Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease.

INTRODUCTION: Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited and conflicting. METHODS: We conducted a prospective study of women enrolled in the Nurses' Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders. RESULTS: Among 170,805 women, we confirmed 269 incident cases of CD (incidence 8/100,000 person-years) and 338 incident cases of UC (incidence 10/100,000 person-years) over 26 years and 3,317,338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92). CONCLUSIONS: A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.

Sleep duration affects risk for ulcerative colitis: a prospective cohort study.

BACKGROUND & AIMS: Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. METHODS: We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with >90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration <6 h/day (11/100,000 person-years) or >9 h/day (20/100,000 person-years) had a higher incidence of UC (P < .05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations <6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations >9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. CONCLUSIONS: On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.

A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis.

BACKGROUND & AIMS: Increased intake of dietary fiber has been proposed to reduce the risk of inflammatory bowel disease (Crohn's disease [CD] and ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. METHODS: We collected and analyzed data from 170,776 women, followed up over 26 years, who participated in the Nurses' Health Study, followed up for 3,317,425 person-years. Dietary information was prospectively ascertained via administration of a validated semiquantitative food frequency questionnaire every 4 years. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). RESULTS: We confirmed 269 incident cases of CD (incidence, 8/100,000 person-years) and 338 cases of UC (incidence, 10/100,000 person-years). Compared with the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval, 0.39-0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% confidence interval, 0.58-1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. CONCLUSIONS: Based on data from the Nurses' Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.

Oral contraceptives, reproductive factors and risk of inflammatory bowel disease.

BACKGROUND: Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC). OBJECTIVE: To determine whether this association is confounded or modified by other important lifestyle and reproductive factors. DESIGN: A prospective cohort study was carried out of 117,375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115,077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2 years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs. RESULTS: Among 232,452 women with over 5,030,196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (pheterogeneity=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD. CONCLUSION: In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.

Association between depressive symptoms and incidence of Crohn's disease and ulcerative colitis: results from the Nurses' Health Study.

BACKGROUND & AIMS: Depression and psychosocial stress are believed to contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Although many mechanisms have been proposed to link these disorders, few prospective studies have examined the relationship between depressed mood and incidence of CD or UC. METHODS: We analyzed data from 152,461 women (aged 29-72 years) enrolled since 1992-1993 in the Nurses' Health Study cohorts I and II. Self-reported depressive symptoms were assessed by using the Mental Health Index (MHI)-5, a validated 5-item subscale of the 36-item Short-Form health survey, which is designed to estimate psychological distress on the basis of scores that range from 0 to 100. Self-reported CD and UC were confirmed through blinded record review by 2 gastroenterologists. Cox proportional hazards models were used to associate recent (within 4 years) and baseline MHI-5 scores with risk for CD or UC, adjusting for other risk factors. RESULTS: During 1,787,070 person-years of follow-up, we documented 170 cases of CD and 203 cases of UC. Compared with women with recent MHI-5 scores of 86-100, women with recent depressive symptoms (MHI-5 scores <52) had an increased risk of CD (multivariate-adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.40-3.98; P trend = .001). Baseline depressive symptoms, assessed from the baseline MHI-5 score, were also associated with CD, although with a lower HR (1.62; 95% CI, 0.94-2.77). Recent (HR, 1.14; 95% CI, 0.68-1.92) and baseline depressive symptoms were not associated with increased risk of UC (HR, 1.07; 95% CI, 0.63-1.83). CONCLUSIONS: On the basis of data from the Nurses' Health Study, depressive symptoms increase the risk for CD, but not UC, among women. Psychological factors might therefore contribute to development of CD. Further studies are needed to determine the mechanisms of this association.

Hormone therapy increases risk of ulcerative colitis but not Crohn's disease.

BACKGROUND & AIMS: Estrogen has been proposed to modulate gut inflammation through an effect on estrogen receptors found on gastrointestinal epithelial and immune cells. The role of postmenopausal hormone therapy on risk of Crohn's disease (CD) and ulcerative colitis (UC) is unclear. METHODS: We conducted a prospective cohort study of 108,844 postmenopausal US women (median age, 54 years) enrolled in 1976 in the Nurses' Health Study without a prior history of CD or UC. Every 2 years, we have updated information on menopause status, postmenopausal hormone use, and other risk factors. Self-reported diagnoses of CD and UC were confirmed through medical record review by 2 gastroenterologists who were blinded to exposure information. We used Cox proportional hazards models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Through 2008, with more than 1.8 million person-years of follow-up, we documented 138 incident cases of CD and 138 cases of UC. Compared with women who never used hormones, the multivariate-adjusted HR for UC was 1.71 (95% CI, 1.07-2.74) among women who currently used hormones and 1.65 (95% CI, 1.03-2.66) among past users. The risk of UC appeared to increase with longer duration of hormone use (P(trend) = .04) and decreased with time since discontinuation. There was no difference in risk according to the type of hormone therapy used (estrogen vs estrogen plus progestin). In contrast, we did not observe an association between current use of hormones and risk of CD (multivariate-adjusted HR, 1.19; 95% CI, 0.78-1.82). The effect of hormones on risk of UC and CD was not modified by age, body mass index, or smoking. CONCLUSIONS: In a large prospective cohort of women, postmenopausal hormone therapy was associated with an increased risk of UC but not CD. These findings indicate that pathways related to estrogens might mediate the pathogenesis of UC.

Higher predicted vitamin D status is associated with reduced risk of Crohn's disease.

BACKGROUND & AIMS: Vitamin D influences innate immunity, which is believed to be involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, data examining vitamin D status in relation to risk of CD and UC are lacking. METHODS: We conducted a prospective cohort study of 72,719 women (age, 40-73 y) enrolled in the Nurses' Health Study. In 1986, women completed an assessment of diet and lifestyle, from which a 25-hydroxy vitamin D [25(OH)D] prediction score was developed and validated against directly measured levels of plasma 25(OH)D. Through 2008, we confirmed reported diagnoses of incident CD or UC through medical record review. We used Cox proportional hazards modeling to examine the hazard ratio (HR) for incident CD or UC after adjusting for potential confounders. RESULTS: During 1,492,811 person-years of follow-up evaluation, we documented 122 incident cases of CD and 123 cases of UC. The median predicted 25(OH)D level was 22.3 ng/mL in the lowest and 32.2 ng/mL in the highest quartiles. Compared with the lowest quartile, the multivariate-adjusted HR associated with the highest quartile of vitamin D was 0.54 (95% confidence interval [CI], 0.30-.99) for CD (P(trend) = .02) and 0.65 (95% CI, 0.34-1.25) for UC (P(trend) = .17). Compared with women with a predicted 25(OH)D level less than 20 ng/mL, the multivariate-adjusted HR was 0.38 (95% CI, 0.15-0.97) for CD and 0.57 (95% CI, 0.19-1.70) for UC for women with a predicted 25(OH)D level greater than 30 ng/mL. There was a significant inverse association between dietary and supplemental vitamin D and UC, and a nonsignificant reduction in CD risk. CONCLUSIONS: Higher predicted plasma levels of 25(OH)D significantly reduce the risk for incident CD and nonsignificantly reduce the risk for UC in women.

Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study.

BACKGROUND: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC). OBJECTIVE: To assess the association between aspirin and NSAID use and incident CD and UC. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study I. PATIENTS: 76,795 U.S. women who provided biennially updated data about aspirin and NSAID use. MEASUREMENTS: Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure). RESULTS: 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1,295,317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100,000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100,000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease. LIMITATIONS: Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported. CONCLUSION: Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents. PRIMARY FUNDING SOURCE: American Gastroenterological Association, IBD Working Group, Broad Medical Research Program, and National Institutes of Health.

A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women.

OBJECTIVES: Long-term data on the influence of cigarette smoking, especially cessation, on the risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited. METHODS: We conducted a prospective study of 229,111 women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Biennially, we collected updated data on cigarette smoking, other risk factors, and diagnoses of CD or UC confirmed by medical record review. RESULTS: Over 32 years in NHS and 18 years in NHS II, we documented 336 incident cases of CD and 400 incident cases of UC. Compared with never smokers, the multivariate hazard ratio (HR) of CD was 1.90 (95% confidence interval (CI), 1.42-2.53) among current smokers and 1.35 (95% CI, 1.05-1.73) among former smokers. Increasing pack-years was associated with increasing risk of CD (Ptrend < 0.0001), whereas smoking cessation was associated with an attenuation of risk. By contrast, the multivariate HR of UC was 0.86 (95% CI, 0.61-1.20) among current smokers and 1.56 (95% CI, 1.26-1.93) among former smokers. The risk of UC was significantly increased within 2-5 years of smoking cessation (HR, 3.06; 95% CI, 2.00-4.67) and remained persistently elevated over 20 years. CONCLUSIONS: Current smoking is associated with an increased risk of CD, but not UC. By contrast, former smoking is associated with an increased risk of UC, with risk persisting over two decades after cessation.

Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America.

BACKGROUND: Studies of pediatric inflammatory bowel disease (IBD) have varied in the criteria used to classify patients as having Crohn disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). Patients undergoing an initial evaluation for IBD will often undergo a series of diagnostic tests, including barium upper gastrointestinal series with small bowel follow-through, abdominal CT, upper endoscopy, and colonoscopy with biopsies. Other tests performed less frequently include magnetic resonance imaging scans, serological testing, and capsule endoscopy. The large amount of clinical information obtained may make a physician uncertain as to whether to label a patient as having CD or UC. Nevertheless, to facilitate the conduct of epidemiological studies in children, to allow the entry of children into clinical trials, and to allow physicians to more clearly discuss diagnosis with their patients, it is important that clinicians be able to differentiate between CD and UC. METHODS: A consensus conference regarding the diagnosis and classification of pediatric IBD was organized by the Crohn's and Colitis Foundation of America. The meeting included 10 pediatric gastroenterologists and 4 pediatric pathologists. The primary aim was to determine the utility of endoscopy and histology in establishing the diagnosis of CD and UC. Each member of the group was assigned a topic for review. Topics evaluated included differentiating inflammatory bowel disease from acute self-limited colitis, endoscopic and histological features that allow differentiation between CD and UC, upper endoscopic features seen in both CD and UC, ileal inflammation and "backwash ileitis" in UC, patchiness and rectal sparing in pediatric IBD, periappendiceal inflammation in CD and UC, and definitions of IC. RESULTS: Patients with UC may have histological features such as microscopic inflammation of the ileum, histological gastritis, periappendiceal inflammation, patchiness, and relative rectal sparing at the time of diagnosis. These findings should not prompt the clinician to change the diagnosis from UC to CD. Other endoscopic findings, such as macroscopic cobblestoning, segmental colitis, ileal stenosis and ulceration, perianal disease, and multiple granulomas in the small bowel or colon more strongly suggest a diagnosis of CD. An algorithm is provided to enable the clinician to differentiate more reliably between these 2 entities. CONCLUSIONS: The recommendations and algorithm presented here aim to assist the clinician in differentiating childhood UC from CD. We hope the recommendations in this report will reduce variability among practitioners in how they use the terms "ulcerative colitis," "Crohn disease," and "indeterminate colitis." The authors hope that progress being made in genetic, serological, and imaging studies leads to more reliable phenotyping.

Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study.

INTRODUCTION: High intake of dietary n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of ulcerative colitis (UC) and Crohn's disease (CD). However, results have been heterogeneous suggesting that genetic variations in PUFA metabolism may modify this risk. METHODS: We conducted a case-control study nested within 2 prospective cohorts, the Nurses' Health Study (NHS) and NHS II. Among women providing blood (n = 62,437) or buccal cells (n = 59,543) for genotyping, we confirmed new diagnoses of CD or UC. Dietary intake was assessed 4 years before diagnosis. Confirmed cases were matched 1:2 to controls. Subjects were genotyped for single nucleotide polymorphisms at CYP4F3, FADS1, and FADS2 loci. Conditional logistic regression models examined the interaction between genotype, n3:n6 PUFA intake and risk of CD and UC. RESULTS: Our study included 101 CD and 139 UC patients matched to 495 controls. On multivariable analysis, high intake of n3:n6 PUFA (above median) demonstrated a trend toward reduced risk of UC (Odds ratio [OR] 0.71, 95% confidence interval [CI], 0.47-1.09, P = 0.11). High n3:n6 PUFA intake was associated with a reduced risk of UC in individuals with the GG/AG genotype at a single nucleotide polymorphism in CYP4F3 (OR 0.57, 95% CI, 0.32-0.99) but not those with the AA genotype (OR 0.95, 95% CI, 0.47-1.93) (P-interaction = 0.049). No gene-diet interactions were noted for CD. CONCLUSIONS: The association between dietary n3:n6 PUFA intake and risk of UC may be modified variants at CYP4F3. Further gene-environment studies of the association between diet and IBD risk are warranted.

Identification and Characterization of a Novel Association between Dietary Potassium and Risk of Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Recent animal studies have identified that dietary salt intake may modify the risk and progression of autoimmune disorders through modulation of the IL-23/TH17 pathway, which is critical in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We conducted a prospective study of U.S. women enrolled in the Nurses' Health Study (NHS) and NHSII who provided detailed and validated information on diet and lifestyle beginning in 1984 in NHS and 1991 in NHSII. We confirmed incident cases of UC and CD reported through 2010 in NHS and 2011 in NHSII. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. In a case-control study nested within these cohorts, we evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes involved in TH17 pathway and dietary potassium on risk of CD and UC. In a cohort of healthy volunteers, we also assessed the effect of supplemental potassium on development of naïve and memory T cells, differentiated with TGFß1 or TH17 conditions. RESULTS: Among a total of 194,711 women over a follow-up of 3,220,247 person-years, we documented 273 cases of CD and 335 cases of UC. Dietary intake of potassium (Ptrend = 0.005) but not sodium (Ptrend = 0.44) was inversely associated with risk of CD. Although, both dietary potassium and sodium were not significantly associated with risk of UC, there was a suggestion of an inverse association with dietary potassium (Ptrend = 0.08). The association of potassium with risk of CD and UC appeared to be modified by loci involved in the TH17 pathway that have previously been associated with susceptibility to CD, particularly SNP rs7657746 (IL21) (Pinteraction = 0.004 and 0.01, respectively). In vitro, potassium enhanced the expression of Foxp3 in both naïve and memory CD4+ T cells via activating Smad2/3 and inhibiting Smad7 in TH17 cells. CONCLUSION: Dietary potassium is inversely associated with risk of CD with both in vitro and gene-environment interaction data suggesting a potential role for potassium in regulating immune tolerance through its effect on Tregs and TH17 pathway.

Zinc intake and risk of Crohn's disease and ulcerative colitis: a prospective cohort study.

BACKGROUND: Diet plays a role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Dietary zinc may influence risk of disease through effects on autophagy, innate and adaptive immune response and maintenance of the intestinal barrier. METHODS: We analysed data from 170 776 women from the Nurses Health Study I and Nurses Health Study II, who were followed for 26 years. Zinc intake was assessed using semi-quantitative food frequency questionnaires administered every 4 years. Incident CD and UC were ascertained by medical record review. Cox proportional hazards models adjusting for potential confounders determined the independent association between zinc intake and incident disease. RESULTS: Over 3 317 550 person-years (p-y) of follow-up, we identified 269 incident cases of CD and 338 incident cases of UC. Zinc intake ranged from 9 mg/day in the lowest quintile to 27 mg/day in the highest quintile. Compared with women with the lowest quintile of intake, the multivariate hazard ratios (HR) for CD were 0.92 [95% confidence interval (CI), 0.65 ­ 1.29) for women in the second quintile of intake, 0.60 (95% CI, 0.40 ­ 0.89) for the third quintile, 0.57 (95% CI, 0.38 ­ 0.86) for fourth quintile and 0.74 (95% CI, 0.50 ­ 1.10) for the highest quintile (Ptrend = 0.003). The association was stronger for dietary zinc (HR 0.63, 95% CI, 0.43 ­ 0.93, comparing extreme quintiles) than for zinc intake from supplements. Neither dietary nor supplemental zinc modified risk of UC. CONCLUSIONS: In two large prospective cohorts of women, intake of zinc was inversely associated with risk of CD but not UC.

Measures of obesity and risk of Crohn's disease and ulcerative colitis.

BACKGROUND: Obesity is associated with intestinal-specific inflammation. Nonetheless, a specific role of obesity in the etiology of inflammatory bowel disease is unclear. METHODS: We conducted a prospective cohort study of U.S. women enrolled in 1989 in the Nurses' Health Study II. At baseline, we collected information on height, weight, waist and hip circumference, weight at age 18, and body shape at age 20. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Among 111,498 women (median age, 35 yr), we documented 153 cases of Crohn's disease (CD) and 229 cases of ulcerative colitis (UC) more than 18 years of follow-up, encompassing 2,028,769 person-years. Compared with women with normal BMI, the multivariate-adjusted hazard ratios of CD were 2.33 (95% CI, 1.15-4.69) for obese women at age 18 and 1.58 (95% CI, 1.01-2.47) for obese women at baseline. Increasing weight gain between age 18 and baseline was associated with increased risk of CD (Ptrend = 0.04). Adolescent body habitus was also associated with risk of CD with a multivariate-adjusted hazard ratio of CD of 1.63 (95% CI, 1.07-2.50) for women with overweight/obese body shape compared with women with a thin/slender body shape. We did not observe a significant association between any of these anthropometric measures and risk of UC. CONCLUSIONS: In a large prospective cohort of U.S. women, measures of adiposity were associated with an increased risk of CD but not UC. Additional studies are needed to elucidate the biological mechanisms by which excess adiposity may increase the risk of CD.

Endogenous levels of circulating androgens and risk of Crohn's disease and ulcerative colitis among women: a nested case-control study from the nurses' health study cohorts.

BACKGROUND: Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We conducted a nested case-control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. RESULTS: Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08-0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). CONCLUSIONS: Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted.

High School Diet and Risk of Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Diet may play an important role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC); yet, there are few prospective studies of dietary factors. None have examined the association between adolescent diet and risk of inflammatory bowel diseases (CD and UC). METHODS: This study included women enrolled in Nurses' Health Study II who completed a validated high school dietary questionnaire in 1998. We examined the effect of dietary patterns (prudent or Western diet) and individual components of each patterns. We documented incident cases of CD and UC through 2011 based on physician review of medical records and used Cox proportional hazards models adjusting for confounders to estimate hazard ratios and confidence intervals for CD and UC. RESULTS: Over 763,229 person-years of follow-up, we identified 70 incident cases of CD and 103 cases of UC. Compared with women in the lowest quartile of a prudent diet score (characterized by greater intake of fruits, vegetables, and fish), women in the highest quartile had a 53% lower risk of CD (hazard ratio, 0.47; 95% confidence interval, 0.23-0.98; P trend = 0.04). Specifically, greater intake of fish (P trend = 0.01) and fiber (P trend = 0.06) were associated with lower risk of CD. In contrast, Western diet score was not associated with risk of CD. Neither dietary patterns nor individual food or nutrient groups was associated with UC. CONCLUSIONS: Adolescent diet is associated with risk of CD, but not UC, offering insights into disease pathogenesis.

Early life factors and risk of inflammatory bowel disease in adulthood.

BACKGROUND: Early life factors have been postulated to play a role in development of immune tolerance and intestinal microbiome, which in turn may influence the risk of inflammatory bowel disease. METHODS: We conducted a prospective cohort study of 60,186 U.S. women enrolled since 1976 in the Nurses Health Study (NHS) I and 86,495 women enrolled since 1989 in the NHS II with no history of ulcerative colitis (UC) or Crohn's disease (CD). Information about breastfeeding, birth weight, and preterm birth were collected in 1992 in NHS I and 1991 in NHS II. Diagnoses of CD and UC were confirmed through review of medical records. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. RESULTS: Among 146,681 women over 3,373,726 person-years of follow-up, we documented 248 cases of CD and 304 cases of UC through 2007 in NHS II and 2008 in NHS I. The median age of diagnosis was 51 for CD and 49 for UC. Compared with women who were not breastfed, women who were breastfed had multivariate-adjusted hazard ratios of 0.99 (95% confidence interval, 0.76-1.30) for CD and 1.03 (95% confidence interval, 0.81-1.32) for UC. Similarly, low or high birth weight and preterm birth were not significantly associated with risk of UC or CD. CONCLUSIONS: In 2 large prospective cohorts of U.S. women, we did not observe a significant association between early life factors including having been breastfed, birth weight, preterm birth, and risk of adult-onset UC and CD.

Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses' Health Study cohorts.

OBJECTIVE: To examine the association between physical activity and risk of ulcerative colitis and Crohn's disease. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study and Nurses' Health Study II. PARTICIPANTS: 194,711 women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses' Health Study and 1989 in the Nurses' Health Study II and followed up through 2010. MAIN OUTCOME MEASURE: Incident ulcerative colitis and Crohn's disease. RESULTS: During 3,421,972 person years of follow-up, we documented 284 cases of Crohn's disease and 363 cases of ulcerative colitis. The risk of Crohn's disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn's disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn's disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn's disease among women in the highest fifth of physical activity was 8 and 6 events per 100,000 person years compared with 11 and 16 events per 100,000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn's disease (all P for interaction >0.35). CONCLUSION: In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn's disease but not of ulcerative colitis.