Current Gastroenterology Reports (2020) 22: 21

https://doi.org/10.1007/s11894-020-00760-8

PEDIATRIC GASTROENTEROLOGY (S ORENSTEIN AND S KHAN, SECTION EDITORS)

The Effects of the Rome IV Criteria on Pediatric

Gastrointestinal Practice
Desiree F. Baaleman 1,2 & Carlo Di Lorenzo 1 & Marc A. Benninga 2 & Miguel Saps 3

Published online: 19 March 2020

# The Author(s) 2020

Abstract
Purpose of Review To evaluate the impact of the implementation of the Rome IV criteria on pediatric gastrointestinal practice.
Recent Findings In 2016, the Rome IV criteria were published, providing an update of symptom-based criteria to diagnose
children with functional gastrointestinal disorders (FGIDs).
Summary For neonates and toddlers, Wessel’s criteria for diagnosing infant colic were abandoned, and a differentiation was
made between toilet-trained and non-toilet-trained children in the diagnosis of functional constipation. For children and adoles-
cents, two new disorders (functional nausea and functional vomiting) are described, and in the diagnosis of functional dyspepsia,
pain does not have to be the chief complaint anymore. This change has made functional dyspepsia the most common functional
abdominal pain disorder, exceeding the prevalence of irritable bowel syndrome (IBS). Lastly, the diagnosis of abdominal
migraine was narrowed, causing an appropriate drop in its prevalence.

Keywords Rome IV . Infants . Children . Functional gastrointestinal disorders . Infant colic . Functional abdominal pain

Introduction advance research on and treatment for patients with functional

gastrointestinal complaints. The diagnostic criteria are regularly
Functional gastrointestinal disorders (FGIDs) are common in updated to account for new developments in epidemiology,
children of all age groups [1•, 2•]. In the absence of biomarkers pathophysiology, diagnostic testing, and treatment [8]. The cur-
or specific tests to diagnose FGIDs, their diagnosis is based on rent pediatric criteria divide FGIDs according to age groups
symptom-based criteria. The current criteria used to diagnose (neonates and toddlers—0 to 3 years old—and children and
FGIDs were published in 2016 and are called the Rome IV adolescents—4 to 18 years old) (see Table 1). Within the chil-
criteria [3••, 4••]. These criteria replace the previous Rome III dren and adolescents’ group of diagnoses, there are three diag-
criteria [5, 6] and are the second revision of the pediatric FGID nostic categories based on the most bothersome symptom ac-
criteria who were first described in 1999 as the Rome II pedi- cording to the patient’s own report (or parental report in youn-
atric criteria [7]. The consensual definition of criteria is impor- ger children): disorders of nausea and vomiting, disorders of
tant in order to select homogeneous groups of patients to abdominal pain, and defecation disorders [3••, 4••].
This review provides an overview of the most relevant chang-
This article is part of the Topical collection on Pediatric Gastroenterology es in the Rome IV criteria in each age group, the impact of these
changes in the epidemiology of FGIDs, and the clinical implica-
* Desiree F. Baaleman tions for daily practice. At the end of each section, the reader will
desiree.baaleman@nationwidechildrens.org find a brief outline on considerations for future research.

1
Division of Gastroenterology, Hepatology, and Nutrition,
Nationwide Children’s Hospital, Columbus, OH, USA
2
Infants and Toddlers
Department of Pediatric Gastroenterology and Nutrition, Emma
Children’s Hospital, Amsterdam UMC, University of Amsterdam,
Amsterdam, the Netherlands Infant Colic
3
Division of Pediatric Gastroenterology, Hepatology, and Nutrition,
Holtz Children’s Hospital, Miller School of Medicine, University of The most important modification in the diagnosis of FGIDs in
Miami, Miami, FL, USA neonates and toddlers concerns the diagnostic criteria for
21 Page 2 of 7 Curr Gastroenterol Rep (2020) 22: 21

Table 1 FGIDs according to Rome IV [3••, 4••] in significant changes in epidemiology when comparing
Functional gastrointestinal disorders in neonates and toddlers community-based studies using the Rome III and Rome IV
Infant regurgitation criteria [1•]. The treatment of infant colic is currently based on
Infant rumination syndrome
expert-opinions and should, in the absence of red-flags, focus
Cyclic vomiting syndrome
on reassuring and supporting parents [11].
Infant colic
For research purposes, there are additional criteria to diag-
nose infant colic: the caregiver should report that the infant
Functional diarrhea
has cried or fussed for 3 or more hours per day during 3 or
Infant dyschezia
more days in 7 days in a telephone or face-to-face screening
Functional constipation
interview with a researcher or clinician. Crying or fussing
Functional gastrointestinal disorders in children and adolescents should be confirmed to be 3 h or more when measured by at
Functional nausea and vomiting disorders least one prospectively kept, 24-h behavior diary. These addi-
Cyclic vomiting syndrome tional criteria will secure a specific diagnosis for research;
Functional nausea and functional vomiting however, they also increase the necessary effort to set up a
Rumination syndrome research study. No studies have been conducted to establish if
Aerophagia the changes of the research criteria for infant colic will influ-
Functional abdominal pain disorders ence the frequency of diagnosis.
Functional dyspepsia Future research in infant colic should focus on investigat-
Postprandial distress syndrome ing the role of the microbiome in the pathophysiology and
Epigastric pain syndrome possible treatment of infant colic, on developing an objective
Irritable bowel syndrome (IBS) method to measure the severity of infant colic for research
Predominant constipation (IBS-C) purposes, and on establishing evidence-based management
Predominant diarrhea (IBS-D) strategies for treating infant colic.
Mixed bowel habits (IBS-M)
Unclassified (IBS-U) Functional constipation
Abdominal migraine
Functional abdominal pain-not otherwise specified can be diagnosed in both age groups. There are different
Functional defecation disorders definitions for functional constipation in neonates and toddlers
Functional constipation versus children and adolescents. The committee harmonized
Nonretentive fecal incontinence the duration criterion in both age groups to 1 month and made
additional adjustments to the criteria for the younger children.
After reviewing the Rome III diagnostic criteria, the members
infant colic. The Rome IV pediatric committee established of the committee thought that some aspects of the criteria were
different diagnostic criteria for clinical and research purposes. not pertinent to children in diapers. The Rome IV now differ-
For clinical purposes, the criteria are no longer based on entiates between children with and without toilet training.
Wessel et al.’s “rule of threes” (crying more than 3 h a day, Non-toilet-trained children may be diagnosed with functional
for more than 3 days a week, for more than 3 weeks in a row) constipation if they show at least two of the following criteria:
[9]. According to the committee, these criteria were arbitrary, two or fewer defecations per week, a history of excessive stool
culturally dependent, impractical, and did not reflect the im- retention, a history of painful or hard bowel movements, a
pact of the child’s symptoms on the family [3••]. Therefore, history of large-diameter stools, and/or the presence of a large
the new clinical criteria are based on symptoms that have been fecal mass in the rectum. For toilet-trained children, two ad-
shown to cause higher distress to parents. Besides this, the age ditional criteria may be used: at least one episode of inconti-
of diagnosis of infant colic was extended to infants up to nence per week and/or a history of large-diameter stools that
5 months of age. Infant colic is characterized as recurrent may obstruct the toilet. Since the new criteria, one study found
and prolonged periods of crying, fussing, or irritability, with- a rise in prevalence of functional constipation in infants and
out obvious cause and not resolvable or preventable by care- toddlers from 4.7 to 12.1% [1]. Unpublished data by some of
givers, without evidence of failure to thrive, fever, or illness in the authors of this manuscript did not confirm this rise; how-
an infant under 5 months at the onset and resolution of symp- ever, they did find a significant higher prevalence in toilet-
toms. With these new criteria, the committee attempted to trained young children compared with non-toilet-trained
reduce family distress by providing early and timely reassur- young children.
ance, education, and support to the parents of infants with Future research should focus on assessing the impact of the
colic, factors that are the mainstay of management [10]. changes made in the Rome IV criteria compared with previous
Changes in the diagnostic criteria for infant colic did not result versions in terms of prevalence of constipation and treatment.
Curr Gastroenterol Rep (2020) 22: 21 Page 3 of 7 21

Next to this, randomized controlled trials should be set up to and, as such, frequently manifest in the same patient. In order
evaluate the influence of foods and laxatives in this age group. to clarify the diagnosis in patients with overlapping symptoms
(e.g., children with cyclic vomiting syndrome and abdominal
migraine can have both abdominal pain and vomiting), the
Children and Adolescents Rome IV criteria stress that the primary diagnosis should be
based on the most bothersome symptom. This consideration
There have been multiple modifications in the diagnostic has diagnostic and therapeutic implications in clinical prac-
criteria in this age group. Specific changes were also made tice, as children with abdominal migraine are not always re-
to each category of FGIDs. In the past, there was a common ferred to a pediatric gastroenterologist and are instead seen by
criterion to all FGIDs: a requirement for “absence of inflam- neurologists, who use different diagnostic criteria (ICHD) and
matory, anatomic, metabolic, or neoplastic process that ex- frequently recommend different treatments [16, 17].
plains the subject’s symptoms.” This criterion has been The Rome III criteria made no reference to children with
substituted by “after appropriate medical evaluation, the isolated nausea or to the overlap of nausea with non-cyclical
symptoms cannot be attributed to another medical condition.” disorders. In the previous version of the criteria, nausea was
The reasoning behind this change was the common perception only mentioned in the setting of cyclic vomiting syndrome or
among the members of the committee that the previous state- abdominal migraine. Studies have shown that nausea is a com-
ment could be misconstrued as a mandate to conduct exhaus- mon symptom in children with functional abdominal pain
tive testing prior to establishing diagnosis. However, in the disorders [18] and that some children have nausea or vomiting
absence of biomarkers, testing is not always necessary. The that presents in a non-stereotypical and cyclical fashion [19].
rephrasing of the criterion leaves the decision of determining Moreover, studies have shown that nausea is a highly
what type of testing (if any) is to be conducted with the phy- invalidating symptom and that children with severe and
sician. Although the result of this change has not yet been prolonged nausea have a poor quality of life [20]. As a result,
evaluated, it was hoped that this would reduce the amount of the Rome IV criteria established two new diagnoses: function-
unnecessary testing in subjects with FGIDs [12]. al nausea and functional vomiting. Functional nausea is ap-
The Rome IV criteria underscored the importance of plied to the group of children that report bothersome nausea as
recognizing the presence of overlapping comorbidities. the predominant symptom, occurring at least twice per week,
Children with FGIDs frequently meet criteria for two for at least 2 months, and generally not related to meals, nor
FGIDs simultaneously or in succession. The committee consistently associated with vomiting. To diagnose a patient
also encourages clinicians to consider the possibility of with functional vomiting, the child must have at least one
an overlap between FGIDs and organic diseases. For ex- episode of vomiting per week. The vomiting should not be
ample, it is known that a large proportion of children (up related to an eating disorder, to rumination, or be self-induced.
to 25% in some studies) diagnosed with inflammatory The current evidence suggests that functional nausea and
bowel disease have symptoms of functional origin that vomiting can be diagnosed in children. Epidemiological stud-
are not explained by the underlying inflammatory process ies conducted in the USA and Latin-America have shown that
[13]. The recognition of the overlap of functional symp- these disorders are uncommon. The prevalence of functional
toms in organic diseases moves away from the reduction- nausea is approximately 0.1–0.5%, and the prevalence of
istic assumption that all symptoms reported by patients functional vomiting is approximately 0.6–1.4% [1•, 2•].
with organic diseases should have an organic origin. The The newly defined diagnoses allow labeling a subset of
understanding that alterations of brain-gut axis can ex- patients seen in clinic. Providing a patient with a diagnosis
plain the symptoms in children with functional or organic helps reassure the families and children while at the same time
diseases has important treatment implications. It justifies may avoid unnecessary testing in search of an elusive disease.
the use of mind-body treatments such as cognitive behav- Education of families on the diagnosis can provide a sense of
ioral therapy, guided imagery, or hypnotherapy to allevi- relief that can positively influence the prognosis [21]. Due to
ate symptoms [14] in children with both functional and/or the recent inclusion of the diagnoses of functional and nausea
organic diagnoses. and vomiting in children, there is still lack of evidence for
specific pharmacological and non-pharmacological treatments
Functional Disorders of Nausea and Vomiting [22]. In the absence of evidence-based recommendations for
their treatment, management principles are extrapolated from
The criteria for the diagnosis of cyclic vomiting syndrome clinical trials aimed at treating other diseases/disorders with
have been modified and are now in line with the common symptoms. Pharmacological treatments, as well as
NASPGHAN guidelines for diagnoses and treatment [15]. complementary treatments such as some herbal therapies, cog-
Cyclic vomiting syndrome, abdominal migraine, and migraine nitive behavioral therapy, and hypnotherapy, which have been
headaches are considered part of the same family of disorders shown to be effective in children with severe nausea due to
21 Page 4 of 7 Curr Gastroenterol Rep (2020) 22: 21

chemotherapy or post-surgery [23], can be indicated in chil- prevalence of IBS, which was previously found to be the most
dren with these diagnoses. Similar to the treatment of most prevalent functional abdominal pain disorder in the regions of
FGIDs, an interdisciplinary approach addressing psychosocial the conducted studies and in a worldwide meta-analysis [24]. A
burden is sought [19]. recent study studying the prevalence of functional dyspepsia in
Future research on functional nausea and vomiting adults in the USA, Canada, and the UK also found functional
should focus on establishing the natural history of these dyspepsia to be more common than IBS [25]. Because of the
disorders, understanding the risk and protective factors for previous predominance in prevalence of IBS, most published
their development, and designing clinical trials to obtain research was focused on this diagnosis, and little attention was
evidence-based data for their treatment. However, due to being paid to functional dyspepsia, which was thought to be
the low prevalence of these disorders, clinical trials will uncommon. Thus, currently, there are neither guidelines for the
likely need to be multicenter. treatment of children with functional dyspepsia nor prospective
randomized studies to provide recommendations. A recent sys-
Functional Abdominal Pain Disorders tematic review found that there is no available evidence to
support the use of any pharmacological drugs to treat children
The group of disorders characterized by the predominance of with functional dyspepsia [22]. However, the committee made
abdominal pain has been renamed as functional abdominal pain recommendations for the treatment of each subtype based on
disorders. It was thought that the Rome III criteria term of expert opinion and adult based data. For the epigastric pain
“abdominal pain predominant functional gastrointestinal disor- syndrome subtype, the committee recommended the use of
ders” was cumbersome and that new and more intuitive termi- proton pump inhibitors as first line treatment. Tricyclic antide-
nology was needed. This group of disorders includes functional pressants are recommended for the most severe or recalcitrant
abdominal pain-not otherwise specified (FAP-NOS), which re- cases. For the postprandial distress syndrome subtype, the com-
places the Rome III diagnoses of functional abdominal pain and mittee recommends the use of fundal relaxant medications (i.e.,
functional abdominal pain syndrome, two diagnosis that were cyproheptadine) and prokinetics, such as erythromycin.
thought to be a spectrum of severity within the same disorder. Retrospective studies have shown that cyproheptadine may be
Three other diagnoses are included in this category: functional beneficial and safe for children with symptoms of dyspepsia
dyspepsia, irritable bowel syndrome (IBS), and abdominal mi- [26]. Although approximately one third of children will report
graine. Each of these diagnoses underwent changes. side effects, those are usually minor and limited to somnolence,
increased appetite, and weight gain [27]. Other medications
Functional Dyspepsia with 5HT-1 agonist effect, such as buspirone, have been used
with some success in small trials in adults [28]. There are few
In contrast to the Rome III criteria, the Rome IV definition of prokinetics with pediatric evidence available in the USA. The
functional dyspepsia does not require patients to describe pain Food and Drug Adminsitration (FDA) has issued a black box
as the predominant symptom. Patients may present with at warning to the use of metoclopramide due to the risk of tardive
least one of the following symptoms: postprandial fullness, dyskinesia associated with prolonged use [29]. Domperidone is
early satiation, epigastric pain, or burning. With this new def- not available in the USA, but can be more easily obtained in
inition came two subtypes: epigastric pain syndrome and post- many other countries. Risk of QT prolongation should be con-
prandial distress syndrome. Epigastric pain syndrome is char- sidered with its use [30] as well as with antibiotics that have a
acterized by epigastric pain that is not modified with bowel motilin agonist effect, such as erythromycin and azithromycin,
movements, as would be the case in IBS. Postprandial distress which are sometimes used as prokinetics. Newly FDA ap-
syndrome includes children who have early satiety or discom- proved prokinetics for the use in adult patients include
fort that may not allow them to finish their meal and occasion- tegaserod and prucalopride. Pediatric studies have also shown
ally even leads to weight loss. While the latter is associated that gastro-electrical stimulation may be useful in children with
with meals, it is not always the case with epigastric pain syn- functional dyspepsia [31, 32].
drome. Based on the new definitions of subtypes, children Prospective, preferably multicenter, studies should be de-
diagnosed with functional dyspepsia in Rome III would now signed to assess the pathophysiology of each subtype of func-
mostly fulfill the criteria for epigastric pain syndrome in Rome tional dyspepsia in children, to establish the risk factors for
IV. Studies comparing the prevalence of functional abdominal their development and prognosis, and to assess the efficacy of
pain disorders between the Rome III criteria and the Rome IV the various treatment options.
criteria found that with the new definition, functional dyspep-
sia is now the most common disorder in this group (3.0– Abdominal Migraine
7.6%), with postprandial distress syndrome being the most
common subtype (2.7–7.2%) [1•, 2•]. Interestingly, in these With the change of diagnostic criteria from the Rome II to
studies, the prevalence of functional dyspepsia exceeds the Rome III edition, the prevalence of this diagnosis greatly
Curr Gastroenterol Rep (2020) 22: 21 Page 5 of 7 21

increased to what was thought to be an unusual high prevalence An important consideration made by the committee was to set
[33]. The committee considered that such a high prevalence did criteria to differentiate IBS-C from functional constipation. The
not reflect clinical practice. Studies have shown that the Rome committee recommends that patients with abdominal pain and
III abdominal migraine diagnosis was easily misclassified and constipation should first be treated for constipation. When
regularly overlapped with the diagnosis of IBS [33–36]. The symptoms of abdominal pain persist despite adequate treatment
committee made changes in the abdominal migraine diagnosis of constipation, the patient is to be diagnosed with IBS-C and
to solve this problem. The new diagnosis of abdominal mi- treated according to evidence-based guidelines [21].
graine is more stringent and better defines the period between For the treatment of IBS, education, establishing a thera-
symptomatic attacks. The Rome IV criteria include paroxysmal peutic alliance and providing reassurance, may be sufficient.
and stereotypical episodes of intense, acute periumbilical, mid- In other cases, additional therapeutic strategies can be applied.
line or diffuse abdominal incapacitating pain as the predomi- There is increasing evidence for a non-pharmacological treat-
nant symptom, lasting at least 1 h and interfering with daily ment approach, including biopsychosocial modifying thera-
activities. The pain should be associated with at least 2 of the pies and dietary interventions [21, 43]. In patients who prefer
following: anorexia, nausea, vomiting, headache, photophobia, a pharmacological approach, the Rome IV Interactive Clinical
or pallor, and the episodes should occur at least twice within Decision Toolkit recommends antispasmodics as first line and
6 months [4••]. As a result of these changes in diagnostic the use of tricyclic antidepressants in recalcitrant cases [44].
criteria, the prevalence of abdominal migraines decreased from The treatment of the patient’s stool problems may require
23 to 0.5–1.1% [1•, 2•]. This prevalence most likely better additional medications. Laxatives can be used in cases of con-
reflects the “real” prevalence of this disorder. This more specific stipation and medications that decrease motility and secretions
diagnosis of patients with abdominal migraine has important can be used in cases of diarrhea. Common medications used in
implications for treatment, as management strategies between IBS-D are loperamide and cholestyramine. Studies in adults
abdominal migraine and IBS differ. Primary interventions for have shown significant benefit from the use of lubiprostone,
abdominal migraine include preventive measures such as prucalopride, and linaclotide over placebo in IBS-C [45]. For
avoidance of triggers, behavior therapy, and dietary modifica- adults with IBS-D, the use of bile acid sequestrants may be
tions [37]. Pharmacological treatment should be considered if beneficial, as up to 50% of adults with functional diarrhea and
symptoms are refractory to these interventions [37]. Up until IBS-D have bile acid malabsorption [46]. Rifaximin,
now, only one small (n = 16) double blind placebo controlled eluxadoline, and alosetron have been shown to be beneficial
study has evaluated the effect of pizotifen (not available in the in the treatment of IBS-D in adults but no trials have been
USA) as a prophylactic treatment, which showed a positive conducted in children [47].
effect [38]. Amitriptyline can be used in the prevention of ab- There is a paucity of validation of the Bristol Scale and
dominal migraine and cyclic vomiting. The recommended little evidence to support treatments for the various IBS sub-
doses for abdominal migraine range 0.2–0.4 mg/kg [39], while types in children. Large clinical trials should be conducted in
for cyclic vomiting syndrome, the guideline recommends slow- this regard and to better characterize the IBS diagnosis and its
ly increasing the dose up to 1.0–1.5 mg/kg [15]. subtypes and to test the Rome IV proposed differences be-
The committee believes that abdominal migraine, cyclic tween IBS-C and functional constipation.
vomiting, and migraine headache share the same pathophysi-
ology, but none of the current hypotheses have been definitely Functional Defecation Disorders
confirmed [37]. There is a need for studies to better character-
ize this family of disorders, the common triggers, natural his- In the category of functional defecation disorders, only minor
tory, and treatment options. adjustments were made to the children and adolescent group.
The necessary duration for diagnosis of functional constipa-
Irritable Bowel Syndrome tion was shortened from 2 to 1 month to emphasize the im-
portance of early treatment that was shown to improve the
In line with adult diagnostic criteria, four subtypes of IBS have prognosis. Studies comparing the Rome III and Rome IV
been defined [40]. The new classification allows differentiation criteria have shown that the reduction in the time criterion
of treatments for patients with different subtypes of IBS. The did not modify the prevalence of functional constipation in
subtypes are based on the predominant stooling pattern accord- children and adolescents [1•, 2•, 48].
ing to the Bristol Stool Scale and are defined as IBS with con-
stipation (IBS-C), diarrhea (IBS-D), mixed bowel habits (IBS-
M), and an unclassified group for those who do not fit in these Conclusion
subtypes. IBS-C seems to be the most common subtype in
children and adolescents in most studies; however, it is not The Rome IV criteria have changed the framework in which
uncommon for patients to change subtype over time [41, 42]. physicians examine, diagnose, and treat children. With the
21 Page 6 of 7 Curr Gastroenterol Rep (2020) 22: 21

introduction of functional nausea and functional vomiting as 3.•• Benninga MA, Nurko S, Faure C, Hyman PE, Roberts ISJ,
Schechter NL. Childhood functional gastrointestinal disorders: ne-
defined disorders and the significant changes in diagnostic
onate/toddler. Gastroenterology. 2016;150(6):1443–55. e2 The
criteria for infant colic, abdominal migraine, and functional Rome IV criteria for neonates/toddlers.
dyspepsia, prevalence and patient characteristics have 4.•• Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van
changed, warranting new studies involving the different pa- Tilburg M. Childhood functional gastrointestinal disorders: child/
tient populations. Additionally, and in view of the differences adolescent. Gastroenterology. 2016;150(6):1456–68. e2 The Rome
IV criteria for children/adolescents.
in results between clinical trials conducted in children and 5. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS,
adults, pediatric trials should be designed to establish Staiano A, et al. Childhood functional gastrointestinal disorders:
evidence-based beneficial treatment strategies specifically child/adolescent. Gastroenterology. 2006;130(5):1527–37.
for children. 6. Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF,
Taminiau J. Childhood functional gastrointestinal disorders: neo-
nate/toddler. Gastroenterology. 2006;130(5):1519–26.
Compliance with Ethical Standards 7. Rasquin-Weber A, Hyman PE, Cucchiara S, Fleisher DR, Hyams
JS, Milla PJ, et al. Childhood functional gastrointestinal disorders.
Conflict of Interest Miguel Saps has served as a Scientific Consultant Gut. 1999;45 Suppl 2:Ii60–8. https://doi.org/10.1136/gut.45.2008.
for Allergan, Ironwood, and Forest. Marc A. Benninga has served as a ii60.
Scientific Consultant for Allergan, Norgine, Coloplast, Danone, 8. Drossman DA. The functional gastrointestinal disorders and the
FrieslandCampina, Sensus, and Takeda. These companies have had no Rome III process. Gastroenterology. 2006;130(5):1377–90.
input or involvement in any aspect of this study. The other authors have 9. Wessel MA, Cobb JC, Jackson EB, Harris GS, Detwiler AC.
no conflicts of interest to disclose. Paroxysmal fussing in infancy, sometimes called “colic”.
Pediatrics. 1954;14(5):421–35.
Human and Animal Rights All reported studies/experiments with hu- 10. Vandenplas Y, Benninga M, Broekaert I, Falconer J, Gottrand F,
man or animal subjects performed by the authors have been previously Guarino A, et al. Functional gastro-intestinal disorder algorithms
published, unless stated otherwise, and complied with all applicable eth- focus on early recognition, parental reassurance and nutritional
ical standards (including the Helsinki declaration and its amendments, strategies. Acta Paediatr. 2016;105(3):244–52. https://doi.org/10.
institutional/national research committee standards, and international/na- 1111/apa.13270.
tional/institutional guidelines). 11. Zeevenhooven J, Browne PD, L’Hoir MP, de Weerth C, Benninga
MA. Infant colic: mechanisms and management. Nat Rev
Open Access This article is licensed under a Creative Commons Gastroenterol Hepatol. 2018;15(8):479–96. https://doi.org/10.
Attribution 4.0 International License, which permits use, sharing, adap- 1038/s41575-018-0008-7.
tation, distribution and reproduction in any medium or format, as long as 12. Choung RS, Rubio-Tapia A, Lahr BD, Kyle RA, Camilleri MJ,
you give appropriate credit to the original author(s) and the source, pro- Locke GR, et al. Evidence against routine testing of patients with
vide a link to the Creative Commons licence, and indicate if changes were functional gastrointestinal disorders for celiac disease: a population-
made. The images or other third party material in this article are included based study. Clin Gastroenterol Hepatol. 2015;13(11):1937–43.
in the article's Creative Commons licence, unless indicated otherwise in a https://doi.org/10.1016/j.cgh.2015.05.014.
credit line to the material. If material is not included in the article's 13. Watson KL Jr, Kim SC, Boyle BM, Saps M. Prevalence and impact
Creative Commons licence and your intended use is not permitted by of functional abdominal pain disorders in children with inflammatory
statutory regulation or exceeds the permitted use, you will need to obtain bowel diseases (IBD-FAPD). J Pediatr Gastroenterol Nutr.
permission directly from the copyright holder. To view a copy of this 2017;65(2):212–7. https://doi.org/10.1097/mpg.0000000000001479.
licence, visit http://creativecommons.org/licenses/by/4.0/. 14. Rutten JM, Reitsma JB, Vlieger AM, Benninga MA. Gut-directed
hypnotherapy for functional abdominal pain or irritable bowel syn-
drome in children: a systematic review. Arch Dis Child. 2013;98(4):
252–7. https://doi.org/10.1136/archdischild-2012-302906.
15. Li BU, Lefevre F, Chelimsky GG, Boles RG, Nelson SP, Lewis DW,
References et al. North American Society for Pediatric Gastroenterology,
Hepatology, and Nutrition consensus statement on the diagnosis
Papers of particular interest, published recently, have been and management of cyclic vomiting syndrome. J Pediatr
Gastroenterol Nutr. 2008;47(3):379–93. https://doi.org/10.1097/
highlighted as: MPG.0b013e318173ed39.
• Of importance 16. The International Classification of Headache Disorders, 3rd edition
•• Of major importance (beta version). Cephalalgia. 2013;33(9):629–808. doi:https://doi.
org/10.1177/0333102413485658.
1.• Robin SG, Keller C, Zwiener R, Hyman PE, Nurko S, Saps M, et al. 17. Spiri D, Rinaldi VE, Titomanlio L. Pediatric migraine and episodic
Prevalence of pediatric functional gastrointestinal disorders utiliz- syndromes that may be associated with migraine. Ital J Pediatr.
ing the Rome IV criteria. J Pediatr. 2018;195:134–9 Study on the 2014;40:92. https://doi.org/10.1186/s13052-014-0092-4.
prevalence of functional gastrointestinal disorders in infants 18. Kovacic K, Williams S, Li BUK, Chelimsky G, Miranda A. High
and toddlers, and children and adolescents. prevalence of nausea in children with pain-associated functional
2.• Saps M, Velasco-Benitez CA, Langshaw AH, Ramírez-Hernández gastrointestinal disorders: are Rome criteria applicable? J Pediatr
CR. Prevalence of functional gastrointestinal disorders in children Gastroenterol Nutr. 2013;57(3):311–5. https://doi.org/10.1097/
and adolescents: comparison between Rome III and Rome IV MPG.0b013e3182964203.
criteria. J Pediatr. 2018;199:212–6 Study on the prevalence of 19. Kovacic K, Di Lorenzo C. Functional nausea in children. J Pediatr
functional gastrointestinal disorders in children and Gastroenterol Nutr. 2016;62(3):365–71. https://doi.org/10.1097/
adolescents. mpg.0000000000001076.
Curr Gastroenterol Rep (2020) 22: 21 Page 7 of 7 21

20. Russell AC, Stone AL, Walker LS. Nausea in children with func- physician diagnosis and daily symptoms. Neurogastroenterol Motil.
tional abdominal pain predicts poor health outcomes in young 2013;25(4):302–e246. https://doi.org/10.1111/nmo.12056.
adulthood. Clin Gastroenterol Hepatol. 2017;15(5):706–11. 35. Helgeland H, Flagstad G, Grøtta J, Vandvik PO, Kristensen H,
https://doi.org/10.1016/j.cgh.2016.07.006. Markestad T. Diagnosing pediatric functional abdominal pain in
21. Sandhu BK, Paul SP. Irritable bowel syndrome in children: patho- children (4–15 years old) according to the Rome III criteria: results
genesis, diagnosis and evidence-based treatment. World J from a Norwegian prospective study. J Pediatr Gastroenterol Nutr.
Gastroenterol. 2014;20(20):6013–23. https://doi.org/10.3748/wjg. 2009;49(3):309–15.
v20.i20.6013. 36. Saps M, Sztainberg M, Pusatcioglu C, Chogle A. Tu2007 Accuracy
22. Browne PD, Nagelkerke SCJ, van Etten-Jamaludin FS, Benninga of diagnosis for abdominal migraine in children. Gastroenterology.
MA, Tabbers MM. Pharmacological treatments for functional nau- 2014;146(5):S–897.
sea and functional dyspepsia in children: a systematic review. 37. Mani J, Madani S. Pediatric abdominal migraine: current perspec-
Expert Rev Clin Pharmacol. 2018;11(12):1195–208. https://doi. tives on a lesser known entity. Pediatric Health Med Ther. 2018;9:
org/10.1080/17512433.2018.1540298. 47–58. https://doi.org/10.2147/PHMT.S127210.
23. RICHARDSON J, SMITH JE, MCCALL G, RICHARDSON A, 38. Symon DN, Russell G. Double blind placebo controlled trial of
PILKINGTON K, KIRSCH I. Hypnosis for nausea and vomiting in pizotifen syrup in the treatment of abdominal migraine. Arch Dis
cancer chemotherapy: a systematic review of the research evidence. Child. 1995;72(1):48–50. https://doi.org/10.1136/adc.72.1.48.
Eur J Cancer Care. 2007;16(5):402–12. https://doi.org/10.1111/j.
39. Bahar RJ, Collins BS, Steinmetz B, Ament ME. Double-blind pla-
1365-2354.2006.00736.x.
cebo-controlled trial of amitriptyline for the treatment of irritable
24. Korterink JJ, Diederen K, Benninga MA, Tabbers MM.
bowel syndrome in adolescents. J Pediatr. 2008;152(5):685–9.
Epidemiology of pediatric functional abdominal pain disorders: a
https://doi.org/10.1016/j.jpeds.2007.10.012.
meta-analysis. PLoS One. 2015;10(5):e0126982–e. https://doi.org/
10.1371/journal.pone.0126982. 40. Drossman DA, Hasler WL. Rome IV—functional GI disorders:
25. Aziz I, Palsson OS, Törnblom H, Sperber AD, Whitehead WE, disorders of gut-brain interaction. Gastroenterology. 2016;150(6):
Simrén M. Epidemiology, clinical characteristics, and associations 1257–61.
for symptom-based Rome IV functional dyspepsia in adults in the 41. Giannetti E, de’Angelis G, Turco R, Campanozzi A, Pensabene L,
USA, Canada, and the UK: a cross-sectional population-based Salvatore S, et al. Subtypes of irritable bowel syndrome in children:
study. Lancet Gastroenterol Hepatol. 2018;3(4):252–62. https:// prevalence at diagnosis and at follow-up. J Pediatr. 2014;164(5):
doi.org/10.1016/S2468-1253(18)30003-7. 1099–103.e1. https://doi.org/10.1016/j.jpeds.2013.12.043.
26. Rodriguez L, Diaz J, Nurko S. Safety and efficacy of cyprohepta- 42. Self MM, Czyzewski DI, Chumpitazi BP, Weidler EM, Shulman
dine for treating dyspeptic symptoms in children. J Pediatr. RJ. Subtypes of irritable bowel syndrome in children and adoles-
2013;163(1):261–7. https://doi.org/10.1016/j.jpeds.2012.12.096. cents. Clin Gastroenterol Hepatol. 2014;12(9):1468–73. https://doi.
27. Madani S, Cortes O, Thomas R. Cyproheptadine use in children org/10.1016/j.cgh.2014.01.031.
with functional gastrointestinal disorders. J Pediatr Gastroenterol 43. Newlove-Delgado TV, Martin AE, Abbott RA, Bethel A,
Nutr. 2016;62(3):409–13. https://doi.org/10.1097/mpg. Thompson-Coon J, Whear R, et al. Dietary interventions for recur-
0000000000000964. rent abdominal pain in childhood. Cochrane Database Syst Rev.
28. Tack J, Janssen P, Masaoka T, Farré R, Van Oudenhove L. Efficacy 2017;3(3):CD010972-CD. https://doi.org/10.1002/14651858.
of buspirone, a fundus-relaxing drug, in patients with functional CD010972.pub2.
dyspepsia. Clin Gastroenterol Hepatol. 2012;10(11):1239–45. 44. IV R. Interactive Clinical Decision Toolkit. 2016 http://
https://doi.org/10.1016/j.cgh.2012.06.036. theromefoundation.org/rome-iv-interactive-clinical-decision-toolkit/.
29. US Food and Drug Administration. FDA requires boxed warning Accessed 12/5/2019.
and risk mitigation strategy for metoclopramide-containing drugs: 45. Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG,
agency warns against chronic use of these products to treat gastro- et al. Linaclotide for irritable bowel syndrome with constipation: a
intestinal disorders. Silver Spring, MD: FDA. 2009. https:// 26-week, randomized, double-blind, placebo-controlled trial to
wayback.archive-it.org/7993/20170112033201/http://www.fda. evaluate efficacy and safety. Am J Gastroenterol. 2012;107(11):
gov/NewsEvents/Newsroom/PressAnnouncements/2009/ 1702–12. https://doi.org/10.1038/ajg.2012.254.
ucm149533.htm. 46. Wedlake L, A’Hern R, Russell D, Thomas K, Walters JR, Andreyev
30. Morris AD, Chen J, Lau E, Poh J. Domperidone-associated QT HJ. Systematic review: the prevalence of idiopathic bile acid mal-
interval prolongation in non-oncologic pediatric patients: a review absorption as diagnosed by SeHCAT scanning in patients with
of the literature. Canadian J Hosp Pharm. 2016;69(3):224–30. diarrhoea-predominant irritable bowel syndrome. Aliment
https://doi.org/10.4212/cjhp.v69i3.1560. Pharmacol Ther. 2009;30(7):707–17. https://doi.org/10.1111/j.
31. Lu PL, Teich S, Lorenzo CD, Skaggs B, Alhajj M, Mousa HM. 1365-2036.2009.04081.x.
Improvement of quality of life and symptoms after gastric electrical 47. Brenner DM, Sayuk GS. Current US Food and Drug Administration-
stimulation in children with functional dyspepsia. Neurogastroenterol approved pharmacologic therapies for the treatment of irritable bowel
Motil. 2013;25(7):567–e456. https://doi.org/10.1111/nmo.12104. syndrome with diarrhea. Adv Ther. 2019;37:83–96. https://doi.org/
32. Teich S, Mousa HM, Punati J, Di Lorenzo C. Efficacy of permanent 10.1007/s12325-019-01116-z.
gastric electrical stimulation for the treatment of gastroparesis and 48. Jativa-Marino E, Rivera-Valenzuela MG, Velasco-Benitez CA,
functional dyspepsia in children and adolescents. J Pediatr Surg. Saps M. The prevalence of functional constipation in children
2013;48(1):178–83. https://doi.org/10.1016/j.jpedsurg.2012.10.038. was unchanged after the Rome IV criteria halved the diagnosis
33. Baber KF, Anderson J, Puzanovova M, Walker LS. Rome II versus period in Rome III. Acta Paediatr. 2019. https://doi.org/10.1111/
Rome III classification of functional gastrointestinal disorders in apa.14880.
pediatric chronic abdominal pain. J Pediatr Gastroenterol Nutr.
2008;47(3):299–302.
34. van Tilburg MAL, Squires M, Blois-Martin N, Leiby A, Langseder Publisher’s Note Springer Nature remains neutral with regard to jurisdic-
A. Test of the child/adolescent Rome III criteria: agreement with tional claims in published maps and institutional affiliations.