Older Adult-Onset of Inflammatory Bowel Diseases Is Associated With Higher Utilization of Analgesics: A Nationwide Cohort Study.

INTRODUCTION: Patients with inflammatory bowel diseases (IBD) commonly require analgesic medications to treat pain, which may be associated with complications. We examined trends of analgesic use according to age at IBD onset. METHODS: This nationwide cohort study included adults diagnosed with IBD between 1996 and 2021 in Denmark. Patients were stratified according to their age at IBD onset: 18-39 years (young adult), 40-59 years (adult), and older than 60 years (older adult). We examined the proportion of patients who received prescriptions for analgesic medications within 1 year after IBD diagnosis: strong opioids, tramadol, codeine, nonsteroidal anti-inflammatory drugs, and paracetamol. Multivariable logistic regression analysis was performed to examine the association between age at IBD onset and strong opioid prescriptions and the composite of strong opioid/tramadol/codeine prescriptions. RESULTS: We identified 54,216 adults with IBD. Among them, 25,184 (46.5%) were young adults, 16,106 (29.7%) were adults, and 12,926 (23.8%) were older adults at IBD onset. Older adults most commonly received analgesic prescriptions of every class. Between 1996 and 2021, strong opioid, tramadol, and codeine prescriptions were stable, while paracetamol prescriptions increased and nonsteroidal anti-inflammatory drug prescriptions decreased. After multivariable logistic regression analysis, older adults had higher adjusted odds of receiving strong opioid prescriptions (adjusted odds ratio 1.95, 95% confidence interval 1.77-2.15) and the composite of strong opioid/tramadol/codeine prescriptions (adjusted odds ratio 1.93, 95% confidence interval 1.81-2.06) within 1 year after IBD diagnosis compared with adults. DISCUSSION: In this nationwide cohort, older adults most commonly received analgesic prescriptions within 1 year after IBD diagnosis. Additional research is needed to examine the etiology and sequelae of increased analgesic prescribing to this demographic.

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.

Children born preterm or small for gestational age to mothers with multiple sclerosis: Do these children have an increased risk of infections in early life?

BACKGROUND: Mothers with multiple sclerosis are at increased risk of preterm birth and small for gestational age infants. Both conditions pose a risk of morbidity, including early-life infections. OBJECTIVE: This study aimed to assess the risk of infections in the first 3 years of life among children born preterm or small for gestational age to mothers with multiple sclerosis. METHODS: We used Danish national health registers to establish the study cohort of all births by women with MS born from 1995 to 2023. In Cox regression models, we estimated hazard ratios (HRs) of infections in preterm or small for gestational age children. RESULTS: Preterm children had an adjusted HR of 1.49 (95% confidence interval (95% CI) 1.15-1.93) for hospital-diagnosed infection and 0.88 (95% CI 0.72-1.06) for antibiotic prescriptions. Small for gestational age children had an adjusted HR of 0.81 (95% CI 0.54-1.22) for hospital-diagnosed infection and 1.07 (95% CI 0.82-1.38) for antibiotic prescriptions. CONCLUSION: Children born preterm to mothers with multiple sclerosis had an increased risk of hospital-diagnosed infections in the first 3 years of life, but not of mild-to-moderate infections evaluated on prescriptions. Children born small for gestational age did not have an increased risk of infections.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

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.

Diabetes mellitus and the risk of post-acute COVID-19 hospitalizations-a nationwide cohort study.

AIMS: This cohort study, based on Danish health registers, examined the post-acute consequences of hospitalization for COVID-19 in patients with diabetes. METHODS: The study population comprised all Danish citizens (≥18 years old) who had diabetes when the pandemic started. A patient was exposed if he/she had a hospitalization with COVID-19 after 1 March 2020. A patient was unexposed when he/she was not hospitalized with COVID-19 between 1 March 2020 and the end of follow-up (4 January 2022), or the first registered event of interest. The outcomes included post-COVID-19 hospitalizations and death. We used a Cox proportional hazards model with time varying exposure estimating the hazards ratio (HR) to analyze if the hazard for an outcome of interest was impacted by being hospitalized with COVID-19. RESULTS: In patients with type 1 diabetes, 101 were hospitalized with COVID-19, and 25,459 were not. We did not have sufficient statistical power to identify differences in risk for those with type 1 diabetes. In type 2 diabetes, 1515 were hospitalized with COVID-19, and 95,887 were not. The adjusted HRs of post-acute hospitalization for respiratory diseases and infections were 1.71 (95% CI 1.45-2.03) and 1.87 (95% CI 1.61-2.18), respectively. The HR of death was 2.05 (95% CI 1.73-2.43). Patients with uncertain type had results similar to those with type 2 diabetes. CONCLUSIONS/INTERPRETATION: In type 2 diabetes and diabetes of uncertain type, hospitalization with COVID-19 was associated with an increased risk of post-acute hospitalization for respiratory diseases, infections and death.

A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases.

BACKGROUND: There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD. METHODS: We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis. RESULTS: 30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24-1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005-2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes. CONCLUSIONS: The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not.KEY MESSAGESWhat is already known?o The gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual's risk of inflammatory and autoimmune disease (IAD).What is new here?o Patients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy.How can this study help patient care?o Future research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.

In this nationwide Danish cohort study of all Danish UC patients diagnosed in the period from 1988 to 2015, the risk of being diagnosed with inflammatory and autoimmune disease is higher for patients who underwent total colectomy compared to UC patients without total colectomy.

Psychiatric disorders, diagnosed in psychiatric clinics, in patients with back pain: A cohort study.

Aims: The aim of this study was to evaluate whether patients with a non-specific back pain disorder are more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder (such as a herniated disc or inflammatory back disorder). Methods: This was a retrospective cohort study using Danish registries. Results: Our study population included 24,518 patients younger than 61 years and 12,274 patients older than 61 years. In both subpopulations, 60% had a non-specific back pain diagnosis (BPD). In the younger subpopulation, 2.1% of the patients with a non-specific BPD and 1.3% of the patients with a specific BPD had a psychiatric diagnosis within one year of their BPD. In the older subpopulation, 0.6% of patients had a psychiatric diagnosis in both BPD groups. The most frequent psychiatric diagnoses were stress-related disorders. In the younger subpopulation, patients with non-specific back pain had a higher risk of being diagnosed with a psychiatric disorder than patients with specific back pain (adjusted odds ratio 1.56, 95% confidence interval 1.25-1.94). The type of BPD had no effect on the risk of having a psychiatric diagnosis among older patients. Conclusions: Patients with a non-specific back pain disorder younger than 61 years were more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder. We recommend that spine specialists pay special attention to patients younger than 61 years with a back pain disorder to prevent them from developing a psychiatric disorder.

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.

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.

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.

The Danish National Register of assisted reproductive technology: content and research potentials.

The Danish National Register of assisted reproductive technology (ART) was initially established in 1994. The register comprises complete information on all ART procedures in public and private clinics in Denmark from 2013 and onwards, including baseline information on the cause of infertility and a number of health-related patient characteristics. The register enables monitoring and research on infertility treatment and reproductive topics in single women or couples seeking assisted reproduction, and the register is thus a key component of the Danish health information system within human reproduction. We aimed to provide an updated description of the register including advantages and pitfalls when using the register for reproductive epidemiological research, and a description of the accessibility for researchers. The Danish ART register is a valuable tool for epidemiological research. However, the inherent strengths and limitations ought to be in perspective when designing studies and interpreting the study results. Reports with annually aggregated data on ART treatments, can be accessed on the Danish Health Data Authority web page and researchers may obtain access to individual pseudonomized data via secure servers at the Danish Health Data Authority and Statistics Denmark.

Live-born children after assisted reproduction in women with type 1 diabetes and type 2 diabetes: a nationwide cohort study.

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes are among the most prevalent chronic diseases in women in the fertile years and women with diabetes may experience several reproductive issues. We aimed to examine the chance of biochemical pregnancy, clinical pregnancy and live birth after assisted reproductive technology (ART) treatment in women with type 1 and type 2 diabetes and whether obesity per se influenced the results. METHODS: This nationwide register-based cohort study is based on the Danish ART Registry comprising 594 women with either type 1 diabetes or type 2 diabetes from 2006 to 2017. RESULTS: Relative to women without diabetes, the adjusted OR (95% CI) of a live birth per embryo transfer was 0.50 (0.36, 0.71) in women with type 2 diabetes and 1.10 (0.86, 1.41) in women with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our data on the efficacy of ART treatment in women with type 1 and type 2 diabetes is the first in this field. When compared with women without diabetes, women with type 1 diabetes had an equivalent chance of a live birth per embryo transfer whereas women with type 2 diabetes had a reduced chance. The findings in women with type 2 diabetes did not seem to be driven by obesity per se as the same pattern was seen in both normal-weight and obese women. Graphical abstract.

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.

The efficacy of assisted reproductive treatment in women with epilepsy.

RESEARCH QUESTION: The question of interest for this study was to examine the chance of a live birth following assisted reproductive technology (ART) treatment in women with epilepsy compared with women without epilepsy. In sub-analyses, the chance of biochemical and clinical pregnancies, and the impact of antiepileptic drugs (AED) treatment prior to embryo transfer, was analysed. DESIGN: This register-based cohort study was based on the Danish ART register comprising all women who underwent embryo transfer during 2006 to 2017, which included 730 ART treatments in 264 women with a history of epilepsy, and 128,387 ART treatments in 42,938 women without epilepsy. Adjustments were made for comorbidity, women's age, calendar year, type of infertility treatment and cause of infertility. A possible impact of AED use at the time of embryo transfer was studied in a sub-analysis. The primary outcome was live birth within a period of 140-308 days after the date of embryo transfer. RESULTS: The adjusted odds ratio for a live birth per embryo transfer in women with epilepsy, relative to women without epilepsy, was 1.06 (95% confidence interval [CI] 0.88-1.28). The adjusted odds ratio for a live birth among users of an AED was 1.22 (95% CI 0.77-1.92) relative to women who had stopped the use of AED prior to embryo transfer. CONCLUSIONS: The chances of a live birth per embryo transfer were similar in women with and without epilepsy. These are novel and reassuring findings on the efficacy of infertility treatment in women with epilepsy.

Live birth in women with multiple sclerosis receiving assisted reproduction.

RESEARCH QUESTION: Multiple sclerosis is predominant in women during the childbearing years and, in case of problems with conceiving naturally, assisted reproductive technology (ART) becomes relevant. The efficacy of ART treatment in women with multiple sclerosis has not previously been studied. Our aim was to examine the chance of a liveborn infant after an embryo transfer in women with multiple sclerosis and to examine whether corticosteroids before embryo transfer had a beneficial effect. DESIGN: This cohort study is based on nationwide Danish health registries, including all women who underwent embryo transfers between 1 January 1995 to 31 December 2017. The exposed cohort comprised 2267 embryo transfers in women with multiple sclerosis and the unexposed cohort comprised 200,684 in women without multiple sclerosis. Multilevel logistic regression analysis was used to compute the crude and the adjusted risk estimates. RESULTS: A total of 21.97% of the embryo transfers in women with multiple sclerosis resulted in a liveborn infant compared with 24.17% in women without multiple sclerosis, and the adjusted odds ratio was 0.91 (95% CI 0.81 to 1.02). The adjusted odds ratio of live birth in women with multiple sclerosis using corticosteroids before embryo transfer was 0.90 (95% CI 0.49 to 1.68), compared with women with multiple sclerosis receiving no corticosteroids. CONCLUSION: The chance of a live birth was not decreased in women with multiple sclerosis undergoing ART compared with women without multiple sclerosis. The use of corticosteroids had no effect on the result. These novel results on ART treatment are useful when counselling women with multiple sclerosis undergoing assisted reproduction.

Decreased chance of a live born child in women with rheumatoid arthritis after assisted reproduction treatment: a nationwide cohort study.

OBJECTIVES: No studies have examined the efficacy of assisted reproductive technology (ART) treatment in women with rheumatoid arthritis. Therefore, we examined the chance of live birth after ART treatment in women with rheumatoid arthritis compared with women without rheumatoid arthritis. METHODS: Our cohort study is based on nationwide Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 30 June 2017. The cohorts comprised 1149 embryo transfers in women with rheumatoid arthritis, and 198 941 embryo transfers in women without rheumatoid arthritis. Our outcome was live birth per embryo transfer, and we controlled for multiple covariates in the analyses. In subanalyses, we examined a chance of biochemical/clinical pregnancy after ART and a possible impact of corticosteroid use prior to embryo transfer. RESULTS: The adjusted OR (aOR) for a live birth per embryo transfer in women with rheumatoid arthritis, relative to women without rheumatoid arthritis, was 0.78 (95% CI 0.65 to 0.92). The aORs for biochemical and clinical pregnancies were 0.81 (95% CI 0.68 to 0.95) and 0.82 (95% CI 0.59 to 1.15), respectively. Corticosteroid prescription prior to embryo transfer increased the OR for live birth (aOR=1.32 (95% CI 0.85 to 2.05)). CONCLUSIONS: The chance of a live birth was significantly reduced in women with rheumatoid arthritis receiving ART treatment, relative to women without rheumatoid arthritis, and our result suggested that the problem was related to an impaired chance of embryo implantation. The role of corticosteroid use prior to embryo transfer must be a subject for further research.

Colon cancer patients with a serious psychiatric disorder present with a more advanced cancer stage and receive less adjuvant chemotherapy - A Nationwide Danish Cohort Study.

BACKGROUND: Psychiatric patients with colorectal cancer may have delayed diagnosis and be oncologically undertreated. METHODS: The Danish Colorectal Cancer Group database comprised 25,194 colorectal cancer patients (CRC), (colon cancer (CC, n = 16,641), rectal cancer (RC, n = 8553)), having an operation in 2007-2013, were alive at least 30 days after operation, of which 422 have had at least one hospital contact for a serious psychiatric disorder; ICD-10: DF20-29: primary psychotic disorders, or DF30-39: affective disorders (exposed) in a period of 3650-120 days before the operation date. Pearson chi-squared test for cancer stage was calculated. Odds Ratio (OR) with 95% confidence interval (CI) for having had a palliative vs an intended curative aim of the operative treatment for CRC patients (cohort 1), and for having an oncological treatment for each cancer site CC or RC (cohort 2 and 3) in patients with and without a psychiatric history was estimated. We adjusted the OR for: age, gender, comorbidity index, cancer stage, socio-economic position group, and educational level. RESULTS: A higher cancer stage at the time of operation in patients with psychiatric disorders compared with patients without such a history was seen and may possibly point towards a delay in the diagnosis or in the treatment of CC in patients with psychiatric disorders. They also had decreased adjusted OR for having an oncological treatment, OR 0.55, 95% CI (0.40-0.76)), which was not explained by cancer stage. For patients with RC no difference was seen. CONCLUSIONS: Attention for CC patients with pre-existing serious psychiatric disorders is recommended.