The use of opioids nine months after surgery for Crohn's disease - a nationwide cohort study.

BACKGROUND: The risk of chronic opioid use after surgery for Crohn's disease (CD) is not known. AIM: The aim of this study is to examine the chronic opioid use after surgery according to age at time of surgery and to opioid use prior to surgery. METHODS: This nationwide cohort study included patients with a first surgery for CD (January 1, 1996 through 2021). We examined prescribed opioids 9 months after surgery and estimated adjusted odds ratios (OR) for chronic opioid use in elderly (≥60 years), adults (≥40 and <60 years), and young adults (≥18 and <40 years) according to opioid use prior to surgery. Chronic opioid use was defined as prescriptions in at least two of three consecutive quarters. RESULTS: A total of 797 patients had surgery as elderly, 1603 as adults, and 2786 as young adults. Across all age groups, 18%-38% received opioid prescriptions throughout 9 months after surgery, if opioids were prescribed prior to surgery. If opioids were not prescribed prior to surgery, the corresponding proportions were 2%-5%. If patients were prescribed opioids (≥1) prior to surgery, the adjusted ORs (95% CIs) for their chronic use after surgery in elderly, adults, and young adults were 10.37 (6.77-15.88), 10.48 (7.74-14.19), and 6.55 (4.93-8.72), respectively. CONCLUSION: Clinicians should be aware that in patients with a need for opioids before surgery, the surgery may not change the need for opioids. Future research should examine effective analgesic strategies that help minimise opioid use in this population.

Neonatal outcomes in women with Multiple Sclerosis - Influence of disease activity: A Danish nationwide cohort study.

BACKGROUND: Maternal Multiple Sclerosis (MS) has been associated with an increased risk of adverse birth outcomes. We hypothesized that active disease during conception and pregnancy plays an important role in this context, which this study aims to address. METHODS: We used the Danish registers to conduct a nationwide cohort study. Information on maternal disease activity during pregnancy was retrieved using proxies from the linked registers (hospitalization, magnetic resonance imaging of the brain, and use of systemic corticosteroids during pregnancy). Neonates, exposed in utero to maternal disease activity constituted the exposed cohort and the unexposed cohort constituted neonates without in utero exposure to maternal disease activity. The examined outcomes were preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies. In logistic regression models we estimated the odds ratios (OR) with adjustment for confounders such as maternal age, comorbidities, parity, smoking, calendar year of birth, and disease-modifying treatment. RESULTS: Among the study population of 2492 children of mothers with MS we identified 273 (11 %) neonates exposed to maternal disease activity during pregnancy, and 2219 (89 %) neonates without exposure to disease activity. The adjusted odds ratios (aOR) for preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies among children born to women with disease activity during pregnancy were 0.92 (95 % confidence interval (95 % CI) 0.53-1.60), aOR 1.19 (95 % CI 0.62-2.26), aOR 2.57 (95 % CI 0.93-7.15) and aOR 0.93 (95 % CI 0.48-1.83), respectively. CONCLUSIONS: Women with MS having disease activity during pregnancy did not have a statistically significantly increased risk of adverse neonatal outcomes compared to women with MS without disease activity, which is overall reassuring results. We believe, that this will be useful knowledge for patients and clinicians in planning a pregnancy and preparing a birth plan.

Does Surgery Before Pregnancy in Women With Inflammatory Bowel Disease Increase the Risk of Adverse Maternal and Fetal Outcomes? A Danish National Cohort Study.

INTRODUCTION: Up to 15% of women with Crohn's disease (CD) or ulcerative colitis (UC) undergo bowel surgery before pregnancy, and there is little data on pregnancy outcomes in this population. We aimed to assess maternal/fetal outcomes in women with CD or UC who underwent surgeries before pregnancy. METHODS: In this nationwide study, we included all pregnancies in women with CD or UC from 1997 to 2022 and examined 6 categories of CD and UC surgeries before pregnancy. We used multilevel logistic regression to compute crude and adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) for the risk of pregnancy and offspring complications in women who did, vs did not, undergo surgery before pregnancy. RESULTS: There were 833 UC and 3,150 CD pregnancies with prior surgery and 12,883 UC and CD 6,972 pregnancies without surgery. For UC, prior surgery was associated with Cesarian section (C-section) (ileoanal pouch: aOR: 20.03 [95% CI 10.33-38.83]; functional ileostomy: aOR:8.55 [6.10-11.98]; diverting ileostomy: aOR: 38.96 [17.05-89.01]) and preterm birth (aOR: 2.25 [1.48-3.75]; 3.25 [2.31-4.59]; and 2.17 [1.17-4.00]) respectively. For CD and prior intestinal surgery, the risks of C-section (aOR: 1.94 [1.66-2.27]), preterm birth (aOR: 1.30 [1.04-1.61]), and low 5-minute Apgar (aOR: 1.95 [95% CI 1.07-3.54]) increased and premature rupture of membranes (aOR: 0.68 [0.52-0.89]) decreased. For CD with only prior perianal surgery, the risk of C-section (aOR: 3.02 [2.31-3.95]) increased and risk of gestational hypertension/preeclampsia/eclampsia (aOR: 0.52 [0.30-0.89]) decreased. DISCUSSION: Providers should be aware there is an increased likelihood of C-section and certain perinatal complications in patients with CD or UC surgery before pregnancy.

Implication of Inflammatory Bowel Disease Diagnosed Before the Age of 18 for Achieving an Upper Secondary Education: A Nationwide Population-Based Cohort Study.

BACKGROUND: Educational achievement may be adversely affected by chronic conditions in childhood and adolescence. This study aimed to examine the effect of being diagnosed with IBD on achievement of an upper secondary education and the influence of disease severity and psychiatric comorbidity. METHODS: This cohort study was based on nationwide Danish administrative registries. We compared a cohort of patients with IBD with a matched population-based cohort. The IBD cohort included patients born between 1970 and 1994 who were diagnosed with IBD (age <18 years). The outcome was achieving an upper secondary education and was analyzed using Cox regression. The impact of disease severity (expressed by surgery or corticosteroid prescriptions) or psychiatric comorbidity within the IBD cohort was assessed using Poisson regression. RESULTS: We identified 3178 patients with IBD (Crohn's disease [CD] n = 1344, ulcerative colitis [UC] n = 1834) and matched them with 28 204 references. The hazard ratio of achieving an upper secondary education was 1.14 (95% confidence interval, 1.07-1.21) for CD and 1.16 (95% confidence interval, 1.10-1.23) for UC. In the IBD cohort, having surgery, a steroid prescription, or a comorbid psychiatric condition was associated with a lower chance of achieving an upper secondary education. CONCLUSION: Being diagnosed with IBD before 18 years of age increased the chance of achieving an upper secondary education. However, patients with more severe disease or psychiatric comorbidity were at higher risk of not achieving an upper secondary education than patients with milder disease.

The IBD-FITT study - moderate-intensity exercise for patients with inflammatory bowel disease with moderate disease activity: an open-label randomized controlled trial.

BACKGROUND: Inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients' general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). METHODS: We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60-80% of patients' maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15-25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). DISCUSSION: This will be a clinical trial investigating the effect of exercise on patients with Crohn's disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

Use of Tramadol vs Traditional Opioids and Adverse Outcomes in Patients with Inflammatory Bowel Disease: A Danish Nationwide Cohort Study.

BACKGROUND: Use of traditional opioids (TOs) for pain management has been associated with adverse outcomes among patients with inflammatory bowel diseases (IBDs). It is unknown if similar associations exist for tramadol, a partial opioid agonist and serotonin and norephinephrine reuptake inhibitor. We sought to compare adverse outcomes associated with tramadol vs TOs in an IBD population. METHODS: This nationwide cohort study included adults with IBD diagnosed from 1995 to 2021 in Denmark with subsequent prescriptions for tramadol or TOs. For each analgesic, 2 populations were assessed: initial users (first prescription) and persistent users (first 3 consecutive prescriptions within 365 days). Outcomes included infection, bowel obstruction/ileus, IBD surgery, and mortality within 90 days after the initial use index date (date of first prescription) and within 365 days after the persistent use index date (date of third prescription). Odds ratios adjusted for demographics, comorbidities, and IBD severity were calculated using multivariable logistic regression. RESULTS: We identified 37 377 initial users and 15 237 persistent users of tramadol or TOs. Initial users of tramadol had lower adjusted odds of infection (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.99), bowel obstruction/ileus (aOR, 0.74; 95% CI, 0.53-1.03), and mortality (aOR, 0.43; 95% CI, 0.35-0.55), and a higher adjusted odds of IBD-related surgery (aOR, 1.27; 95% CI, 1.02-1.60) vs initial users of TOs. Similar results were found for persistent users. CONCLUSIONS: Tramadol was associated with lower odds of infection, bowel obstruction/ileus, and mortality vs TOs among patients with IBD. These associations may be impacted by residual confounding.

Adverse birth outcomes and early-life infections after in utero exposure to corticosteroids for inflammatory bowel disease: a Danish nationwide cohort study.

BACKGROUND: Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring. METHODS: We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment. RESULTS: After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39). CONCLUSIONS: This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased.

Patients with elderly onset inflammatory bowel disease have a decreased chance of initiation of all types of medications and increased risk of surgeries-A nationwide cohort study.

OBJECTIVE: In patients with elderly (≥60 years) onset inflammatory bowel disease (IBD), we studied initiation of medications, drug persistency and surgeries. DESIGN: A nationwide cohort study based on Danish registries, comprising incident IBD patients ≥18 years from 1995 to 2020 (N = 69,039). Patients were divided into elderly (N = 19,187) and adult onset (N = 49,852). Outcomes were initiation of thiopurines, 5-ASA, biologics and corticosteroids within 1 and 5 years after diagnosis, and for those who initiated medications, we estimated drug persistency. Surgeries were examined within 1 and 5 years. We used regression models controlling for covariates. RESULTS: In elderly patients, the adjusted hazard ratios (aHR) for initiating thiopurines, 5-ASA and biologics within 1 year were 0.44 (95% CI 0.42-0.47), 0.77 (95% CI 0.75-0.79) and 0.29 (95% CI 0.26-0.31) respectively. The results were similar within 5 years. In elderly patients, drug persistency for thiopurines, 5-ASA and biologics was not impaired within 5 years. The aHR of stopping steroids within 1 and 5 years were 0.80 (95% CI 0.76-0.84) and 0.77 (95% CI 0.74-0.80) respectively. The risk of surgeries was increased in the elderly patients (in ulcerative colitis, within 5 years, aHR 1.39 [95% CI 1.27-1.52], and in Crohn's disease 1.13 [95% CI 1.04-1.23]). CONCLUSION: We found significantly low chance of initiation of IBD medications in elderly patients, the reason may not be due to mild disease course. In elderly patients, drug persistency was comparable to adults. Clinicians should carefully consider whether they underuse IBD-specific medications in elderly patients, and special attention should be applied to timely discontinuation of corticosteroids.

COVID-19 Does Not Lead to an Increase in Corticosteroid Prescriptions in IBD Patients: A Nationwide Cohort Study.

BACKGROUND: It is not known whether coronavirus 2019 (COVID-19) is a trigger for disease activity in patients with inflammatory bowel diseases (IBD). In patients with IBD, we aimed to examine the association between COVID-19 infection and prescriptions of systemic and local corticosteroids (used as proxy for disease activity). METHODS: This nationwide cohort study was based on Danish health registries and included all patients in Denmark with ulcerative colitis (UC) or Crohn's disease (CD) by the start of the pandemic (March 1, 2020) and who had a positive COVID-19 polymerase chain reaction (PCR) test from March 1, 2020, to July 31, 2022. We calculated rates of corticosteroid prescriptions 6 months before and 6 months after a positive COVID-19 PCR test, and we calculated adjusted incidence rate ratios (aIRR). RESULTS: We included 30,102 patients with IBD and a positive COVID-19 test (11,159 with CD, 18,493 with UC). The aIRR for having corticosteroid prescriptions after a COVID-19 positive test was 0.85 (95% confidence interval [CI], 0.79-0.91). When we stratified for underlying disease, the aIRR for having corticosteroid after a COVID-19 positive test in UC was 0.82 (95% CI, 0.75-0.90), and in CD 0.91 (95% CI, 0.81-1.02). Stratifications according to calendar periods and age groups showed consistent results. CONCLUSIONS: An infection with COVID-19 did not result in a higher rate of filled corticosteroid prescriptions. Using corticosteroids as a proxy for disease activity, COVID-19 did not seem to trigger disease activity, which is a reassuring result for patients with IBD.

An infection with COVID-19 did not result in a higher rate of filled corticosteroid prescriptions. Using corticosteroids as a proxy for disease activity, COVID-19 did not seem to trigger disease activity, which is a reassuring result for patients with IBD.

The safety of paternal and maternal use of 5-aminosalicylic acid during conception and pregnancy: a nationwide cohort study.

BACKGROUND: Data on the safety of paternal use of 5-aminosalicylic acid (5-ASA) prior to conception are lacking, and the safety of maternal use of 5-ASA during pregnancy has not been examined in nationwide data. AIMS: To examine offspring outcomes after paternal pre-conception use of 5-ASA, and after maternal use during pregnancy METHODS: This nationwide cohort study was based on Danish health registries. The study population included live born singletons of patients with ulcerative colitis (UC) or Crohn's disease (CD). Paternal exposure included 2168 children fathered by men treated with 5-ASA, and 7732 unexposed. Maternal exposure included 3618 children exposed in utero to 5-ASA, and 7128 unexposed. The outcomes were pre-term birth, small for gestational age (SGA), low Apgar score and major congenital abnormalities (CAs) according to EUROCAT guidelines. RESULTS: The vast majority of fathers and mothers used mesalazine. In children fathered by men with UC using 5-ASA, we found no increased risk of pre-term birth, SGA or low Apgar score. The hazard ratio (HR) of CAs was 1.30 (95% CI 0.92-1.85). In children of fathers with CD, the odds ratio (OR) of SGA was 1.52 (95% CI 0.65-3.55). After maternal 5-ASA exposure, the OR of SGA in children of women with UC was 1.46 (95% CI: 0.93-2.30); for CAs in children of women with CD, HR was 1.44 (95% CI 0.84-2.47). CONCLUSIONS: Paternal and maternal use of 5-ASA was safe across offspring outcomes; none of the findings reached statistical significance. The safety of 5-ASA formulations that are used infrequently cannot be settled here.

Physical activity measured by accelerometry in paediatric and young adult patients with inflammatory bowel disease.

OBJECTIVES: Physical activity in paediatric and young adult patients suffering from inflammatory bowel disease (IBD) may play an important role in the overall health status. However, physical activity in these patients has not been reported using objective methods. We aimed to describe accelerometry-measured physical activity levels in paediatric and young adult IBD patients with either ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We recruited Danish patients with IBD aged 10-20 years in clinical remission and with a faecal calprotectin below 200 µg/mg. Physical activity was assessed using tri-axial wrist accelerometry over seven days and quantified using the activity-related acceleration derived as the conventional Euclidian Norm Minus One (ENMO) metric expressed in milli-gravity units (mg). Time spent in Moderate-to-Vigorous Physical Activity (MVPA) was classified as ENMO > 210 mg in 5 s epoch resolution (unbouted). RESULTS: We included 61 patients with a median age of 17 years [Inter Quartile Range, IQR 14-19]. The total volume of activity expressed as average acceleration (ENMO) per day was 31.5 mg (95% CI 29.1-33.9). Time spent in unbouted MVPA was 32 min per day (95% CI 26-37). There was no significant difference in activity volume between patients with UC to patients with CD, the adjusted linear regression coefficient was - 1.7 mg (95% CI -6.2-2.7). Activity volume was higher for males (36.2 mg, 95% CI 31.9-40.5) than for females (27.8 mg, 95% CI 25.6-30.0), and younger patients were more active than older patients; Activity volume in 10-13 year olds was 37.2 mg (95% CI 28.6-45.7), whereas it was 28.5 mg (95% CI 25.2-31.7) for those aged 18-20 years. CONCLUSIONS: We collected tri-axial accelerometry in young patients with IBD in clinical remission, and described their level of physical activity by the conventional ENMO measure. We found no statistically significant difference in patients with UC compared to patients with CD. The volume of physical activity was higher in males compared to females, and inversely associated with age.

Paternal use of medications for inflammatory bowel disease and the risk of hospital-diagnosed infections in the offspring: a nationwide cohort study.

BACKGROUND: Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce. AIM: To examine the risk of childhood infections associated with fathers' use of anti-inflammatory/immunosuppressive medications taken before conception. METHODS: This is a nationwide cohort study based on Danish health registries, comprising all live-born singleton children born between January 1997 and February 2019 who were fathered by men with IBD. Exposed cohorts included children fathered by men treated with 5-aminosalicylates (5-ASAs), thiopurines, corticosteroids or anti-tumour necrosis factor-α (anti-TNF-α) agents within 3 months before conception. The unexposed cohort included children not exposed to paternal IBD medications. Outcomes were the first infection, diagnosed in the hospital setting in the first year of life, and from the age of 1 to 3 years. RESULTS: In all, 2178 children were fathered by men exposed to 5-ASAs, 843 to thiopurines, 417 to systemic corticosteroids and 436 to anti-TNF-α agents; 6799 children were unexposed. The adjusted hazard ratio (aHR) for infections within the first year of life for 5-ASAs was 0.78 (95% CI, 0.66-0.91), thiopurines 0.89 (95% CI, 0.73-1.09), systemic corticosteroids 0.95 (95% CI, 0.70-1.29), and anti-TNF-α agents 1.17 (95% CI, 0.94-1.46). The aHR for infections from 1 to 3 years for 5-ASAs was 0.97 (95% CI, 0.83-1.13), thiopurines 0.87 (95% CI, 0.71-1.07), systemic corticosteroids 1.25 (95% CI, 0.94-1.65), and anti-TNF-α agents 0.79 (95% CI, 0.60-1.03). CONCLUSION: Fathers' use of anti-inflammatory/immunosuppressive medications before conception was not significantly associated with childhood infections. These results fill an important research gap regarding paternal medication safety.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

INTRODUCTION: Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. METHODS: In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. RESULTS: Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. DISCUSSION: Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.

Does Disease Activity After Induction Treatment With Biologics Predict Short-Term Outcome in Crohn's Disease and Ulcerative Colitis?

BACKGROUND: Secondary loss of response to biological therapy is a challenge when treating Crohn's disease (CD) and ulcerative colitis (UC). Currently, no single marker has been found to be valid as a prognostic indicator of response to biologic therapy in patients with CD and UC. In this study, we aimed to assess whether disease activity after 14 weeks of biologic therapy has a prognostic impact on surgery and steroid-free remission during 6 months following completion of induction therapy. METHODS: In an unselected cohort study based on data from 4 national Danish health registries, we identified 493 patients with UC and 620 patients with CD who completed induction therapy with biologics from 2016 to 2019. Following induction therapy with biologics, we defined disease activity based on C-reactive protein and clinical scores of disease activity. The composite endpoint, "not being well treated," included surgery or use of corticosteroid within 6 months following induction therapy. RESULTS: In patients with UC with disease activity following induction therapy, the adjusted odds ratio for surgery or steroid treatment during 6 months of follow-up was 3.9 (95% CI, 1.6-9.3) compared with patients without disease activity, and in patients with CD, the adjusted odds ratio was 3.6 (95% CI, 1.7-7.6). CONCLUSIONS: A positive treatment response to biologic treatment after induction therapy (measured by C-reactive protein and clinical scores) predicts a better short-term outcome in patients with CD and UC.

Postpartum Surgical Complications in Women with Inflammatory Bowel Disease After Caesarian Section: A Danish Nationwide Cohort Study.

BACKGROUND AND AIMS: Our aim is to determine the 30-day postpartum surgical complications in women with inflammatory bowel disease [IBD] who undergo a caesarian section rather than a vaginal delivery. METHODS: Using the Danish national registries, we established a study population of liveborn singleton births from January 1, 1997, through December 2015. We examined all mothers with IBD who had a caesarian section or a vaginal delivery. We examined 30-day maternal postpartum abdominal and perineal surgical outcomes and adjusted for multiple confounders. We examined acute versus elective caesarian sections and the effect of immunosuppressive therapies on outcomes. RESULTS: In women with IBD, 2.1% undergoing caesarian section [n = 3255] versus 0.3% undergoing vaginal delivery [n = 6425] had a surgical complication. Women with IBD who had a caesarian section were more likely to have small bowel and colon surgery (adjusted odds ratio [aOR] 5.00, 95% confidence interval [CI] 2.00-12.51). Similar results were found regardless of acute [aOR 4.51, 95% CI 1.48-13.76] or elective [aOR 6.52, 95% CI 2.45-17.33] caesarian section. The risk of surgery after caesarian section was increased regardless of immunosuppressive use [aOR with immunosuppressives 8.79, 95% CI 2.86-27.05; and aOR without immunosuppressives 4.49, 95% CI 1.74-11.58]. CONCLUSIONS: The risk of a surgical complication after caesarian section as compared with a vaginal delivery is increased in women with IBD, regardless of whether the caesarian is performed for acute or elective reasons and/or of immunosuppressive use before delivery. Due to this increased risk, physicians should perform a caesarian delivery as the exception rather than the rule.

Post COVID-19 hospitalizations in patients with chronic inflammatory diseases - A nationwide cohort study.

OBJECTIVE: To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. DESIGN AND SETTING: Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. POPULATION: From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. MAIN OUTCOME MEASURES: We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. RESULTS: A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25-75% percentiles: 4.38-8.12), and among the unexposed the median time of follow up was 6.59 months (25-75% percentiles: 4.17-8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02-1.58)) and infections (aHR 1.55 (95% CI 1.26-1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96-1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91-1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA. CONCLUSIONS: After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA.

Outcome of COVID-19 in hospitalized patients with chronic inflammatory diseases. A population based national register study in Denmark.

OBJECTIVE: COVID-19 has substantial morbidity and mortality. We studied whether hospitalized patients with COVID-19 and chronic inflammatory diseases experienced worse outcomes compared to patients hospitalized with COVID-19 without chronic inflammatory diseases. METHODS: Danish nationwide registers were used to establish a cohort of hospitalized patients with COVID-19 and inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) (exposed), and a control cohort without these diseases (unexposed) between March 1, 2020, and October 31, 2020. We compared median length of hospital stay, used median regression models to estimate crude and adjusted differences. When estimating crude and adjusted odds ratio (OR) for continuous positive airway pressure (CPAP) and mechanical ventilation, in-hospital death, 14-day and 30-day mortality, we used logistic regression models. RESULTS: We identified 132 patients with COVID-19 and IBD, RA, SpA, or PsA, and 2811 unexposed admitted to hospital with COVID-19. There were no differences between exposed and unexposed regarding length of hospital stay (6.8 days vs. 5.5 days), need for mechanical ventilation (7.6% vs. 9.4%), or CPAP (11.4% vs. 8.8%). Adjusted OR for in-hospital death was 0.71 (95% CI 0.42-1.22), death after 14-days 0.70 (95% CI 0.42-1.16), and death after 30-days 0.68 (95% CI 0.41-1.13). CONCLUSION: Hospitalized patients with COVID-19 and chronic inflammatory diseases did not have statistically significant increased length of hospital stay, had same need for mechanical ventilation, and CPAP. Mortality was similar in hospitalized patients with COVID-19 and chronic inflammatory diseases, compared to patients hospitalized with COVID-19 and no chronic inflammatory diseases.

Hospitalization for COVID-19 in patients treated with selected immunosuppressant and immunomodulating agents, compared to the general population: A Danish cohort study.

AIMS: In the Danish population, we examined whether patients treated with thiopurines, methotrexate, systemic corticosteroids, anti-tumour necrosis factor (TNF)-α agents, anti-interleukin therapeutic agents, selective immunosuppressive agents and cyclosporine/tacrolimus had an increased risk of hospitalization for COVID- 19, compared to the background population. METHODS: A nationwide cohort study including all people alive in Denmark on 1 March 2020. Exposed patients constituted those exposed to thiopurines (n = 5484), methotrexate (n = 17 977), systemic corticosteroids (n = 55 868), anti-TNF-α agents (n = 17 857), anti-interleukin therapeutic agents (n = 3744), selective immunosuppressive agents (n = 3026) and cyclosporine/tacrolimus (n = 1143) in a period of 12 months prior to 1 March 2020 (estimated time of outbreak in Denmark). We estimated the adjusted risk of hospitalization for COVID-19 for patients treated with the above-mentioned categories of medications, compared to the rest of the population. RESULTS: The adjusted odds ratios of hospitalization in patients treated with corticosteroids and cyclosporine/tacrolimus were 1.64 (95% confidence interval [CI] 1.35 to 2.00) and 4.75 (95% CI 1.96 to 11.49), respectively. The risks of hospitalization in patients treated with thiopurines, methotrexate, and anti-TNF-α agents, were 1.93 (95% CI 0.91 to 4.08), 0.74 (95% CI 0.43 to 1.28), 1.00 (95% CI 0.52 to 1.94), respectively. The number of outcomes in patients treated with anti-interleukin therapeutic agents and selective immunosuppressive agents was too small for analysis. CONCLUSION: Patients treated with systemic corticosteroids and cyclosporine/tacrolimus had a significantly increased risk of being hospitalized for COVID-19. Our study does not uncover whether the increased risk is related to the drug itself, the underlying condition for which the patient is treated or other factors.

In utero exposure to thiopurines/anti-TNF agents and long-term health outcomes during childhood and adolescence in Denmark.

BACKGROUND: Data on long-term health outcomes of children exposed in utero to thiopurines and anti-TNF medications are lacking. AIMS: To examine the association between in utero exposure to thiopurines and anti-TNF medications and child health outcomes of site-specific groups of infections, using a composite endpoint including psychiatric diagnoses/autism spectrum disorder (ASD)/attention deficit hyperactivity disorder (ADHD), and malignancies during childhood/adolescence. METHODS: A nationwide cohort study based on Danish health registries included 1 311 009 live born children during 1995 through 2015. Outcomes were based on hospital diagnoses (in-patients/out-patients/emergency department contacts). RESULTS: In total, 1048 children were exposed in utero to thiopurines and 1 309 961 were unexposed. The adjusted hazard ratios (HRs) for site-specific groups of infections in the first 3 years of life were close to unity. The adjusted HR of psychiatric diagnoses/ASD/ADHD was 1.11 (95% CI 0.81-1.52). The HR of malignancies was not calculated (only two events among the exposed). In total, 493 children were exposed in utero to anti-TNF medications and 728 055 were unexposed. Within the first year of life, the adjusted HR of respiratory, urological/gynaecological infections and other infections were 1.34 (95% CI 1.03-1.74), 2.36 (95% CI 1.15-4.81) and 1.61 (95% CI 1.21-2.13), respectively. We found no increased risk of other adverse outcomes. CONCLUSIONS: After in utero exposure to thiopurines, we found no increased risk of infections, psychiatric diagnoses/ASD/ADHD, or malignancies during childhood/adolescence. After in utero exposure to anti-TNF medications, the risk of respiratory, urological/gynaecological infections and other infections was increased during the first year of life.

Comparison of Time to Pregnancy in Women With and Without Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Patients are often diagnosed with inflammatory bowel diseases (IBD) during their peak reproductive years. We investigated how IBD affects fertility in a population study of women in Denmark. METHODS: We collected data from the Danish National Birth Cohort, a nationwide study of 92,274 pregnant women recruited from 1996 through 2002. Women who had been actively trying to conceive reported their time to pregnancy through a computer-assisted telephone interview at approximately 16 weeks of gestation. Information regarding IBD was retrieved from the Danish National Patient Register. Using regression models and adjusting for important confounders, we compared time to pregnancy in women with and without IBD. RESULTS: We calculated time to pregnancy for 74,471 pregnancies in women without IBD, 340 pregnancies in women with ulcerative colitis (UC), and 206 pregnancies in women with Crohn's disease (CD). Compared to non-IBD pregnancies, the adjusted relative risk ratios for time to pregnancy of more than 12 months in women with IBD, UC, and CD were 1.28 (95% CI, 0.99-1.65), 1.10 (95% CI, 0.80-1.51), and 1.54 (95% CI, 1.03-2.30), respectively. The adjusted relative risk ratio was 2.54 (95% CI, 1.39-4.65) for a time to pregnancy of more than 12 months in women who had CD surgery prior to conception vs non-IBD pregnancies. There were too few patients with UC with surgery prior to conception to perform meaningful analyses of this group. CONCLUSIONS: In a study of women with IBD not confounded by voluntary childlessness, we found that women with CD, especially those who have undergone surgery, have a significant increase in time to pregnancy compared to women without IBD. This indicates reduced fertility in subgroups of women with IBD.