside
bonds with the purpose of producing shorter chains.
ANT-REGURGITATION COMPOSITION MANTAINING GUT MOTILITY International Patent
Application No. PCT/EP2014/059312

48. • Purpose: The aim of the study was to evaluate the efficacy of a new anti-regurgitation (AR)
formula (Novalac), thickened with an innovative complex including Carob and fibers, on the
daily number of regurgitations and to assess its impact on stool consistency and frequency.
• Methods: Infants < 5 months, presenting at least 5 regurgitations/day were recruited. The
efficacy of the new formula on regurgitation (daily number and Vandenplas score), stool
frequency and consistency were assessed at day 14 and 90.
• Results: In all infants, regurgitations improved after 2 weeks. The daily number of
regurgitations decreased significantly. There was no significant change in stool consistency
at day 14. After 3 months, 97.5% of infants had formed or soft stools. Growth was
appropriate
• Conclusion: The new AR formula thickened with an innovative complex is very effective in
reducing the daily number of regurgitations without having a negative impact on stools
consistency.
Christophe Dupont, Yvan Vandenplas Pediatr Gastroenterol Hepatol Nutr 2016 June 19(2):104-109
Efficacy and Tolerance
of a New Anti-Regurgitation Formula

49. Effect of Thickening Milk Formula Feedings With
Rice Cereal
0.0
0.5
1.0
Adapted from Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr. 1987;110(2):181–186
Caloric Density
(cal/cc)
Vomiting
(episodes/90 min)
Sleep Time
(min asleep/90 min)
Crying Time
(min crying/90 min)
Unthickened Thickened
p=.015 p=.026 p=.042
0
1
2
3
4
5
0
10
20
30
40
50
0
5
10
15
20
25
n=20

50. Esophageal pH probe study
parameters, outcome:
Reflux index
(percentage of time pH < 4).
KwokTC, OjhaS, DorlingJ. Feed thickener for infants up to six months of age with gastro-oesophageal reflux. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD003211.

51. Number of reflux
episodes lasting > 5 minutes.

52. Positioning

53. Erect position
• No regurgitation
• Gravity- aided emptying of the stomach
• But babies are most of the time supine!

54. Right lateral decubitus
• Gravity- aided emptying of the stomach
• +++ regurgitation

55. Left lateral decubitus
• Minimal regurgitation
• Difficult emptying of the stomach

56. Left lateral
decubitus
with 30°
elevation
• No regurgitation
• Gravity- aided emptying of the stomach

57. 30°

58. 30°
30°

59. A B

60. A A B B

63. The Effect of Body Positioning on Gastroesophageal Reflux
in Premature Infants
 Study design Premature infants with frequent regurgitation and
postprandial desaturation (n = 22) underwent a 24-hour recording
of MII-pH. With the infants in 4 different positions: supine (S), prone
(P), on the right side (RS), and on the left side (LS).
 Results All infants were analyzed for 20 hours. The mean number of
recorded GER episodes was 109. The LS position showed the lowest
esophageal acid exposure (0.8%) in the early postprandial period,
and the P position showed the lowest esophageal acid exposure
(5.1%) in the late postprandial period.
 Conclusion Placing premature infants in the left lateral position in
the postprandial period is a simple intervention to limit GER.
GIACOMO FALDELLA, et al. J Pediatr 2007;151:591-6
Acid
reflux
Non-Acid
reflux
Supine 17.6 1.3
Prone 4.4 0.3
Left side 7.5 0.7
Right side 21.4 1.2

64. Effect of Sleep Position on GER in Infants and Sudden
Infant Death Syndrome (SIDS) Mortality
Reflux Index1
(% time pH <4)
Supine 15.3 0.05* 2.3 1.0
Left side 7.7 0.05* 1.1 3.5†
Right side 12.0 0.05* 1.8 3.5†
Prone 6.7 4.4 1.0 13.9
*Mortality rate for all non-prone positions combined
†Combined odds ratio
1 Tobin JM, McCloud P, Cameron DJ. Posture and gastro-oesophageal reflux: a case for left lateral positioning. Arch Dis Child. 1997;76(3):254–358
2 Skadberg BT, Morild I, Markestad T. Abandoning prone sleeping: Effect on the risk of sudden infant death syndrome. J Pediatr. 1998;132(2):340–343
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):613–621
SIDS Mortality2
(per 1000 live births)
Reflux Index
Odds Ratio
SIDS Mortality
Odds Ratio3

65. Avoid tobacco smoke exposure
 Tobacco smoke is known to lower esophageal sphincter pressure and to
promote GER in adults.
 A study in infants found that those with biochemically confirmed perinatal
exposure to tobacco smoke had significantly more frequent and more
proximally migrating reflux events, as measured by esophageal impedance
testing, compared with unexposed infants.
Effects of Smoking Exposure in Infants on Gastroesophageal Reflux as a Function of the Sleep-Wakefulness State. Djeddi D, Stephan-Blanchard E, LékéA, Ammari M, Delanaud S, Lemaire-Hurtel
AS, Bach V, Telliez F J Pediatr. 2018;201:147. Epub 2018 Jul 2.

66. Avoid overfeeding
 Because simple reflux is promoted by gastric distention, providing smaller
feedings often reduces the frequency or quantity of reflux.
 For infants with suboptimal weight gain, it may be helpful to provide
smaller but more frequent feedings and/or to concentrate the formula.

67. Other modifications
 Avoid car seat position
 Avoid tight fitting diapers
 Extensively hydrolysate formulas are more digestible than non-hydrolyzed
proteins and allow an accelerated gastric emptying.
 Treat constipation (Colo-gastric break)

68. Efficacy of Conservative Therapy for Infant Gastroesophageal Reflux
 Objective: To determine the efficacy of non-pharmacologic conservative therapy for infant
gastroesophageal reflux disease (GERD).
 Study design: Consenting parents of the first 50 screened infants who met
inclusion/exclusion criteria including abnormal (>16/42) scores on the Infant
Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R; n = 40) were taught
conservative therapy measures: feeding modifications, positioning, and tobacco smoke
avoidance. We compared I-GERQ-R scores and symptom response details before and 2
weeks after.
 Results: The median initial and final scores were 23 (16-36) and 18 (7-34; P < .000001).
78% improved ; 59% improved at least the threshold of 5 points; 24% became normal.
Efficacy of conservative therapy as taught in the primary care setting for symptoms suggesting infant gastroesophageal reflux. Orenstein SR, McGowan JD J Pediatr. 2008;152(3):310.

69. Temporal association between reflux-like behaviors and
gastroesophageal reflux in preterm and term infants
 Signs commonly ascribed to GER in preterm infants include: feeding
intolerance or aversion, poor weight gain, frequent regurgitation, apnea,
cough, desaturation and bradycardia and behavioral signs.
 The temporal association of these perceived signs of GER with either acidic
or nonacidic reflux episodes as measured by MII and pH is not supported,
and the signs will usually improve with time without treatment.
Funderburk A, et al. J Pediatr Gastroenterol Nutr. 2016;62(4):556–561

70. Apnea & GERD
 A study of 119 premature infants with a mean gestational age of 28 weeks
used 12-hour cardiorespiratory monitoring to record 6255 acidic GER
episodes.
 Apnea ≥15 seconds was associated with only 1 percent of the GER
episodes. There was no difference in the rate of apnea ≥15 seconds before,
during, or after GER episodes.
 GER did not prolong apnea duration.
 Similar findings were shown in a subsequent study from the same tertiary
center, in which less than 3 percent of all cardiorespiratory events (defined
as apnea ≥10 seconds, bradycardia ≤80 bpm, and oxygen desaturation
≤85%) were preceded by GER.
Characterization of cardiorespiratory events following gastroesophageal reflux in preterm infants. Di Fiore J, Arko M, Herynk B, Martin R, Hibbs AM J Perinatol. 2010 Oct;30(10):683-7. Epub 2010 Mar 11.
Apnea is not prolonged by acid gastroesophageal reflux in preterm infants. Di Fiore JM, Arko M, Whitehouse M, Kimball A, Martin RJ Pediatrics. 2005;116(5):1059.

71. Medical management

72. Treating physiologic GER in infants
 Once the diagnosis of GER is established
 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 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):548–557

73. Mechanism of action of Histamine Receptor Antagonists
(H2RAs) and Proton Pump Inhibitors (PPIs).
Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov. 2003 Feb; 2(2): 132-9.

74. Mechanism of action of Histamine Receptor Antagonists
(H2RAs) and Proton Pump Inhibitors (PPIs).
Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov. 2003 Feb; 2(2): 132-9.

75. Medication Dose Age limit
PPI
Omeprazole 0.7-3.3 mg/Kg/d, max20mg/d > 2 years
Lansoprazole 0.7-3.3 mg/Kg/d > 1 year
Esomeprazole <20Kg: 10 mg/d
>20 Kg: 10-20 mg/d
> 1 year
Pantoprazole >15 Kg to <40 Kg: 20 mg/d For erosive esophagitis in children
>5yr
H2RA
Famotidine 1 mg/Kg/d divided in 2-3 doses; max 20mg/d > 1month
Ranitidine 5-10mg/Kg/d divided in 2-3 doses; max300mg/d > 1month
Cimetidine No pediatric indication
Antacids
Calcium carbonate > 2 year
Sucralfate No pediatric indication
Van Pinxteren B, Sigterman KE, Bonis P, et al Cochrane Database Syst Rev 2010;(11):CD002095.
Khan M, Santana J, Donnellan C, et al. Cochrane Database Syst Rev 2007;(2):CD003244.

76. Effect of H2RAs on Healing of Esophagitis
N = 26 children with esophagitis treated with nizatidine 10 mg/kg/d or placebo for 8 weeks
Nizatidine
Placebo
Esophagitis
Healing
15%
69%
“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):51–55

77. Effect of Omeprazole on Esophagitis
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):800–807
N = 65 children
with erosive
esophagitis
% of
Patients
100
80
60
40
20
0
Healed with
3.5 mg/kg/day
95%
72%
44%
Healed with
1.4 mg/kg/day
Healed with
0.7 mg/kg/day

78. Optimal Timing of PPI Dose
Single PPI dose:
Administer half-hour
before breakfast
If second PPI dose:
Administer half-hour
before evening meal

79. 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 adverse events
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):548–557

80. Pharmacologic
Agent Class
Adverse Effects/Safety Concerns
Histamine 2 Receptor Antagonists
(E.g., ranitidine, famotidine)
Increased risk of infection, allergic disease, necrotizing
enterocolitis (NEC), intraventricular hemorrhage (IVH),
death
Proton Pump Inhibitors
(E.g., omeprazole, lansoprazole,
esomeprazole)
Increased risk of infection, fracture, allergic disease,
cardiac arrhythmia
Erythromycin Increased risk of pyloric stenosis, cardiac arrhythmia
Metoclopramide Dystonic reactions (notably: tardive dyskinesia), abnormal
eye movements, irritability, drowsiness, apnea

81. Goals of Pharmacotherapy
1. Control symptoms
2. Promote healing
3. Prevent complications
4. Improve health-related quality of life
5. Avoid adverse effects of treatment

82. Surgical Treatment of Refractory GERD
 Fundoplication is an anti-reflux surgery that may benefit children with
confirmed GERD who have failed optimal medical therapy, who are
dependent on medical therapy over a long period, or who have life-
threatening complications of GERD.
 Side effects include: bloating syndrome, impaired gastric
accommodation, gastric hypersensitivity, rapid gastric emptying,
retching, or dysphagia
 Scoliosis and epilepsy in children with neurologic impairments, decrease
the success rate of anti-reflux therapy.
 In this group of children, fundoplication is associated with a 40% surgical
failure rate, 12% to 30% rate of recurrent reflux, 59% experiencing
postoperative complications, and a 1-3% mortality rate.
Hauer JM. JAMA Pediatr 2014;168(2):188.

83. Vomiting and regurgitation
Good feeding
Good weight gain
Happy spitter
No complications
No medical treatment
Vomiting and regurgitation
Poor feeding
Poor weight gain
Irritable and fussy
Complications
Medical/surgical treatment
GER GERD

84. History & PE
Red
Flags
Investigate or refer
Yes

85. History & PE
Red
Flags
Investigate or refer
Yes
1. Bilious vomiting
2. Hematemesis, hematochezia
3. Consistently forceful vomiting
4. Onset of vomiting after 6 months of life
5. Constipation and/or Diarrhea
6. Abdominal tenderness, distension
7. Poor weight gain or weight loss

86. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment

87. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
1. Thickened formula
2. Positioning (left side decubitus with 30
degrees elevation) after meals
3. Reduced feeding volumes
4. Avoid car seats position
5. Avoid Passive smoking
6. Avoid tight diapers
7. Reversed upright position for burping
8. Treat constipation
9. Reassure parents

88. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
Improved
Continue treatment
No
Consider eHF
If breastfed, maternal
avoidance diet
Yes

89. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
Improved
Continue treatment
No
Yes
Improved
Continue treatment
Yes
No Consider 2-4 weeks of acid
suppression trial
Consider eHF
If breastfed, maternal
avoidance diet

90. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
Improved
Continue treatment
No
Yes
Improved
Continue treatment
Yes
No Consider 2-4 weeks of acid
suppression trial
Improved Yes
No
Revisit differential
diagnosis, investigate or
refer
Consider eHF
If breastfed, maternal
avoidance diet

91. Take home message
1. GER is a physiologic process, LESR is a useful process
2. In most cases a history and physical examination, with attention to warning
signals, are sufficient to reliably diagnose GER/GERD
3. Upper GI, endoscopy, pH probe and Multi-channel intraluminal impedance
are used to confirm GERD’s complications, or to R/O other conditions
4. Non-pharmacological management is successful in most cases
5. Medical treatment is prescribed to treat esophagitis
6. More than 95% of All GER will disappear by 12 months of age