Introduction

Functional Gastrointestinal Disorders (FGIDs) in pediatrics according to the Rome IV Criteria have been defined as a diverse and variable combination of recu rrent or chronic gastrointestinal symptoms that, after adequate medical evaluation, are not attributable to other medical conditions¹.

The prevalence of FGIDs according to the Rome III Criteria worldwide in children between four and 18 years of age ranges from 7.7% to 28.8%^2,3,4,5,6; recently Robin et al, according to the Rome IV Criteria, des cribed a prevalence of 25.0%⁷ in 959 North American children.

Although the frequent overlapping of these FGIDs in the same patient is described¹, there is little literature on the main overlapping FGIDs and the characteristics of this group of children. The importance of studying this overlap in FGIDs lies in the fact that it will contri bute to a better understanding of the physiopathology and pathogenesis of the biopsychosocial model of FGIDs in children, from the genetic, nutritional, envi ronmental, psychosocial, cultural, socioeconomic and infectious, among others, and thus better define the epidemiology, symptoms, comorbidity and quality of life related to the health of children with FGIDs.

The objective of this study is to describe the pre valence and possible risk factors in Latin American (Latam) school children and adolescents of presenting overlapping FGIDs.

Patients and Methods

This non-experimental cross-sectional observatio nal descriptive study of prevalence type was conducted from the FINDERS (Functional International Digesti ve Epidemiological Research Survey Group) databa se, a transnational research group made up of several members of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LAS- PGHAN).

Data collection methods were the same in all par ticipating countries (Colombia, Ecuador, El Salvador, Mexico, Panama, and Nicaragua)^{8,9,10,11,12,13}. From each coun try, the main public and private schools that agreed to participate in this study were chosen; and within each school, Latam children between the ages of eight and 18 who signed an informed consent and whose parents and/or guardians signed an informed consent were included. The sociodemographic variables taken into ac count were age, gender, country of origin, and school. Children with organic gastrointestinal disorders such as gastroesophageal reflux disease, Helicobacter pylori gastritis, Hirschsprung’s disease, cerebral palsy, vesi coureteral reflux, convulsive syndrome, heart disease, celiac disease, and inflammatory bowel disease were excluded due to known history. The Rome III Criteria through the Questionnaire on Pediatric Gastrointes tinal Symptom for Children and Adolescents (QPGS- III), which has been validated and tested in Spanish¹⁴, was used to identify FGIDs. Children between the ages of eight and ten did so in a guided manner with one of the principal investigators, and children between the ages of11 and 18 did so by self-report. According to the Scoring Instructions for Child/Adolescent Self-Report Form for the Rome III Diagnostic Questionnaire on Pediatric Gastrointestinal Symptoms for Children and Adolescents¹⁵, the diagnosis of functional abdominal pain (FAP) requires the exclusion of other FGIDs such as functional dyspepsia (FD), irritable bowel syndro me (IBS), and abdominal migraine (AM). However, for the purposes of this study and in the future to allow comparison of these results with the new classification of the Rome IV Criteria for the group of FGIDs rela ted to abdominal pain, which describes two subtypes of FD (postprandial distress syndrome and epigastric pain syndrome); four subtypes of IBS (with diarrhea, with constipation, with diarrhea and constipation, and without diarrhea and without constipation) and groups in one single type the FAP not differently specified¹, all overlaps were taken into account.

The age groups considered were schoolchildren (between eight and 12 years of age) and adolescents (between 13 and 18 years of age); in addition whether they attend to a public or private school, and the FGIDs identified were FD, IBS, AM, FAP, FAP Syndro me (FAPS), functional constipation (FC), non-retenti ve fecal incontinence (NRFI), adolescent rumination syndrome (ARS), cyclic vomiting syndrome (CVS), and aerophagia (AE). For the purposes of this inves tigation, FAP and FAPS were considered as one enti ty (FAP). The overlap of FGIDs was considered when two, three or four and more FGIDs were presented in the same child.

The study was approved by the Ethics Commit tee of the Universidad del Valle de Cali, Colombia; the Ethics Committee in Clinical Research (CEIC) of the Benjamin Bloom National Children’s Hospital of San Salvador, El Salvador; the Ethics Committee of the Universidad Central del Ecuador, Quito, Ecuador, and the Research Committee of the Hospital del Niño Dr. José Renán Esquivel of Panama City, Panama; as well as by the Rectors of the Educational Institutions of Managua, Nicaragua; Cuernavaca and Monterrey, Mexico.

Statistical analysis carried out with the Stata 15 software (StataCorp, College Station, TX) included the Student T-test for two means, Chi-square and Fisher’s exact test. For the possible risk factors for overlapping FGIDs, uni and multivariate analyses were conducted and the calculation of ORs was performed between the exposure of interest variable (gender, age, origin, school) and the effect variable (presence or absence of overlapping FGIDs). A p <0.05 was considered statis tically significant.

Results

A total of 6,193 children were analyzed from Colombia (n = 4,394), Ecuador (n = 417), El Salva dor (n = 399), Mexico (n = 362), Panama (n = 321), and Nicaragua (n = 300), aged 11.8±2.2 years (range 8-18 years), 62,2% schoolchildren between eight and 12 years old, 50.4% female, 68.0% attend to a public school, 23.4% with a diagnosis of at least one FGID, where the main FGID was the FC (11.7%), the IBS (4.9%), and the FAP (2.6%) (Table 1).

Table 1 General characteristics of Latin American schoolchildren and adolescents. N = 6193. 

Overlapping FGIDs were presented in the same child, in 8.4% out of the 6,193 studied Latam children (65.1% with two FGIDs; 24.7% with three FGIDs, and 10.2% with four or more FGIDs), where the main over laps were the IBS+ FAP (2.6%), and the IBS+ FAP+FC (1.1%) (Table 2).

Table 2 Overlapping functional gastrointestinal disorders in Latin american schoolchildren and adolescents. N = 6193. 

There was predominance of the female gender and having some FGIDs (OR = 1.16 95%CI = 1.03 1.31 p = 0.0107); in the female gender and having two FGIDs (OR = 1.41 95%CI = 1.12-1.77 p = 0.0024), and in the female gender and having four or more FGIDs (OR = 2.16 95%CI = 1.18-4.11 p = 0.0075); and when analyzing the presence of two FGIDs, three FGIDs, and four or more FGIDs with age, gender, and school, no significant differences were found (p > 0.05) (Table 3).

Table 3 Risk factors in Latin american schoolchildren and adolescents with overlapping functional gastrointestinal disorders. N = 6193. 

Discussion

The lowest prevalence in these six Latam coun tries for presenting some FGIDs under the Rome III Criteria in Spanish was 13.3% in Nicaragua¹³, and the highest prevalence was 28.7% in Panama¹², lower than that described by Gulewitsch et al which was 7.7% in 1,537 German children between six and ten years of age², and similar to that reported by Lewis et al in 949 interviewed mothers of North American children bet ween four and 18 years of age which was 23.1%³, by Scarpato et al in 13,750 Mediterranean European chil dren aged 4-18 years which was 27.6%⁴, by Bouzious et al in 1,658 Greek children aged 6-14 years which was 23.1%⁵, and by Devanarayana et al in 427 Sri Lankan children aged 12-16 years which was 28.8%⁶. According to the Rome IV Criteria, Robin et al in 1,147 Nor th American children between four and 18 years of age recently describe a 25.0%, prevalence to present some FGIDs, being the main FGIDs the FC (14.1%)⁷, as well as this study, whose prevalence was between 10.0% and 15.9%, and the same as reported worldwide between 4.2% and 14.1%.

The Rome IV Criteria in schoolchildren and ado lescents dedicate only a couple of paragraphs to des cribe that different FGIDs often overlap in the same patient¹ and that studies have shown that there may be overlap of more than one FAP disorder in an individual patient¹⁶, however, they do not relate the characteristics of these. In this study, the prevalence of presen ting two, three, and four or more FGIDs in the same child was 5.5%; 2.1% and 0.9%, respectively. Scarpato et al⁴, and Bouzios et al⁵ report prevalences between 2.8%-6.0%; 0.4%-1.0%, and 0.1%-0.3%, respectively, of present two, three, and four or more FGIDs in the same child (Table 4).

Table 4 Comparison of prevalence in schoolchildren and adolescents with overlapping functional gastrointestinal disorders. N = 6193. 

In this study there was no case of overlap between IBS with constipation (IBS-c) and FC, however, Rajin-drajith et al¹⁷ in 1,792 Sri Lankan adolescents, 54.6% female, describe a 56.0% of overlapping between IBS-c and FC. Similarly, in this study, no children with IBS and FD are reported, but Friesen et al¹⁸ in 100 children between the ages of eight and 17 years (average age 13 years nine months), 76% female, report a 33% of overlapping between IBS and FD, with no variation in symptoms/syndromes by FD subtypes. In the results of the current research, there is no overlap between IBS and AM, however, Gulewitsch et al² identify 3.4% of this overlap.

The Pediatric Rome III Criteria¹⁵ do not allow to classify the subtypes of FD as in this study, however, Turco et al¹⁹, in 100 Italian children, median age ten years, range 4.3-16.8 years, reported a 36% overlap between FD of the subtype epigastric pain and FD of the postprandial distress type.

Few studies describe which FGIDs overlap. This study reports the following overlapping FGIDs, among others: AM+FC, FC+AE, AM+AE, and FC+ARS, also reported by Bouzious et al⁵ and IBS+FAP, AM+FC, AM+CVS, IBS+AM+FAP, and IBS+AM+ARS, also identified by Helgeland et al²⁰, in 142 children in Norway, aged 9.4 ± 2.7 years, 63% girls.

Like Devanarayana et al²¹, who found overlap of AE and other FGIDs in 23.9%, this study presented cases of children with AE+FAP, AE+FC, and AE+AM.

The predominance of female gender in the overlap of FGIDs in the same child found in this study is also described by Bouzios et al⁵ (OR = 1.28; 95%CI = 1.03 1.64; p = 0.035) and by Scarpato et al⁴.

The strengths of the study include the large sample size, as well as the fact that it was conducted in both public and private schools in several cities in several Spanish-speaking Latin American countries. In addi tion, the same methodology proposed by FINDERS (Functional International Digestive Epidemiological

Research Survey Group) was used in all countries, allowing for comparison.

Among the limitations of the study, although it in cludes several cities in several countries, the possibili ty that the results cannot be generalized to all of Latin America cannot be ruled out. In addition, we do not perform a systematic evaluation or anamnesis on the surveyed children, and simultaneous medical diagno ses that are not described in the study may be presen ted. Likewise, no other possible psychological, social, racial, ethnic, anthropometric, nutritional, infectious, and environmental risk factors, among others, were asked that could explain the biopsychosocial model of this entity. Finally, our data were obtained by self-re porting in the school environment, and there is no data from caregivers, which allows for some degree of bias.

In conclusion, there is a low prevalence of FGIDs in the same Latam schoolchild and adolescent, with predominance of the female gender, and a very variable presentation, which invites future studies to deepen more about the FGIDs overlapping in children and their better understanding.

Ethical responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed according to the Declaration of Helsinki and the World Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regulations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.