Relation of body mass index to risk of developing inflammatory bowel disease amongst women in the Danish National Birth Cohort

Background Crohn's disease (CD) has traditionally been associated with weight loss and low BMI, yet paradoxically obesity has recently been suggested as a risk factor for CD, but not for ulcerative colitis (UC). We therefore hypothesized that the relation between BMI and CD is U shaped. Aim To conduct a large population-based prospective cohort study of BMI and later risk of IBD, taking age at IBD diagnosis into account. Methods A cohort of 74,512 women from the Danish National Birth Cohort, with BMI measured pre-pregnancy and 18 months after delivery, was followed for 1,022,250 person-years for development of IBD, according to the Danish National Patient Register. Associations were tested by Cox regression. Results Overweight subjects (25 <= BMI<30 kg/m2) had the lowest risk of CD, whereas obesity (BMI >= 30kg/m2) increased the risk of CD at all ages, and low BMI (BMI<18.5kg/m2) associated with CD diagnosed at age 18-<40 years. Hence, using normal weight subjects as the reference, adjusted HRs for risk of developing CD (at age 18-<40 years) were 1.8(95% CI, 0.9-3.7) for underweight, 0.6(0.3-1.2) for overweight, and 1.5(0.8-2.7) for obese individuals (pre-pregnancy BMI). HRs were greater for BMI determined 18 months after delivery. Splines for CD risk according to waist: height ratio confirmed a U-shaped relationship with CD occurring < 40 years, and a linear relationship with CD diagnosed at age 40+. There was no relationship between BMI and risk of UC. Conclusion For the first time, we demonstrate that both high BMI and low BMI are risk factors for CD. Underweight may be a pre-clinical manifestation of disease being present many years before onset with obesity being a true risk factor. This raises the question as to whether there may be two distinct forms of CD.