Introduction

Functional dyspepsia (FD) is a common disorder in childhood. This disorder is associated with upper gastrointestinal symptoms, including epigastric pain or burning sensation, early satiety, and postprandial fullness, unrelated to bowel movements or other etiology to explain these symptoms. This disorder can cause a significant deterioration in the quality of life^1,2.

In recent years, FD’s prevalence has increased (3%-27%), with a high demand for consultation of pediatric specialties. In many cases, FD may be associated with other gastrointestinal functional disorders, one of the most common after irritable bowel syndrome. Approximately 4.5% of children worldwide experience symptoms of FD at some point in their lives^2,3.

Patients with functional gastrointestinal disorders (FGIDs), which include FD, have higher rates of anxiety, depression, poor coping skills, and somatization symptoms than children without FGIDs. Children with FD may be associated with significant morbidity, and symptoms may negatively impact the child’s quality of life, adversely affecting school attendance³.

Over time, FD diagnostic criteria have evolved. For the first time, the Rome IV criteria identified epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) as two subtypes of FD in children, as recognized in adults.^3-5

According to the Rome IV Criteria, no studies have demonstrated the prevalence of FD in Cuban children. Understanding the associated factors would be extremely useful for diagnosing and managing this disorder. Thus, this study aims to determine the prevalence of FD in Cuban adolescents and their possible associations.

Methodology

The study was conducted between March 2, 2020, and January 7, 2021, in 3 schools (2 primary schools and 1 basic secondary) in La Havana, Cuba. It was applied using the methodology in previous studies and those currently in progress by our group, Functional International Digestive Epidemiological Research Survey (FINDERS), an established international collaborative group that conducts epidemiological studies in Latin American children. Thus, parents or guardians of adolescents between fourth and ninth grades were invited and agreed to participate in the study after signing an informed consent/assent. We used the Questionnaire of Pediatric Gastrointestinal Symptoms-Rome IV Criteria (QPGS-IV) in Spanish, which has an appropriate criterion validity⁶. Sociodemographic (age, gender, race); personal (cesarean section, preterm birth); family (only child, firstborn, separated/divorced parents, intrafamily FGIDs); clinical (weight, height, body mass index [BMI], height-for-age, dengue history), and epidemiological (overlap, confinement) variables were obtained. The Hospital Dr. Luis Díaz Soto’s Ethics Committee approved this study. Statistical analysis included the student’s t-test two-sided, the Chi-Square test, and Fisher’s exact test. To evaluate the possible risk factors for DF, a univariate and multivariate analysis was performed, calculating the odds ratio (OR) with its corresponding 95% confidence intervals (CI) and a p significant < 0.05.

Results

From a group of 318 adolescents who answered the QPGS-IV in Spanish, 29.1% showed some FGID. We identified FD in 3.5% (2.2% postprandial distress syndrome -PDS, and 1.3% epigastric pain syndrome -EPS) (Table 1).

Table 1
Prevalence of FGIDs in Cuban schoolchildren

FAD: functional abdominal distension.

n = 318
FGIDs
No	225 (70,9)
Yes	93 (29,1)
Associated with nausea and vomiting	5 (1,5)
Functional nausea and vomiting	3 (0,9)
Nausea	1 (0,3)
Vomiting	2 (0,6)
Aerophagia	1 (0,3)
Cyclic vomiting syndrome	1 (0,3)
Associated with abdominal pain	16 (5,0)
Functional dyspepsia	11 (3,5)
PDS	7 (2,2)
EPS	4 (1,3)
Irritable bowel syndrome	1 (0,3)
With diarrhea and constipation	1 (0,3)
Abdominal Migraine	1 (0,3)
FAD not otherwise specified	3 (0,9)
Associated with defecation	72 (22,6)
Functional constipation	72 (22,6)

The 11 children with FD were 11.4 ± 1.2 years, 81.8% were female and 54.4% mestizo, 54.5% were firstborn, 72.7% had separated/divorced parents, and 63.6% and 100.0%, respectively, were eutrophic for BMI and height-for-age according to the World Health Organization (WHO). There was an overlap of FD in 8 of the 11 children, primarily with functional constipation in 7 children. There were no significant differences between the sociodemographic (age, gender, race); personal (cesarean section, preterm birth); family (only child, firstborn, separated/divorced parents, intrafamily FGIDs); clinical (weight, height, BMI, height-for-age, dengue history), and epidemiological (overlap, confinement) variables (Table 2).

Table 2
General characteristics of children with functional dyspepsia

N/A: not applicable; H/A: height-for-age.

n = 11
	FD	Postprandial	Epigastric pain	p
	n = 11	n = 7	n = 4
Sociodemographic variables
Age
Average ± standard deviation	11.4 ± 1.2	11.4 ± 1.1	11.5 ± 1.7	0.9072
Range	10 and 14	11 and 14	10 and 14
Age groups
Schoolchildren (10-12 years)	9 (81.8)	6 (85.7)	3 (75.0)	0.618
Adolescents 13-18 years old	2 (18.2)	1 (14.3)	1 (25.0)
Gender
Female	9 (81.8)	6 (85.7)	3 (75.0)	0.618
Male	2 (18.2)	1 (14.3)	1 (25.0)
Race
Hispanic	6 (54.5)	5 (71.4)	1 (25.0)	0.197
White	4 (36.4)	2 (28.6)	2 (50.0)	0.470
Afro-descendant	1 (9.1)	0 (0.0)	1 (25.0)	0.364
Personal variables
C-Section	4 (36.4)	1 (14.3)	3 (75.0)	0.088
Preterm birth	2 (18.2)	0 (0.0)	2 (50.0)	0.109
Family variables
Only child	3 (27.3)	1 (14.3)	2 (50.0)	0.279
Firstborn	6 (54.5)	4 (57.1)	2 (50.0)	0.652
Separated/divorced parents	8 (72.7)	4 (57.1)	4 (100.0)	0.212
Intra-family FGIDs	0 (0.0)	0 (0.0)	0 (0.0)	N/A
Clinical variables
Nutritional condition
According to BMI
Eutrophic	7 (63.6)	5 (71.4)	2 (50.0)	0.470
Malnourished	4 (36.4)	2 (28.6)	2 (50.0)	0.470
Overweight/obese	4 (36.4)	2 (28.6)	2 (50.0)	0.470
Overweight	1 (9.1)	1 (14.3)	0 (0.0)	0.636
Obese	3 (27.3)	1 (14.3)	2 (50.0)	0.279
According to H/A
Eutrophic	11 (100.0)	7 (100.0)	4 (100.0)	N/A
Altered height	0 (0.0)	0 (0.0)	0 (0.0)
History of dengue	2 (18.2)	1 (14.3)	1 (25.0)	0.618
Epidemiological variables
Overlapping	8 (72.7)	5 (71.4)	3 (75.0)	0.721
Constipation	6 (54.5)	3 (42.9)	3 (75.0)	0.348
Constipation and nausea	1 (9.1)	1 (14.3)	0 (0.0)	0.636
Vomiting	1 (9.1)	1 (14.3)	0 (0.0)	0.636
Confinement	4 (36.4)	1 (14.3)	3 (75.0)	0.088

The prevalence of FD was higher in females (OR: 5.33; 95%CI: 1.06-51.45; p = 0.019). The same was the case for children whose parents were separated/divorced (OR: 4.74; 95%CI: 1.09-28.31; p = 0.014), predominantly in paternal absence (OR: 3.64; 95%CI: 0.88-17.42; p = 0.033) rather than maternal absence. The multivariate analysis did not show any variable contributing to FD overlap prevalence (Table 3).

Table 3
Association between FD, overlapping, and variables

n = 11
	Functional dyspepsia			Overlapping
	OR	95 % CI	p	OR	95 % CI	p
Age groups
Schoolchildren (10-12 years)	1.00			1.00
Adolescents 13-18 years old	0.51	0.05-2.57	0.3933	0.79	0.07-4.55	0.7806
Gender
Male	1.00			N/A
Female	5.33	1.06-51.45	0.0194
Race
Hispanic	1.80	0.44-7.67	0.3376	2.34	0.44-15.31	0.2362
White	0.79	0.16-3.24	0.7220	0.49	0.04-2.82	0.3842
Afro-descendant	0.44	0.01-3.32	0.4394	0.64	0.01-5.17	0.6799
Confinement	0.36	0.07-1.49	0.1053	0.62	0.11-3.45	0.5152
C-section	0.57	0.12-2.34	0.3849	0.64	0.09-3.40	0.5553
Preterm birth	1.62	0.16-8.47	0.5420	2.6	0.24-15.21	0.2363
Only child	2.18	0.35-9.68	0.2562	0.85	0.01-6.94	0.8865
Firstborn	1.50	0.36-6.39	0.5108	1.23	0.22-6.73	0.7706
History of dengue	1.39	0.13-7.17	0.6809	0.93	0.02-7.55	0.9468
Separated/divorced parents	4.74	1.09-28.31	0.0141	2.87	0.54-18.79	0.1362
Father	3.64	0.88-17.42	0.0328	2.01	0.36-11.04	0.3180
Mother	1.63	0.03-13.16	0.650	2.30	0.04-19.52	0.4343
Intra-family FGIDs	N/A			N/A
Nutritional condition
According to BMI
Eutrophic	1.00			1.00
Malnourished	0.57	0.12-2.34	0.3849	0.14	0.003-1.15	0.0378
Overweight/obese	0.61	0.12-2.51	0.4505	0.15	0.03-1.23	0.0467
Overweight	0.20	0.004-1.46	0.0929	N/A
Obese	2.18	0.35-9.68	0.2562	0.81	0.01-6.58	0.8485
According to H/A
Eutrophic	N/A			N/A
Altered height

Discussion

As far as we know, this is the first study that evaluated the prevalence and factors associated with FD in Cuban children according to the Rome IV criteria. Findings in this research showed that 29.1% of adolescents met the criteria for some FGID, FD was identified in 3.5%, and PDS is more frequent than EPS.

Our results are similar to those reported by Saps et al⁷ in Colombian children, with a 3% FD prevalence, which is lower than the results reported by Robin et al⁸ in North American children and by Baleeman et al⁹ in Colombian children, between 7.2% and 16.1%, respectively, and higher than those reported by Zeevenhooven et al¹⁰ in adolescents from Curacao, whose prevalence for FD was 1.9%. One of the possible explanations for these different figures, among others, is how these interviews were conducted. The data from North American children⁸ were taken from the mothers’ self-responses. Conversely, Colombian children^7,9 completed the questionnaires through self-response, and the QPGS-III was applied to the children in Curaçao¹⁰, while the data interpretation to identify any FGID was conducted according to QPGS-IV.

On the other hand, other authors have only studied FD as part of FGIDs. Some of them^1,8,11, like us, have described a higher prevalence to present the PDS over the EPS subtype. Even Wei et al¹¹ found a 0.3% overlap between both FD subtypes, similar findings to ours with only 1 patient presenting such overlap, and different from the high prevalence reported by Turco et al¹. The latter found a 36.0% overlap between both FD subtypes, which suggests a common pathophysiological mechanism. However, it is worth noting that Turco et al¹ classified FD subtypes according to the QPGS-III for adults.

Our results show that FD occurred more in female adolescents, as described by Kumagai et al¹², but different from Wei et al¹¹ and Turco et al¹, who did not find this association. Other authors have described some possible factors for presenting FD like Wei et al¹¹ that found age (OR: 1.112; 95%CI: 1.031-1.201; p = 0.006) and independent living from parents (OR: 1.677; 95%CI: 1.255-2.242; p < 0.001) as possible causes to develop FD. In their study with Japanese children, Kumagai et al¹² associated FD prevalence with sleeping habits. Although many patients with FD associate their dyspeptic symptoms with eating habits, few studies show that dietary factors may be involved in developing this FGID. For example, Wei et al¹¹ describe that delayed school meals (OR: 2.107; 95%CI: 1.447-3.068; p < 0.001), skipping breakfast (OR: 2.192; 95%CI: 1.103-3.688; p = 0.003), eating frequently (OR: 2.296; 95%CI: 1.347-3.912; p = 0.002), and eating cold foods daily (OR: 2.736; 95%CI: 1.263-5.927; p = 0.011) are possible food-related risk factors leading to FD. Likewise, Kumagai et al¹² found that impaired eating habits constitute a risk factor for developing FD.

Another risk factor we found leading to develop FD is children from separated parents. According to the biopsychosocial model, we cannot ignore that psychosocial factors play a crucial role in the pathogenesis of FGIDs. Stress has pathophysiological effects on the gastrointestinal tract, triggering or exacerbating abdominal pain through visceral hypersensitivity and changes in motility. Children with depressive or anxious symptoms are more likely to develop FGIDs^1,5,12. Divorce is a major stressor at this age. Several Latin American studies associate the presence of separated/divorced parents with the prevalence of FGIDs ^13,14, consistent with this study. Wei et al¹¹ also identified that children living independently from their parents were at higher risk of developing FD, comparable to the separated parents in this study. These two factors may trigger anxiety and stress in these patients.

Thus, the main strength of our study is that it is the first cross-sectional study conducted on Cuban adolescents that determined the prevalence of FD and its associated factors. However, this study also has limitations since, like other studies using the Questionnaires of Pediatric Gastrointestinal Symptoms, Rome IV version, it includes failure to ensure external validity of the results since the symptoms depend on the adolescent’s report, which is based on the recollection of the event and its frequency, so there may be a memory bias. On the other hand, with the existing situation due to the 2019 coronavirus disease (COVID-19) and school closures, the series could not be larger and more representative.

In conclusion, functional dyspepsia is most common in female adolescents, PDS is the most frequent subtype, and its presence is associated with separated/divorced parents.

Referencias

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Manini ML, Camilleri M. How does one choose the appropiatre pharmacotherapy for pediatric patients whith functional dyspepsia? Expert Opin Pharmacother. 2019;20(16):1921-1924. https://doi.org/10.1080/14656566.2019.1650021

Romano C, Valenti S, Cardile S, Benninga MA. Functional Dyspepsia: An Enigma in a Conundrum. J Pediatr Gastroenterol Nutr. 2016;63(6):579-84. https://doi.org/10.1097/MPG.0000000000001344

Blesa LC. Trastornos digestivos funcionales pediátricos. Criterios Roma IV. En: AEPap (editor). Curso de Actualización Pediatría 2017. Madrid: Lúa Ediciones 3.0; 2017. p. 99-114.

Thapar N, Benninga MA, Crowell MD, Di Lorenzo C, Mack I, Nurko S, et al. Paediatric functional abdominal pain disorders. Nat Rev Dis Primers. 2020;6(1):89. https://doi.org/10.1038/s41572-020-00222-5

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Saps M, Velasco-Benítez CA, Langshaw AH, Ramírez-Hernández CR. Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria. J Pediatr. 2018;199(8):212-6. https://doi.org/10.1016/j.jpeds.2018.03.037

Robin S, Keller C, Zwiener R, Hyman PE, Nurko S, Saps M, et al. Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria. J Pediatr. 2018;195(4):134-9. https://doi.org/10.1016/j.jpeds.2017.12.012

Baaleman DF, Velasco-Benítez CA, Méndez-Guzmán LM, Benninga MA, Saps M. Can We Rely on the Rome IV Questionnaire to Diagnose Children With Functional Gastrointestinal Disorders? J Neurogastroenterol Motil. 2021;27(4):626-31. https://doi.org/10.5056/jnm20179

Zeevenhooven J, Van der Heijden S, Devanarayana NM, Rajindrajith S, Benninga MA. Epidemiology of Functional Abdominal Pain Disorders and Funcional Defecation Desorders in Adolescents in Curacao. J Pediatr Gastroenterol Nutr. 2020;70(4):71-6. https://doi.org/10.1097/MPG.0000000000002623

Wei Z, Yang X, Xing X, Dong L, Wang J, Qin B. Risk factors associated with functional dyspepsia in Chinese children: a cross-sectional Study. BMC Gastroenterology. 2021;21(1):1-8. https://doi.org/10.1186/s12876-021-01800-x

Kumagai H, Yokoyama K, Imagawa T, Yamagata T. Functional dyspepsia and irritable bowel syndrome in teenagers: Internet survey. Pediatr Int. 2016;58(8):714-20. https://doi.org/10.1111/ped.12884

Zablah R, Velasco-Benítez CA, Merlos I, Bonilla S, Saps M. Prevalencia de trastornos funcionales gastrointestinales en niños en edad escolar en El Salvador. Rev Gastroenterol Mex. 2015;80(3):186-91. https://doi.org/10.1016/j.rgmx.2015.03.008

Saps M, Moreno-Gómez JE, Ramírez-Hernández CR, Rosen JM, Velasco-Benítez CA. A nationwide study on the prevalence of functional gastrointestinal disorders in school-children. Bol Med Hosp Infant Mex. 2017;74(6):407-12. https://doi.org/10.1016/j.bmhimx.2017.05.005

Notes

Author notes

*Correspondence: Carlos Alberto Velasco Benitez. carlos.velasco@correounivalle.edu.co