nature publishing group ORIGINAL CONTRIBUTIONS FUNCTIONAL GI DISORDERS 2250 The American Journal of GASTROENTEROLOGY VOLUME 104 | SEPTEMBER 2009 www.amjgastro.com INTRODUCTION Irritable bowel syndrome (IBS) is characterized by abdomi- nal pain or discomfort associated with altered defecation and bowel habits in the absence of a structural explanation (1–5). Worldwide, the estimated prevalence of IBS ranges from 6 to 20% in the general population. Although the majority of patients do not seek professional help, IBS is the most com- mon disorder seen among gastroenterological outpatients. he environment in early life is thought to play an impor- tant role in the development of IBS (6). Small size at birth has been shown to be associated with an increased prevalence of IBS among twins (7). Traumatic early-life events such as child- hood abuse and parental neglect have been shown to be asso- ciated with increased risks of IBS in later life (6). In animal models, early-life events such as maternal separation in the irst few weeks ater birth result in altered visceral perception, one of the hallmarks of IBS, and concomitant changes in stress response (8–10). Both animal and human studies provide evi- dence for an acute and long-term dysregulation of the stress- response system, ater stressful events during the perinatal period (11,12) or during childhood (13,14). In addition, dys- regulation of the hypothalamic–pituitary–adrenal (HPA) axis has been reported among people with IBS, with elevated base- line cortisol levels, increased diurnal HPA-axis activity, and an Exposure to Severe Wartime Conditions in Early Life Is Associated With an Increased Risk of Irritable Bowel Syndrome: A Population-Based Cohort Study Tamira K. Klooker , MD 1 , Breg Braak, MD 1 , Rebecca C. Painter, MD, PhD 2 , Susanne R. de Rooij, PhD 2 , Ruurd M. van Elburg, MD, PhD 3 , Rene M. van den Wijngaard, PhD 1 , Tessa J. Roseboom, PhD 2,5 and Guy E. Boeckxstaens, MD, PhD 1,4,5 OBJECTIVES: Stressful events during early life have been suggested to play an important role in the development of the irritable bowel syndrome (IBS). In this study, we evaluate whether an exposure to severe wartime conditions during gestation and in early life are associated with an increased prevalence of IBS. METHODS: We assessed the prevalence of IBS using the Rome II questionnaire among 816 men and women (aged 58 ±1 years) who were born as term singletons in Wilhelmina Gasthuis, Amsterdam, The Netherlands around the time of World War II. RESULTS: Of a total of 816 participants, 9.6% ( n = 78, 52F) met the criteria for IBS. Exposure to severe wartime conditions in utero was not associated with the prevalence of IBS in adulthood (8.3%). Early-life exposure to severe wartime conditions was associated with an increased prevalence of IBS. The prevalence of IBS among individuals exposed up to 0.5 years of age, 1 year of age, and 1.5 years of age was 8.1%, 12.5%, and 15.3%, respectively. The increased IBS prevalence was not associated with an increased stress response. CONCLUSIONS: Our data indicate that exposure to severe wartime conditions in early life is associated with an increased risk of developing IBS. To what extent this is attributable to the stressful environment of war, to severe undernutrition, or to the increased prevalence of infectious diseases is, however, unclear. Am J Gastroenterol 2009; 104:2250–2256; doi:10.1038/ajg.2009.282; published online 9 June 2009 1 Department of Gastroenterology and Hepatology, Academic Medical Center , Amsterdam, The Netherlands; 2 Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center , Amsterdam, The Netherlands; 3 Division of Neonatology, Department of Pediatrics, VU University Medical Center , Amsterdam, The Netherlands; 4 Department of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium; 5 These authors contributed equally. Correspondence: Guy E. Boeckxstaens, MD, PhD, Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Herestraat 45, Leuven 3000, Belgium. E-mail: Guy.Boeckxstaens@med.kuleuven.be Received 14 January 2009; accepted 8 April 2009