Shamir et al JPGN
Volume 57, Supplement 1, December 2013
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crying and colic in popular parenting magazines. J Dev Behav Pediatr
2008;29:508–11.
105. Headley J, Northstone K. Medication administered to children from
0 to 7.5 years in the Avon Longitudinal Study of Parents and Children
(ALSPAC). Eur J Clin Pharmacol 2007;63:189–95.
106. Perry R, Hunt K, Ernst E. Nutritional supplements and other com-
plementary medicines for infantile colic: a systematic review. Pedia-
trics 2011;127:720–33.
107. Aviner S, Berkovitch M, Dalkian H, et al. Use of a homeopathic
preparation for ‘‘infantile colic’’ and an apparent life-threatening
event. Pediatrics 2010;125:e318–23.
108. Rogovik AL, Goldman RD. Treating infants’ colic. Can Fam Physi-
cian 2005;51:1209–11.
109. Landgren K, Kvorning N, Hallstrom I. Feeding, stooling and sleeping
patterns in infants with colic—a randomized controlled trial of mini-
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ential susceptibility. Dev Psychopathol 2011;23:131–48.
Other Functional Gastrointestinal
Disorders in Infants and
Young Children
Carlo Di Lorenzo
F unctional gastrointestinal disorders (FGIDs) are conditions
defined by clusters of symptoms related to a disorder in
function at the level of the GI tract and/or in the central processing
of information originating from the GI tract. Although FGIDs are
common in adults and children, they are often considered by the lay
public and by many medical providers to be rare in infants and
toddlers. Indeed, conditions that would readily be accepted as
benign in older children, such as constipation or regurgitation,
often prompt extensive workup by concerned physicians and
anxious parents. Among the most common FGIDs in the first
few months of life are infant regurgitation and infantile colic,
2 conditions that are usually time limited and resolve or improve
by 6 to 8 months of age. Despite their favorable prognosis, such
From the Division of Pediatric Gastroenterology, Hepatology and
Nutrition, Nationwide Children’s Hospital and Ohio State University,
Columbus.
Correspondence to Carlo Di Lorenzo, MD, Division of Pediatric
Gastroenterology, Nationwide Children’s Hospital, 700 Children’s Dr,
Columbus, OH 43205 (e-mail: carlo.dilorenzo@nationwidechildrens.
org).
The author reports no conflicts of interest.
Copyright # 2013 by European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition and North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
DOI: 10.1097/01.mpg.0000441933.15093.c3
S36
Copyright 2013 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
multiple dietary changes and use of medications of uncertain
benefit. Other FGIDs, which occur in the first 24 months of life,
include infantile dyschezia, rumination syndrome, functional diar-
rhea, cyclic vomiting syndrome, and functional constipation. The
prevalence of these conditions seems to be similar in different
countries characterized by diverse socioeconomic factors, health
care structure, and dietary habits. This article represents an over-
view of some of the main FGIDs in infancy (Table 1). Infant colic is
extensively discussed in this supplement; cyclic vomiting syndrome
and functional constipation are more common in older children and
do not have any peculiar characteristic when presenting earlier in
life and are not addressed.
The common factor in all of the FGIDs of infancy, much like
in other FGIDs in older children, is the lack of a biological marker.
Thus, as in the field of psychiatry, another discipline with rare
demonstrable abnormal findings on diagnostic laboratory or radio-
logic testing, pediatricians and subspecialists rely on clusters of
symptoms to make a positive diagnosis. The Rome symptoms-
based criteria for FGID were published to facilitate diagnosis of
such disorders and avoid extensive, usually fruitless, testing.
Initially developed for adult conditions only, the Rome criteria
have been adapted to children and have become widely used in
pediatrics. One of the Rome III committees specifically addressed
FGIDs in the infant and toddler periods (1). Such criteria, initially
based mostly on expert opinion, have undergone several iterations
in an attempt to become more evidence based.
INFANT REGURGITATION
Infant regurgitation often is considered responsible for
multiple GI and extraintestinal symptoms. The evidence disputes
some of these beliefs, and it has been suggested that there has been
an overtreatment of what should actually be considered a normal
physiologic event (2). In young infants, daily regurgitation is
within the range of expected behaviors, and the great majority of
regurgitating infants are thriving and do not develop any disease.
Infant regurgitation seems to peak at 4 to 6 months and decreases
in frequency during the second semester of life (3). At 1 year of
age, <10% of infants still exhibit daily regurgitation. Despite the
high prevalence of this symptom and the overall well-being of
affected infants, almost 25% of the parents are concerned enough
to seek medical advice because they are worried about the severity
of the regurgitation (4). Exclusively breast-fed infants seem to
regurgitate less than partially breast-fed babies (5). The forceful-
ness of regurgitation or its outflow through the mouth or nares
carries little diagnostic relevance. Alarm signs that should trigger
an evaluation for gastroesophageal reflux (GER) disease include
failure to thrive, food refusal, swallowing difficulties, hematem-
esis, apnea, and recurrent pneumonia. Bilious emesis and delayed
neurodevelopmental progress necessitate prompt referral for more
in-depth testing. Regurgitation persisting past the first year of life
justifies the use of imaging studies to exclude an anatomical
abnormality, such as a malrotation or a gastric outlet obstruction.
In 2009, the North American and the European Societies for
Pediatric Gastroenterology, Hepatology, and Nutrition jointly
published practice guidelines that discuss evidence for when to
evaluate and treat an infant with regurgitation and suspected GER
(6). The guidelines expressly stated that GER ‘‘is not a common
cause of unexplained crying, irritability, or distressed behavior in
otherwise healthy infants.’’ Treatment directed at gastric acid
suppression exerts little effect on infantile regurgitation and may
be associated with adverse effects (7). Thickening the formulas
with cereals or using ‘‘antiregurgitant’’ formulas decrease over-
regurgitation (8,9).
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 JPGN
Volume 57, Supplement 1, December 2013 Infant Crying, Colic, and GI Discomfort in Early Childhood

TABLE 1. FGIDs of infants and toddlers

Disorder Prevalence Pathophysiology Treatment Outcome

Infant regurgitation 24% of 4- to 6-mo-old High-volume liquid feedings, Education, smaller feedings, Resolves in 90% by
infants regurgitate immaturity of gut motility, feeding thickening 12 mo of age
4 times/day infant positioning
Infant rumination Uncommon (decreasing?) Emotional and sensory deprivation Behavioral interventions, Unknown
improved nurturing, jejunal
tube feedings
Infant dyschezia Common Uncoordinated defecation dynamics Education and reassurance, Resolves in most cases
avoidance of anal stimulations by 6–7 mo of age
Functional diarrhea Common Dietary and motility abnormalities; Education, dietary changes Usually resolves by
increased mucosal secretion? 4 y of age

Infant colics are described elsewhere and cyclic vomiting and functional constipation are similar in younger and older children. FGIDs ¼ functional
gastrointestinal disorders.

INFANT RUMINATION
Infant rumination has been defined as a disorder that must
include all of the following aspects: repetitive contractions of the
abdominal muscles, diaphragm, and tongue; regurgitation of gastric
content into the mouth, which is either expectorated or rechewed
and reswallowed; onset between 3 and 8 months; does not respond
to treatment of GER or formula changes; is not associated with signs
of distress; and does not occur during sleep or when the infant is
interacting with individuals in the environment (1). It is unclear how
common this condition is, but it has received little attention in the
past 2 decades in the medical literature. It is probably most common
in infants with severe neurodevelopmental delay. The most com-
prehensive review of the topic is attributed to Fleisher, who in 1994
discussed the difference among ‘‘innocent vomiting’’ (an entity
which is probably akin to infant regurgitation), ‘‘nervous vomit-
ing,’’ and infant rumination syndrome (10). Nervous vomiting was
thought to accompany other symptoms of impaired maternal–infant
reciprocity and often associated with failure to thrive. Fleisher
described infant rumination as an acquired skill used by an emotion-
ally deprived infant for the purpose of self-stimulation and needs
satisfaction. According to Fleisher and in line with initial reports in
the medical literature (11,12), this condition was often lethal, unless
improved mothering and increased environmental stimulation was
provided. It is likely that the condition described as infant rumina-
tion syndrome in the Rome criteria includes both Fleisher’s nervous
vomiting and rumination syndrome. Behavioral therapy with use of
aversive techniques and positive reinforcement has been shown to
be an effective treatment for rumination syndrome (12,13). Once
the nutritional deficiencies are corrected and the ruminant behavior
has improved, it usually does not recur (14).
INFANT DYSCHEZIA
Infant dyschezia is a condition that despite being extremely
common had received little or no attention in the medical literature
until the Rome Committee attempted to define it based on charac-
teristic symptoms (1). It also is known as ‘‘grunting baby syn-
drome,’’ based on the behavior of the infant, who seems to struggle
to have a bowel movement. Parents describe otherwise healthy
infants with dyschezia as straining for several minutes, often crying,
and turning red or purple in the face with effort. The symptoms
persist until there is passage of soft or liquid stool. Often well-
meaning parents try to alleviate the child’s perceived pain by
stimulating the anus with a suppository or a thermometer, an act
that usually leads to stooling and resolution of the distressed
behavior. This ‘‘success’’ then leads the parents to replicate the
intervention every time the grunt reoccurs. Failure to coordinate
increased intraabdominal pressure with relaxation of the pelvic
floor is thought to be the underlying pathophysiological mechanism
in infant dyschezia. The simultaneous contractions of abdominal
and gluteal muscles are not conducive to successful passage of
stools and some infants struggle in acquiring the necessary beha-
vioral skills needed for a pleasant defecation. Unlike infant colic,
the distress occurs only during the act of defecation. The symptoms
begin in the first months of life and resolve spontaneously after a
few weeks, once the infant has mastered more effective defecation
dynamics. The clinician must provide effective reassurance to the
parents that there is no disease and no testing or treatment is
necessary. Reassurance includes listening to the parents’ worries,
performing a thorough physical examination (including anal inspec-
tion), providing a plausible explanation for the symptom, and
expressing an expectation for spontaneous recovery. Repeated anal
stimulation is discouraged so as not to delay the infant’s learning the
correct defecation process.
FUNCTIONAL DIARRHEA
Functional diarrhea (commonly also known as toddlers’
diarrhea or chronic nonspecific diarrhea) is defined by the daily
painless passage of 3 large, unformed stools for 4 weeks with
onset between 6 and 36 months of age (1). The stooling occurs
during waking hours and there is no failure to thrive if the diet has
adequate calories (15). Parents often become concerned that their
child may have malabsorption when they find in the stools mucous
or easily identifiable pieces of undigested food (usually vegetable
matter) eaten just a few hours earlier. Although the frequency of the
defecations may increase and the stools may become looser, the
child does not seem to be in pain, and the condition resolves
spontaneously by school age. A dietary history often uncovers
overfeeding, excessive carbohydrate ingestion (especially fruit
juice and sorbitol), and low fat intake. In the absence of failure
to thrive, malabsorption is unlikely. Pathophysiology has been
thought to involve abnormalities in the control of postprandial
motility, increased activities of (Naþ-Kþ)-adenosine triphosphatase
and percentage of activation and basal activity of adenylate cyclase,
and bile salt malabsorption (16–18). Behavioral problems relating
to sleep, crying and irritability, activity, and discipline also were
found to be significantly more frequent or severe in a group of
children with chronic nonspecific diarrhea (19). Therapeutic inter-
ventions for functional diarrhea should focus on increasing dietary
fiber and fat intake and avoid excessively restrictive diets that may
cause calorie deprivation.

www.jpgn.org S37

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 Shamir et al
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9. Vandenplas Y. Thickened infant formula does what it has to do: decrease
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ing, nervous vomiting, and infant rumination syndrome. J Pediatr
1994;125 (6 Pt 2):S84–94.
11. Menking M, Wagnitz JG, Burton JJ, et al. Rumination—a near fatal
psychiatric disease of infancy. N Engl J Med 1969;280:802–4.
12. Luckey RE, Watson CM, Musick JK. Aversive conditioning as a means
of inhibiting vomiting and rumination. Am J Ment Defic 1968;73:139–42.
13. Whitehead WE, Drescher VM, Morrill-Corbin E, et al. Rumination
syndrome in children treated by increased holding. J Pediatr Gastro-
enterol Nutr 1985;4:550–6.
14. Sheinbein M. Treatment for the hospitalized infantle ruminator: pro-
grammed brief social behavior reinforcers. Clin Pediatr (Phila)
1975;14:719–24.
15. Cohen SA, Hendricks KM, Eastham EJ, et al. Chronic nonspecific
diarrhea. A complication of dietary fat restriction. Am J Dis Child
1979;133:490–2.
16. Fenton TR, Harries JT, Milla PJ. Disordered small intestinal motility: a
rational basis for toddlers’ diarrhoea. Gut 1983;24:897–903.
17. Kneepkens CM, Jakobs C, Douwes AC. Apple juice, fructose, and
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Gastrointestinal Food Allergy and
Intolerance in Infants and
Young Children
Ralf G. Heine
I nfants and young children may present with a diverse range of
gastrointestinal (GI) allergies and intolerances that are triggered
S38
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JPGN
Volume 57, Supplement 1, December 2013
by specific food proteins or other food constituents (eg, carbo-
hydrates, fat). It may be clinically difficult to distinguish these
conditions because there is significant overlap in symptoms. There
are several well-characterized food allergic GI conditions that
usually manifest in the first weeks to months of life and may even
occur in exclusively breast-fed infants. GI food allergy needs to be
distinguished from nonimmunological intolerance reactions to
foods. Examples are carbohydrate or fat malabsorption, which
presents with diarrhoea and abdominal pain following ingestion
of the offending food. In addition, dietary factors may directly
influence gut functioning and motility. For example, dietary long-
chain triglycerides may delay gastric emptying, which predisposes
to vomiting or upper abdominal pain. Because of the diverse
spectrum of diseases and underlying mechanisms it may sometimes
be difficult to define an exact diagnosis, and empirical treatment of
suspected adverse reactions to foods with dietary manipulations is
common practice.
GI FOOD ALLERGY
With the rise in allergic disorders, GI food allergies have
become a relatively common problem in infants and young children
(1). Population-based studies on the epidemiology of challenge-
proven immunoglobulin E (IgE)–mediated food allergy in 1-year-
old Australian infants found a high prevalence of >10% (2).
Although non-IgE-mediated food allergy is thought to be relatively
common, its exact prevalence in infancy is not known. GI food
allergy involves non-IgE-mediated, delayed GI reactions that may
cause upper and lower GI pathologies, including mucosal inflam-
mation, ulceration, small intestinal villous damage, changes in
intestinal permeability, or motility abnormalities. Symptoms in
young children include persistent vomiting/regurgitation, chronic
diarrhoea, feeding difficulties, unsettled behaviours, and sleep
pattern disturbance.
Relatively little progress has been made in developing
diagnostic tests for cell-mediated GI food allergy. Because no
single diagnostic test for non-IgE-mediated food allergy is avail-
able, the diagnosis relies on clinical improvement after food
elimination and relapse upon challenge. GI biopsies may provide
further important diagnostic clues. The cumbersome diagnostic
process and lack of characteristic symptoms may lead to significant
diagnostic delay and may result in adverse clinical outcomes,
including growth impairment or nutritional deficiency states (eg,
iron-deficiency anaemia). Early diagnosis and appropriate treat-
ment are therefore crucial in preventing the nutritional compli-
cations of GI food allergy.
Food Protein–Induced Enteropathy
Infants and young children with food protein–induced
enteropathy typically present with chronic diarrhea and failure to
thrive. Cow’s milk and soy milk protein are considered the main
offending food allergens. The prevalence of food protein–induced
enteropathy appears to have decreased since the development
of ‘‘humanized’’ cow’s milk and soy formula. Current reliable
From the Department of Gastroenterology & Clinical Nutrition, Royal
Children’s Hospital, Melbourne, Australia.
Correspondence to Ralf G. Heine, MD, Department of Gastroenterology &
Clinical Nutrition, Royal Children’s Hospital Melbourne, Parkville
3052, Victoria, Australia (e-mail: ralf.heine@rch.org.au).
The author reports no conflicts of interest.
Copyright # 2013 by European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition and North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
DOI: 10.1097/01.mpg.0000441934.92221.ca
www.jpgn.org