Document Type : original article


1 Department of Pediatrics, Clinical Research Development Unit, Hajar Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran.

2 Department of Epidemiology and Biostatistics, School of Health Modeling in Health Research Center, Shahrekord University of Medical Sciences.

3 Shahrekord UniversityDepartment of Pediatrics, Clinical Research Development Unit, Hajar Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran. of Medical Sciences


Background: A number of researches have discussed the overlap of symptoms or the simultaneous occurrence of allergic proctocolitis due to consuming cow's milk allergy and gastroesophageal reflux in infants. The present study aimed to assess the relationship between gastroesophageal reflux disease and allergic proctocolitis (eosinophilic) in one- to six- month-old infants.
Methods: This case-control study was performed on one- to six-month-old infants referred to the Pediatric Gastroenterology Clinic for whom gastroesophageal reflux disease was diagnosed as the case group (n=95); and the same number of age-matched infants without gastrointestinal problems referred for periodic care were included as the controls.  (n = 95). The diagnosis of allergic proctocolitis was made for subjects whose WBC and RBC were found to be higher than the normal range in their stool samples.
Results: The prevalence of allergic proctocolitis in the two groups with and without reflux was 36.8% and 5.3%, respectively, indicating a significant difference (P < 0.001). According to the multiple logistic regression model, the chance of developing allergic proctocolitis in the case group with gastroesophageal reflux was 12.2 times higher than the control group (OR = 12.2, P< 0.001). Boys were also 2.6 times more likely to be affected by proctocolitis than girls (OR = 2.6, P = 0.025).
Conclusion: Developing gastroesophageal reflux, especially in boys, will be associated with an increased risk of developing allergic proctocolitis.


  1. Akhparov NN, Boranbayeva R, Suleimanova SB, Temirkhanova M. Current issues of gastro-oesophageal reflux disease surgical treatment in children. Afr J Paediatr Surg. 2021; 18(3):127-32.
  2. Friedman C, Sarantos G, Katz S, Geisler S. Understanding gastroesophageal reflux disease in children. Jaapa. 2021; 34(2):12-8.
  3. Simon M, Levy EI, Vandenplas Y. Safety considerations when managing gastro-esophageal reflux disease in infants. Expert Opin Drug Saf. 2021; 20(1):37-49.
  4. Rodgers A. Gastro-oesophageal reflux in preterm infants: American Academy of Pediatrics guideline 2018. Arch Dis Child Educ Pract Ed. 2021; 106(2):107.
  5. Burris AD, Burris J, Järvinen KM. Cow's Milk Protein Allergy in Term and Preterm Infants: Clinical Manifestations, Immunologic Pathophysiology, and Management Strategies. Neoreviews. 2020; 21(12):e795-e808.
  6. Tsabouri S, Nicolaou N, Douros K, Papadopoulou A, Priftis KN. Food Protein Induced Proctocolitis: A Benign Condition with an Obscure Immunologic Mechanism. Endocr Metab Immune Disord Drug Targets. 2017; 17(1):32-7.
  7. Nowak-Węgrzyn A. Food protein-induced enterocolitis syndrome and allergic proctocolitis. Allergy Asthma Proc. 2015; 36(3):172-84.
  8. Atanaskovic-Markovic M. Refractory proctocolitis in the exclusively breast-fed infants. Endocr Metab Immune Disord Drug Targets. 2014; 14(1):63-6.
  9. Dupont C. Diagnosis of cow's milk allergy in children: determining the gold standard? Expert Rev Clin Immunol. 2014; 10(2):257-67.
  10. Wang J, Sampson HA. Food allergy. The Journal of clinical investigation. 2011; 121(3):827-35.
  11. Errázuriz G, Lucero Y, Ceresa S, Gonzalez M, Rossel M, Vives A. [Clinical characteristics and management of infants less than 1-year-old suspected with allergy to cow's milk protein]. Rev Chil Pediatr. 2016; 87(6):449-54.
  12. Heine RG. Gastrointestinal food allergies. Food Allergy: Molecular Basis and Clinical Practice. 101: Karger Publishers; 2015. p. 171-80.
  13. Magazzù G, Scoglio R. Gastrointestinal manifestations of cow's milk allergy. Ann Allergy Asthma Immunol. 2002; 89(6 Suppl 1):65-8.
  14. Forget P, Arends JW. Cow's milk protein allergy and gastro-oesophageal reflux. Eur J Pediatr. 1985; 144(4):298-300.
  15. Omari T, Tobin JM, McCall L, Savage K, Ferris L, Hammond P, Kritas S, Quinn P, Abu-Assi R, Moore D, Davidson G, Gold M, Heine RG. Characterization of Upper Gastrointestinal Motility in Infants With Persistent Distress and Non-IgE-mediated Cow's Milk Protein Allergy. J Pediatr Gastroenterol Nutr. 2020; 70(4):489-96.
  16. Cavataio F, Iacono G, Montalto G, Soresi M, Tumminello M, Campagna P, Notarbartolo A, Carroccio A. Gastroesophageal reflux associated with cow's milk allergy in infants: which diagnostic examinations are useful? Am J Gastroenterol. 1996; 91(6):1215-20.
  17. Salvatore S, Agosti M, Baldassarre ME, D’Auria E, Pensabene L, Nosetti L, Vandenplas Y. Cow’s Milk Allergy or Gastroesophageal Reflux Disease—Can We Solve the Dilemma in Infants? Nutrients. 2021; 13(2):297.
  18. Atarod L, Bahreh-mand S, Aghamohammadi A, Ghasemi M. Evaluation of gastroesophageal reflux in infants with cow milk allergy. 2007.
  19. Nelson SP, Chen EH, Syniar GM, Christoffel KK. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med. 1997; 151(6):569-72.
  20. Yukselen A, Celtik C. Food allergy in children with refractory gastroesophageal reflux disease. Pediatr Int. 2016; 58(4):254-8.
  21. Salvatore S, Agosti M, Baldassarre ME, D'Auria E, Pensabene L, Nosetti L, Vandenplas Y. Cow's Milk Allergy or Gastroesophageal Reflux Disease-Can We Solve the Dilemma in Infants? Nutrients. 2021; 13(2):297.
  22. Lucarelli S, Di Nardo G, Lastrucci G, D'Alfonso Y, Marcheggiano A, Federici T, Frediani S, Frediani T, Cucchiara S. Allergic proctocolitis refractory to maternal hypoallergenic diet in exclusively breast-fed infants: a clinical observation. BMC Gastroenterol. 2011; 11:82.
  23. Farahmand F, Najafi M, Ataee P, Modarresi V, Shahraki T, Rezaei N. Cow's milk allergy among children with gastroesophageal reflux disease. Gut and liver. 2011; 5(3):298.
  24. Karimi K, Jannat Alipour Z, Hakim F, Farahi Rostami R, Jassemi Zergani F, Fotokian Z. Assessment of gastroesophageal reflux in children (2-12 Month) based on clinical findings and ultrasonography. SSU_Journals. 2012; 20(3):295-305.
  25. Leung AK, Hon KL. Gastroesophageal reflux in children: an updated review. Drugs Context. 2019; 8:212591.
  26. Curien-Chotard M, Jantchou P. Natural history of gastroesophageal reflux in infancy: new data from a prospective cohort. BMC Pediatr. 2020; 20(1):152.
  27. Moghtaderi M, Farjadian S, Imanieh MH, Hosseini Teshnizi S. Cowâ s Milk Sensitization in Young Children with Gastroesophageal Reflux Disease. Int J Pediatr. 2017; 5(12):6189-94.
  28. Sardecka I, Łoś-Rycharska E, Ludwig H, Gawryjołek J, Krogulska A. Early risk factors for cow's milk allergy in children in the first year of life. Allergy Asthma Proc. 2018; 39(6):e44-e54.