Surgery for Crohn's Disease Is Associated with a Dysbiotic Microbiome and Metabolome: Results from Two Prospective Cohorts.

BACKGROUND AND AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, E lenta, A equalofaciens and G pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In two different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria as well as secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD. METHODS: This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response. RESULTS: The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR. CONCLUSIONS: Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Antibody and T cell responses to coronavirus disease 2019 vaccines in patients with inflammatory bowel disease do not correlate. Most patients with inflammatory bowel disease mount a T cell response despite being on biologic therapies, those on anti-tumor necrosis factor may have a higher T cell response. Anti-tumor necrosis factor therapy has been associated with a lower antibody response to coronavirus disease 2019 vaccines, but the T cell response is augmented.

Older Adult Patients Use More Aminosalicylate Monotherapy Compared With Younger Patients With Inflammatory Bowel Disease: TARGET-IBD.

GOAL: The goal of this study was to describe medication utilization patterns in older inflammatory bowel disease (IBD) patients. BACKGROUND: Despite a growing population of older patients with Crohn's disease (CD) and ulcerative colitis (UC), questions remain regarding medication utilization patterns in comparison to younger populations. MATERIALS AND METHODS: We collected data from the 34 sites in TARGET-IBD, a multicenter, observational cohort. The primary outcome in this study was the IBD-specific therapy utilized among older patients with IBD compared with younger age groups. Therapy use was analyzed using pairwise comparisons and then the odds of IBD-specific therapy use among patients older than age 65 were evaluated using multivariable logistic regression models. RESULTS: We identified 2980 patients with IBD (61% CD). In multivariable analysis, younger patients with UC were significantly less likely to utilize aminosalicylate monotherapy when compared with patients above 65 years [age 18 to 29: adjusted odds ratio (aOR)=0.51, 95% confidence interval (CI): 0.33-0.78]. In patients with CD, younger patients were significantly less likely to use aminosalicylate monotherapy when compared with patients above 65 (greatest difference age 18 to 29: aOR=0.31, 95% CI: 0.18-0.52). Younger patients with CD and UC were significantly more likely to use anti-tumor necrosis factor monotherapy than patients above 65 years (age 18 to 29: aOR=3.87, 95% CI: 2.47-6.06 and aOR=2.68, 95% CI: 1.29-5.58, respectively). CONCLUSIONS: Older patients with IBD demonstrate significant differences in medication utilization, including more aminosalicylate monotherapy and less anti-tumor necrosis factor monotherapy compared with younger age groups. Given the aging population in the United States, these utilization patterns may have long-term implications for disease control.

The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).

BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn's disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

Trends in Morbidity and Mortality Following Colectomy Among Patients with Ulcerative Colitis in the Biologic Era (2002-2013): A Study Using the National Inpatient Sample.

BACKGROUND: Total abdominal colectomy (TAC) is a treatment modality of last recourse for patients with severe and/or refractory ulcerative colitis (UC). The goal of this study is to evaluate temporal trends and treatment outcomes following TAC among hospitalized UC patients in the biologic era. METHODS: We queried the National Inpatient Sample (NIS) to identify patients older than 18 years with a primary diagnosis of ulcerative colitis (UC) who underwent TAC between 2002 and 2013. We evaluated postoperative morbidity and mortality as outcomes of interest. Logistic regression was used to explore factors associated with postoperative morbidity and mortality after TAC. RESULTS: A weighted total of 307,799 UC hospitalizations were identified. Of these, 27,853 (9%) resulted in TAC. Between 2002 and 2013, hospitalizations for UC increased by over 70%; however, TAC rates dropped significantly from 111.1 to 77.1 colectomies per 1000 UC admissions. Overall, 2.2% of patients died after TAC. Mortality rates after TAC decreased from 3.5% in 2002 to 1.4% in 2013. Conversely, morbidity rates were stable throughout the study period. UC patients with emergent admissions, higher comorbidity scores and who had TAC in low volume colectomy hospitals had poorer outcomes. Regardless of admission type, outcomes were worse if TAC was performed more than 24 h after admission. CONCLUSIONS: Despite increased hospitalizations for UC, rates of TAC have declined during the post-biologic era. For UC patients who undergo TAC, mortality has declined significantly while morbidity remains stable. Older age, race, emergent admissions and delayed surgery are predictive factors of both postoperative morbidity and mortality.

Alterations in brain white matter microstructural properties in patients with Crohn's disease in remission.

Patients with inflammatory bowel disease have been shown to have abnormal brain morphometry or function, which are associated with psychological symptoms such as stress, depression or anxiety. The present work recruited 20 Crohn's disease patients in remission (CDs) and 20 age-gender-handedness-education matched healthy controls (HCs) and compared their brain white matter microstructural properties using Diffusion Tensor Imaging (DTI). Additionally, we examined the correlations between the microstructural properties and cognition (verbal fluency language task, VF) and affect (anxiety) in both groups as well as disease duration in CDs. Results showed that CDs exhibited significant alterations in microstructural properties compared to HCs in various white matter tracts relevant to language function despite no significant difference in VF scores. Furthermore, CDs' microstructural changes exhibited correlations with anxiety level and disease duration. These findings suggest that CD patients may experience changes in white matter microstructural properties which may be a biomarker of neuropsychiatric comorbidities of CD.

Immunogenicity of High Dose Influenza Vaccine for Patients with Inflammatory Bowel Disease on Anti-TNF Monotherapy: A Randomized Clinical Trial.

BACKGROUND: Patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor alpha (TNF) agents may have lower immune response to the influenza vaccine. We aimed to evaluate the immunogenicity of the high dose (HD) vs standard dose (SD) influenza vaccine in patients with IBD on anti-TNF monotherapy. METHODS: We performed a randomized clinical trial at a single academic center evaluating the immunogenicity of the HD vs SD influenza vaccine in patients with IBD on anti-TNF monotherapy. Influenza antibody concentration was measured at immunization, at 2 to 4 weeks postimmunization, and at 6 months. RESULTS: Sixty-nine patients with IBD were recruited into the study, 40 on anti-TNF monotherapy, and 19 on vedolizumab, along with 20 healthy controls (HC). Patients with IBD receiving the HD influenza vaccine had significantly higher H3N2 postimmunization antibodies compared with those who received the SD influenza vaccine (160 [interquartile range 80 to 320] vs 80 [interquartile range 40 to 160]; P = 0.003). The H1N1 postimmunization levels were not significantly higher in the HD influenza vaccine (320 [interquartile range 150 to 320] vs 160 [interquartile range 80 to 320]; P = 0.18). Patients with IBD receiving the HD influenza vaccine and those on vedolizumab who received SD had equivalent antibody concentrations to HC (H1N1 P = 0.85; H3N2 P = 0.23; B/Victoria P = 0.20 and H1N1 P = 0.46; H3N2 P = 0.21; B/Victoria P = 1.00, respectively). CONCLUSIONS: Patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher postimmunization antibody levels compared with SD vaccine. Clinicaltrials.gov (#NCT02461758).

A Verbal Fluency Task-Based Brain Activation fMRI Study in Patients with Crohn's Disease in Remission.

BACKGROUND AND PURPOSE: In this pilot study, we investigated functional brain activation changes in patients with Crohn's disease (CD) in remission compared to age and gender-matched healthy controls (HCs). METHODS: Data from 20 patients with CD in remission (age range 19-63 years) and 20 HCs (matched in age and gender) were analyzed. Task functional MRI (fMRI) data were collected while participants performed a cognitive (phonemic verbal fluency) task in the scanner. All participants also performed the same task outside the scanner. RESULTS: Task fMRI results showed greater bi-hemispheric activation in CD patients compared to controls. Because this pattern is commonly reported with normal aging, we performed further analyses to investigate fMRI responses in a subset of the younger CD patients (N = 12, age < = 35 years) compared to matched young HCs (age < = 35 years), and an older cohort of HCs (age > = 50 years). Results showed that task activation patterns were similar between young CD patients and older HCs, and that both groups differed significantly from younger HCs. Activation intensity in specific brain regions for patients was associated with disease duration. CONCLUSIONS: These results suggest that CD patients in remission may show accelerated signs of aging in terms of brain responses to a typical cognitive task. Future work with larger sample size will need to replicate these results as well as investigate the influence of factors, such as chronicity of the disease and medication effects on task-associated brain activation patterns in this patient population.

Alterations in resting-state functional connectivity in patients with Crohn's disease in remission.

Previous studies have found neural alterations in regions involved in cognitive and affective functions among Crohn's disease (CD) patients. The present work recruited 18 CD patients and 18 age-gender matched healthy controls (HC) and specifically compared differences in resting-state functional connectivity (RSFC) within the executive control network (ECN) which has been implicated in cognitive function and default mode network (DMN), which has been implicated in affective function. Additionally, we examined the correlations between RSFC in ECN and verbal fluency (VF) in both groups as well as RSFC in DMN and anxiety level in the CD group. Results showed significantly increased RSFC between the right middle frontal gyrus and right inferior parietal lobule in ECN, as well as increased RSFC between the right precuneus and right posterior cingulate cortex in DMN, among CD patients compared to HC. However, the correlations between ECN/DMN and behavioral scores in each group were not significant, which was possibility due to the limited sample size. These findings suggest that CD patients may experience changes in the connectivity patterns in ECN and DMN. Increased connectivity observed on these networks could be a potential biomarker of a neuropsychiatric manifestation of CD.

Musculoskeletal Injuries Are Commonly Reported Among Gastroenterology Trainees: Results of a National Survey.

BACKGROUND: Endoscopy-related musculoskeletal injuries are increasingly recognized among gastroenterologists. While injury rates and risk factors have been studied among practicing gastroenterologists, little is known about rates among trainees during fellowship. AIMS: This study analyzes the prevalence of endoscopy-related overuse injuries and risk factors for injuries among a national sample of gastroenterology (GI) fellows. We also surveyed GI fellowship program directors and fellows about perceptions of overuse injuries during GI training. METHODS: We distributed a 29-item electronic survey to GI fellows at accredited programs in the USA in April 2016. Survey items included demographic information, questions pertaining to injuries, and level of agreement on the importance of ergonomics training in GI fellowship. Additionally, we distributed a 7-item electronic survey to fellowship program directors evaluating perception of overuse injuries and prevention during fellowship training. Fisher's exact test determined factors associated with sustaining an injury. RESULTS: An estimated 1509 fellows received the survey. Eleven percent (n = 165) of gastroenterology fellows completed the survey. Twenty percent reported having a musculoskeletal injury. Female gender was the only factor associated with a higher rate of reported injury (p < 0.01). The most common injuries reported were thumb and other hand-related pain (n = 28 [64%]). CONCLUSIONS: Musculoskeletal injuries may affect up to 20% of GI fellows. Female fellows more frequently report injuries and may be at particularly high risk which has not been found in previously reported surveys of practicing gastroenterologists. Standardized curricula on ergonomic considerations and injury prevention are needed to enhance GI fellowship training and reduce injury rates.

Immunosuppression Does Not Affect Antibody Concentrations to Measles, Mumps, and Rubella in Patients with Inflammatory Bowel Disease.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends using the immunization record and not serologic testing to determine immunity against measles and rubella in the general population, due to potential false negatives. However, it is unknown whether the immune response is less durable among patients who are immunosuppressed. AIMS: The primary aim of this study was to evaluate sustained vaccine-induced measles, mumps, and rubella (MMR) antibody concentrations in immunosuppressed patients with inflammatory bowel disease (IBD). METHODS: We performed a cross-sectional study to compare antibody concentrations following the two-dose (MMR) vaccine among 46 patients with IBD and 20 healthy controls (HC). Three IBD groups stratified by the immunosuppressive regimen that preceded study entry for at least 3 months: (1) thiopurine monotherapy, (2) anti-TNF monotherapy, or (3) combination therapy (anti-TNF agent combined with an immunomodulator) were enrolled. RESULTS: All subjects had measurable antibody concentrations to the three vaccine viruses. Age and time since receipt of MMR series were similar in both groups. There were no difference in the antibody concentration of measles (IBD 667 mIU/ml vs HC 744 mIU/ml; p = 0.45), mumps (IBD 339 EU/ml vs HC 402 EU/ml; p = 0.62), or rubella (IBD 25 mIU/ml vs HC 62 mIU/ml; p = 0.11) among the groups. No differences in antibody concentrations were found among the IBD treatment groups. CONCLUSION: Immunosuppressed patients with IBD have sustained antibody concentrations comparable to healthy controls. Thus, gastroenterologist should follow the ACIP recommendations and use the immunization record when available to determine immunity to measles and rubella in patients with IBD. Clinical Trials Registry # NCT02434133.

Preventive Health Care Among Postpartum Women With Inflammatory Bowel Disease: Results From the PIANO Registry.

BACKGROUND: Health care maintenance (HCM) is reduced among inflammatory bowel disease (IBD) patients. This study aims to characterize rates of HCM in a closely monitored subpopulation-postpartum women with IBD-and identify predictors of noncompliance. METHODS: A national prospective pregnancy registry was utilized to collect completion rates of HCM recommendations (cervical cancer screening; osteoporosis screening; pneumococcal, hepatitis A, hepatitis B, and influenza vaccines). Completion of a recommendation at least once during follow-up was sufficient, except for influenza vaccine, which was assessed yearly. Patients were classified by drug exposures: immunomodulator (Group A), biologic (Group B), combination therapy (Group AB), and unexposed. Confounders assessed were steroid exposure, IBD flare, IBD care site, primary care provider (PCP) access, marital status, income, education level, and race. RESULTS: There were 628 postpartum IBD women with at least 1 year of follow-up. HCM rates were as follows: cervical cancer screening (84%), osteoporosis screening (54%), pneumococcal (50%), hepatitis A (61%), hepatitis B (81%), and influenza (72%) vaccines. The unexposed group demonstrated lower pneumococcal vaccination rates than groups A, B, and AB. Group B demonstrated lower cervical cancer screening rates than the unexposed. PCP access and low education predicted hepatitis vaccine noncompliance. Unmarried status and low income predicted cervical cancer screening noncompliance. Low income predicted influenza vaccine noncompliance. CONCLUSIONS: Postpartum women have multiple providers, yet they complete HCM at suboptimal rates. Risk factors include biologic exposure, unmarried status, low income, low education, and access to a PCP. Awareness among providers and patients is important and needs to be enhanced.

Clear liquid diet before bowel preparation predicts successful chromoendoscopy in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Chromoendoscopy (CE) has been shown to generate both a superior diagnostic yield and dysplasia detection rate than conventional white-light endoscopy and requires a high-quality bowel preparation. The aim of this study was to identify predictors of the ability to perform CE in patients with inflammatory bowel disease (IBD). METHODS: We performed an observational study of patients with IBD undergoing colorectal cancer surveillance examinations with CE. Same-day colonoscopy surveys were used to collect patient and procedural variables. Multivariate logistic regression was used to establish odds ratios of successful completion of CE. RESULTS: Eighty-eight patients with IBD were enrolled. We found that patients who did not follow a clear liquid diet before colonoscopy had much lower odds of being able to undergo CE (odds ratio, 0.106; 95% confidence interval, 0.013-0.845; P < .034). Further, we found that previously identified risk factors (older age, history of diabetes mellitus, the timing and split dosing of preparation solution, and procedure time (AM or PM), chronic narcotic use, and history of constipation) for inadequate bowel preparation were not associated with the ability to perform CE. CONCLUSIONS: Following a clear liquid diet the entire day before the procedure was highly predictive of the ability to perform CE. However, established risk factors for inadequate bowel preparation did not inhibit the ability to perform CE in our population. Endoscopists performing CE should consider recommending that patients follow a clear liquid diet the entire day before their examination.

Lower Sustained Diphtheria and Pertussis Antibody Concentrations in Inflammatory Bowel Disease Patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients. AIMS: The aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster. METHODS: We performed a cross-sectional study evaluating antibody responses to Tdap vaccine among IBD patients compared to HC. Our study consisted of three patient groups: adults with IBD stratified by maintenance medication regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3) combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate)). RESULTS: Ninety IBD patients and 20 HC participated. Pertussis pertactin antibody concentrations were significantly lower in IBD patients (p = 0.021) compared to HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to those on thiopurine monotherapy (p = 0.028). Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001), and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to the thiopurine monotherapy group (p < 0.001). CONCLUSION: IBD patients on anti-TNF agents had lower antibody concentrations to diphtheria and pertussis. These findings suggest a need for different Tdap booster schedules for IBD patients on anti-TNF therapy. Clinical Trials Registry NCT02434133.

Symptomatic Microscopic Colitis Atop Quiescent Inflammatory Bowel Disease: A Case Series.

Microscopic colitis (MC) has rarely been described to be the cause of watery diarrhea in those with established inflammatory bowel disease (IBD), and instead has been presented as a herald syndrome to eventual IBD or incidentally found in asymptomatic IBD patients. We report a case series of 7 patients with IBD who presented with a watery diarrheal exacerbation due to new-onset MC. We propose that new-onset MC should be considered in the differential diagnosis of watery diarrhea occurring in patients with long-standing IBD and that evaluation should include colonoscopy with biopsies obtained throughout the colon.

Placental inflammation is not increased in inflammatory bowel disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental inflammation than non-IBD controls. METHODS: Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5 Crohn's disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory response. The history and birth outcomes of all IBD subjects were reviewed and matched to 26 non-IBD controls by gestational age at delivery. RESULTS: Of women with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of the IBD patients had mild-moderate disease flares during pregnancy. Five (36%) patients required corticosteroids, 2 (14%) were maintained on an immunomodulator, and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their pregnancy. Chorioamnionitis was the only identified placental pathology present in the placentas reviewed, occurring less frequently in cases compared to controls (7% vs. 27%, P=0.32). CONCLUSIONS: Placental inflammatory activation does not appear to be responsible for the increase in adverse birth outcome in women with IBD. Further studies are necessary to validate these findings in IBD to explain poor birth outcomes.

The role of integrin antagonists in the treatment of inflammatory bowel disease.

INTRODUCTION: Ulcerative colitis (UC) and Crohn's disease are chronic inflammatory diseases of the bowel associated with complex inflammatory cascades within the mucosal lining of the gut. AREAS COVERED: INTEGRINS and their use as therapies in UC and Crohn's. EXPERT OPINION: The anti-adhesion molecules are a welcome addition to the armamentarium of medical therapies for inflammatory bowel disease.

Menstrual cycle changes in women with inflammatory bowel disease: a study from the ocean state Crohn's and colitis area registry.

BACKGROUND: The effect of the inflammatory bowel diseases (IBD) on menstrual function is largely unknown. The aims of this study were to determine whether changes in menstrual function occur in the year before IBD diagnosis or in the initial years after diagnosis. METHODS: Women aged 18 years and older in the Ocean State Crohn's and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. Menstrual cycle characteristics were retrospectively assessed. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes. RESULTS: One hundred twenty-one patients were studied. Twenty-five percent of patients experienced a change in cycle interval in the year before IBD diagnosis and 21% experienced a change in the duration of flow. Among women with dysmenorrhea, 40% experienced a change in the intensity of their menstrual pain and 31% experienced a change in its duration. Overall cycle regularity increased over time. Quality of life was significantly lower in women without regular cycles across all time points. CONCLUSIONS: Changes in menstrual function occur frequently in the year before IBD diagnosis; therefore, screening for menstrual irregularities should be considered in women with newly diagnosed IBD. Patients can be reassured that cycles typically become more regular over time.