The American Journal of GASTROENTEROLOGY VOLUME 105 | APRIL 2010 www.amjgastro.com ORIGINAL CONTRIBUTIONS nature publishing group 940 PEDIATRICS INTRODUCTION Functional constipation is a widespread symptom in children. Although the reported prevalence vary widely because of differ- ent definitions (2–23%) (1–3), it can have a great impact on the child’s quality of life (4). Studies have shown that the frequency of irritable bowel syndrome (IBS) in adults is higher in those who had history of childhood constipation, suggesting that risk factors may start early in life (5,6). e pathophysiology of childhood constipation seems multi- factorial. Genetic predisposition (7), history of gastroenteritis (8), inadequate oral intake (9,10), low-birth weight and prematurity (11), and obesity (12) have all been suggested as potential deter- minants of this common clinical problem. Another determinant of interest is food hypersensitivity. Several studies showed that in a subset of children, constipation may be a symptom of cow’s milk allergy (13–17). Iacono et al. (15) showed that in 68% of the cases, improvement was reached aſter dietary elimination of cow’s milk in children with functional constipation. A food protein that may also have a function within this respect is gluten that has been started to be consumed in the first year of the child’s life (18). Recently, a hypothesis has been submitted by Infant Nutritional Factors and Functional Constipation in Childhood: The Generation R Study J.C. Kiefte-de Jong, MSc 1,2 , J.C. Escher, MD, PhD 3 , L.R. Arends, PhD 4,5 , V.W.V. Jaddoe, MD, PhD 1,2,6 , A. Hofman, MD, PhD 6 , H. Raat, MD, PhD 7 and H.A. Moll, MD, PhD 2 OBJECTIVES: Food allergy and celiac disease may lead to childhood constipation. Early introduction of food allergens and gluten in the first year of life has been suggested to have a function in these food intolerances, but it is unclear whether this also holds true for development of childhood constipa- tion. The aim of this study was to assess the association between the timing of introduction of food allergens and gluten early in life and functional constipation in childhood. METHODS: This study was embedded in the Generation R study, a population-based prospective cohort study from fetal life until young adulthood. Functional constipation at 24 months of age was defined in 4,651 children according to the Rome II criteria of defecation frequency < 3 times a week or the presence of mainly hard feces for at least 2 weeks. RESULTS: At the age of 24 months, 12% of the children had functional constipation. Children with functional constipation got introduced to gluten more often before or at the age of 6 months than children without functional constipation (37% and 27%, respectively). After adjustment for birth weight, gestational age, gender, ethnicity, maternal education, and family history of atopy and chronic intestinal disorders, functional constipation was significantly associated with early gluten introduction (odds ratio (OR): 1.35; 95% confidence interval (CI): 1.10–1.65). No association was found between timing of introduction of cow’s milk, hen’s egg, soy, peanuts, and tree nuts with functional constipation. A history of cow’s milk allergy in the first year of life was significantly associated with functional constipation in childhood (OR: 1.57; 95% CI: 1.04 – 2.36). CONCLUSIONS: These results suggest that early gluten introduction in the first year of life provide a trigger for functional constipation in a subset of children. In case of functional constipation, there also might be a role for cow’s milk allergy initiated in the first year of life. Am J Gastroenterol 2010; 105:940–945; doi:10.1038/ajg.2010.96; published online 2 March 2010 1 Department of the Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands; 2 Department of Pediatrics, Erasmus Medical Center , Rotterdam, The Netherlands; 3 Department of Pediatric Gastroenterology, Erasmus Medical Center , Rotterdam, The Netherlands; 4 Department of Biostatistics, Erasmus Medical Center , Rotterdam, The Netherlands; 5 Department of Psychology, Erasmus Medical Center , Rotterdam, The Netherlands; 6 Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; 7 Department of Public Health, Erasmus Medical Center , Rotterdam, The Netherlands. Correspondence: H.A. Moll, MD, PhD, Department of Pediatrics, Erasmus Medical Center , PO Box 2060, Rotterdam 3000 CB, The Netherlands. E-mail: h.a.moll@erasmusmc.nl Received 30 November 2009; accepted 8 February 2010