Endoscopy and noninvasive tests in pediatric disorders of gut–brain interaction: A multicenter retrospective study of the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition

Objectives: Disorders of gut–brain interactions (DGBIs) are highly prevalent in pediatric gastroenterology and often lead to the use of invasive and noninvasive diagnostic tests, despite the guidance provided by the Rome IV criteria. Rome IV promotes a positive diagnostic approach based on the identification of specific symptoms occurring at defined frequencies, unexplained after thorough medical evaluation. This study aimed to evaluate the frequency and diagnostic accuracy of these tests in pediatric DGBIs. Methods: We conducted a retrospective analysis of pediatric patients (aged 2–16 years) evaluated for suspected DGBIs, as defined by the Rome IV criteria, across five national pediatric gastroenterology centers. Patients with known underlying organic gastrointestinal diseases were excluded. Patients were grouped based on the presence or absence of “red flags” for organic pathology, including a positive family history for gastrointestinal diseases, persistent pain outside the periumbilical area, nocturnal symptoms, persistent, bilious, or bloody vomiting; presence of blood in stools or anemia; unexplained fever; altered growth parameters, delayed or abnormal puberty; associated gastrointestinal or extraintestinal symptoms; and abnormal physical findings. Clinical data, final diagnoses, and all performed tests were recorded. Statistical analysis assessed the frequency and diagnostic accuracy of each test, and a multivariate model developed to improve diagnostic accuracy. Results: We included 500 patients with suspected DGBIs from five centers: 52.5% were female, and the median age was 9.1 ± 4.5 years. Red flags were present in 45% of patients, showing a higher frequency of positive family history, elevated inflammatory serological markers, and fecal calprotectin (FC) levels. Patients with red flag underwent more endoscopies; however, no significant increase in the detection of organic disease was observed. No single test alone demonstrated sufficient accuracy in predicting organic pathology. A multivariate model combining the presence of red flags, positive family history, elevated serum platelet count, and increased FC achieved the highest accuracy (area under the curve: 0.711, 95% confidence interval: 0.63–0.79). Conclusions: A model combining red flags for organic disease, positive family history, elevated serum platelet count, and increased FC may aid in the identification of organic diseases in children with suspected DGBIs. Prospective studies are needed to validate this model and to support the diagnostic process when Rome IV criteria alone do not distinguish between organic and functional disorders.