Gastroesophageal Reflux in Children GER in Children
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Editor
Yvan Vandenplas
Universitair Ziekenhuis Brussel, Kidz Health Castle, Brussels, Belgium
ISBN 978-3-319-60677-4 e-ISBN 978-3-319-60678-1
https://doi.org/10.1007/978-3-319-60678-1
Library of Congress Control Number: 2017951902
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Preface
The diagnosis and management of gastro-oesophageal reflux disease
(GERD) remains a challenge. Each author of this book is a worldwide
recognized authority in different aspects related to GERD. Therefore, we
are convinced that this book will help our readers to better understand the
debates about GERD and its diagnosis and management. Each chapter
discusses a different topic or aspect of GERD, going from basic science to
clinical data.
Up to now, such a book has never been written. At the best, there is a
chapter on GERD in a book on GERD focusing on adults in order to
highlight the differences between adults and children (“children are indeed
not small adults”), or there is a chapter on GERD in a textbook of paediatric
gastroenterology. We felt that there was a need for an in-depth book on
different aspects of GERD in childhood.
Why is GERD in childhood such a debated topic? The changing
spectrum of symptoms according to age is a major reason. Symptoms are
non-specific in infants and young children. Regurgitation and crying are
manifestations of GERD in infants, but most infants that regurgitate do not
have GERD, and many infants that cry do not suffer from GERD. But when
physiologic GER or regurgitation stops and when it becomes GERD are not
clear. In fact, there is a continuum between physiologic reflux and disease.
So, parental distress and compliance and the attitude of the healthcare
provider will decide whether an infant is considered to have physiologic
reflux or (mild) reflux disease. As a consequence, the diagnosis of GERD is
also a matter of controversies. There is no golden standard technique,
although 24-h multiple intraluminal impedance in combination with pH
monitoring seems to be the best, certainly in patients that do not present
with overt regurgitation and/or vomiting. Endoscopy with biopsies is
recommended to rule out other diseases than GERD. If symptoms are non-
specific, diagnostic techniques are debated; treatment is as well discussed.
Nutritional treatment seems “on the winning hand” in these infants with
physiologic regurgitation or those with not-severe GERD. While anti-acid
medication is overused in distressed infants, there is only limited evidence
for its efficacy in young children. Effective and safe medication enhancing
motility and lower oesophageal sphincter function would be welcomed.
The European Society for Paediatric Gastroenterology, Hepatology and
Nutrition (ESPGHAN) and North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition (NASPGHAN) published in
2009 and 2017 common guidelines on the diagnosis and management of
GERD in children. While efforts were made to make these
recommendations as much as possible “evidence based”, it is clear that
evidence for many aspects is missing. A summary of the 2017 guidelines
can be found at the end of this book.
We do hope that this book will help to better understand the actual
knowledge and controversies on GERD in children.
We look forward to a successful and worldwide spreading of this book.
Yvan Vandenplas
Brussels, Belgium
Acknowledgements
I am pleased and honoured that so many key opinion leaders contributed to
this book. Thanks to their valuable input, this book will become the
reference work on paediatric gastro-oesophageal reflux disease. This is the
second book on this topic. The first one was published in 1992,
Oesophageal pH Monitoring for Gastro-Oesophageal Reflux in Infants and
Children , and was in fact my PhD thesis. This book was published 4 years
after having obtained my certificate as a paediatrician, and now, in 2017, I
am 4 years away from retirement. Thanks to the never-ending support of
my family, it was possible to devote so much time to this passion.
Contents
1 Epidemiology
Silvia Salvatore and Yvan Vandenplas
2 Pathophysiology of GastroesophagealReflux Disease
Samuel Nurko
3 Esophageal Clearance in GastroesophagealReflux
Maheen Hassan, Frederick W. Woodey and Hayat Mousa
4 Symptoms
Paolo Quitadamo and Annamaria Staiano
5 Diagnosis of GastroesophagealReflux Disease
Yvan Vandenplas
6 Manometry
Taher Omari
7 Multichannel Intraluminal Impedance and pH Monitoring (pH-MII)
in Infants and Children
Maartje M. J. Singendonk, F. Jaime, S. Salvatore, M. M. Tabbers,
M. A. Benninga and Y. Vandenplas
8 GastroesophagealReflux (GER) in the Preterm Baby
Christophe Dupont
9 GastroesophagealReflux and the Neurologically Impaired Patient
Efstratios Saliakellis and Nikhil Thapar
10 GERD and Dysphagia
Nathalie Rommel and Gigi Veereman
11 GastroesophagealReflux and Esophageal Atresia
Frederic Gottrand, Madeleine Gottrand, Rony Sfeir and
Laurent Michaud
12 GOR(D) and Apnoea
Silvia Salvatore and Yvan Vandenplas
13 GastroesophagealReflux and Respiratory Tract Symptoms
Daniel R. Duncan and Rachel L. Rosen
14 Gastro-oesophageal Reflux and Cow’s Milk Allergy
Francesco Valitutti, Anna Rybak and Osvaldo Borrelli
15 GastroesophagealReflux and Cystic Fibrosis
Jernej Brecelj
16 GERD and Eosinophilic Esophagitis
Jorge Amil Dias
17 Duodenogastroesophageal Reflux
Ilse Hoffman
18 Gastroesophageal Reflux Disease and Helicobacter pylori in Children
Nicolas Kalach
19 The Management of Infant Regurgitation
S. Salvatore, M. M. Tabbers, M. M. J. Singendonk, F. Savino,
A. Staiano, M. A. Benninga, K. Huysentruyt and Y. Vandenplas
20 GER and Hypnotherapy
A. M. Vlieger
21 GER and Complementary Medicine
H. S. van der Heijden and M. M. Tabbers
22 Gastro-oesophageal Reflux and Probiotic
Flavia Indrio and Fernanda Cristofori
23 GastroesophagealReflux and Prokinetics
Mário C. Vieira
24 GER and Antacid Medications
Jose M. Garza and Carlo Di Lorenzo
25 GastroesophagealReflux and Surgery
Juan A. Tovar
26 Endoscopic Approaches to the Treatment of GERD
Mike Thomson
© Springer International Publishing AG 2017
Yvan Vandenplas (ed.), Gastroesophageal Reflux in Children, https://doi.org/10.1007/978-3-319-
60678-1_1
1. Epidemiology
Silvia Salvatore1 and Yvan Vandenplas2
(1) Department of Paediatrics, Università dell’Insubria, Varese, Italy
(2) Department of Paediatrics, UZ Brussel, Vrije Universiteit Brussels,
Brussels, Belgium
Silvia Salvatore
Email: [email protected]
Abstract
Determination of the exact prevalence of gastroesophageal reflux (GER)
and GER disease (GERD) at any age is virtually impossible mainly because
symptoms are not specific, not all patients seek medical help, many patients
are not (fully) investigated, and prospective data are limited. Many
epidemiologic studies evaluated in infancy the frequency of regurgitation
which is a common physiologic symptom in the first months of life with a
spontaneous recovery in nearly all infant. Many other esophageal and
extraesophageal symptoms and signs of GER(D) have been reported, but
sensitivity and specificity are low, the causal relation is uncertain, and there
is a lack of diagnostic gold standard technique. While reflux occurs
physiologically at all ages, there is also a continuum between physiologic
GER and GERD leading to different manifestations and complications
depending on individual sensitivity and perception, defense mechanisms,
mucosal resistance, and possible genetic influence. In selected population
such as children with neurological impairment, cystic fibrosis, and
esophageal atresia, severe persisting GER and esophageal complications
have been frequently reported. Whether early treatment of GER(D)
significantly changes, the incidence or severity of symptoms and
complications in adults is uncertain.
Keywords Reflux – GER – GERD – Regurgitation – Natural history –
Esophagitis – Infants – Children
Introduction
Epidemiology of gastroesophageal reflux (GER) and GER disease (GERD)
in infants and children is unclear because of several factors influencing both
incidence and prevalence rates. Definition, age, clinical manifestations,
selection of population, diagnostic criteria, nutrition, over-the-counter
treatment, and parental and patient concern are all important determinants
of the high heterogeneity in the literature data.
GER, the involuntary passage of gastric contents into the esophagus,
occurs several times per day in every human, particularly after meals, and is
a completely normal physiologic process [1–3]. Most reflux episodes are
asymptomatic, of short duration, and limited to the distal esophagus.
Regurgitation, also called spitting up, posseting, or spilling, is the passage
of GER into the pharynx, mouth, or the perioral external area [1].
Regurgitation is frequent in healthy infants especially in the first months of
life, with a peak incidence around 3–4 months, and after intake of large
volumes of milk as happens in young infants. Vomiting is a forceful
expulsion of gastric contents from the mouth, is a more complex
coordinated motor response, and is a consequence of the activation of
receptors both inside and outside the gastrointestinal tract, often confused
with regurgitation [4, 5]. GERD occurs when GER causes troublesome
symptoms and/or complications [2, 3]. Despite that the semantic difference
between GER and GERD is clear, the clinical distinction is often
challenging, even for physicians.
Pitfalls
The spectrum of GER symptoms is wide and unspecific (such as
behavioral, respiratory, feeding, or sleeping problems with or without
esophageal signs and symptoms such as regurgitation or vomiting) [1]. The
presenting symptoms of GERD also differ according to age [6] and may be
secondary to other conditions (cow’s milk allergy, malformation, metabolic,
renal, and neurologic disorders) [1].
GERD frequently causes an impaired quality of life, easy to report for
adult patients but difficult to quantify in infancy and childhood when it is
mainly determined by parental perception and coping.
The absence of a gold standard test for the diagnosis of GERD and the
complementary results of all the available investigations hamper the
difficulty to clarify the epidemiology of GERD.
Symptoms showed a poor correlation with pH monitoring or endoscopy
results, especially in children [1]. Mucosal complications of GERD such as
erosive esophagitis, stenosis, and Barrett’s esophagus are less frequent in
children than in adults, but the exact occurrence in pediatrics may be
underestimated because of limited endoscopic approach in pediatric patients
with GER(D) symptoms and because no symptom is predictive of
esophagitis. The natural history, evolution, and progression of GERD for an
individual patient also depend on genetic, environmental, and mucosal
factors [7].
In the last 10 years, different European and American guidelines on the
diagnosis and management of GER in children have been published [1, 8,
9]. However, considering symptoms without investigations, overdiagnosis
of GERD and thus overtreatment with medication (mainly acid inhibitors)
are common especially in infants and young children [10].
GER(D) in Infants
The most frequently reported symptom of GER in infants is regurgitation
but is neither sensitive nor specific to diagnosis of GERD.
Epidemiological data show that spilling or regurgitation in infancy is
very common between 1 and 6 months of age, with a peak at the age of 3–4
months, and spontaneous and almost complete resolution (in 95% of cases)
by 1 year of age with a similar figure all over the world [11–18] (Fig. 1.1).
Fig. 1.1 Natural evolution of physiologic regurgitation in infants
The oldest epidemiological report dates from 1992 and is a cross-
sectional retrospective study from France [19]. Chouhou reported that a
history-based diagnosis of GER was made by a physician in 18% of a
population of unselected infants younger than 10 months of age [19]. Since
then, data from the USA, Australia, India, Indonesia, Italy, Japan, Spain,
and Thailand have been reported in cross-sectional or prospective studies
with different frequencies of regurgitation considered (Table 1.1).
Table 1.1 Summary of the studies reporting regurgitation in infancy (modified from [17])
Number of Geographical Age Prevalence of Diagnostic criteria References
infants area (months) regurgitation
948 USA 0–3 50% ≥1 episode per day [12]
4 67%
10–12 5%
128 USA 1 26% I-GERQ-R [24]
2 13%
4 8%
6 3%
264 (0–3 USA 0–12 26% Rome III [18]
years)
Number of Geographical Age Prevalence of Diagnostic criteria References
infants area (months) regurgitation
693 Australia 3–4 41% Spilling most feed each [22]
day
921 Japan 1 47–14% ≥1 to ≥3 episodes per day [16]
4 29–11%
7 6–6%
216 Thailand 2 87% Daily regurgitation [34]
4 70%
6 46%
8 23%
12 8%
9660 Italy 0–12 7% Rome II [23]
children
2879 Italy 0–6 23% Loss of most part of the [13]
meal without retching
2642 Italy 0–24 12% Rome II [15]
138 Indonesia 0–3 77% ≥1 episode per day [21]
4–6 44%
7–9 9%
9–12 12%
130 Indonesia 0–2 20% ≥4 episodes per day [14]
1 73% ≥1 episode per day
5 50%
3487 Spain 0–4 6% Not specified [69]
In the Chicago area, regurgitation of at least one episode a day was
reported in half of 0- to 3-month-olds [12]. Peak-reported regurgitation by
Nelson and coworkers was 67% at 4 months; the prevalence of symptoms
decreased dramatically from 61 to 21% between 6 and 7 months of age and
to 5% at 10–12 months of age [12]. In India, 55% of the infants aged 1–6
months had daily regurgitation [20]. According to a cross-sectional survey
in Indonesia, regurgitation (of at least once a day) was reported more
frequently in the first 3 months of life and in 77% of infants younger than 3
months [21], with a reported peak prevalence of 81% during the first month
of life but with a sharp decrease between the 4–6- and 7–9-month-old
groups (from 44 to 9%) reaching a rate similar to the other geographical
reports [21].
Martin et al. performed a prospective follow-up study in the Adelaide
area (Australia) in 836 infants followed for 2 years from birth with daily
symptom diaries [22]. Spilling of most feeds each day was common in
