Linking IgE-mediated CMPA to functional gastrointestinal disorders

Eur J Pediatr. 2025 Oct 14;184(11):688. doi: 10.1007/s00431-025-06533-7.

Abstract

Numerous factors have been implicated in the development of functional gastrointestinal disorders (FGID). In this study, we aimed to investigate whether a diagnosis of cow's milk protein allergy (CMPA) in infancy is a risk factor for the development of FGID in the long term and whether there is a difference between patients with IgE-mediated and non-IgE-mediated CMPA with regard to the development of FGID. The study included 250 patients aged 4-18 years who had been diagnosed with CMPA in infancy. The control group consisted of 250 children of a similar age without CMPA. A questionnaire including Rome IV criteria was prepared and administered to the parents of 500 children. FGID were observed in 70 (28%) patients with CMPA and in 76 (30.4%) patients without CMPA (p = 0.623). Functional abdominal pain-not otherwise specified (FAP-NOS), irritable bowel syndrome (IBS), and non-retentive fecal incontinence (NRFI) were significantly more common in patients without CMPA (p = 0.009, p = 0.016, p = 0.034, respectively). FGID were observed in 36 (33.6%) patients with IgE-mediated CMPA as opposed to 34 (23.8%) patients with non-IgE-mediated CMPA (p = 0.115). Functional dyspepsia (FD), FAP-NOS, and IBS were significantly more common in patients with IgE-mediated CMPA (p ≤ 0.001, p = 0.001, p = 0.002, respectively).

Conclusion: Although the frequency of FGID development did not increase in the long term in our CMPA patients, FD, FAP-NOS, and IBS were significantly more common in these patients, particularly in those with IgE-mediated CMPA. This suggests that subclinical CMPA may persist in patients with IgE-mediated CMPA.

What is known: • Literature indicates that CMPA is a predisposing or accompanying factor for FGID in children.

What is new: • Our study include the large number of patients and its case-control design. Additionally, there is no existing study in the literature comparing patients with IgE-mediated and non-IgE-mediated CMPA.

Keywords: Cow’s milk protein allergy; Functional gastrointestinal disorders; Pediatric.

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gastrointestinal Diseases* / diagnosis
  • Gastrointestinal Diseases* / epidemiology
  • Gastrointestinal Diseases* / etiology
  • Gastrointestinal Diseases* / immunology
  • Humans
  • Immunoglobulin E* / blood
  • Immunoglobulin E* / immunology
  • Male
  • Milk Hypersensitivity* / complications
  • Milk Hypersensitivity* / diagnosis
  • Milk Hypersensitivity* / immunology
  • Milk Proteins* / immunology
  • Risk Factors
  • Surveys and Questionnaires

Substances

  • Immunoglobulin E
  • Milk Proteins