Behaviors
associated with onset of gastroesophageal reflux
episodes in infants
Prospective study
using split-screen video and pH
probe
Feranchak AP, Orenstein SR, Cohn JF.
Department of Pediatrics,
Children's Hospital of Pittsburgh
To identify behaviors associated with the
onset of gastroesophageal reflux episodes in
infants both systematically and prospectively,
each of 10 patients (aged 2 to 32 weeks) was
studied during 2 hours of intraluminal
esophageal pH probe monitoring, using a
split-screen audiovisual recording technique.
Videotape analysis of eight infants who had
scoreable reflux events revealed six discrete
behaviors closely associated temporally (P <
.001 to < .05) with the onset of reflux
events: "discomfort" (crying or frowning),
"emission" (of liquid or gas, i.e.,
regurgitation, drooling, or burping),
yawning,
stridor,
stretching,
and mouthing. Three behaviors (hiccuping,
sneezing, and thumb-sucking) were infrequent but
were significantly associated with onset of
reflux events in one or two patients each. A
tenth behavior, coughing or gagging, was
significantly associated with onset of reflux
events in two patients, but not in the rest,
despite relatively frequent occurrence.
Exploration of temporal relations between reflux
and each behavior suggested that discomfort,
emission, mouthing, and cough-gag may have
caused reflux episodes, and that all 10 of the
behaviors may have been caused by reflux
episodes. These findings and a "quiet period"
immediately preceding episodes in six of the
infants suggest interesting pathophysiologic
mechanisms in infants which require further
evaluation.
Introduction
During the past several decades, while
methods to identify nonregurgitant
gastroesophageal reflux, such as pH probe, have
come into wide use, investigators have noted
some behaviors to be associated with reflux
events in infants and older individuals. In many
cases, these associations were general rather
than temporal: patients with chronic cough,
intractable hiccups, and severe stridor had
abnormal quantities of reflux, and the behavior
in question improved concurrently with treatment
of their reflux. Additionally, there have been
reports linking individual instances of
esophageal acidification - either spontaneous or
induced - to behaviors including cough, hiccups
and stridor. The present study differs from both
of these types of previous reports by being a
systematic prospective approach to the question
of behaviors associated with reflux episodes in
unselected infants with reflux disease.
To record the behaviors and esophageal pH in
a reliable manner susceptible to review and
analysis, we utilized audiovideo recording. To
assure the synchronization of the behavioral
data and the reflux data, we used a split-screen
technique. In a small sample of infants, we
identified 10 discrete behaviors statistically
associated with onset of reflux events.
Discussion
The significant association of discrete
behaviors with onset of reflux episodes in
unselected subjects studied prospectively
supports the more anecdotal information
previously available for many of those
behaviors. The association of these behaviors
with onset of reflux is particularly striking
when one considers the low frequency of many of
the behaviors and the resultant low power to
demonstrate the association. Only three of the
behaviors (discomfort, cough-gag, and stretch)
occurred more than 20 times during the entire
study.
Three possible causal relationships may be
surmised between reflux episodes and
simultaneous discrete behaviors. The behavior
may cause the reflux, the behavior may result
from the reflux, or both may be caused by a
third event.
Behaviors may cause reflux by increasing the
abdominothoracic pressure gradient - i.e., by
increasing abdominal positive pressure (cough,
sneeze, crying) or by increasing thoracic
negative pressure (stridor, hiccups). They may
also cause reflux by inducing transient lower
esophageal sphincter relaxations, as occurs with
belching other factors which promote such
relaxations are as yet poorly defined, but might
include mouthing, thumb-sucking,
yawning, or
stretching,
as suggested by work demonstrating myIohyoid
activity at onset of 42% of such sphincter
relaxations.
Behaviors may result from reflux if they are
manifestations of airway soiling (cough,
sneeze), of esophagitis (discomfort), or of
reflex bronchospasm, laryngospasm, or diaphragm
activity (cough, stridor, hiccups).
Behaviors may also be caused by reflux if
they are used to clear refluxate from the
esophagus (mouthing, salivation/ drooling, and
possibly thumb-sucking,
stretching,
or yawning).
These possible relationships are discussed in
detail below.
Discomfort was associated with reflux
episodes in all six subjects who manifested any
associations between behaviors and reflux.
Extrapolating from the experience described by
adults, discomfort from heartburn is a likely
result of acid contacting an inflamed esophagus
in infants. Indeed, excessive crying,
irritability and/or sleep disturbance often
presenting as "colic" has been noted in 85% of a
series of infants with esophagitis. Heartburn is
the most likely explanation for the discomfort
manifested by our subjects in the 15-second
temporal segment immediately following the pH
drop. For occasions when the discomfort occurred
in the preceding temporal segment, the
behavioral manifestations of discomfort may have
produced the reflux event by increasing
abdominal pressure, although in an earlier
study, we found that crying per se did not seem
to increase reflux frequency.
Emission of liquid (regurgitation, drooling)
or gas (belching) was related to reflux episodes
in three subjects. Because the recording
technique did not definitely discriminate
between regurgitation of apple juice and
drooling of saliva, drooling and regurgitation
were not distinguished. Additionally, emission
of gas and liquid were scored together. Although
liquid regurgitation occurred simultaneously
with reflux, reflux was sometimes preceded by
belching or followed by drooling. The
association of belching and reflux has
previously been explored; transient relaxation
of the lower esophageal sphincter occurs with
both. Acid reflux might also induce drooling, as
stimulation of salivation is one part of the
normal mechanism for clearance of refluxed
material from the esophagus. The fact that only
a minority of the subjects regurgitated during
acid reflux underscores the protective roles
that peristalsis and upper esophageal sphincter
tone normally play in returning refluxed
material to the stomach.
Yawning has not been linked to reflux
previously but was significantly associated with
onset of reflux in three of our subjects. In
each instance,
yawning
followed reflux by a few seconds and was
accompanied by a rise in pH, suggesting that
yawning may
aid clearance of refluxate. The function of the
yawn has
received little attention. Previously suggested
functions have included prevention of
atelectasis, augmentation of venous return and
reduction of peripheral circulatory resistance
and amplification of the sense of smell. Further
study is needed to determine whether the
yawn
modifies gastroesophageal anatomy or pressure
relationships to assist clearance of esophageal
acid.
Stretching followed reflux in the one baby
in whom it was associated with reflux. Like
yawning,
which often accompanies it,
stretching
may aid refluxate clearance by modifying the
gastroesophageal junction. It may also be a
nonfunctional response to irritation due to
reflux.
Stridor was associated with reflux in two
subjects and followed the reflux in both cases.
Neither of these infants presented for reflux
evaluation because of stridor. In each case, the
episodes of stridor were rather subtle,
consisting of audible inspiration occurring
after reflux for only a few breaths. Stridor has
been associated with gastroesophageal reflux in
a few published case reports but the underlying
mechanism remains unclear. Our data conform to
the concept that reflux may cause stridor by
stimulating an inflamed mucosa to produce reflex
laryngospasm. The temporal sequence in our two
infants did not suggest the converse, that
stridor caused reflux (by augmenting the
gastroesophageal pressure gradient), although
this has also been proposed to occur.
Hiccups previously have been linked to
esophageal irritation, and possible mechanisms
have been proposed. Hiccups might induce reflux
through an effect on esophageal motility or by
augmenting the gastroesophageal pressure
gradient (inspiration against a closed glottis
increasing both the negative intrathoracic
pressure and the positive intragastric
pressure). Conversely, reflux might induce
hiccups; a single report documents the
production of hiccups by esophageal
acidification in a patient with peptic
esophagitis.2 Hiccups are particularly prominent
in infants; a group of premature infants
hiccuped during 2.5% of monitored time. Many
parents of infants we have evaluated for reflux
have described frequent postprandial hiccups.
The two infants in the present study who
displayed a significant association between
hiccups and spontaneous esophageal acidification
further support this association. Since reflux
preceded their hiccups, reflux most likely
caused their hiccups.
Coughing or gagging occurred after reflux in
both infants in whom it occurred with reflux,
suggesting the protective function of clearing
the larynx or more distal airway. This
protective function is also implicated in
reports of chronic cough ameliorated by therapy
of reflux and by other reports of cough
following reflux. One of our subjects also
refluxed after coughing, suggesting that the
increased abdominal pressure may have provoked
reflux.
Sneezing followed reflux in one baby. Like
cough, sneezing is protective, clearing the
nasopharynx of refluxed material. Conversely,
although not suggested by the temporal
relationship in our patient, sneezing might
cause reflux by increasing abdominal
pressure.
Mouthing, associated with reflux in one
infant, occurred both before and after reflux
episodes, suggesting bidirectional causality.
Thus, after reflux, mouthing may represent a
clearance attempt; preceding reflux, it may
induce lower esophageal sphincter
relaxation.
Thumb-sucking occurred after reflux in the
one infant manifesting this association. Such
sucking might increase refluxate clearance by
stimulation of salivation and swallowing, or it
might be a nonspecific self-soothing behavior
due to the discomfort of reflux. It is unlikely
that such sucking causes reflux, in spite of the
lower esophageal sphincter relaxation which
occurs with swallowing, since an earlier study
did not demonstrate an increase in reflux
frequency to be caused by pacifier-sucking in
seated infants.
The quiet period we observed preceding some
episodes of reflux may correspond to a similar
phenomenon previously noted by others. However,
other studies have linked movement with reflux
episodes. These differences may be due to the
underlying behavior state (e.g., if quiet
precedes reflux awake, but movement precedes
reflux during sleep), or to different types of
reflux produced (e.g., if quiet precedes
nonregurgitant reflux, but movement precedes
regurgitant reflux) and will be interesting to
study in the future.
The diversity of behaviors in response to
reflux shown by our subjects is consistent with
our current understanding of the diverse
responses to reflux disease: some individuals
with mild esophagitis have severe chest pain and
others have no pain - despite severe
esophagitis; some have bronchospasm and others
do not; some have marked regurgitation and
others do not.
This study does not address the issue of
whether these behaviors are more common in
infants with reflux disease; it simply shows
that the behaviors are more likely to occur
during the onset of reflux episodes than during
periods without esophageal acidification.
The apple juice feedings we used differ from
standard milk feedings in their pH; thus, our
observations may be most readily generalized to
acid reflux occurring late postprandially.
Although the study's conclusions might be
questioned because the person coding the
behaviors was not formally prevented from
observing pH values on the other side of the
screen, the practical demands of the
observational task of coding in real time
preclude this from happening.
The repeated statistical testing introduces
the risk of a type I error. When the subjects
are aggregated, the symptom "discomfort" is the
only one which clearly reaches significance when
the Bonferroni correction is used to protect
against such an error, although the conservative
nature of the Bonferroni correction suggests
that perhaps mouthing, emission, and
yawning
might also reasonably be considered significant.
Considering the study's design as a single
subject study with eight replications, and again
using the Bonferroni correction within subjects,
the data in Table 3 can be conservatively
considered significant for discomfort in two
patients,
yawn in one
patient, stridor in one patient, thumb-sucking
in one patient, and cough/gag in one patient.
Thus, the seven behaviors which this study most
clearly associates with onset of reflux episodes
are discomfort, emission,
yawning,
stridor, mouthing, thumb-sucking, and cough/gag.
Sneezing and hiccuping occurred a total of only
one and five times, respectively, during the
entire study, so the power to detect an
association with reflux onsets was minimal.
The implications of this study are twofold.
First, recognition of these associations may
allow clinicians to detect subtle signs of
reflux episodes in infants who do not spit up.
Second, the associations may illuminate the
pathophysiology of reflux episodes or the causes
of some of the behaviors, such as
yawns or
hiccups. Our findings from this preliminary
study should be used to generate more specific
hypotheses for further, more focused controlled
study.
In summary, we have found a temporal
association of 10 behaviors with the onset of
reflux episodes in infants. Further study is
needed to confirm these findings, to elaborate
the direction of causality, and to clarify the
underlying mechanisms.
