Chapter
Sleep and Gastroesophageal Reflux
R. Bradley Troxler and Susan M. Harding
INTRODUCTION
Gastroesophageal reflux disease (GERD) is common in chil-
dren of all ages and can impact sleep. In infants, it is the most
common GI problem presenting to the pediatrician’s office.1
Despite its high prevalence, minimal research is available
examining the impact of GERD on sleep in children.
Gastroesophageal reflux (GER) is the retrograde passage of
gastric contents into the esophagus and it is normally seen
post-prandially. Regurgitation is a symptom of GER and is
common in infants.2 The refluxate is acidic and contains
digestive enzymes that can injure the mucosal lining of the
esophagus and upper airway. Intrinsic protective mechanisms
exist to prevent or minimize this damage. Reflux becomes
pathologic GERD when GER episodes are more frequent
and produce symptoms including heartburn, esophagitis,
failure to thrive, or respiratory symptoms such as cough and
wheeze.2
We will discuss esophageal physiology during wakefulness
and sleep, along with the epidemiology and clinical manifes-
tations of GERD, and its impact on sleep in pediatric popula-
tions. The diagnosis and treatment of GERD in pediatric
populations and future directions in sleep-related GERD
research will be discussed.
ESOPHAGEAL PHYSIOLOGY
The esophagus develops initially during the fourth week of
gestation as a small outgrowth of the endoderm and later
includes all three germ layers: the endoderm, mesoderm, and
ectoderm. These layers give rise, respectively, to the epithelial
lining; muscular layers, angioblast, and mesenchyme; and the
neural components.3
The esophagus slowly increases its length so that at 20
weeks of gestation, esophageal length approximates 11 cm.4
Esophageal length doubles during the first year of life.3 Ulti-
mately, the esophageal body in adults has a length of 18–22 cm,
with the lower esophageal sphincter (LES) representing the
distal 2–4 cm of the esophagus.5 The LES grows from a few
millimeters in newborns and reaches its adult length during
adolescence. In older children, the proximal 1.5–2 cm of the
LES is encircled by the crural diaphragm and sits in the tho-
racic cavity, and the lower 2 cm resides in the abdominal
cavity.5
The esophagus consists of three functionally distinct zones,
including the upper esophageal sphincter (UES), the esopha-
geal body, and the lower esophageal sphincter (LES).3
The UES is an intraluminal high-pressure zone located
between the pharynx and the cervical esophagus. The anterior
wall includes the posterior surface of the cricoid cartilage, the
arytenoid cartilage, and the interarytenoid muscles. The pos-
terior wall includes the cricopharyngeus and thyropharyngeus
muscles. The UES prevents refluxate from getting into the
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11  
upper airway, and it prevents air from entering the esophagus
during inspiration. The UES opens during belching, rumina-
tion, deglutition, regurgitation, and vomiting.3
The esophageal body begins at the edge of the cricopha-
ryngeal muscle and, in adults, is comprised of striated skeletal
muscle for the first 4–5 cm, followed by a transitional zone
that contains both skeletal muscle and smooth muscle cells.
The distal 10–14 cm comprises smooth muscle cells.3
The LES is a high-pressure zone controlling the flow of
materials between the esophagus and the stomach. The LES
comprises an intrinsic muscular layer (intrinsic LES) and the
extrinsic LES, which is the crural diaphragm.5 These two
components of the LES are superimposed and linked together
by the phrenoesophageal ligament. Both the intrinsic and
extrinsic components of the LES contribute to LES compe-
tence. The LES is tonically contracted at rest and relaxes with
esophageal distention and deglutination. The crural dia-
phragm portion of the LES creates spike-like increases in
LES pressure during inspiration and relaxes with esophageal
distention and vomiting.5
The esophagus accomplishes its role as a conduit to move
food from the mouth to the stomach through peristalsis. The
esophagus exhibits three different forms of peristalsis: primary
peristalsis, secondary peristalsis, and deglutitive inhibition.6
Primary peristalsis is a reflex esophageal contraction that is
initiated by swallowing and a contraction wave that moves
from the pharynx to the stomach. This propulsive force is
caused by the sequential contraction of the esophageal muscle
layers. In children, the typical amplitude of the contraction
ranges between 40 and 89 mmHg, has a duration of 2.5–5
seconds, and a propagation velocity of 3.0 cm/second.7,8
Secondary peristalsis occurs with esophageal luminal dis-
tention and is not associated with a swallow. It helps remove
refluxate that was not cleared with primary peristalsis.6
Deglutitive inhibition results when a second swallow is
initiated while a prior peristalsis is still occurring. This results
in complete inhibition of the peristaltic contraction caused by
the first swallow. With successive swallows, the esophagus
remains in stasis until a final swallow produces a large ‘clearing
wave’ that sweeps the esophagus of its contents.6
The LES is constantly adapting to the changing pressure
gradients between the stomach and the esophagus in order to
maintain competency. During inspiration, the pressure gradi-
ent between the stomach and esophagus is 4–6 mmHg and is
countered by an LES pressure between 10 and 35 mmHg.
During the migrating motor complex of esophageal contrac-
tions, the LES vigorously contracts to prevent reflux of
stomach contents into the esophagus. During inspiration,
there is an increasingly negative intra-esophageal pressure,
while abdominal muscle contractions augment gastric pres-
sure. Both of these situations increase the pressure gradient,
predisposing to GER events. However, the contraction of the
crural diaphragm during abdominal muscle contraction, vom-
iting, or straining helps to prevent reflux.5 In addition to
83
84    Principles and Practice of Pediatric Sleep Medicine
Table 11.1  Factors that Influence Lower Esophageal (LES) Pressure and Transient Lower Esophageal Sphincter
Relaxation (TLESR) Frequency.9
INCREASES LES
PRESSURE
Food(s) Protein
Hormone(s) Gastrin, motilin, substance P
Neural agent(s) α-Adrenergic agonists,
β-adrenergic antagonists,
cholinergic agonists
Medication(s) Metoclopramide,
domperidone,
prostaglandin F2α,
cisapride
L-NAME, N(G)-nitro-L-arginine methyl ester.
Reprinted with permission from Wiley-Blackwell, publisher: From Kahrilas P, Pandolfino J. Esophageal Motor Function. In: Yamada, T, editor. Textbook of Gastroenterology. Hoboken, NJ:
Wiley-Blackwell; 2009. p. 187–206.9
abdominal and intrathoracic pressures, the LES pressure is
influenced by many other factors, as listed in Table 11.1.9
During swallowing, the LES relaxes within 1–2 seconds of
the primary peristaltic contraction and this relaxation lasts
approximately 5–10 seconds. When the bolus arrives at the
LES, the LES pressure declines to gastric pressure, and the
sphincter remains closed. Then, the intrabolus pressure forces
the LES to open and the bolus enters the stomach. After 5–7
seconds, the LES rebounds to its original pressure and the
LES undergoes an after-contraction, which ends the peristal-
tic contraction wave.6
Gas is vented from the stomach by belching, where there
is a transient relaxation of the LES (TLESR). TLESRs are
abrupt declines in the LES pressure to gastric pressure that
are not related to primary peristalsis, secondary peristalsis, or
swallowing. There is also inhibition of the crural diaphragm
with TLESRs.10 TLESRs have a typical duration of 10–45
seconds. TLESRs occur up to six times per hour in normal
adults and are more frequent immediately post-prandially.
They occur during arousals but not during stable sleep.11
TLESRs can be triggered by gastric distention or vagal
stimulation that occurs with endotracheal intubation. Gamma-
amino-butyric acid (GABA) serves as an inhibitor of
TLESRs.5 Table 11.1 also reviews factors influencing
TLESRs.9
LES pressures in children range between 10 and 40 mmHg.
LES pressures that are 5 mmHg above the intragastric pres-
sure are usually sufficient to prevent GER.5,12 LES motor
patterns in infants and children are similar to those observed
in adults.5
MECHANISMS OF GASTROESOPHAGEAL REFLUX
Gastroesophageal reflux occurs when intra-abdominal pres-
sure exceeds intrathoracic pressure and the LES barrier. GER
is prevented by normal LES function. The intra-abdominal
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DECREASES LES PRESSURE INCREASES TLESR DECREASES TLESR
FREQUENCY FREQUENCY
Fat, chocolate, ethanol, peppermint Fat
Secretin, cholecystokinin, glucagon, Cholecystokinin
gastric inhibitory polypeptide,
vasoactive intestinal polypeptide,
progesterone
α-Adrenergic antagonists, L-Arginine Baclofen, metabotropic
β-adrenergic agonists, cholinergic glutamate receptor
antagonists, serotonin antagonists, cannaboid
receptor agonists,
L-NAME, serotonin
Nitrates, calcium chanel blockers, Sumatriptan Atropine, morphine,
theophylline, morphine, loxiglumide
meperidinem, diazepam,
barbituates
portion of the esophagus is squeezed closed by abdominal
pressure. In addition, the acuity of the angle where the esopha-
gus enters the stomach (angle of His) serves as a component
of the barrier at the gastroesophageal junction. A compro­
mise in this region, as seen in hiatal hernia, predisposes to
GER.5
The majority (81% to 100%) of GER episodes in infants,
children, and adults are caused by TLESRs.13 Omari et al.
noted that 82% of GER episodes in premature infants and
91% of GER episodes in term infants occurred in association
with TLESRs.14,15 Kawahara et al. noted TLESRs in associa-
tion with 58% to 69% of GER episodes in children being
evaluated for GERD.13
Protective mechanisms limit damage to the esophagus and
airway. Immediately after the refluxate enters the lower
esophagus, the UES contracts to prevent entry into the
pharynx. Secondary peristalsis also occurs, which helps clear
the refluxate. Saliva, which contains bicarbonate, is then swal-
lowed, neutralizing any adherent acidic remnants. Finally,
mucosal glands in the esophagus produce mucus and bicarbo-
nate, limiting esophageal mucosal damage.6
Airway protective mechanisms include the UES reflex,
whose function depends on refluxate volume. Small refluxate
volumes result in UES contraction, while large volumes stim-
ulate a vagally mediated relaxation of the UES, allowing the
refluxate to enter the pharynx. Simultaneously, this vagal
response evokes a centrally meditated apnea with laryngeal
closure to prevent aspiration. In older children, apnea is not
provoked, but a coughing spell occurs in this situation.16
ESOPHAGEAL PHYSIOLOGY DURING SLEEP
Sleep and the circadian rhythm alter upper gastroesophageal
function. Gastric acid secretion peaks between 8 p.m. and 1
a.m.11 Gastric myoelectric function is disrupted by sleep,
resulting in delayed gastric emptying.11 There is also delayed

esophageal acid clearance during sleep. These factors predis-
pose to GER during sleep.
The UES pressure decreases with sleep onset. Kahrilas
et al. reported that UES pressure decreases from 40 ± 17 mmHg
during wakefulness to 20 ± 17 mmHg during N1 sleep, and
was lowest (8 ± 3 mmHg) during N3 sleep.17 The UES con-
tractile reflex is also altered during sleep. The UES contractile
reflex is triggered by smaller volumes of refluxate during REM
sleep, and does not occur during N3 sleep.18 The UES reflex
is preempted by coughing and/or arousal. Basal LES pressure
does not change during sleep. The frequency of TLESRs
declines during sleep time. Almost all TLESRs occur during
wakefulness or during brief arousals from sleep.18
In addition, swallowing frequency decreases by 50% to 80%
during sleep time compared to wakefulness.11 Similar to
TLESRs, swallowing occurs during arousals and is almost
nonexistent during stable sleep.19 Salivary secretion is not
detectable during stable sleep.11 Esophageal acid clearance is
also delayed during sleep. Orr et al. observed that 15 mL of
0.1 N HCl was cleared from the distal esophagus within 25
minutes during sleep, whereas it took only 6 minutes to clear
when awake.19 Sleep prolongs the latency to the first swallow
if esophageal acid is present. Finally, during sleep, 40% of the
refluxate reaches the proximal esophagus near the UES com-
pared to <1% during wakefulness.20 This, in addition to the
lower UES pressure during sleep, might predispose to micro-
aspiration of refluxate into the pharynx.
Despite the lack of some GERD-protective mechanisms
during sleep, individual GER events are much less frequent
during sleep than during wake. However, if GER occurs, the
events are of a longer duration, and are more likely to result
in esophagitis and Barrett’s esophagus.11
GASTROESOPHAGEAL REFLUX DISEASE (GERD)
Gastroesophageal reflux disease is a common pediatric illness
and has protean manifestations.21 GERD can present with
recurrent vomiting (regurgitation), poor weight gain, heart-
burn, chest pain, esophagitis, vomiting, Sandifer syndrome,
hematemesis, anemia, Barrett’s esophagus, esophageal adeno-
carcinoma, asthma exacerbation, chronic cough, acute life-
threatening events (ALTEs), recurrent pneumonia, sleep
apnea, and dental erosions.2,22 A prospective Italian study
documents that 12% of infants had regurgitation and 1% of
children met criteria for GERD.23 Among US adolescents,
aged 10 to 17 years, 5.2% reported heartburn and 8.2%
reported acid regurgitation during the previous week.24 GERD
is also more frequent during early childhood when large fluid
boluses are used for feeding.2
Adolescents and older children experience similar clinical
presentations as adults with GERD. Typical complaints
include heartburn, dyspepsia, and regurgitation. Gupta et al.
described the presenting symptoms of GERD in pediatric
patients.22 The most common symptoms included abdominal
pain (70%), regurgitation (69%), and cough (69%). In patients
between 1 and 36 months of age, symptoms of GERD
included regurgitation (98%), irritability (41%), feeding prob-
lems (10%), failure to thrive (7%) and respiratory problems
(18.6%).22 Toddlers and younger children (less than 6 years)
more likely reported cough, anorexia/food refusal, and vomit-
ing.22 In a Finnish study examining children with GERD
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Sleep and Gastroesophageal Reflux    85
(mean age 6.7 years), the presenting symptoms included
abdominal pain (63%), heartburn (34%), regurgitation (22%),
vomiting (16%), retrosternal pain (18%), and respiratory
symptoms (29%).25 Adolescents with GERD reported esopha-
geal symptoms (22.4%), regurgitation (21.4%), dysphagia
(14.5%), shortness of breath (24.4%), wheezing (1.7%), and
cough (17.9%).26
Extra-esophageal manifestations of GERD are also present
in children.27 El-Serag et al. compared 1980 children with
GERD (mean age 9.2 years) to a control group without
GERD, examining the association of GERD with upper and
lower respiratory disorders.27 They demonstrated that chil-
dren with GERD were more likely to have sinusitis (4.2% vs.
1.4%), laryngitis (0.7% vs. 0.2%), asthma (13.2% vs. 6.8%),
pneumonia (6.3% vs. 2.3%), and bronchiectasis (1.0% vs.
0.1%). After adjusting for age, gender, and ethnicity, GERD
remained associated with all of these conditions.27
SLEEP-RELATED GERD
Sleep-related GERD
Sleep-related GERD may present with nocturnal awakenings
with a sour taste in the mouth, burning discomfort in the
chest, or nocturnal arousals. These arousals may disrupt sleep,
leading to daytime sleepiness or insomnia.11
Few studies examine the epidemiology, severity, or range of
clinical impact that is associated with sleep-related GERD in
children. In children, GERD during sleep is associated with
increased sleep arousals, sleep fragmentation, and other sleep
disturbances.21 Kahn et al. evaluated 50 infants with occa-
sional regurgitation and noted that 41 of the 50 infants had
proximal GER events, with 97 episodes occurring during
sleep time. Reflux during sleep time occurred commonly
during wakefulness (41%), or was associated with arousals.28
This study did not determine whether arousals led to the
reflux or if the reflux led to the arousal from sleep.28 Ghaem
et al. examined 72 children with GERD and 3102 controls,
with a questionnaire, finding that children with GERD (aged
3 to 12 months) were less likely to have ever slept through
the night by 12 months of age (20%) compared to the con-
trols.29 Fifty percent of GERD children awakened and
required parental attention more than three times nightly.
These findings continued in children with GERD aged 12–24
months and 24–36 months, with only 8% and 4% sleeping
through the night compared to 45% and 56% of controls.
Sixty percent of 12–24-month-olds and 50% of 24–36-month-
olds with GERD woke up more than three times nightly.
Children with GERD had more awakenings and were less
likely to sleep through the night.29
A prospective randomized, controlled study in adolescents
with GERD (ages 12 to 17 years) assessed the impact of 8
weeks of a proton pump inhibitor (esomeprazole) on quality
of life (QOL) using the Quality of Life in Reflux and Dys-
pepsia Questionnaire.30 After 8 weeks of PPI, there was an
improvement in the sleep dysfunction domains of the QOL
instrument in the PPI-treated group. These findings suggest
that GERD treatment may improve sleep in adolescents.30
Obstructive Sleep Apnea
Both GERD and obstructive sleep apnea (OSA) share con-
founding variables and risk factors, including obesity.11 The
86    Principles and Practice of Pediatric Sleep Medicine
relationship between sleep-related GERD and OSA was
assessed by Wasilewska and Kaczmarski with simultaneous
esophageal pH monitoring and polysomnography in 24 chil-
dren (ages 2 to 36 months) with sleep disturbances indicative
of GERD and possible sleep-disordered breathing.31 Children
with sleep-related GERD had a higher REM apnea–hypopnea
index (AHI) (23.4 events per hour) compared to children
without sleep-related GERD (AHI: 4.9 events per hour).
These observations suggest that GERD is associated with
more severe OSA during early childhood.31
The impact of sleep-related GERD among children aged
6 to 12 years was assessed by Noronha et al.32 Eighteen chil-
dren with OSAS and tonsilar hypertrophy were evaluated
with polysomnography with concomitant esophageal pH
monitoring and the OSA-18 Questionnaire. The AHI was
greater than 1.0 for all patients and 41.1% of patients had
esophageal pH values below 4 for more than 10% of sleep
time. The esophageal pH values correlated with emotional
distress and daytime problems on the OSA-18. A temporal
correlation between individual GER events and apnea–
hypopnea events was not apparent.32
A second study, by Wasilewska et al., assessed 57 children
with OSA, 19 of whom had residual OSA after prior ade-
notonsillectomy, using pH monitoring and polysomnography
to determine the risks for residual OSA. Compared to newly
diagnosed patients, children with residual OSA had more
severe OSA (AHI 20.61 versus 8.57, p = 0.03), lower mean
intraluminal esophageal pH (5.36 versus 5.86, p = 0.007),
higher reflux index (9.67% versus 4.35%, p = 0.006), and a
lower minimum esophageal pH during sleep (1.53 versus
2.15, p = 0.04). The minimal value of esophageal pH was
noted to correlate with respiratory indices on the polysom-
nography, a particularly interesting finding as this value is
often not reported and is not required to diagnose GER.33
Asthma, Laryngospasm, Hoarseness
Sleep-related GERD can trigger asthma and/or laryngospasm
during sleep. There is an association between GERD and
asthma but the direction of causality is not known, and may
be bi-directional. Proposed mechanisms of interaction include
microaspiration and a vagally mediated reflex bronchocon-
striction.11 A systematic review assessed the association of
pediatric asthma and GERD.34 Twenty articles met the a
priori inclusion criteria. Estimates of GERD prevalence in
children with asthma ranged from 19.3% to 80.0%. Five
studies compared 1314 asthma patients to 2434 controls.
Based on these data, the average GERD prevalence in pedi-
atric asthmatics was 22.0% compared to 4.8% in the controls.
The pooled odds ratio (OR) for having GERD in the asthma
group was 5.6 (95% confidence interval (CI) of 4.3–6.9).34
A prospective cohort of 1037 New Zealanders was exam-
ined for GER symptoms and airway responsiveness at ages
11 years and 26 years.35 GER symptoms that were at least
‘moderately bothersome’ were associated with asthma (OR
3.2, 95% CI 1.7–7.2), wheeze (OR 4.3, 95% CI 2.1–8.7), and
nocturnal cough (OR 4.3, 95% CI 2.1–8.7) independent of
body mass index. Women with GER symptoms were more
likely to have airflow obstruction. The direction of causality
is not clear since patients with airway hyper-responsiveness at
age 11 were more likely to report GER symptoms at age 26.35
The effect of GERD therapy on asthma outcomes shows
conflicting data in children.36,37 Khoshoo and Haydel described
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44 pediatric asthmatics with GERD who were treated with
omeprazole and metoclopramide, ranitidine, or fundoplica-
tion.36 Patients treated with omeprazole/metoclopramide or
fundoplication had significantly fewer asthma exacerbations
(0.33 and 0.66) over 6 months compared to patients on rani-
tidine (2.2).36 Antithetically, Størdal et al. performed a rand-
omized trial utilizing omeprazole or placebo for 12 weeks in
38 children with asthma and GERD (mean age 10.8 years).37
After 12 weeks, esophageal acid contact times decreased in
the omeprazole group, but there were no differences in the
asthma symptom score, lung function, or number of rescue
beta-agonist uses between groups.37 More information regard-
ing the association between GERD and asthma in children is
needed.
Sleep-related GERD may be associated with laryngeal
findings as the acidic refluxate migrates into the larynx. Block
and Brodsky reported a retrospective review of 337 children
(mean age 7.2 years) with hoarseness.38 Eighty-eight percent
had laryngeal reflux and 30% had cough. Among the patients
with cough and hoarseness (99 patients), 66% were found to
have GERD. Also, 50% of patients who were treated for
GERD utilizing a variety of behavioral and medical therapies
had improvement or resolution of their hoarseness at 3
months, and 68% had resolution by 4.5 months.37
Acute Life-Threatening Events (ALTEs)
Acute life-threatening events are episodes occurring in infants
that are frightening to the observer. Findings include apnea,
color change, sudden limpness, and/ or choking and gagging.
Many disorders are implicated in ALTEs including seizures,
infections, arrhythmias, and GERD.39 In a systematic review
of 2912 publications including 643 infants with ALTEs,
GERD was diagnosed in 227 (35%) infants, seizures in 83
(13%), lower respiratory tract infection in 58 (9%), and in 169
(26%) infants, no diagnosis was made.39 Despite the high
prevalence of GERD, there are few data to support the role
of GERD in ALTEs.39 Molloy et al. noted that there is rarely
a temporal relationship between GERD events and apnea in
premature infants.40 Finally, Semeniuk et al. evaluated 264
patients aged 4 to 102 months with GERD and found 8
patients with symptoms of ALTEs. They describe GERD as
a causative factor of ALTEs in only 4.8% of their cohort.41
GERD DIAGNOSIS
For patients presenting with stereotypical features of sleep-
related GERD, a thorough history and physical examination
are sufficient to make the diagnosis.2 Questions directed at
the frequency of nighttime awakenings, substernal chest pain,
indigestion, heartburn, nocturnal cough or choking, or chronic
vomiting should lead to the diagnosis in most older children
or adolescents.2 Other patients may have only extra-esophageal
symptoms and present with excessive daytime sleepiness
without an obvious historical cause, or waking up with laryn-
gospasm, wheeze, or cough. Additionally, patients may note
refluxate on their pillows.11 However, historical findings do
not discriminate patients with esophagitis.2
Esophageal pH monitoring identifies acid GER episodes,
and can be used in patients without typical GER symptoms.
Esophageal pH monitoring is performed by placing a
pH probe at a level corresponding to 87% of the nares–LES

distance, based on published regression equations, by fluoros-
copy or through manometric measurement of the LES loca-
tion. Interpretation of the results involves calculating the
reflux index, which is the percentage of the recording time
when esophageal pH falls below 4.0. The mean upper limit
of normal is 12% in children up to 11 months, and 6% in
children and adults.2 The test is performed over 24 hours to
increase the test’s sensitivity and specificity, which approxi-
mates 90%.42 The reproducibility of the test ranges between
69–85%.42 Additionally, esophageal pH monitoring can be
integrated with polysomnography to allow unified visualiza-
tion of the patient’s sleep and esophageal pH.11
Esophageal electrical impedance monitoring allows for the
detection of liquid and gas in the esophagus, regardless of
pH.11 It is commonly combined with pH monitoring. Since
a large number of GER events, especially post-prandial GER,
are non-acidic, this technology allows for detection of more
GER episodes. This technology is expensive, however, and
requires a high degree of skill to interpret and has not been
widely available to date. In addition, the clinical importance
of non-acidic GER on sleep is unclear.11
GERD TREATMENT
Management options for GERD include non-pharmacologic
behavioral interventions, medical therapy, and surgical therapy.
Appropriate treatment requires a thorough knowledge of
chrono-therapeutic principles in order to obtain optimal
control of GERD.2 Figure 11-1 reviews behavioral and
medical therapy of GERD in children.2
Behavioral Interventions
Behavioral interventions during early childhood include
formula thickening, positioning changes, nasogastric/
nasojejeunal feeds, and elevation of the head of the bed by 30
degrees during sleep.2 Milk thickening agents decrease regur-
gitation that aids in weight gain. However, these agents did
not improve esophageal acid contact times, number of reflux
episodes lasting greater than 5 minutes, or number of reflux
episodes per hour.43 Positioning may also prevent GER epi-
sodes in infants. Tobin et al. studied 24 infants with GERD
less than 5 months old with esophageal pH monitoring while
being placed in different positions.44 Esophageal acid contact
times were greatest in the supine position (15.3%) and lowest
in the prone position (6.7%). There are conflicting data
regarding the benefit of elevating the head of the bed by 30
degrees. The authors note that the left decubitis position
(esophageal acid contact time 7.7%) is a suitable alternative
to prone positioning for the postural management of infants
with symptomatic GERD.44 Note that this recommendation
is in contrast to the American Academy of Pediatrics recom-
mendation that infants should sleep in the supine position.45
Supine positioning confers the lowest risk of SIDS and is
the preferred sleeping position for infants. Prone positioning
should only be considered in unusual cases where the risk
of complications from GERD outweighs the potential of
SIDS.2
The efficacy of non-pharmacological therapy in infant
GERD was recently evaluated by Orenstein and McGowan.46
Caregivers of infants implemented a program utilizing
GER feeding modifications, positioning, and tobacco smoke
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Sleep and Gastroesophageal Reflux    87
avoidance. Outcomes included the Infant Gastroesophageal
Reflux Questionnaire-Revised. Among the 37 infants fol-
lowed, GER scores improved in 59%, and 24% of patients no
longer met diagnostic criteria for GERD after 2 weeks.46
Behavioral interventions during childhood and adolescence
include weight management, dietary changes, sleep positional
therapy, and smoking cessation.11 There are minimal data
examining behavioral therapy in children. Medications that
can decrease LES pressure or increase the likelihood of GERD
include theophylline, anticholinergics, prostaglandins, calcium
channel blockers, and alendronate.11 Avoidance of these med-
ications should be considered; however, there are no data in
children examining the impact of these medications on
GERD.
Pharmacological Therapy
Pharmacological treatment of GERD includes gastric acid
secretion inhibitors and prokinetic agents. Antacids have
major side effects and toxicities in children and are not recom-
mended.2 Furthermore, H2 receptor antagonists are associated
with side effects and are not recommended for long-term
treatment in children.2 Also, currently available prokinetic
agents should not be used in children.2 Proton pump inhibi-
tors are used and are well tolerated in children.
Histamine-2 Receptor Antagonists
Histamine-2 receptor antagonists (H2RAs) inhibit the
histamine-2 receptor of the gastric parietal cell and decrease
gastric acid secretion. H2RAs have a relatively quick onset of
action and are useful for episodic symptom relief. A systematic
evaluation of the side effects of H2RAs in children has not
been performed. Commonly used H2RAs include famotidine,
cimetidine, nizatidine, and ranitidine. Famotidine, the most
commonly studied H2RA, has been shown to cause agitation
and signs concerning for headaches in infants.47 Other side
effects include dizziness, constipation, anemia, and urticaria.
Cimetidine has been associated with gynecomastia, neutrope-
nia, thrombocytopenia, and reduces the hepatic metabolism
of medications such as theophylline.2 Tolerance to the H2RA
class of medications does develop in both children and adults.
Thus, H2RAs are not ideal for chronic therapy for GERD in
pediatric populations.
Proton Pump Inhibitors
Proton pump inhibitors (PPIs) inhibit the hydrogen–
potassium ATPase channels that are the final step in gastric
acid secretion. PPIs bind covalently with the cysteine residues
of the hydrogen–potassium ATPase pump. PPIs are more
effective at suppression of acidic secretions than the H2RAs.11
Commonly used PPIs include omeprazole, lansoprazole, pan-
toprazole, rabeprazole, and esomeprazole. There is some vari-
ation in the rates of activation and plasma half-life with the
different PPIs; however, average half-life approximates 1–2
hours. Due to covalent bonding to the ATPase pump, the
duration of action ranges from 15 hours for lansoprazole to
28 hours for omeprazole, and 46 hours for pantoprazole. PPIs
are slow to achieve steady-state inhibition and generally
require 3 days to achieve maximum impact. Children, ages 1
to 10 years, metabolize PPIs faster than adults and require a
higher per kilogram dose compared to adults.48 PPIs should
be tapered and not discontinued abruptly as this would result
in gastric acid hypersecretion.
88    Principles and Practice of Pediatric Sleep Medicine

Infants Children Adolescents

(Less than 12 months old) (1–12 years old) (12–18 years old)

Behavioral Hydrolyzed protein formula No evidence to support

interventions for 2–4 weeks dietary restriction in children or adolescents

Thickening formula decreases
number of regurgitation episodes
Prone positioning is best for GERD,
Medical but supine position recommended
Interventions due to risk of SIDS
Adult studies support limiting late night eating
Weight loss if obese
Avoid foods that decrease LES tone (peppermint,
caffeine, chocolate, alcohol, high-fat meals)

Gastric Anti-secretory Therapy (Histamine-2 Receptor Antagonists)

10–20 mg/kg/day PO div 1600 mg/day PO div

Cimetidine 20–40 mg/kg/day PO div Q6H
Q8–12 hours Q6-12 hours
<3 mos: 0.5 mg/kg/day PO 1–2 mg/kg/day div BID
Famotidine 20–40 mg PO BID
3–12 mos: 1 mg/kg/day PO div BID max 40 mg/day
150 mg PO BID, max 300
Nizatidine >6 mos: 5–10 mg/kg/day PO div BID 5–10 mg/kg/day PO div BID
mg per day
5–10 mg/kg/day PO div BID; 5–10 mg/kg/day PO div BID;
Ranitidine 150 mg po BID
max 300 mg/day max 300 mg/day

Gastric Anti-secretory Therapy (Proton-Pump Inhibitors)*

Esomeprazole Not approved 1–11 yr: 10 mg PO QD 20–40 mg PO QD

<30 kg: 15 mg PO QD
Lansoprazole Not approved 15–30 mg PO QD
>30 kg: 30 mg PO QD
10–20 kg: 10 mg PO QD or
Omeprazole Not approved 1 mg/kg/day PO div BID 20 mg PO QD
>20 kg: 20 mg PO QD
>5 yrs: 15–40 kg: 20 mg PO QD
Pantoprazole Not approved 20–40 mg PO QD
>40 kg: 40 mg PO QD

Rabeprazole Not approved Not approved 20–40 mg PO QD

Gastric Acid Buffers/Barriers (Antacids, Alginate, Sucralfate)

Not recommended in chronic therapy as safe and convenient alternatives exist (H2RAs and PPIs)

Prokinetic therapies (Cisapride, bethanachol, baclofen, metoclopramide)

Currently insufficient evidence to justify the use of these agents in the treatment of GERD

Figure 11-1  Summary of behavioral and medical therapies for pediatric GERD. *Preferred therapy. Adapted from 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 (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol
Nutr 2009;49(4):498–547.2

Minor side effects occur in 1–3% of patients on PPIs and
include headache, diarrhea, abdominal pain, nausea, and rash.
Major side effects are rare and include interstitial nephritis
with omeprazole, hepatitis with omeprazole or lansoprazole,
and visual disturbances with pantoprazole and omeprazole.49
There is a high frequency of nocturnal acid breakthrough
among children on PPIs. Pfefferkorn et al. studied 18 chil-
dren with esophagitis (mean age of 10.3 years) treated with
1.4 mg/kg of PPI divided twice daily and underwent esopha-
geal pH testing after 3 weeks of therapy.50 They demonstrated
that 89% of the patients had nocturnal acid breakthrough on
the PPI.50
Finally, PPIs are most effective if they are administered as
a single daily dose, 30 minutes before breakfast. This dosing
corresponds with the timing of activation of stomach proton-
potassium pumps after the overnight fast.11
Risks of Chronic Acid Suppression
Children taking H2RAs or PPIs long term are at an increased
risk of developing community-acquired pneumonia, acute

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gastroenteritis., and Clostridium difficile infection. These
risks are thought to be conferred due to the medications
limiting the gastric acid’s ability to kill possible pathogenic
microorganisms.51
Referral to a Pediatric Gastroenterologist
In general, medical therapy with a PPI should be continued
for 3 months. If GERD-related symptoms resolve, then the
PPI should be stopped with plans for patient follow-up for
evaluation of any recurrent symptoms. However, if the patient
continues to have persistent GERD symptoms after 3 months
of PPI therapy, then evaluation by a pediatric gastroenterolo-
gist should be considered. Other indications for a pediatric
gastroenterologist referral include ‘alarming’ symptoms such
as upper gastrointestinal bleeding, persistence of failure to
thrive, acute worsening of weight loss or having difficulty
swallowing or controlling secretions.2
Positive Airway Pressure
Continuous positive airway pressure (CPAP) is used for suc-
cessful OSA treatment in children.52 Despite this, there
are scant data examining the effect of CPAP on sleep-
related GERD in children. In adults, CPAP controls OSA
and decreases sleep-related GERD symptoms and esophageal
acid contact times.11 CPAP increases esophageal, LES, and
gastric pressures.53 The differential pressure between the
esophagus and stomach (the so-called barrier pressure)
increases with CPAP. Finally, CPAP causes a disproportionate
increase in LES pressure compared to esophageal and gastric
pressures. This increase may be due to reflex activation of
the LES, or by the transmission of the CPAP pressure to
the LES.53
Surgical Therapy
Surgical fundoplication involves wrapping a portion of the
stomach around the LES to strengthen or tighten the LES.
Published reports vary widely in the success of surgical inter-
ventions for GERD in children, with success rates ranging
from 40% to 95%. Complication rates from open and laparo-
scopic reflux surgery are similar.54 Complications of GERD
surgery include splenectomy (0.2%), esophageal laceration
(0.2%), infection, recurrent GERD (2.5–40%), small bowel
obstruction, gastroparesis, and dumping syndrome. Long-
term outcome studies of fundoplication show that 14% of
children have GERD recurrence after Nissen fundoplications,
and 20% have GERD recurrence in loose wrap procedures
(i.e., <360 degree wrap).2 Optimally, prior to considering sur-
gical therapy, the child should be evaluated carefully by a
pediatric gastroenterologist.
FUTURE DIRECTIONS
Minimal data exist evaluating sleep-related GERD in chil-
dren. There is also a need for well-designed randomized
trials evaluating the efficacy of GERD therapy in sleep-
related GERD in children. Data emerging from adults
cannot be extrapolated to children. Furthermore, pediatri­
cians need to be educated that GERD does occur during
sleep time and can adversely affect sleep and daytime func-
tioning as well as potentially contribute to other comorbid
disease states.
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Sleep and Gastroesophageal Reflux    89
CONCLUSION
During sleep, there is significant alteration in the physiology
of the gastroesophageal system that increases the likelihood
of GER. Sleep-related GERD is associated with GER symp-
toms and alters sleep architecture. Sleep-related GERD can
impact sleep, contribute to excessive daytime sleepiness,
impair quality of life, impact asthma severity, impact laryngi-
tis, and is associated with OSA. There is still much research
needed to assess the exact impact of sleep-related GERD on
pediatric health and disease. Hopefully, future research will
provide better methods of GERD identification, treatment,
and prevention.
Clinical Pearls
• Transient relaxations of the lower esophageal sphincter are
responsible for most gastroesophageal reflux (GER)
episodes that commonly occur during arousals from sleep.
• Weekly heartburn is reported in 5.2% and/or regurgitation
is reported in 8.2% of US adolescents.
• Sleep-related GER is associated with GER symptoms during
sleep, arousals, obstructive sleep apnea, asthma,
laryngospasm, hoarseness, and acute life-threatening
events.
• Diagnosis of sleep-related GER includes symptoms and
esophageal pH and impedance monitoring.
• Treatment includes behavioral interventions, pharmacologic
therapy (primarily proton pump inhibitors) and, in carefully
evaluated children, surgical fundoplication.
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