- Email: [email protected]
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria
ARTICLE IN PRESS THE JOURNAL OF PEDIATRICS • www.jpeds.com
ORIGINAL ARTICLES
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria Miguel Saps, MD1, Carlos Alberto Velasco-Benitez, MD2, Amber Hamid Langshaw, MD1, and Carmen Rosy Ramírez-Hernández, MD3 Objectives To assess the prevalence of functional gastrointestinal disorders (FGIDs) in children using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV with Rome III criteria. Study design This was a cross-sectional study using the same methods as our previous study on FGIDs in Colombia. The Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV version was translated into Spanish, followed by reverse translation. Terms were adjusted to children’s language by using focus groups of children. School children aged 8-18 years completed the Spanish version of the Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV. Data were compared with Rome III data. Results In total, there were 3567 children (from 6 cities): 1071 preadolescents (8-12 years) and 2496 adolescents (13-18 years). Average age 13.7 ± 2.4 years (56.5% girls). A total of 21.2% of children had at least 1 FGID. Prevalence was significantly lower than Rome III (P = .004). Similar to Rome III, disorders of defecation were the most common, followed by abdominal pain, and disorders of nausea and vomiting. Prevalence of abdominal migraine decreased (P = .000) and functional dyspepsia increased (P = .000). The new diagnoses functional vomiting and functional nausea were present in 0.7% of all children. Conclusions The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs; however, the relative frequency of each subgroup of disorders did not change. New diagnoses of the Rome IV criteria were present in a small percentage of children. (J Pediatr 2018;■■:■■-■■). unctional gastrointestinal disorders (FGIDs) are the most common cause of consultation to pediatric gastroenterology.1 In children, FGIDs are associated with low quality of life, psychological distress, school absenteeism, and poor physical and social functioning.2 A large proportion of children with FGIDs continue to experience symptoms for several years despite treatment.3 In many cases, FGIDs are forerunners for adult symptoms. A total of 25% of children who present with recurrent abdominal pain will evolve into adults with irritable bowel syndrome (IBS).4 Adults who had recurrent abdominal pain as children have greater use of psychoactive medications, susceptibility to physical illness, and anxiety and depressive symptoms than healthy control patients.5 The diagnosis of FGIDs is clinical and based on the Rome criteria. In 2016, the Rome committee issued a new set of diagnostic criteria (Rome IV criteria)6 in substitution of the previous criteria (Rome III).7 In children and adolescents, the Rome IV criteria established modifications in all diagnostic categories. Among the most important changes, the Rome IV criteria introduced new diagnoses (functional nausea and functional vomiting, functional abdominal pain not otherwise specified), subcategories of previously existing diagnoses (IBS with diarrhea, constipation, mixed and unclassified; functional dyspepsia: postprandial distress syndrome type and epigastric pain type). Rome IV also modified the time required to diagnose some of the disorders, changed the diagnostic criteria of abdominal migraine, which were thought to be too vague and inaccurate, and changed some of the criterions for the diagnoses of cyclic vomiting syndrome. The prevalence of FGIDs per the pediatric Rome III criteria has been investigated in several studies conducted in multiple countries and in every continent.8-18 However, only 1 large study has investigated the prevalence of each FGID in children and adolescents using the Rome IV criteria.18 This study, conducted in the US, surveyed mothers of children aged 4-18 years and found that 25.0% of children qualified for at least 1 FGID according to the Rome IV criteria. To date, no studies have been published in children from Latin America. In the past, we have conducted a series of epidemiologic studies on FGIDs in children from Latin America using the Rome III criteria. Among those studies, From the 1Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Miller we surveyed 4394 school children from 7 cities in Colombia and found that 23.7% School of Medicine, University of Miami, Miami, FL; 2 Department of Pediatrics, Universidad del Valle de Cali, of participants met criteria for at least 1 FGID. 9 In the current study, we Cali; and 3Hospital Regional María Inmaculada de surveyed a large sample of school children from Colombia using validated Florencia, Caquetá, Colombia
F
FGID IBS QPGS
Functional gastrointestinal disorder Irritable bowel syndrome Questionnaire of Pediatric Gastrointestinal Symptoms
M.S. was part of the Rome IV Committee. The Rome foundation did not participate in the study or the decision to submit the paper for publication. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. © 2018 Elsevier Inc. All rights reserved. https://doi.org10.1016/j.jpeds.2018.03.037
1 FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
THE JOURNAL OF PEDIATRICS • www.jpeds.com
Volume ■■
•
■■ 2018
questionnaires to diagnose FGIDs and compared the epidemiologic data with the results obtained in our previous study using the Rome III criteria.
Methods This was a cross-sectional observational study that used the same methods as in our previous epidemiologic study on FGIDs in Colombia.9 The Questionnaire of Pediatric Gastrointestinal Symptoms (QPGS) Rome IV was translated into Spanish following the guidelines of the Rome committee.10 In short, the QPGS was translated into Spanish by 2 bilingual physicians. The Spanish version was then given to a focus group of children in Cali. Children in the focus group were selected randomly among clinic patients. The focus group included a pair of children/adolescents (one of each sex) of all ages ranging from 8 to 18 years of age (total 20 children/adolescents). Participants in the focus group were given the Spanish version of the QPGS-IV and suggested wording changes when appropriate to assure understanding. The child/adolescent-friendly version was then translated into English. A member of the research team who did not participate in the translation reviewed the final version to assure fidelity with the original English version of the QPGS- IV. An invitation to participate and a consent form was sent to the parents of all school-children (8-18 years of age) from 12 schools in 6 cities in Colombia. School children whose parents signed a consent form and assented to participate were given an informative session in school to instruct them on the completion of the Spanish version of the QPGS-IV. Once all questions were answered, children privately completed the QPGS-IV in class. Members of the research team were available to answer any questions during survey completion. Completed QPGS-IV forms were collected by members of the research team to assure confidentiality. Children with a history of organic diseases or eating disorders were excluded (Figure). The study was approved by the school authorities and the institutional review board of the Universidad del Valle, Cali, Colombia. Prevalence data were pooled for analysis. Averages and SDs or percentages of the study sample were calculated. Data were analyzed with the 2-sided Student t test for continuous variables and c2 and Fisher exact tests for categorical variables when appropriate (Stata 10 software; StataCorp, College Station, Texas). Calculation of OR with 95% CI was performed between the variables of interest (age group, sex, and education) and the effect variable (presence or absence of FGID). P values less than .05 were considered statistically significant.
Figure. Flow diagram of patient enrollment and inclusion.
755) (Table II) distributed in 6 cities and 3 regions (of a total of 6 regions in Colombia) completed the study. Geographic regional distribution of participants was Pacific region: Cali (n = 1567), Tuluá (n = 436), Palmira (n = 541); Andean region: Bucaramanga (n = 368), La Unión (n = 319); and Amazon region: Florencia (n = 336). Of all participants, 21.2% of school children met Rome IV criteria for at least 1 FGID. The prevalence of FGIDs was significantly lower than in the previous study conducted in Colombia using Rome III (P = .004) questionnaires (QPGSIII). Similar to the Rome III study, disorders of defecation were
Table I. Characteristics of children with and without FGIDs Rome IV Characteristics
Results A total of 4192 children/adolescents initially were enrolled into the study (Table I). After exclusions (8.9%) (Figure), a total of 3567 school children (1071 preadolescents 8-12 years and 2496 adolescents 13-18 years), mean age 13.7 ± 2.4 years (56.5% girls), from 9 schools (public school, 2810 and private school,
Age group School age Adolescent Sex Female Male Education Public Private
FGIDs +
FGIDs –
OR
95% CI
P value
214 541
857 1955
1.00 1.10
0.92-1.32
.2564
510 245
1506 1306
1.80 1.00
1.51-2.14
0
104 29
2706 726
1.00 1.03
0.65-1.59
.8570
2
Saps et al FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
■■ 2018
ORIGINAL ARTICLES
Table II. Prevalence of pediatric FGIDs in Rome III vs Rome IV studies Rome III Types of FGIDs No FGIDs FGIDs Functional nausea and vomiting disorders Aerophagia Cyclic vomiting syndrome Rumination syndrome Functional nausea and functional vomiting Functional nausea Functional vomiting Functional abdominal pain disorders Functional dyspepsia Postprandial distress syndrome Epigastric pain syndrome IBS IBS—diarrhea IBS—constipation IBS—mixed IBS—undetermined Abdominal migraine Functional abdominal pain—not otherwise specified Functional defecation disorders Functional constipation Nonretentive fecal incontinence
Rome IV
n = 4394
%
n = 3567
%
P value
3354 1040 71 37 17 17 n/a n/a n/a 457 46 n/a n/a 222 n/a n/a n/a n/a 76 113 512 509 3
76.3 23.7 1.6 0.8 0.4 0.4 n/a n/a n/a 10.4 1.0 n/a n/a 5.1 n/a n/a n/a n/a 1.7 2.5 11.7 11.6 0.1
2812 755 76 19 16 16 25 3 22 294 108 97 11 83 4 21 15 43 18 85 385 382 3
78.8 21.2 2.2 0.5 0.5 0.5 0.7 0.1 0.6 8.2 3.0 2.7 0.3 2.3 0.1 0.6 0.4 1.2 0.5 2.4 10.8 10.7 0.1
.004 .084 .052 .436 .436
.000 .000
.000
.000 .251 .070 .067 .571
n/a, not applicable.
the most common, followed by disorders of abdominal pain and disorders of nausea and vomiting. Compared with Rome III, we found a significantly lower prevalence of abdominal migraine (P = .000) and IBS (P = .000) and an increase in functional dyspepsia (P = .000). A small proportion of school children (0.7%) met criteria for the new diagnoses of functional vomiting and functional nausea. There was no significant difference in prevalence in the other diagnoses within the group of disorders of nausea and vomiting and no significant difference in disorders of defecation compared with the Rome III study (Table II).
Discussion This study investigated the prevalence of FGIDs in children and adolescents of Latin America using the Rome IV criteria. One previous epidemiologic study used the Rome IV criteria in children.18 Both studies, the current study and the study by Robin et al, compared the prevalence of FGIDs using the Rome III with the Rome IV criteria, although with different methodology.18 The comparison of epidemiologic data from large studies using both versions of the Rome criteria helps understand the effects of the established changes in diagnostic criteria between Rome III and Rome IV (Table III). Although the large US-based study (959 children) conducted by Robin et al18 interviewed mothers of children aged 4-18 years of age from all states, our study interviewed 3567 school children from 6 cities dispersed through 3 regions in Colombia. Both studies found a high prevalence of FGIDs (Robin et al 25%, the current study 21.2%). Functional constipation was the most common FGID in the Rome III study
(11.6%) and both Rome IV studies, the current one (10.7%) and the study of Robin et al18 (14.1%). Similar to the USbased study, we found that the prevalence of abdominal migraine decreased (P = .000), although the prevalence of functional dyspepsia increased (P = .000) when using the Rome IV criteria compared with the Rome III criteria. However, in contrast to the study of Robin et al,18 which did not find cases of rumination, we found a low prevalence of this diagnosis (0.4%), which was not significantly different than our previous Colombian study (0.5%).9 One of the challenges of introducing new diagnoses, which in cases with scant evidence is mostly based on expert opinion, is the demonstration that those diagnoses in fact exist. Our study shows that the new diagnoses introduced in the pediatric Rome IV criteria, such as functional nausea and functional vomiting, exist and can be diagnosed with the Rome IV questionnaires. We found a prevalence of functional nausea of 0.08% and functional vomiting of 0.6%. Likewise, we found that the newly introduced diagnostic subgroups of functional dyspepsia, postprandial distress syndrome and epigastric pain syndrome, were present in 2.7% and 0.3%, respectively.
Table III. Demographic differences between Rome III and Rome IV studies Rome IV
Rome III
Demographics
n = 3567
n = 4394
P value
Age, y Sex, male Education, public
13.7 ± 2.4 43.50% 96.30%
11.9 ± 2.3 51.90% 80.70%
.0000 .1878 .0000
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
3
THE JOURNAL OF PEDIATRICS • www.jpeds.com In line with Robin et al and other pediatric studies published before the Rome IV criteria,19 postprandial distress syndrome was the most common form of functional dyspepsia. The recognition that as in the case of postprandial distress syndrome the diagnosis of dyspepsia can be made in the absence of abdominal pain explains the significant increase of prevalence in functional dyspepsia found when the Rome IV criteria is applied in lieu of the Rome III criteria (Rome III 1% vs Rome IV 3%). A similar case can be made with the diagnostic subgroups of IBS that were not present in the Rome III criteria. We found that each of these subgroups were found among the school children who participated in our study. Similar to other pediatric studies,20 we also found that IBS with constipation was the most common subtype of IBS. This information is relevant at the time of planning recruitment strategies for clinical trials on the different subtypes of IBS. Among the diagnoses that already existed in the Rome III criteria, abdominal migraine was the diagnosis that underwent more substantial modifications. It was the opinion of the Rome IV committee that the prevalence of abdominal migraine found in some studies (up to 23%)21 using the Rome III criteria did not reflect the expert committee–perceived clinical reality. A study on clinic patients who were known not to have abdominal migraine showed that when using the QPGS III, a large proportion of children met the criteria for abdominal migraine, with most of them having IBS.22 Thus, the committee thought that major changes in its diagnosis were needed, including more stringent criteria and modifications in wording to enhance the accuracy of diagnosis of abdominal migraine. Using the Rome IV criteria, both the current study and Robin et al18 found a low prevalence of abdominal migraine, which is in line with the expected prevalence as discussed in the Rome committee meetings. Compared with our previous study using the Rome III criteria,9 we found a greater prevalence of FGIDs among girls compared with boys. Moreover, we also found a lower prevalence of FGIDs in general, and IBS in particular when using the Rome IV criteria. Although we cannot explain the reasons for these changes in prevalence, the population in this study is significantly older (Rome III 11.9 years; Rome IV 13.7%) than in the Rome III study and has a significantly lower percentage of children from private schools (Rome III 19.3%; Rome IV, 6.7%). Although these factors were associated with significant differences in prevalence in our previous studies (greater prevalence of FGIDs in younger children than adolescents23 and in children from private schools compared with public schools9), in the current study there were no significant differences in prevalence between younger and older children and children from private and public schools. We cannot exclude that specific characteristics of the schools and cities that did not participate in our previous study (Palmira, Tuluá, and Bucaramanga) could explain these changes in prevalence. Some of the strengths of our study include the large sample size, the inclusion of children of public and private schools from different cities, the use of questionnaires translated into Spanish and adapted to the local children’s language, and the similarity
Volume ■■ in methods with previous investigations by our group that allows comparisons among studies. Limitations of our study include the inability to assure the external validity of our results. Our sample is predominantly from public schools, with a small representation of children of private schools. Although the sample of children that participated in the study is geographically distributed among different regions in Colombia, not all regions in Colombia are represented, and the results of our study may not reflect the reality of all children in Colombia. In addition, the data provided by the children are based on recollection of symptoms, and we cannot assure the accuracy of their recall.24 However, a similar case can be made in every study that uses the QPGS issued by the Rome Foundation, as those are based on patients or parents recall of symptoms. In conclusion, FGIDs are commonly present among children of Colombia. The newly incorporated diagnoses to the Rome IV criteria seem to represent disorders that are present in school children. The prevalence of functional dyspepsia has increased when using the Rome IV criteria compared with the Rome III criteria, predominantly due to a high prevalence of the subgroup of postprandial distress syndrome. This suggests that the assumption made by the Rome committee that the diagnosis of functional dyspepsia is possible in the absence of epigastric pain (as it was previously required by the Rome III criteria) is correct. Because of the likely different pathophysiology of the different subtypes of IBS and functional dyspepsia, the definition of these subtypes will benefit clinical trials aimed at treating specific subtypes of disorders. The identification of study subjects with individual subtypes could potentially allow targeted recruitment and lower the sample size of the trial by decreasing randomness. ■ Submitted for publication Jan 2, 2018; last revision received Feb 24, 2018; accepted Mar 15, 2018 Reprint requests: Miguel Saps, MD, MCCD 3005A, 1601 NW 12th Ave, Miami, FL 33136. E-mail: [email protected]
References 1. Rouster AS, Karpinski AC, Silver D, Monagas J, Hyman PE. Functional gastrointestinal disorders dominate pediatric gastroenterology outpatient practice. J Pediatr Gastroenterol Nutr 2016;62:847-51. 2. Saps M, Seshadri R, Schaffer G, Sztainberg M, Marshall B, Di Lorenzo C. A prospective school-based study of abdominal pain and other common somatic complaints in children. J Pediatr 2009;154:322-6. 3. Gieteling MJ, Bierma-Zeinstra SM, Passchier J, Berger MY. Prognosis of chronic or recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr 2008;47:316-26. 4. Jarrett M, Heitkemper M, Czyzewski DI, Shulman R. Recurrent abdominal pain in children: forerunner to adult irritable bowel syndrome? J Spec Pediatr Nurs 2003;8:81-9. 5. Campo JV, Di Lorenzo C, Chiappetta L, Bridge J, Colborn DK, Gartner JC Jr, et al. Adult outcomes of pediatric recurrent abdominal pain: do they just grow out of it? Pediatrics 2001;108:E1. 6. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2016;130:1527-37. 7. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130:1527-37.
4
Saps et al FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
■■ 2018
ORIGINAL ARTICLES
8. Dhroove G, Saps M, Garcia-Bueno C, Levya Jiménez A, RodriguezReynosa LL, Velasco-Benítez CA. Prevalence of functional gastrointestinal disorders in Mexican school children. Rev Gastroenterol Mex 2017;82:13-8. 9. Saps M, Moreno-Gomez JE, Ramirez CR, Rosen JM, Velasco-Benitez CA. A nationwide study on the prevalence of functional gastrointestinal disorders in children. Bol Med Hosp Infant Mex 2017;74:407-12. 10. Sperber AD. Translation and validation of study instruments for crosscultural research. Gastroenterology 2004;126:S124-8. 11. Chogle A, Velasco-Benitez CA, Koppen IJ, Moreno JE, Ramírez Hernández CR, Saps M. A population-based study on the epidemiology of functional gastrointestinal disorders in young children. J Pediatr 2016;179:13943. 12. Lu PL, Saps M, Chanis RA, Velasco-Benítez CA. The prevalence of functional gastrointestinal disorders in children in Panama: a school-based study. Acta Paediatr 2016;105:e232-6. 13. Saps M, Nichols-Vinueza D, Rosen JM, Velasco CA. Prevalence of functional gastrointestinal disorders in Colombian school children. J Pediatr 2014;164:542-5. 14. Jativa E, Velasco CA, Kopen I, Jativa Cabezas Z, Saps M. Prevalence of functional gastrointestinal disorders in school children in Ecuador. J Pediatr Gastroenterol Nutr 2016;63:25-8. 15. Scarpato E, Kolacek S, Jojkic-Pavkov D, Konjik V, Živkovic´ N, Roman E, et al. Prevalence of functional gastrointestinal disorders in children and adolescents in the Mediterranean region of Europe. Clin Gastroenterol Hepatol 2017;doi:10.1016/j.cgh.2017.11.005. pii: S1542-356531316-2, Epub ahead of print.
16. Udoh E, Devanarayana NM, Rajindrajith S, Meremikwu M, Benninga MA. Abdominal pain-predominant functional gastrointestinal disorders in adolescent Nigerians. J Pediatr Gastroenterol Nutr 2016;62:588-93. 17. Devanarayana NM, Adhikari C, Pannala W, Rajindrajith S. Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria. J Trop Pediatr 2011;57:34-9. 18. Robin S, Keller C, Zwiener R, Hyman PE, Nurko S, Saps M, et al. Prevalence of Rome IV functional gastrointestinal disorders in children and adolescents in the United States. Gastroenterology 2017;152:S649. 19. Turco R, Russo M, Martinelli M, Castiello R, Coppola V, Miele E, et al. Do distinct functional dyspepsia subtypes exist in children? J Pediatr Gastroenterol Nutr 2016;62:387-92. 20. Giannetti E, de Angelis G, Turco R, Campanozzi A, Pensabene L, Salvatore S, et al. Subtypes of irritable bowel syndrome in children: prevalence at diagnosis and at follow-up. J Pediatr 2014;164:1099-103. 21. Lewis ML, Palsson OS, Whitehead WE, van Tilburg MAL. Prevalence of functional gastrointestinal disorders in children and adolescents. J Pediatr 2016;177:39.e3-43.e3. 22. Saps M, Sztainberg M, Pusatcioglu C, Chogle A. Accuracy of diagnosis for abdominal migraine in children. Gastroenterology 2014;146:S897. 23. Lu PL, Velasco-Benítez CA, Saps M. Gender, age, and prevalence of pediatric irritable bowel syndrome and constipation in Colombia: a population-based study. J Pediatr Gastroenterol Nutr 2017;64:e137-41. 24. Chogle A, Sztainberg M, Youssef NN, Miranda A, Nurko S, Hyman P, et al. Accuracy of pain recall in children. J Pediatr Gastroenterol Nutr 2012;55:288-91.
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
5
ORIGINAL ARTICLES
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria Miguel Saps, MD1, Carlos Alberto Velasco-Benitez, MD2, Amber Hamid Langshaw, MD1, and Carmen Rosy Ramírez-Hernández, MD3 Objectives To assess the prevalence of functional gastrointestinal disorders (FGIDs) in children using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV with Rome III criteria. Study design This was a cross-sectional study using the same methods as our previous study on FGIDs in Colombia. The Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV version was translated into Spanish, followed by reverse translation. Terms were adjusted to children’s language by using focus groups of children. School children aged 8-18 years completed the Spanish version of the Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV. Data were compared with Rome III data. Results In total, there were 3567 children (from 6 cities): 1071 preadolescents (8-12 years) and 2496 adolescents (13-18 years). Average age 13.7 ± 2.4 years (56.5% girls). A total of 21.2% of children had at least 1 FGID. Prevalence was significantly lower than Rome III (P = .004). Similar to Rome III, disorders of defecation were the most common, followed by abdominal pain, and disorders of nausea and vomiting. Prevalence of abdominal migraine decreased (P = .000) and functional dyspepsia increased (P = .000). The new diagnoses functional vomiting and functional nausea were present in 0.7% of all children. Conclusions The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs; however, the relative frequency of each subgroup of disorders did not change. New diagnoses of the Rome IV criteria were present in a small percentage of children. (J Pediatr 2018;■■:■■-■■). unctional gastrointestinal disorders (FGIDs) are the most common cause of consultation to pediatric gastroenterology.1 In children, FGIDs are associated with low quality of life, psychological distress, school absenteeism, and poor physical and social functioning.2 A large proportion of children with FGIDs continue to experience symptoms for several years despite treatment.3 In many cases, FGIDs are forerunners for adult symptoms. A total of 25% of children who present with recurrent abdominal pain will evolve into adults with irritable bowel syndrome (IBS).4 Adults who had recurrent abdominal pain as children have greater use of psychoactive medications, susceptibility to physical illness, and anxiety and depressive symptoms than healthy control patients.5 The diagnosis of FGIDs is clinical and based on the Rome criteria. In 2016, the Rome committee issued a new set of diagnostic criteria (Rome IV criteria)6 in substitution of the previous criteria (Rome III).7 In children and adolescents, the Rome IV criteria established modifications in all diagnostic categories. Among the most important changes, the Rome IV criteria introduced new diagnoses (functional nausea and functional vomiting, functional abdominal pain not otherwise specified), subcategories of previously existing diagnoses (IBS with diarrhea, constipation, mixed and unclassified; functional dyspepsia: postprandial distress syndrome type and epigastric pain type). Rome IV also modified the time required to diagnose some of the disorders, changed the diagnostic criteria of abdominal migraine, which were thought to be too vague and inaccurate, and changed some of the criterions for the diagnoses of cyclic vomiting syndrome. The prevalence of FGIDs per the pediatric Rome III criteria has been investigated in several studies conducted in multiple countries and in every continent.8-18 However, only 1 large study has investigated the prevalence of each FGID in children and adolescents using the Rome IV criteria.18 This study, conducted in the US, surveyed mothers of children aged 4-18 years and found that 25.0% of children qualified for at least 1 FGID according to the Rome IV criteria. To date, no studies have been published in children from Latin America. In the past, we have conducted a series of epidemiologic studies on FGIDs in children from Latin America using the Rome III criteria. Among those studies, From the 1Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Miller we surveyed 4394 school children from 7 cities in Colombia and found that 23.7% School of Medicine, University of Miami, Miami, FL; 2 Department of Pediatrics, Universidad del Valle de Cali, of participants met criteria for at least 1 FGID. 9 In the current study, we Cali; and 3Hospital Regional María Inmaculada de surveyed a large sample of school children from Colombia using validated Florencia, Caquetá, Colombia
F
FGID IBS QPGS
Functional gastrointestinal disorder Irritable bowel syndrome Questionnaire of Pediatric Gastrointestinal Symptoms
M.S. was part of the Rome IV Committee. The Rome foundation did not participate in the study or the decision to submit the paper for publication. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. © 2018 Elsevier Inc. All rights reserved. https://doi.org10.1016/j.jpeds.2018.03.037
1 FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
THE JOURNAL OF PEDIATRICS • www.jpeds.com
Volume ■■
•
■■ 2018
questionnaires to diagnose FGIDs and compared the epidemiologic data with the results obtained in our previous study using the Rome III criteria.
Methods This was a cross-sectional observational study that used the same methods as in our previous epidemiologic study on FGIDs in Colombia.9 The Questionnaire of Pediatric Gastrointestinal Symptoms (QPGS) Rome IV was translated into Spanish following the guidelines of the Rome committee.10 In short, the QPGS was translated into Spanish by 2 bilingual physicians. The Spanish version was then given to a focus group of children in Cali. Children in the focus group were selected randomly among clinic patients. The focus group included a pair of children/adolescents (one of each sex) of all ages ranging from 8 to 18 years of age (total 20 children/adolescents). Participants in the focus group were given the Spanish version of the QPGS-IV and suggested wording changes when appropriate to assure understanding. The child/adolescent-friendly version was then translated into English. A member of the research team who did not participate in the translation reviewed the final version to assure fidelity with the original English version of the QPGS- IV. An invitation to participate and a consent form was sent to the parents of all school-children (8-18 years of age) from 12 schools in 6 cities in Colombia. School children whose parents signed a consent form and assented to participate were given an informative session in school to instruct them on the completion of the Spanish version of the QPGS-IV. Once all questions were answered, children privately completed the QPGS-IV in class. Members of the research team were available to answer any questions during survey completion. Completed QPGS-IV forms were collected by members of the research team to assure confidentiality. Children with a history of organic diseases or eating disorders were excluded (Figure). The study was approved by the school authorities and the institutional review board of the Universidad del Valle, Cali, Colombia. Prevalence data were pooled for analysis. Averages and SDs or percentages of the study sample were calculated. Data were analyzed with the 2-sided Student t test for continuous variables and c2 and Fisher exact tests for categorical variables when appropriate (Stata 10 software; StataCorp, College Station, Texas). Calculation of OR with 95% CI was performed between the variables of interest (age group, sex, and education) and the effect variable (presence or absence of FGID). P values less than .05 were considered statistically significant.
Figure. Flow diagram of patient enrollment and inclusion.
755) (Table II) distributed in 6 cities and 3 regions (of a total of 6 regions in Colombia) completed the study. Geographic regional distribution of participants was Pacific region: Cali (n = 1567), Tuluá (n = 436), Palmira (n = 541); Andean region: Bucaramanga (n = 368), La Unión (n = 319); and Amazon region: Florencia (n = 336). Of all participants, 21.2% of school children met Rome IV criteria for at least 1 FGID. The prevalence of FGIDs was significantly lower than in the previous study conducted in Colombia using Rome III (P = .004) questionnaires (QPGSIII). Similar to the Rome III study, disorders of defecation were
Table I. Characteristics of children with and without FGIDs Rome IV Characteristics
Results A total of 4192 children/adolescents initially were enrolled into the study (Table I). After exclusions (8.9%) (Figure), a total of 3567 school children (1071 preadolescents 8-12 years and 2496 adolescents 13-18 years), mean age 13.7 ± 2.4 years (56.5% girls), from 9 schools (public school, 2810 and private school,
Age group School age Adolescent Sex Female Male Education Public Private
FGIDs +
FGIDs –
OR
95% CI
P value
214 541
857 1955
1.00 1.10
0.92-1.32
.2564
510 245
1506 1306
1.80 1.00
1.51-2.14
0
104 29
2706 726
1.00 1.03
0.65-1.59
.8570
2
Saps et al FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
■■ 2018
ORIGINAL ARTICLES
Table II. Prevalence of pediatric FGIDs in Rome III vs Rome IV studies Rome III Types of FGIDs No FGIDs FGIDs Functional nausea and vomiting disorders Aerophagia Cyclic vomiting syndrome Rumination syndrome Functional nausea and functional vomiting Functional nausea Functional vomiting Functional abdominal pain disorders Functional dyspepsia Postprandial distress syndrome Epigastric pain syndrome IBS IBS—diarrhea IBS—constipation IBS—mixed IBS—undetermined Abdominal migraine Functional abdominal pain—not otherwise specified Functional defecation disorders Functional constipation Nonretentive fecal incontinence
Rome IV
n = 4394
%
n = 3567
%
P value
3354 1040 71 37 17 17 n/a n/a n/a 457 46 n/a n/a 222 n/a n/a n/a n/a 76 113 512 509 3
76.3 23.7 1.6 0.8 0.4 0.4 n/a n/a n/a 10.4 1.0 n/a n/a 5.1 n/a n/a n/a n/a 1.7 2.5 11.7 11.6 0.1
2812 755 76 19 16 16 25 3 22 294 108 97 11 83 4 21 15 43 18 85 385 382 3
78.8 21.2 2.2 0.5 0.5 0.5 0.7 0.1 0.6 8.2 3.0 2.7 0.3 2.3 0.1 0.6 0.4 1.2 0.5 2.4 10.8 10.7 0.1
.004 .084 .052 .436 .436
.000 .000
.000
.000 .251 .070 .067 .571
n/a, not applicable.
the most common, followed by disorders of abdominal pain and disorders of nausea and vomiting. Compared with Rome III, we found a significantly lower prevalence of abdominal migraine (P = .000) and IBS (P = .000) and an increase in functional dyspepsia (P = .000). A small proportion of school children (0.7%) met criteria for the new diagnoses of functional vomiting and functional nausea. There was no significant difference in prevalence in the other diagnoses within the group of disorders of nausea and vomiting and no significant difference in disorders of defecation compared with the Rome III study (Table II).
Discussion This study investigated the prevalence of FGIDs in children and adolescents of Latin America using the Rome IV criteria. One previous epidemiologic study used the Rome IV criteria in children.18 Both studies, the current study and the study by Robin et al, compared the prevalence of FGIDs using the Rome III with the Rome IV criteria, although with different methodology.18 The comparison of epidemiologic data from large studies using both versions of the Rome criteria helps understand the effects of the established changes in diagnostic criteria between Rome III and Rome IV (Table III). Although the large US-based study (959 children) conducted by Robin et al18 interviewed mothers of children aged 4-18 years of age from all states, our study interviewed 3567 school children from 6 cities dispersed through 3 regions in Colombia. Both studies found a high prevalence of FGIDs (Robin et al 25%, the current study 21.2%). Functional constipation was the most common FGID in the Rome III study
(11.6%) and both Rome IV studies, the current one (10.7%) and the study of Robin et al18 (14.1%). Similar to the USbased study, we found that the prevalence of abdominal migraine decreased (P = .000), although the prevalence of functional dyspepsia increased (P = .000) when using the Rome IV criteria compared with the Rome III criteria. However, in contrast to the study of Robin et al,18 which did not find cases of rumination, we found a low prevalence of this diagnosis (0.4%), which was not significantly different than our previous Colombian study (0.5%).9 One of the challenges of introducing new diagnoses, which in cases with scant evidence is mostly based on expert opinion, is the demonstration that those diagnoses in fact exist. Our study shows that the new diagnoses introduced in the pediatric Rome IV criteria, such as functional nausea and functional vomiting, exist and can be diagnosed with the Rome IV questionnaires. We found a prevalence of functional nausea of 0.08% and functional vomiting of 0.6%. Likewise, we found that the newly introduced diagnostic subgroups of functional dyspepsia, postprandial distress syndrome and epigastric pain syndrome, were present in 2.7% and 0.3%, respectively.
Table III. Demographic differences between Rome III and Rome IV studies Rome IV
Rome III
Demographics
n = 3567
n = 4394
P value
Age, y Sex, male Education, public
13.7 ± 2.4 43.50% 96.30%
11.9 ± 2.3 51.90% 80.70%
.0000 .1878 .0000
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
3
THE JOURNAL OF PEDIATRICS • www.jpeds.com In line with Robin et al and other pediatric studies published before the Rome IV criteria,19 postprandial distress syndrome was the most common form of functional dyspepsia. The recognition that as in the case of postprandial distress syndrome the diagnosis of dyspepsia can be made in the absence of abdominal pain explains the significant increase of prevalence in functional dyspepsia found when the Rome IV criteria is applied in lieu of the Rome III criteria (Rome III 1% vs Rome IV 3%). A similar case can be made with the diagnostic subgroups of IBS that were not present in the Rome III criteria. We found that each of these subgroups were found among the school children who participated in our study. Similar to other pediatric studies,20 we also found that IBS with constipation was the most common subtype of IBS. This information is relevant at the time of planning recruitment strategies for clinical trials on the different subtypes of IBS. Among the diagnoses that already existed in the Rome III criteria, abdominal migraine was the diagnosis that underwent more substantial modifications. It was the opinion of the Rome IV committee that the prevalence of abdominal migraine found in some studies (up to 23%)21 using the Rome III criteria did not reflect the expert committee–perceived clinical reality. A study on clinic patients who were known not to have abdominal migraine showed that when using the QPGS III, a large proportion of children met the criteria for abdominal migraine, with most of them having IBS.22 Thus, the committee thought that major changes in its diagnosis were needed, including more stringent criteria and modifications in wording to enhance the accuracy of diagnosis of abdominal migraine. Using the Rome IV criteria, both the current study and Robin et al18 found a low prevalence of abdominal migraine, which is in line with the expected prevalence as discussed in the Rome committee meetings. Compared with our previous study using the Rome III criteria,9 we found a greater prevalence of FGIDs among girls compared with boys. Moreover, we also found a lower prevalence of FGIDs in general, and IBS in particular when using the Rome IV criteria. Although we cannot explain the reasons for these changes in prevalence, the population in this study is significantly older (Rome III 11.9 years; Rome IV 13.7%) than in the Rome III study and has a significantly lower percentage of children from private schools (Rome III 19.3%; Rome IV, 6.7%). Although these factors were associated with significant differences in prevalence in our previous studies (greater prevalence of FGIDs in younger children than adolescents23 and in children from private schools compared with public schools9), in the current study there were no significant differences in prevalence between younger and older children and children from private and public schools. We cannot exclude that specific characteristics of the schools and cities that did not participate in our previous study (Palmira, Tuluá, and Bucaramanga) could explain these changes in prevalence. Some of the strengths of our study include the large sample size, the inclusion of children of public and private schools from different cities, the use of questionnaires translated into Spanish and adapted to the local children’s language, and the similarity
Volume ■■ in methods with previous investigations by our group that allows comparisons among studies. Limitations of our study include the inability to assure the external validity of our results. Our sample is predominantly from public schools, with a small representation of children of private schools. Although the sample of children that participated in the study is geographically distributed among different regions in Colombia, not all regions in Colombia are represented, and the results of our study may not reflect the reality of all children in Colombia. In addition, the data provided by the children are based on recollection of symptoms, and we cannot assure the accuracy of their recall.24 However, a similar case can be made in every study that uses the QPGS issued by the Rome Foundation, as those are based on patients or parents recall of symptoms. In conclusion, FGIDs are commonly present among children of Colombia. The newly incorporated diagnoses to the Rome IV criteria seem to represent disorders that are present in school children. The prevalence of functional dyspepsia has increased when using the Rome IV criteria compared with the Rome III criteria, predominantly due to a high prevalence of the subgroup of postprandial distress syndrome. This suggests that the assumption made by the Rome committee that the diagnosis of functional dyspepsia is possible in the absence of epigastric pain (as it was previously required by the Rome III criteria) is correct. Because of the likely different pathophysiology of the different subtypes of IBS and functional dyspepsia, the definition of these subtypes will benefit clinical trials aimed at treating specific subtypes of disorders. The identification of study subjects with individual subtypes could potentially allow targeted recruitment and lower the sample size of the trial by decreasing randomness. ■ Submitted for publication Jan 2, 2018; last revision received Feb 24, 2018; accepted Mar 15, 2018 Reprint requests: Miguel Saps, MD, MCCD 3005A, 1601 NW 12th Ave, Miami, FL 33136. E-mail: [email protected]
References 1. Rouster AS, Karpinski AC, Silver D, Monagas J, Hyman PE. Functional gastrointestinal disorders dominate pediatric gastroenterology outpatient practice. J Pediatr Gastroenterol Nutr 2016;62:847-51. 2. Saps M, Seshadri R, Schaffer G, Sztainberg M, Marshall B, Di Lorenzo C. A prospective school-based study of abdominal pain and other common somatic complaints in children. J Pediatr 2009;154:322-6. 3. Gieteling MJ, Bierma-Zeinstra SM, Passchier J, Berger MY. Prognosis of chronic or recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr 2008;47:316-26. 4. Jarrett M, Heitkemper M, Czyzewski DI, Shulman R. Recurrent abdominal pain in children: forerunner to adult irritable bowel syndrome? J Spec Pediatr Nurs 2003;8:81-9. 5. Campo JV, Di Lorenzo C, Chiappetta L, Bridge J, Colborn DK, Gartner JC Jr, et al. Adult outcomes of pediatric recurrent abdominal pain: do they just grow out of it? Pediatrics 2001;108:E1. 6. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2016;130:1527-37. 7. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130:1527-37.
4
Saps et al FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
■■ 2018
ORIGINAL ARTICLES
8. Dhroove G, Saps M, Garcia-Bueno C, Levya Jiménez A, RodriguezReynosa LL, Velasco-Benítez CA. Prevalence of functional gastrointestinal disorders in Mexican school children. Rev Gastroenterol Mex 2017;82:13-8. 9. Saps M, Moreno-Gomez JE, Ramirez CR, Rosen JM, Velasco-Benitez CA. A nationwide study on the prevalence of functional gastrointestinal disorders in children. Bol Med Hosp Infant Mex 2017;74:407-12. 10. Sperber AD. Translation and validation of study instruments for crosscultural research. Gastroenterology 2004;126:S124-8. 11. Chogle A, Velasco-Benitez CA, Koppen IJ, Moreno JE, Ramírez Hernández CR, Saps M. A population-based study on the epidemiology of functional gastrointestinal disorders in young children. J Pediatr 2016;179:13943. 12. Lu PL, Saps M, Chanis RA, Velasco-Benítez CA. The prevalence of functional gastrointestinal disorders in children in Panama: a school-based study. Acta Paediatr 2016;105:e232-6. 13. Saps M, Nichols-Vinueza D, Rosen JM, Velasco CA. Prevalence of functional gastrointestinal disorders in Colombian school children. J Pediatr 2014;164:542-5. 14. Jativa E, Velasco CA, Kopen I, Jativa Cabezas Z, Saps M. Prevalence of functional gastrointestinal disorders in school children in Ecuador. J Pediatr Gastroenterol Nutr 2016;63:25-8. 15. Scarpato E, Kolacek S, Jojkic-Pavkov D, Konjik V, Živkovic´ N, Roman E, et al. Prevalence of functional gastrointestinal disorders in children and adolescents in the Mediterranean region of Europe. Clin Gastroenterol Hepatol 2017;doi:10.1016/j.cgh.2017.11.005. pii: S1542-356531316-2, Epub ahead of print.
16. Udoh E, Devanarayana NM, Rajindrajith S, Meremikwu M, Benninga MA. Abdominal pain-predominant functional gastrointestinal disorders in adolescent Nigerians. J Pediatr Gastroenterol Nutr 2016;62:588-93. 17. Devanarayana NM, Adhikari C, Pannala W, Rajindrajith S. Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria. J Trop Pediatr 2011;57:34-9. 18. Robin S, Keller C, Zwiener R, Hyman PE, Nurko S, Saps M, et al. Prevalence of Rome IV functional gastrointestinal disorders in children and adolescents in the United States. Gastroenterology 2017;152:S649. 19. Turco R, Russo M, Martinelli M, Castiello R, Coppola V, Miele E, et al. Do distinct functional dyspepsia subtypes exist in children? J Pediatr Gastroenterol Nutr 2016;62:387-92. 20. Giannetti E, de Angelis G, Turco R, Campanozzi A, Pensabene L, Salvatore S, et al. Subtypes of irritable bowel syndrome in children: prevalence at diagnosis and at follow-up. J Pediatr 2014;164:1099-103. 21. Lewis ML, Palsson OS, Whitehead WE, van Tilburg MAL. Prevalence of functional gastrointestinal disorders in children and adolescents. J Pediatr 2016;177:39.e3-43.e3. 22. Saps M, Sztainberg M, Pusatcioglu C, Chogle A. Accuracy of diagnosis for abdominal migraine in children. Gastroenterology 2014;146:S897. 23. Lu PL, Velasco-Benítez CA, Saps M. Gender, age, and prevalence of pediatric irritable bowel syndrome and constipation in Colombia: a population-based study. J Pediatr Gastroenterol Nutr 2017;64:e137-41. 24. Chogle A, Sztainberg M, Youssef NN, Miranda A, Nurko S, Hyman P, et al. Accuracy of pain recall in children. J Pediatr Gastroenterol Nutr 2012;55:288-91.
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria FLA 5.5.0 DTD ■ YMPD9886_proof ■ May 7, 2018
5