P1: ILT/GMI P2: ILT

PP692-473071 DDAS.cls August 27, 2003 15:10

Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003), pp. 17231729 (
C 2003)

Gastroesophageal Reflux Disease

Review of Presenting Symptoms, Evaluation,
Management, and Outcome in Infants
VASUNDHARA TOLIA, MD, FAAP, ANNE WUERTH, RN, and RONALD THOMAS, PhD

We conducted a retrospective review of 342 infants presenting with symptoms suggestive of gastroe-
sophageal reflux disease (GERD) to assess their evaluation, management, and outcome. All infants
underwent extended pH monitoring (EPM) for one or more of the following symptoms: regurgita-
tion, choking, irritability, failure to thrive, apparent life-threatening event, or wheezing. EPM was
considered abnormal if distal reflux index was 5% and/or if the Euler and Byrne score was 50
and these patients were labeled as having GERD. Those with normal EPM parameters were controls.
All infants were <1 year of age (198 boys, 144 girls). Most received conservative treatment with
formula changes and/or thickening and positional management before EPM. Of 342 infants studied,
EPM was normal in 169 patients, ie, controls, and GERD was present in 173 children. GERD was
more prevalent in Caucasians compared to African Americans (P < 0.045). Although a prokinetic
or acid suppression medication or both were given more commonly in infants with GERD, almost
half of infants in the control group also needed pharmacotherapy because of persistent symptoms.
Mean time to resolution of symptoms in the control group infants with normal EPM was 3.5 months,
and in infants with GERD it was 5.4 months (P < 0.001). In conclusion, the Majority of infants with
symptoms suggestive of GERD resolve their symptoms within 36 months of initiating treatment.
Day-to-day variability of the spectrum of GERD may contribute towards normal results of EPM in
some infants who need pharmacotherapy.

KEY WORDS: gastroesophageal reflux disease; infants; pH monitoring; prokinetics; acid suppression; ethnicity.

Gastroesophageal reflux disease (GERD) is a ubiquitous
condition, and its incidence in infancy is estimated to be
approximately 18% (1). Gastroesophageal reflux disease
is being increasingly diagnosed and implicated in a wide
range of pediatric problems. A 20-fold increase in the di-
agnosis of GERD in hospitalized infants as assessed over
a 25-year period from 1971 to 1995 has been reported
(2). The rate as well as total number of cases diagnosed
Manuscript received October 20, 2002; revised manuscript received
June 13, 2003; accepted June 15, 2003.
From the Department of Pediatrics, Children s Hospital of Michigan,
Detroit, Michigan, USA.
Presented in part at XXII International Congress of Pediatrics, August
14, 1998, Amsterdam, The Netherlands.
Address for reprint requests: Dr. Vasundhara Tolia, Childrens Hospi-
tal of Michigan, Wayne State University, 3901 Beaubien Blvd. Detroit,
Michigan 48201, USA.
with GERD based on the diagnostic codes from the In-
ternational Classification of Diseases increased in both
academic and community hospitals alike in this study.
This suggests both an increased awareness of its preva-
lence and/or over diagnosis due to the use of sophisti-
cated diagnostic methods. However, available data on the
course and prognosis of infants diagnosed with GERD are
sparse.
There is a paucity of data on the natural history and
outcome of GERD in infants. The patients in the early re-
ports by Carre did not receive any pharmacotherapy (3, 4).
Subsequently, Shepherd et al published observations on
the clinical profile, course, and outcome with therapy in
126 infants and children diagnosed with GERD by either
one or a combination of investigations that included bar-
ium studies, endoscopy, scans, or pH monitoring (5). They

Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003) 1723
0163-2116/03/0900-1723/0
C 2003 Plenum Publishing Corporation
P1: ILT/GMI P2: ILT
PP692-473071 DDAS.cls August 27, 2003 15:10

TOLIA ET AL

concluded that GERD can cause significant morbidity in pramide) and/or acid suppression agent (ranitidine, cimetidine,
infants; however, therapy was considered effective. famotidine or omeprazole); and surgery. All nonpharmalacologic
Many investigations are utilized for diagnosing GERD, management options had been conducted prior to the referral to
gastrointestinal service.
of which extended pH monitoring (EPM) is considered the The ultimate outcomes at the time of review were determined
most reliable. We performed a retrospective review of the as: time to resolution of symptoms with discontinuation of med-
diagnosis, management, and ultimate outcome of infants ications in months, presence of ongoing disease requiring phar-
who underwent EPM at a tertiary care referral center. Our macotherapy, or as lost to follow-up if the parent failed to keep
aims were to define the course and outcome of pathologic the appointment and could not be contacted. Resolution was de-
fined as absence of presenting symptoms for four continuous
GERD as diagnosed by EPM in comparison to a control weeks during follow-up time as reported by the caretaker.
group in whom the pH evaluation had been normal. Statistical Analysis. For purposes of statistical analysis, the
data for each patient were recorded on a 83-point log sheet and
coded as numerical scores. All the infants evaluated for GERD
MATERIALS AND METHODS with normal EPM were considered the control group and those
with abnormal EPM as having GERD. For linear and continuous
Infants under 1 year of age presenting with spitting/vomiting, data, a t test was used to determine significant differences be-
choking, gagging, irritability with fussing and arching with or tween the control and GERD groups. Fishers exact test was used
without feeding, stridor, apparent life-threatening event (ALTE), to determine significance of ethnic prevalence. Cross-tabulation
and/or other respiratory symptoms who underwent EPM be- of discontinuous, categorical variables was performed to exam-
tween January 1994 and April 1997 were identified from the ine differences in proportions. Statistical significance between
database in the gastroenterology division at the Childrens Hos- groups was determined with Fishers exact text, with signifi-
pital of Michigan. Medical records of these infants were re- cance set at P 0.05, two-tailed. The effect of the ages of in-
viewed for the presenting symptoms, investigations, manage- fants in months between control and GERD groups upon time
ment, course, and outcome. Data on the presenting symptoms to resolution of symptoms was assessed by two-factor analysis
were recorded for one or more symptoms as applicable. Spitting/ of variance (ANOVA). Stepwise (forward conditional) binary
vomiting and irritability was specifically recorded into one of logistic regression was used o determine which symptoms and
four categories: none, 510 episodes/week, 5 episodes/day or associated conditions would predict an abnormal EPM, with sta-
>5 episodes/day. Respiratory symptoms included wheezing, ap- tistical significance at P 0.05. Binary logistic regression was
nea, aspiration pneumonia, ALTE, and/or cyanotic episodes. Ir- used to predict resolution of symptoms with different treatments
ritability was defined as fussing, crying, and arching that was for both the control and GERD groups, ie, position change, for-
not explainable by any other factors causing discomfort, such as mula change or thickening, or pharmacologic therapy). All anal-
hunger, dirty diaper, or naptime. Presence of associated condi- yses were performed using Statistical Software Sciences (SPSS),
tions such as tracheoesophageal fistula, malrotation, prematurity, version 10.0.
bronchopulmonary dysplasia, and neurologic compromise was
noted. A questionnaire was used by phone contact for the legal
guardians of patients with missing data from the medical records. RESULTS
The presence of GERD based on ethnicity was also recorded.
All the diagnostic studies performed on each infant were Demographics, baseline characteristics, presenting
noted. These included barium studies (BS), gastric scintiscans, symptoms, and outcome from the pH monitoring on a
and EPM. An esophagogastroduodenoscopy was performed in total sample of 342 infants are presented in Table 1. All
only 16 patients, so its findings are not considered relevant to
this review.
infants were under 1 year of age. Of these, 169 infants with
Each study was considered normal or abnormal based on the
following criteria: Barium study (BS) was considered abnormal TABLE 1. DATA DEMOGRAPHICS, PRESENTING SYMPTOMS, EPM, AND
if one or more of the following were noted: reflux, malrotation, RESOLUTION TIME
hiatal hernia, or stricture (6). No maneuvers were made to in-
duce reflux. Gastric scintigraphy was conducted as previously Control (N = 169) GERD (N = 173) P
described (7). Percent of the ingested formula emptying out of
the stomach at the end of 1 hr was calculated as gastric emptying. Mean age (months) 3.30 2.34 4.36 2.80 <.001
Male/female 106/63 92/81 NS
All EPM studies were performed as inpatients on formula Regurgitation 138 155 <.05
feedings only according to the standard protocol (8). They were Respiratory 106 85 <.01
considered abnormal or pathologic if either the reflux index, ie, Choking 78 76 NS
percent of time pH < 4.0 was 5.0% or if the Euler and Byrne Irritability 17 38 <.01
score was 50 calculated as x + 4y (9), where x = total number Failure to thrive 17 28 NS
of reflux episodes and y = number of reflux episodes >5 min ALTE 52 34 <.12
in duration). Those with normal pH monitoring criteria were Distal reflux 1.13 0.96 7.15 7.29 <.001
considered the control group. index (mean)
The management options for these infants were recorded as Euler and byrne 23.31 13.63 110.1 65.14 <.001
score (mean)
reassurance: conservative measures such as position change, Time to resolution 3.51 4.45 5.41 5.41 <.001
formula thickening, and/or formula changes; pharmacologic (months)
treatment with either a prokinetic agent (cisapride or metoclo-

1724 Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003)
P1: ILT/GMI P2: ILT
PP692-473071 DDAS.cls August 27, 2003 15:10
OUTCOME OF GASTROESOPHAGEAL REFLUX IN INFANCY
Fig 1. Ethnic differences in the prevalence of GERD patients and controls.
normal EPM comprised the control group and 173 infants
with abnormal study were assigned to GERD group. The
study sample consisted of 106 boys and 63 girls in the con-
trol group, and 92 boys and 81 girls in the GERD group.
Racial distribution in the control group showed that 115
infants were African American, 42 were Caucasians, with
the remaining 12 infants of other ethnicities. In the GERD
group, 106 were African American, 63 were Caucasian,
and 4 were of other ethnic origin. We evaluated the preva-
lence of GERD in relationship to ethnic background. Even
though a majority of our patients were African Americans,
a higher proportion of Caucasian infants (60%) had
GERD compared to African American infants (48%). This
12% difference in proportion was statistically significant
(P < 0.045) suggesting a higher prevalence of GERD in
Caucasians (Figure 1).
Infants with GERD had a higher mean distal reflux
index (7.15% vs 1.13% in the control group) and Euler
and Byrne score (110.1 vs 23.3). The control and GERD
groups were comparable with respect to gender, racial dis-
tribution, and incidence of choking and failure to thrive.
However, infants in the GERD group were slightly older
(mean SD: 4.4 2.8 vs 3.3 2.3 months) and had a
higher incidence of regurgitation and irritability than con-
trol group (for all parameters P < 0.001). Moreover, the
frequencies of regurgitation and irritability in the GERD
group tended to be higher than in the control group. Infants
in the control group had a higher incidence of respiratory
symptoms. Baseline characteristics of the two groups are
shown in Table 1. Associated conditions found in the con-
trol and GERD groups were prematurity (2 and 1 cases,
respectively), bronchopulmonary dysplasia (l case in each
group), neurologic compromise (16 and 22 cases), and res-
piratory distress (38 and 40 cases).
Many patients had radiologic studies performed prior
to referral. Barium studies were performed on 101 of the
342 infants. Eight of 43 infants studied in the control group
Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003)
(19%) had positive barium studies for GERD, compared
with 12 of 62 (19%) in the GERD group. Scintigraphy
was performed in 54 infants and showed abnormal gastric
empyting in 43% of infants from control group and in 40%
with GERD.
Treatment in the control and GERD groups consisted
of positional therapy in 24 and 26 cases, respectively,
formula change in 18 and 21 cases, formula thicken-
ing in 76 and 79 cases, and pharmacotherapy in 74 and
140 cases (P < 0.001 for the last comparison) as shown
in Figure 2. The medications used for pharmacother-
apy were the prokinetic agents cisapride (0.20.3 mg/kg
three or four times daily) and metoclopramide (0.1 mg/kg
four times daily) and/or the acid suppressants ranitidine
(23 mg/kg twice daily), famotidine (0.3 mg/kg twice
daily), cimetidine (8 mg/kg twice daily), and omeprazole
(0.6 mg/kg as a single dose). Since famotidine, cimetidine,
and omeprazole were used in only 4, 2, and 2 patients, re-
spectively, all these patients were analyzed together as
being in the acid suppression treatment group. Pharma-
cotherapy was given to significantly more infants in the
GERD group. Prokinetic drugs only were administered
to 137 infants in the GERD group vs 76 in the control
group (62% of the total group) as shown in Figure 3. Acid
suppressants only were given to 39 and 8 infants, respec-
tively (14%). Both classes of drugs were given to 27 and
5 infants, respectively (9%).
Follow-up ranged from 1 to 39 months (mean duration
4.97 5.04 months). Of the 342 infants in the study, 319
had resolution of their symptoms: 165 of 169 in the con-
trol group (98%) and 154 of 173 in the abnormal group
(89%) (Figure 4). The remaining 23 infants had ongo-
ing symptoms of GERD at last follow-up (19 in the ab-
normal group, 4 in the normal group; P < 0.001). Four
of the 23 with ongoing symptoms underwent surgery.
The mean time to resolution was 3.5 4.4 months (range
021 months) in the control group and 5.4 5.4 months
1725
P1: ILT/GMI P2: ILT
PP692-473071 DDAS.cls August 27, 2003 15:10
Fig 2. Management intervention by groups (N = 342 infants). Figures represent the number of
infants in each group. *P < 0.05.
(range 039 months) in the GERD group (P < 0.001).
There was no difference in time to resolution by ethnicity
using an independent samples test.
A two-factor ANOVA procedure revealed a significant
interaction between the age (in months) of the infants
and the group to which they belonged, ie, GERD versus
control (F = 3.44; P = 0.005). Examination of pairwise
comparisons revealed that the mean time to resolution for
infants with GERD at 3 months of age was 8.25 4.45
months (95% CI of 6.07 to 10.43 months), which is sig-
nificantly greater than that for infants in the control group
(3.22 .2.89 months, 95% CI of 1.35 to 5.10 months,
P = 0.02). Symptoms of regurgitation, respiratory, irri-
tability, choking, failure to thrive, and ALTE were loaded
into a binary logistic regression equation to attempt pre-
diction of having GERD. Of these, only irritability and
regurgitation were significant predictors for the presence
of GERD on EPM.
Interventions of position change, formula change, for-
mula thickening, cisapride, and reglan were also analyzed
using a binary logistic regression procedure to explore
Fig 3. Medications used by groups (N = 342 infants). Figures represent the number of infants in each group.
1726
TOLIA ET AL
the prediction of a resolved outcome. For the control
group, position change and formula thickening were pre-
dictors of a resolved outcome. Utilizing a position change
would increase the chance of a resolved outcome by
0.185 (P = 0.106) in combination with formula thicken-
ing (odds ratio = 0.338; P = 0.161).
DISCUSSION
Gastroesophageal reflux disease includes a wide spec-
trum with truly physiologic reflux at one end to compli-
cated esophagitis at the other, with a majority of patients
belonging between these two extremes (10). Clinical judg-
ment and radiologic investigations are the usual criteria
on which empiric diagnosis of GERD is made by practi-
tioners. Our results demonstrate limited utility of imaging
modalities in making an accurate diagnosis of GERD. A
recent study also recommended EPM over barium exam
as the first line investigation for diagnosing GERD (11).
Determination of gastric emptying on scintigraphy
does not usually add in the diagnostic evaluation of
Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003)
P1: ILT/GMI P2: ILT
PP692-473071 DDAS.cls August 27, 2003 15:10
OUTCOME OF GASTROESOPHAGEAL REFLUX IN INFANCY
Fig 4. Outcome results in the two groups (N = 342 infants). Figures represent the number of infants in each
group. *P < 0.05.
uncomplicated GERD in infancy (7, 8). The data incrimi-
nating delayed gastric emptying in GERD were reported in
children with complicated GERD associated with failure
to thrive and pulmonary symptoms (12). Infants and chil-
dren with mild reflux without associated symptoms had
normal gastric emptying in the same study as well (12).
Over the last two decades, EPM has emerged as the
apparent winner in the GERD diagnosis sweepstakes
(13, 14). It has particular implications with correlation
of atypical manifestations involving upper and lower
respiratory tracts (15, 16), although such an association
is controversial (17, 18). We have observed that infants
tolerate EPM much better than older children and that it
is less invasive than an endoscopy. The diagnostic cutoff
criteria for EPM to distinguish between a normal and ab-
normal amount of reflux vary at different institutions. We
use a reflux index cut off of 5% or a Euler and Byrne
score of 50 to define the presence of GERD with formula
feeding and classified those with normal acid exposure as
controls (19).
While the incidence of irritability was significantly
higher in our patients with GERD, the incidence of ALTE
or questionable apnea was significantly higher in the con-
trol group of infants, again suggesting lack of correlation
between GERD and respiratory symptoms on a consistent
basis (20, 21). None of the infants had an incidence of
ALTE or apnea during the duration of their EPM study.
Such an affect in symptom variability may be secondary
to the dynamic nature of the GERD spectrum and its day-
to-day variability (19).
The management of GERD in infants is usually un-
dertaken in a sequential fashion (10). Simple reassurance
suffices in an otherwise healthy, growing infant with spit-
ting and/or occasional choking or gagging without color
change if the EPM study is normal. This by itself may
Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003)
provide a placebo effect that extends beyond the use of
medications to the comforting elements of the parent
physician interview. A normal study without occurrence
of a complicating situation may also allay parental anxi-
ety considerably. Many conservative measures commonly
used to treat GERD in infants have no proven efficacy,
as shown in a recent systematic review of nonpharma-
cologic therapies (22). It was not unusual to see formu-
las being changed up to five times without much effect.
Dietary management of infants with GERD is an impor-
tant component of conservative treatment and was a fac-
tor predicting earlier resolution in control group. Smaller,
more frequent feedings, avoidance of overfeeding, whey-
hydrolysate formulas, hypoallergenic formulas, and thick-
ening of formulas have all been attempted (10, 22). Of
these, only thickened formulas appear to be associated
with a decreased number of reflux episodes and the level of
refluxate (23). Position changes were also associated with
earlier resolution. This and dietary interventions possibly
allow time in infants with mild reflux for spontaneous res-
olution, as in our control group, and early resolution in
23 months is likely to occur in these patients.
Pharmacologic therapy worked well in most infants
with a prokinetic agent alone or in combination with an
acid suppression agent. In infants, our usual policy is to use
a prokinetic medication initially and add the acid suppres-
sant for ongoing symptoms of suspected or documented
esophagitis later on, if necessary (24). Our data also sug-
gest that a combination of drugs, ie, acid suppression and
a prokinetic is needed more frequently in infants with
GERD than in the control group.
The prevalence of symptoms of GERD during infancy
was solicited by a parental questionnaire filled in the pe-
diatricians office (25). Regurgitation was commonly re-
ported in the first year of life, peaking at 4 months and
1727
P1: ILT/GMI P2: ILT
PP692-473071 DDAS.cls August 27, 2003 15:10
resolving by 7 months of age in most (25). However, none
of these infants was referred for any studies, and the mild
nature of symptoms in this series is also evident by lack
of even conservative interventions in >95% of patients. A
prospective study on infants with spitting from Australia
reports that the symptom resolves in the vast majority by
13 months of age (26). The majority of infants in both
these studies were Caucasians. Our findings of a higher
proportion of Caucasian infants having GERD in compar-
ison to African American infants is new and interesting.
This suggests that racial differences in the nature of GERD
symptoms, as previously reported in adults (27, 28), also
occur in infants. A recent study on the prevalence and nat-
ural course of reflux symptoms in Thai infants suggested
that these infants had earlier resolution of regurgitation in
comparison to their Western cohort (29). This difference
was not related to the type of feedings, ie, formula versus
breast or intake of solid foods.
Our study differs from the study by Shepherd et al in
having uniform diagnostic criteria to distinguish between
normals and abnormals on EPM, rather than relying
on a multitude of tests (5). Although the median age of
their group was 2.5 months, 17% were over 1 year of age.
At the time of their review, availability of therapy was
limited. A major difference in the surgical outcome (1.1%
vs 17%) is noted between the current and previous series
and may reflect limited access to effective pharmacologic
agents at that time. Esophagitis was a major determinant of
ongoing symptoms in their series, whereas the presence of
frequent regurgitation, and irritability were noted to con-
tribute significantly to the persistence of symptoms in ours.
No single test can always reliably distinguish between
a normal and abnormal amount of reflux. The clinician
has to use judgment in deciding the sequence of investi-
gations and/or management options on an individual basis
rather than a shotgun approach. Despite the inherent diffi-
culties in such a retrospective analysis, our study describes
the course and outcome of treated and untreated infants
presenting with GERD symptoms and provides the practi-
tioner anticipatory guidance needed to counsel the parents.
REFERENCES
1. Vandenplas Y, Belli D, Benhamou PH, Cadranel S, Cezard JP,
Cucciara S, Dupont C, Faure C, Gottrand F, Hassall E, Haymans
HS, Kneepkens CM, Sandhu BK: Current concepts and issues in the
management of regurgitation of infants: A reappraisal management
guidelines from a working party. Acta Paediatr 85:531534, 1996
2. Callahan CW: The diagnosis of gastroesophageal reflux in
hospitalized infants: 19711995. JAOA 98:3234, 1998
3. Carre JJ: The natural history of the partial thoracic stomach (hiatal
hernia) in children. Arch Dis Child 35:344348, 1959
4. Carre JJ, Ashley R: The fate of the partial thoracic stomach hiatal
hernia) in chidren. Arch Dis Child 35:484486, 1960
1728
TOLIA ET AL
5. Shepherd R, Wren J, Evans S, Landex M, Ong TH: Gastroe-
sophageal reflux in childrenclinical profile, course and outcome
with active therapy in 126 cases. Clin Pediatr 26:5560, 1987
6. Leonidas JC: Gastroesophageal reflux in infants: role of the upper
gastrointestinal series. AJR 143:13501351, 1984
7. Tolia V, Lin CH, Kuhns L: Evaluation of gastric emptying with 3
different formulas in infants with gastroesophageal reflux. J Pediatr
Gastroenterol Nutr 15:297391, 1992
8. Tolia V, Calhoun J, Kuhns L, Kauffman RE: Lack of correlation
between extended pH monitoring and scitigraphy in the evalua-
tion of ingants with gastroesophageal reflux. J Lab Clin Investi
115:559563, 1990
9. Euler A, Byrne W: Twenty-four hur esophageal intraluminal
pH probe testing: A comparative analysis. Gastroenterology
80:957961, 1981
10. Tolia V: Evaluation and management of pediatric gastroesphageal
reflux. Fam Pract Recert 19:3557, 1997
11. Al-Khawari HA, Sinan TS, Seymour H: Diagnosis of gastr-
oesophageal reflux in children. Comparison between oesophageal
pH and barium examinations. Pediatr Radiol 32:765770, 2002
12. Hillemeier AC, Lange R, McCallum R, Seashore J, Grybowski J:
Delayed gastric emptying in infants with gastroesophageal reflux.
J Pediatr 98:190193, 1981
13. Arasu TS, Wyllie R, Fitzgerald JF, Franken EA, Siddiqui AR,
Lehman GA, Eigen H, Grosfeld JA: Gastroesophageal reflux in
infants and childrencomparative accuracy of diagnostic methods.
J Pediatr 96:798803, 1980
14. Working Group of the European Society of Pediatric Gastroenterol-
ogy and Nutrition: A standardized protocol for the methodology
of esophageal pH monitoring and interpretation of the data for the
diagnosis of gastroesophageal reflux. J Pediatr Gastroenterol Nutr
14:467471, 1992
15. Contencin P, Maurage C, Ployet MJ, Seid AB, Sinaasapel M:
Gastroesophageal reflux and ENT disorders in childhood. Int J
Pediatr Otolaryngol. 32(suppl):S135S144, 1995
16. Colleti, RB, Christie DL, Orenstein SR: Indications for pedi-
atric esophageal pH monitoring. J Pediatr Gastroenterol Nutr;
21:253262, 1195
17. Vijayaratnam V, Lin CHL, Simpson P, Tolia V: Lack of correlation
of respiratory symptoms to proximal esophageal acid reflux in
infants. Pediatr Pulmonol 27(4):231235, 1999
18. Peter CS, Spratowski N, Bohnhourst B, Silny J, Poets CF: Gastroe-
sophageal reflux and apnea of prematurity no temporal relationship.
Pediatrics 109:811, 2002
19. Tolia V, Wuerth A, Thomas R: Variatons in assessment of extended
pH monitoring: (EPM) Is there a single best method? Gastrointest
Endosc 47:AB64(157), 1998
20. Ariagno RL, Guilleminault C, Baldwin R, Owen-Boeddiker M:
Movement and gastroesophageal reflux in awake term infants with
near miss SIDS, unrelated to apnea. J Pediatr 100:894897,
1982
21. Walsh JK, Farrell MK, Keenan WJ, Lucas M, Kramer M: Gastroe-
sophageal reflux in infants: relation to apnea. J Pediatr 99:197201,
1981
22. Rudolph L, Liptak GS, Baker R, Poyle JT, Colletti RB, Gerson
WT, Werlin SL: Guidelines for evaluation and treatment of
gastroesophageal reflux in infants and children: Recommendations
of the North American Society for Pediatric Gatroenterology and
Nutrition. J Pediatr Gastroenterol Nutr 32(suppl 2):S1S31, 2001
23. Tolia V, Kuhns LR, Calhoun I, Kauffman RE: Randomized,
prospective, double-blind trial of metocloprarnide and placebo for
gastroesophageal reflux in infants. J Pediatr 115:141145, 1989
Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003)
P1: ILT/GMI P2: ILT
PP692-473071 DDAS.cls August 27, 2003 15:10
OUTCOME OF GASTROESOPHAGEAL REFLUX IN INFANCY
24. Wenzl TG, Schneider S, Scheele F, Silny J, Heimann G, Skopnik H:
Effects of thickened feeding on gastroesophageal reflux in infants:
a placebo-controlled crossover study using intraluminal impedance.
Pediatrics, 111:e355e359, 2003
25. Nelson SP, Chen EH, Syniar GM, Christoffel KK: Prevalence of
symptoms of gastroesophageal reflux during infancy. Arch Pediatr
Adolesc Med 151:569572, 1997
26. Martin AJ, Pratt N, Kennedy JD, Ryan P, Ruffin RE, Miles H,
Marley J: Natural history and familial relationships of infant
spilling to 9 years of age. Pediatrics 109:10611067, 2002
Digestive Diseases and Sciences, Vol. 48, No. 9 (September 2003)
27. Weinbeck M, Barnert I: Epidemiology of reflux disease and
reflux esophagitis, Scand J Gastroenterol 24(suppl 156):713,
1989
28. Ho KY, Kang Iy, Seow A: Prevalence of gastrointestinal symptoms
in a multi racial Asian population, with reference to reflux type
symptoms. Gastroenterology 93:18161822, 1998
29. Osatakul, S, Sriplung, H, Puetpaiboon, A, Iunjana, C, Charn-
nongpakdi S: Prevalence and natural course of gastroesophageal
reflux symptoms: A 1-year cohort study in Thai infants. J Pediatr
Gastroenterol Nutr 34:6367, 2002
1729
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.