Diagnostic Revision and Organic Disease Risk in Pediatric Rome IV Disorders of Gut–Brain Interaction: A Single-Center Retrospective Cohort

Abstract

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria.

1. Introduction

Pediatric disorders of gut–brain interaction (DGBIs)—historically referred to as functional gastrointestinal disorders—are among the most frequent reasons for pediatric gastroenterology referral and are associated with recurrent symptoms, impaired quality of life, and substantial healthcare utilization [1]. They are currently conceptualized as disorders of brain–gut interaction with multifactorial mechanisms (e.g., visceral hypersensitivity, altered mucosal/immune function, microbiota changes, and psychosocial factors), rather than as the consequence of a single structural lesion [1,2].

The Rome IV criteria (2016) were developed to standardize diagnosis and promote a symptom-based “positive diagnosis” of DGBIs, aiming to reduce unnecessary investigations when alarm features are absent and to facilitate earlier, structured management [3,4]. However, in routine practice, a persistent concern is that some organic disorders may initially mimic DGBIs, particularly when symptom descriptions are non-specific or when early disease presents without clear alarm signs [5,6]. This is especially relevant in pediatrics, where symptom reporting may be less precise and clinical phenotypes can overlap across developmental ages. In addition, much of the epidemiologic literature on pediatric DGBIs relies on questionnaire-based case definitions, which may not systematically exclude organic disease through laboratory or instrumental assessment. Several systematic prevalence studies using Rome IV criteria are based on symptom questionnaires administered to general populations without a standardized diagnostic work-up to rule out organic pathology, potentially limiting diagnostic specificity [7,8]. As a result, real-world estimates of diagnostic instability (i.e., the proportion of children initially labeled as functional who later receive an organic diagnosis) remain clinically important but incompletely characterized across symptom phenotypes.

Therefore, the primary aim of this single-center retrospective cohort study was to evaluate the real-world clinical stability of a Rome IV-oriented diagnostic approach by quantifying how often children and adolescents initially diagnosed with a DGBI were subsequently found to have an organic disorder after further diagnostic work-up and/or exclusion therapies. Secondary aims were (i) to provide an updated estimate of the outpatient prevalence of pediatric DGBIs in an Italian tertiary care setting and (ii) to identify which symptom clusters were associated with a higher likelihood of diagnostic revision. Importantly, this study was not designed to investigate the biological mechanisms underlying DGBIs or to identify biomarkers of functional-only presentations; rather, it was intended to address a practical diagnostic question relevant to routine pediatric gastroenterology care.

2. Results

2.1. Study Population and Baseline Characteristics

A total of 1815 outpatient pediatric gastroenterology records were reviewed for the study period between 2014 and 14 May 2021. Among these, 440 patients met the inclusion criteria, corresponding to an initial prevalence of functional gastrointestinal disorders of 24.24% at first diagnosis.

The study cohort included 220 males (50%) and 220 females (50%), with a mean age of 8.86 ± 4.65 years (range: 0–18 years). Patients were stratified into three age groups: infants (<1 year, n = 13; 2.95%), toddlers (1–3 years, n = 61; 13.86%), and children/adolescents (4–18 years, n = 366; 83.18%) (

Table 1. Baseline demographic characteristics of pediatric patients initially diagnosed with a Rome IV-oriented functional gastrointestinal disorder in the study cohort (n = 440).

Characteristic	Value
Age, years (mean ± SD)	8.86 ± 4.65
Male sex	220 (50.0%)
Female sex	220 (50.0%)
Infants (<1 year)	13 (2.95%)
Toddlers (1–3 years)	61 (13.86%)
Children/adolescents (4–18 years)	366 (83.18%)

).

When chart information was incomplete or follow-up data were missing, caregiver telephone follow-up was used to complete diagnostic reassessment; overall, 86 telephone interviews were conducted among the included patients.

After full diagnostic reassessment—including clinical follow-up, laboratory and instrumental investigations, and response to exclusion therapies—patients were categorized into three final diagnostic groups: organic disorder, organic disorder with concomitant functional component, or functional disorder only.

Overall, 343 patients (77.95%) maintained a final diagnosis of functional disorder, whereas 73 patients (16.59%) were reclassified as having an organic disease. An additional 24 patients (5.45%) were classified as having a mixed diagnosis, consisting of an organic condition associated with a concomitant functional disorder (

Table 2. Final diagnostic categories after reassessment of 440 pediatric patients initially classified as having a functional gastrointestinal disorder.

Final Diagnosis	N	%
Organic disorder	73	16.59
Organic disorder + functional component	24	5.45
Functional disorder only	343	77.95
Total	440	100.00

). These findings indicate that approximately one in five patients initially diagnosed with a functional gastrointestinal disorder had an underlying organic condition identified during further diagnostic work-up.

2.2. Association Between Final Diagnosis and Demographic Variables

The relationship between final diagnostic category and demographic variables was explored. No significant differences were observed between sex and final diagnosis, indicating that the probability of reclassification into organic or mixed diagnoses did not differ between males and females. Similarly, the association between age group and final diagnosis did not reach statistical significance (p = 0.372). However, the majority of patients belonged to the school-age group (4–18 years), representing 83.18% of the cohort. Within this group, 17.76% were ultimately diagnosed with an organic disorder, 6.01% with mixed diagnoses, and 76.23% remained functional.

Infants accounted for a very small proportion of the sample (2.95%), and in this group, the diagnosis of functional disorder was confirmed in 92.31% of cases.

2.3. Gastrointestinal Tract Involvement

The anatomical distribution of symptoms across the gastrointestinal tract was also examined. A statistically significant association was found between final diagnosis category and involvement of the upper or lower gastrointestinal tract (p = 0.001).

Among patients with confirmed functional disorders (n = 343), symptoms predominantly involved the lower gastrointestinal tract, with 230 cases, followed by 96 cases involving the upper gastrointestinal tract and 17 cases affecting both segments.

A similar distribution was observed among organic disorders (n = 73), where 41 cases involved the lower gastrointestinal tract, 28 involved the upper gastrointestinal tract, and 4 involved both segments. In the mixed diagnosis group (n = 24), 13 cases involved the lower gastrointestinal tract, 5 the upper gastrointestinal tract, and 6 both segments (

Table 3. Anatomical distribution of presenting gastrointestinal symptoms (upper, lower, or both) according to final diagnostic category after reassessment.

Final Diagnosis	Upper GI	Lower GI	Both	Total
Functional disorder only	96	230	17	343
Organic disorder only	28	41	4	73
Organic disorder + functional component	5	13	6	24
Functional disorder only	96	230	17	343

). These findings indicate that lower gastrointestinal symptoms were the most frequent clinical presentation across all diagnostic categories, particularly in patients with functional disorders.

2.4. Diagnostic Accuracy According to Presenting Symptom Clusters

Initial clinical presentations were grouped into five symptom clusters: lower recurrent abdominal pain, upper gastrointestinal dyspepsia-related symptoms, vomiting/cyclic vomiting syndrome, diarrhea, and constipation. The relationship between these symptom clusters and the final diagnosis was statistically significant (p = 0.001).

Lower recurrent abdominal pain, including patients with irritable bowel syndrome, showed a functional confirmation rate of 73.04%, while 19.61% of these cases were ultimately diagnosed as organic disorders.

Symptoms related to upper gastrointestinal disorders and dyspepsia represented the cluster with the highest proportion of organic diagnoses (27.03%) and the lowest confirmation rate of functional disorders (68.92%). For functional vomiting and cyclic vomiting syndrome, 16.67% of patients were ultimately diagnosed with organic disorders, 7.14% with mixed diagnoses, and 76.19% retained a functional diagnosis.

Similarly, among patients presenting with diarrhea, 16.67% were reclassified as organic disorders, 10% as mixed diagnoses, and 73.33% remained functional. In contrast, constipation demonstrated the highest diagnostic stability, with 98.89% of cases confirmed as functional disorders and only 1.11% subsequently diagnosed with an organic condition, representing the lowest misdiagnosis rate among the symptom clusters analyzed (

Table 4. Final diagnostic category after reassessment according to presenting symptom cluster at first outpatient evaluation.

Symptom Cluster at First Visit	Organic	Organic + Functional	Functional only	Total
Lower abdominal pain/IBS-spectrum	40	15	149	204
Upper GI/dyspepsia-spectrum	20	3	51	74
Vomiting/cyclic vomiting-spectrum	7	3	32	42
Diarrhea	5	3	22	30
Constipation	1	0	89	90
Total	73	24	343	440

).

2.5. Pre-Pandemic vs. Pandemic Analysis

To explore the potential impact of the COVID-19 pandemic on the diagnosis of pediatric functional gastrointestinal disorders, cases were stratified into pre-pandemic (2014–2019) and pandemic (2020–May 2021) periods.

During the pre-pandemic period, 331 patients received an initial diagnosis of a functional gastrointestinal disorder, of whom 258 (77.71%) were confirmed as having functional disorders after further diagnostic evaluation. During the pandemic period, 109 cases were identified, of which 85 (78.70%) were confirmed as functional disorders. Statistical comparison showed no significant difference between the two periods (p = 0.756) (

Table 5. Confirmation of the initial functional diagnosis after reassessment in the pre-pandemic (2014–2019) and pandemic (2020–May 2021) periods.

Period	Total Initial Functional Diagnoses	Confirmed Functional n (%)	Not Confirmed (Organic or Mixed) n (%)
2014–2019 (pre-COVID)	332	258 (77.71%)	74 (22.29%)
2020–May 2021 (COVID period)	109	85 (78.70%)	24 (21.30%)

p = 0.756 (Pearson’s chi-square test).

).

To account for the shorter observation period in 2021, the number of cases was also analyzed using monthly averages. Between 2014 and 2019, the mean number of functional gastrointestinal disorder cases was 4.61 per month, whereas during 2020–2021 the average increased to 6.29 cases per month. However, despite this apparent increase, the difference was not statistically significant, and the distribution of cases across the years remained relatively stable.

2.6. Prevalence of Confirmed Functional Disorders

Following exclusion of organic diagnoses, 343 patients were ultimately classified as having exclusively functional gastrointestinal disorders, some presenting with more than one functional condition simultaneously (e.g., functional constipation associated with non-retentive fecal incontinence, dyspepsia, or aerophagia). Additionally, 24 patients were classified as having functional gastrointestinal disorders in the presence of an underlying organic condition, highlighting the potential coexistence of organic and functional mechanisms in pediatric gastrointestinal symptomatology. This mixed category was used for cases in which a documented organic diagnosis explained only part of the symptom burden, while a concomitant DGBI-compatible clinical profile remained plausible. As expected in a study based on Rome IV-oriented clinical classification, patients remaining in the functional-only group were not assumed to have an identifiable single structural, infectious, inflammatory, or genetic cause.

3. Discussion

In this single-center retrospective cohort of pediatric gastroenterology outpatients, we found that an initial functional diagnosis was not fully stable over time in a relevant minority of cases after diagnostic reassessment. Specifically, among 440 patients initially labeled as having a functional gastrointestinal disorder, 16.59% received a subsequent organic diagnosis and 5.45% were classified as mixed, suggesting coexistence of an organic condition with a functional component. These findings are clinically relevant because they quantify, in routine specialist practice, how often an initial symptom-based diagnosis is later revised after follow-up and further evaluation. Rather than addressing disease mechanisms, the present study was designed to address a practical clinical question: the real-world stability of a Rome IV-oriented diagnosis in tertiary pediatric care.

A central result of this study is that diagnostic revision was significantly associated with presenting symptom phenotype. When initial presentations were grouped into five symptom clusters, the proportion of organic final diagnoses differed significantly across clusters (p = 0.001).

The highest organic yield occurred in upper gastrointestinal/dyspepsia-related presentations (27.03%), whereas constipation was remarkably stable, with 98.89% of cases confirmed as functional and only 1.11% reclassified as organic. This gradient is clinically plausible: constipation in pediatrics frequently presents with a typical history and physical examination pattern and, in the absence of red flags, is often appropriately diagnosed and managed without extensive testing. Conversely, dyspepsia-like symptoms in children (e.g., epigastric discomfort, nausea, postprandial fullness, regurgitation-like symptoms) overlap substantially with multiple organic entities and may require a lower threshold for targeted investigations, particularly when symptoms persist or recur after initial management. This pattern of association is consistent with prior evidence that the prevalence of organic disease among children with chronic abdominal pain differs by clinical setting, ranging from ~5% in community samples to up to ~40% in pediatric gastroenterology practice, placing our organic-only reclassification rate (16.59%) within the expected specialist-care spectrum [9].

This specialist-care context is important when interpreting our findings, because referral patterns in a tertiary center likely enriched the cohort for more complex, persistent, or diagnostically uncertain cases than would be expected in primary care or community populations.

For lower recurrent abdominal pain/IBS-spectrum presentations, we observed a non-negligible organic reclassification rate (19.61%), reinforcing that abdominal pain phenotypes, while common in DGBIs, remain a challenging diagnostic area in pediatrics and may warrant structured alarm-feature screening and follow-up reassessment when symptoms do not evolve as expected.

Diarrhea-predominant presentations showed an intermediate degree of diagnostic stability in our cohort: 73.33% of cases remained functional after reassessment, whereas 16.67% were reclassified as organic and 10.0% as mixed. This proportion should not be interpreted as the prevalence of functional diarrhea in the general pediatric population, but rather as the proportion of children in this tertiary-care cohort whose diarrhea-predominant presentation remained compatible with a functional/DGBI diagnosis after follow-up and available diagnostic reassessment. In practical terms, this finding suggests that diarrhea represents a clinically heterogeneous phenotype, requiring appropriate follow-up and selective exclusion of organic causes before confirming a functional diagnosis. Because this subgroup was relatively small (n = 30), the estimate should be interpreted cautiously.

In contrast, large community epidemiology studies applying Rome IV using parent-reported online questionnaires report that roughly one quarter of children meet symptom-based criteria for a functional GI disorder, highlighting that questionnaire-derived prevalence estimates are not directly comparable with clinic-based cohorts where follow-up assessment can identify organic and mixed diagnoses [10]. In line with our observation that upper GI/dyspepsia phenotypes carried the highest organic yield, a prospective pediatric study of children fulfilling Rome III functional dyspepsia criteria who underwent endoscopy found organic disease in a subset, with a markedly higher diagnostic yield in the presence of alarm features (33.3% vs. 2.8%) [11].

These findings should be interpreted cautiously. Because our analysis was based on retrospective unadjusted comparisons, we cannot conclude that presenting symptom phenotype alone independently predicts later organic reclassification. Other factors, including age, alarm features, symptom severity or persistence, and differences in diagnostic work-up intensity, including laboratory, endoscopic, or instrumental evaluation, may also have contributed to the observed differences across symptom clusters.

Another relevant finding is the association between final diagnostic category and anatomical symptom distribution (p = 0.001). Across all three final diagnosis categories, lower GI involvement was more frequent than upper GI involvement. This likely reflects the high frequency of constipation and IBS-like presentations in pediatric outpatient gastroenterology. However, the mixed diagnosis group showed a comparatively higher proportion of “both upper and lower GI” involvement (6/24) than the organic-only group (4/73) and the functional-only group (17/343). While this observation should be interpreted cautiously due to the small size of the mixed group, it is consistent with the concept that broader symptom involvement may reflect overlapping mechanisms where an organic trigger and a functional symptom amplification process coexist.

Given the well-recognized psychosocial impact of the pandemic and the putative role of stress in DGBIs, we explored whether the proportion of confirmed functional diagnoses differed between pre-pandemic (2014–2019) and pandemic (2020–May 2021) periods. The proportion of cases ultimately confirmed as functional was similar in the two periods (77.71% vs. 78.70%; p = 0.756). We did observe a higher monthly average number of cases during 2020–2021 (6.29/month) compared with 2014–2019 (4.61/month). However, this increase should be interpreted in light of the shorter observation window for 2021 (first 5 months) and healthcare access changes during lockdown phases, and it does not translate into a statistically significant change in the proportion of confirmed functional diagnoses.

Taken together, these data support a balanced interpretation of symptom-based diagnostic frameworks in pediatric gastroenterology. A Rome IV-oriented approach can efficiently classify many presentations, but the possibility of later diagnostic revision toward an organic condition is not negligible, particularly for upper GI/dyspepsia-like and abdominal pain/IBS-spectrum presentations. From a practical perspective, our findings argue for a symptom-stratified diagnostic pathway: constipation-dominant presentations may be managed more confidently as functional in the absence of alarm features, whereas upper GI and abdominal pain phenotypes may benefit from earlier targeted testing and/or structured follow-up plans to reduce the risk of delayed etiologic diagnosis.

The clinical utility of this study should be interpreted within this diagnostic framework. DGBIs are not expected to have a single identifiable organic substrate in most patients, and the absence of a later organic diagnosis in the functional-only group should not be interpreted as indicating limited clinical relevance. Rather, the value of our findings lies in showing how frequently an initial functional label remains stable in routine practice and in identifying those symptom phenotypes in which closer vigilance, follow-up, or targeted investigations may be more appropriate. In this sense, the study is intended to inform clinical decision-making after an initial symptom-based diagnosis, rather than to define the biological pathophysiology of DGBIs.

An additional message is that a subset of patients will remain clinically complex even after an organic diagnosis is established. The mixed-diagnosis category (5.45%) suggests that symptom persistence may reflect a functional overlay even in the presence of organic disease, emphasizing the importance of multidisciplinary management strategies that address both biological and psychosocial contributors. In our study, this category was used when the identified organic condition did not fully explain the overall symptom burden and a concomitant DGBI-compatible presentation remained clinically plausible.

Strengths of this study include the relatively large outpatient base reviewed (1815 charts), the explicit three-level final diagnostic categorization, and the inclusion of telephone follow-up to reduce missing outcome data in a subset of cases.

Limitations include the retrospective design and reliance on the completeness of medical records. Although diagnostic reassessment was based on all available follow-up, laboratory, instrumental, and therapeutic-response data, and supplemented by caregiver telephone follow-up when feasible, incomplete documentation may still have introduced classification bias. No fully standardized follow-up protocol was in place, as this was a real-world retrospective study, and diagnostic testing was performed according to routine clinical judgment. Accordingly, physician-dependent decision making and variable diagnostic intensity across phenotypes may have influenced the likelihood of detecting organic disease; for example, upper GI symptoms may have prompted more endoscopy or pH-impedance investigations than other presentations.

In addition, potential confounding variables such as age, alarm features, laboratory abnormalities, and differences in endoscopic or instrumental evaluation were not formally adjusted for in adjustable analyses.

Moreover, this was a single-center tertiary-care cohort, and referral bias may have enriched the sample for more complex or persistent cases, thereby limiting generalizability to primary care or community populations. The youngest age stratum was small, limiting inference for infants. The “mixed” category may represent true overlap but can also reflect residual uncertainty when symptoms persist despite treatment of an identified organic condition. Finally, this study was not designed to characterize genetic, infectious, inflammatory, or other biological mechanisms underlying functional-only presentations; therefore, no mechanistic inferences should be drawn from these data.

4. Materials and Methods

4.1. Study Design and Setting

This was a single-center retrospective cohort study conducted at the Pediatric Gastroenterology outpatient clinic of the IRCCS Policlinico San Matteo Foundation (Pavia, Italy).

4.2. Data Source, Study Period, and Eligibility Criteria

Data were retrospectively extracted from outpatient medical records collected between 2014 and 14 May 2021.

Eligible patients were neonates, children, and adolescents aged 0–18 years with an initial diagnosis consistent with a pediatric functional gastrointestinal disorder according to Rome IV criteria (2016). Rome IV diagnostic categories considered for inclusion were: infant regurgitation; infant and adolescent rumination syndrome; functional nausea and functional vomiting; cyclic vomiting syndrome; aerophagia; functional diarrhea; infant dyschezia; functional constipation; nonretentive fecal incontinence; and recurrent abdominal pain disorders (infant colic, functional dyspepsia, irritable bowel syndrome, abdominal migraine, and functional abdominal pain not otherwise specified).

4.3. Chart Review and Diagnostic Reclassification Procedure

For each eligible record, we extracted the initial diagnostic suspicion, initial diagnosis, final diagnosis, and key clinical history elements to verify whether the presentation was compatible with Rome IV symptom-based definitions.

To evaluate potential organic etiologies underlying symptoms initially labeled as functional, we reviewed the following:

• Laboratory investigations: complete blood count, inflammatory markers, anti-tissue transglutaminase and anti-endomysium antibodies, fecal calprotectin, and stool tests for viruses, bacteria, and parasites;
• Instrumental assessment: abdominal ultrasound, esophagogastroduodenoscopy, colonoscopy, and pH-impedance monitoring;
• Response to exclusion therapies/diets: lactose-free diet, gluten-free diet, and low-FODMAP diet.

Based on the combined clinical data, test results, and treatment responses, an underlying organic cause was sought, excluded, or confirmed. For final diagnostic reclassification, an organic disease was defined as a documented non-functional gastrointestinal or systemic condition identified during follow-up and considered clinically sufficient to explain the presenting gastrointestinal symptoms, based on available laboratory findings, instrumental investigations, specialist documentation, and/or clinically meaningful response to targeted therapy or an exclusion diet. A functional-only diagnosis was retained when no documented organic condition emerged during follow-up and the clinical presentation remained compatible with a Rome IV-oriented DGBI diagnosis. A mixed diagnosis was assigned when an identified organic condition explained only part of the symptom burden and a concomitant DGBI-compatible symptom profile remained clinically plausible, including cases in which DGBI-compatible symptoms persisted despite appropriate management of the organic condition.

When records were incomplete or follow-up information was missing, diagnostic classification was completed, when possible, through telephone interviews with caregivers to confirm/exclude functional diagnosis and to collect information on additional tests or organic diagnoses obtained at other centers.

To reduce misclassification, diagnostic reassessment was based on the integration of all available sources of clinical information, including longitudinal follow-up data, laboratory and instrumental findings, and response to exclusion therapies when documented. When chart information was incomplete, caregiver telephone follow-up was used, when feasible, to clarify subsequent investigations and diagnostic evolution. However, no fully standardized follow-up protocol was in place because of the retrospective real-world design of the study; diagnostic work-up and follow-up intensity were determined by routine clinical judgment according to presenting symptoms and clinical evolution.

4.4. Variables and Clinical Stratification

A dedicated database was created including: sex; age at first diagnosis; initial diagnosis and post–first-visit symptoms; short clinical history summary; tests performed and results; and final diagnosis.

Age was grouped into three categories: Infants: <1 year; Toddlers: 1–3 years; Children/adolescents: 4–18 years.

Initial presentations were summarized into five symptom clusters:

(1)

Lower recurrent abdominal pain (including IBS-spectrum; excluding epigastric pain);

(2)

Upper GI/dyspepsia-related symptoms (including infant regurgitation, rumination syndrome, and functional nausea);

(3)

Functional vomiting/cyclic vomiting syndrome;

(4)

Diarrhea;

(5)

Constipation.

Final diagnoses (functional, organic, mixed) were additionally stratified by upper vs. lower GI tract involvement (upper, lower, or both) as recorded in the clinical documentation.

As an exploratory analysis, cases were also grouped by time period: pre-pandemic (2014–2019) vs. pandemic period (2020–May 2021).

4.5. Outcomes

The primary outcome was the proportion of patients initially labeled as functional who were ultimately classified as: DGBI/functional disorder only; Organic disorder; Mixed diagnosis (documented organic disorder with concomitant functional symptoms fulfilling a DGBI-compatible clinical pattern and not fully explained by the organic condition alone).

Secondary outcomes included the following: (i) the outpatient prevalence of confirmed functional diagnoses in the overall series; (ii) differences in final diagnosis across symptom clusters, age, sex, and GI tract involvement; and (iii) the distribution of organic etiologies identified among reclassified cases.

4.6. Statistical Analysis

Categorical variables were described as counts and percentages and compared using Pearson’s chi-square test. Prevalence estimates were reported with binomial 95% confidence intervals using the Clopper–Pearson method. Analyses were performed using Stata 16.1, and p < 0.05 was considered statistically significant. Figures were generated in Excel.

5. Conclusions

In a tertiary pediatric outpatient cohort, an initial functional diagnosis was revised to an organic diagnosis in 16.59% of cases, with an additional 5.45% classified as mixed. Diagnostic revision was associated with presenting phenotype, being highest in upper GI/dyspepsia-related presentations and lowest in constipation, and did not differ significantly between pre-pandemic and pandemic periods. These findings support the use of symptom-stratified evaluation and follow-up alongside Rome IV criteria to minimize missed organic disease while avoiding unnecessary testing in low-risk phenotypes. The present study was intended to assess the real-world diagnostic stability of a symptom-based clinical approach, rather than to define the biological mechanisms underlying DGBIs.