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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.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.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).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.

Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce.To examine the risk of childhood infections associated with fathers' use of anti-inflammatory/immunosuppressive medications taken before conception.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.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).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.

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

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.

This was a nationwide cohort study based on Danish health registers focusing on assisted reproductive technology (ART) treatments in women using donor or partner sperm from 2007 to 2017. Women using donor sperm were subdivided into groups based on relationship status: women with male partners, single women, or women with female partners. The live birth adjusted odds ratios (aORs) after the IUI treatments in women using donor sperm compared with women using partner sperm were 1.48 (95% CI: 1.38–1.59) in women with male partners using donor sperm, 1.20 (95% CI: 1.13–1.28) in single women, and 1.46 (95% CI: 1.32–1.62) in women with female partners. The live birth aORs after IVF treatments in women using donor sperm compared with women using partner sperm were 1.16 (95% CI: 1.02–1.32) in women with male partners using donor sperm, 0.88 (95% CI: 0.80–0.96) in single women, and 1.20 (95% CI: 1.00–1.44), in women with female partners. The use of donor sperm was associated with a higher chance of a live birth after the IUI treatments, but there was no difference after the IVF treatments. Our study invites healthcare professionals to increase their attention toward the different needs and fertility issues of all women attending fertility clinics.

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.

This cohort study, based on Danish health registers, examined the post-acute consequences of hospitalization for COVID-19 in patients with diabetes.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.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.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.

Background: The safety of fathers’ use of antidiabetic drugs in terms of child outcomes is an important clinical question. We aimed to assess the risk of adverse birth and early childhood outcomes after fathers’ use of antidiabetics prior to conception. Methods: A nationwide cohort study based on Danish health registries. The study comprised all live born singleton children in Denmark (1997 through 2018). Children were categorized according to fathers’ filled prescriptions for antidiabetic drugs three months prior to conception. Exposed cohorts: children born after paternal use of insulin or non-insulin anti-hyperglycemic agents. The unexposed constituted children born by fathers not treated with antidiabetics prior to conception. We examined adverse birth outcomes (preterm birth, small for gestational age (SGA)), and adverse childhood outcomes in the first year of life (major congenital malformations (MCMs), and infections diagnosed at a hospital). Results: A total of 1,318,684 children were included. In all, 5527 children were born after paternal use of insulin, 2121 after use of non-insulin anti-hyperglycemic agents, and 1,311,036 were unexposed. After fathers’ use of insulin we did not find increased risk of adverse outcomes. After fathers’ use of metformin, the adjusted OR of MCMs was 1.40 (95% CI 1.11–1.76). After fathers’ use of sulfonylureas, the adjusted OR of SGA was 1.80 (95% CI 1.11–2.93), and for child gastrointestinal infections the adjusted HR was 1.76 (95% CI 1.04–2.99). Conclusions: Fathers’ use of insulin was reassuring. Metformin and sulfonylureas were associated with selected adverse outcomes. Our findings suggest an additional 14 MCMs per 1000 fathers exposed to metformin prior to conception. As there is no meaningful supporting biological rationale, these findings should be confirmed in a different population prior to clinical consequences being drawn.

Assisted reproductive technology (ART) treatments in women with underlying chronic diseases have become increasingly frequent. The objective of this review is to provide an overview of the literature examining the chance of having a live born child after ART in women with chronic diseases, compared to other women receiving ART. We focused on some of the most prevalent chronic diseases in women during their reproductive years, ie ulcerative colitis, Crohn’s disease, rheumatoid arthritis, multiple sclerosis, epilepsy, hyperthyroidism, hypothyroidism, and diabetes mellitus. Secondly, we studied the chance of successful implantation. The literature search was performed in the database Pubmed.gov. including all studies published before October 2020. Title and abstracts of 58 papers were reviewed, 37 papers were excluded and other 8 studies were excluded after full-text evaluation. Only 13 papers were eligible for review. Results indicate that women with ulcerative colitis, Crohn’s disease, rheumatoid arthritis, hyperthyroidism, and diabetes mellitus type 2 might have problems with low implantation rate or early embryo development during ART. On the contrary, the few studies on women with hypothyroidism, diabetes mellitus type 1, and epilepsy suggest an equivalent chance of a live birth compared to other women undergoing ART. A possible explanation behind these differences could reside in the disease-specific dysregulation of the innate or adaptive immune system. To our knowledge, this is the first review on ART in women with chronic diseases, and it has disclosed that the evidence in this area is indeed sparse. We encourage others to examine live birth after ART in women with chronic diseases.

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.

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.

Background and Aims In paediatric patients with Crohn’s disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months. Design Using Danish registries, we identified patients with Crohn’s disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015. Results We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32–0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45–0.97] in patients receiving combination therapy. Conclusions The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.

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.

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.

Purpose Former studies have suggested that women with Crohn's disease (CD) and ulcerative colitis (UC) have a decreased chance of a live born child after assisted reproductive technology (ART) treatment. It is debated whether corticosteroids before ART may improve outcomes, either by decreasing inflammatory bowel disease-related inflammation or increasing endometrial receptivity. We examined the efficacy of corticosteroids before embryo transfer in women with CD and UC. Patients and methods Our cohort study is based on nationwide Danish health registries, comprising women with CD and UC receiving an embryo transfer (1 January 2006 through 2017). Exposed cohorts constituted women with CD and UC who had received corticosteroids within three months before embryo transfer, and the unexposed cohorts women with CD and UC who did not receive corticosteroids. Our primary outcome was live birth. We controlled for multiple covariates in the analyses. Results We examined 2408 embryo transfers. In patients with CD, 114 embryo transfers were preceded by a corticosteroid prescription, and 964 were not. The corresponding numbers in UC were 122 and 1208, respectively. The adjusted odds ratio (aOR) for live birth in women with CD receiving corticosteroids before embryo transfer, relative to women with CD not receiving corticosteroids, was 0.89 (95% CI 0.49-1.63). The corresponding aOR in UC was 0.98 (95% CI 0.55-1.74). Conclusion Corticosteroids prior to ART in women with CD and UC did not increase the chance of a live born child. The exact impact of corticosteroids prior to embryo transfer in patients with CD and UC still remains to be determined.

Background There is lack of knowledge concerning postpartum infections in women with inflammatory bowel disease (IBD). Our aim is to determine the 30-day postpartum infectious complications in women with and without IBD who have a caesarian section, normal vaginal delivery, or assisted vaginal delivery. Methods We used Danish national registries to establish a study population of liveborn, singleton births from January 1, 1997, through December 31, 2015. We examined 30-day postpartum maternal infectious complications in women with and without IBD, according to the mode of delivery. Statistical models were adjusted for multiple confounders. Results In all, 3255 women with and 207 608 without IBD had a caesarian section. Within 30 days postpartum, 4.5% of women with and 3.7% without IBD had an infectious complication. Increased infectious complications included overall infections (adjusted OR [aOR], 1.83; 95% confidence interval [CI], 1.35–2.47), infections of the gastrointestinal tract (aOR, 4.36, 95% CI 2.34-8.10), and infections of the skin and subcutaneous tissue (aOR, 4.45; 95% CI, 2.30–8.50). Other puerperal infections, urological and gynecological, and other infections were increased, although not significantly. For vaginal deliveries, 1.6% of 5771 women with IBD and 1.3% of 793 110 women without IBD had an infectious complication, and the aOR of infections of the gastrointestinal tract was 3.17 (95% CI, 1.47–6.85). There were too few outcomes to calculate the risk of infections after assisted vaginal delivery. Conclusions The risk of a 30-day postpartum infectious complication is increased in women with IBD. Physicians should carefully monitor their patients postpartum to prevent these adverse outcomes.

OBJECTIVE: To examine whether medications used to treat rheumatoid arthritis (RA)/chronic inflammatory bowel disease (IBD), or factors related to the assisted reproductive technology (ART) procedures, impact the success of ART. In women with RA/IBD, initial studies have shown a reduced chance of a live-born child after ART.DESIGN: Cohort study.SETTING: Nationwide Danish health registries.PATIENTS: All Danish women with a fresh embryo transfer from January 1, 2006, through 2018. The cohorts comprised 1,824 embryo transfers in women with RA/IBD and 97,191 embryo transfers in women without RA/IBD.INTERVENTIONS: Observational, noninterventional study.MAIN OUTCOME MEASURE: Live birth per fresh embryo transfer.RESULTS: The chance of a live birth in women with RA/IBD receiving ART, compared with other women receiving ART, had an adjusted odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.68-0.91). Prescribed corticosteroids before embryo transfer were positively associated with a live-born child (adjusted OR, 1.21; 95% CI, 1.12-1.31), while the use of antiinflammatory/immunosuppressive agents did not have significant importance. Intracytoplasmic sperm injection was associated with a reduced chance (adjusted OR, 0.94; 95% CI, 0.90-0.97). Type of hormone treatment protocol did not have significant importance, and transfer at the blastocyst stage was positively associated with a live-born child (adjusted OR, 1.54; 95% CI, 1.46-1.62).CONCLUSIONS: In women with RA and/or IBD, prescribed corticosteroid before embryo transfer and embryo transfer at the blastocyst stage were associated with successful ART. Intracytoplasmic sperm injection was associated with a slightly reduced chance. Antiinflammatory/immunosuppressive agents and type of hormone protocols did not have significant importance.

BACKGROUND: Women with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short-term outcomes in children exposed in utero to these medicines is reassuring, long-term safety data are lacking.AIM: To assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence.METHODS: This nationwide cohort study was based on information using Danish registers and comprised all live-born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%-75% percentiles 5.5-12.4 years); children not exposed were followed for 13.9 years (25%-75% percentiles 8.7-19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease.RESULTS: A total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow-up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35-1.73); for IBD, it was 1.45 (95% CI 0.64-3.27); for asthma 0.94 (95% CI 0.73-1.21), and for congenital malformations, it was 0.95 (95% CI 0.78-1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis.CONCLUSION: We found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.

BACKGROUND: The long-term effects of anti-TNFα therapy in ulcerative colitis are debatable.AIM: To examine whether anti-TNFα therapy changed the colectomy proportion and reduced the use of corticosteroids.METHODS: A nationwide cohort study among patients (age 0-20) diagnosed with ulcerative colitis through 1995-2015 from Danish health registries. We calculated the cumulative 5-year risk of colectomy after diagnosis and used a Cox regression model for comparison between a historical pre-anti-TNFα cohort 1 (1995-2003) and a cohort 2 for the era of anti-TNFα (2004-2015). Based on anti-TNFα users, defined as patients who had at least four anti-TNFα treatments within 4 months, we examined the subsequent need for corticosteroids.RESULTS: We identified 3001 patients from 1995 to 2015. The 5-year cumulative proportion of colectomy in cohort 2 was 9.7% (95% confidence interval [CI] 8.4-11.1) and 12.3% (95% CI 10.4-14.6) in cohort 1. The adjusted 5-year hazard ratio (HR) was 0.76 (95% CI 0.60-0.96) for colectomy in cohort 2 compared to cohort 1. A total of 334 patients received anti-TNFα treatments, and 16.8% (56/334) were prescribed corticosteroids in the subsequent 3-month period. Corticosteroid treatment declined with follow-up after 6 and 12 months, 5.4% and 1.2%, respectively.CONCLUSION: In patient's ≤20 years, the HR for colectomy within a period of 5 years from the time of diagnosis was reduced in the era of anti-TNFα compared to a historical cohort. In patients treated with anti-TNFα, prescriptions of corticosteroids were virtually ceased after 12 months.

Purpose Women with thyroid disorders may have increased infertility and poor reproductive outcomes, but it is unclear if assisted reproductive technology (ART) is effective in this population. The aim of this study was to examine the chance of a pregnancy (biochemical and clinical), and a live birth after ART, in women with thyroid disorders undergoing ART treatment, compared to women without thyroid disorders. Among live-born children, we assessed the risk of congenital malformations. Patients and methods In a nationwide cohort study of all women undergoing ART treatments in Denmark from 1 January 1994 throughout June 2017, we calculated the chance of a pregnancy and a live birth after embryo transfer. Women with thyroid disorders were stratified into two groups: those diagnosed with hypothyroid or hyperthyroid disorders. The adjusted OR (aOR) of a biochemical and a clinical pregnancy, a live born child and a congenital malformation was computed using multilevel logistic regression models. Results In total, 199,674 embryo transfers were included in 2,101 women with thyroid disorders and in 65,526 women without thyroid disorders. The chance of a biochemical pregnancy was significantly reduced in women with hyperthyroidism (aOR=0.80, 95% CI 0.69-0.93), and the aOR of a live birth was 0.86, 95% CI 0.76-0.98. The aOR for a live birth in women with hypothyroidism was 1.03 (95% CI 0.94-1.12). Children of women with hypothyroidism, who were conceived after ART treatment, had a significantly increased risk of any congenital malformation (aOR=1.46 [95% CI 1.07-2.00]). Conclusion Women with hyperthyroidism receiving ART treatment had a decreased chance of a live birth per embryo transfer compared to women without thyroid disorders. Women with hypothyroidism did not have a decreased chance of a live birth but their offspring had an increased risk of congenital malformation.

BACKGROUND: Anti-TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases.AIM: To examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti-TNFα agents for diseases other than inflammatory bowel disease (IBD).METHODS: A nationwide cohort study, based on Danish health registries, of all patients who utilised anti-TNFα agents for non-IBD indications. Included were patients, who had diseases for which anti-TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti-TNFα.RESULTS: In total 17 018 individuals with autoimmune diseases were exposed to anti-TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63 308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4-2.8] and 2.0 [95% CI: 1.5-2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8-2.2] and 1.0 [95% CI:0.6-1.6], and for adalimumab 1.2 [95% CI: 0.8-1.8] and 0.6 [95% CI: 0.3-1.0].CONCLUSIONS: Patients treated for autoimmune diseases with anti-TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases.

BACKGROUND AND AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a de-identified administrative claims database (OptumLabs(®) Data Warehouse), we identified 7,453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis) linked to newborns, with peri-conception medication exposure between 38–60 weeks prior to newborn delivery date (34–58 weeks prior for pre-term newborns), and neonatal follow-up for 3 months after delivery date. Through logistic regression, adjusting for paternal age and race (and in a subset for maternal age, race, presence of IMIDs and non-singleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birthweight in fathers exposed to thiopurines (n=461), methotrexate (n=171), TNFα antagonists (n=1082) or non-TNF-targeting biologic agents (n=132) vs. fathers not exposed to any of these medications (n=5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (RR, 1.12 [95% CI, 0.66–1.76]), methotrexate (RR, 0.67 [0.21–1.55]), TNFα antagonists (RR, 1.14 [0.81–1.57]), and non-TNF-targeting biologic agents (RR, 1.75 [0.80–3.24]) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on sub-analyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7,453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.

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.

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.

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.

Introduction Research on long-term outcomes of children exposed to inflammatory bowel disease [IBD] in utero is lacking. Maternal inflammation, IBD medications, or other factors may increase the risk of developmental disabilities in the offspring. Methods We used the Danish National Birth Cohort, an ongoing prospective study that includes 100 419 pregnancies of 92 274 women, in conjunction with the Danish National Registries, to evaluate cognitive and motor development of the children of women with and without IBD. We analysed basic measures of childhood development at 6-month and 18-month interviews with the mother and with validated questionnaires filled out by the parents when the child was 7 years old. We adjusted for multiple confounders, including preterm birth. Results At 6 months, we included 484 children of women with IBD and 69 571 unexposed children; at 18 months, 471 exposed and 66 018 unexposed; at 7 years, 391 exposed and 54 356 unexposed. At 18 months, exposed children were significantly less likely to ‘use word-like sounds’ but there was no difference between use of ‘sentences of 2 words’. At 6 and 18 months, there were no other obvious differences in language and motor development. At 7 years, cognitive scores [emotional, conduct, hyperactivity, peer, and social scores] and motor development [gross/fine motor skills and general coordination] were similar between the two groups. Conclusions Children exposed to IBD in utero and unexposed children scored similarly on survey-based tools assessing basic measures of neurodevelopment over 7 years. These results are reassuring for current and future parents with IBD.

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.

Background and Aims Previous studies indicate an increased risk of sexual dysfunction in women with inflammatory bowel disease [IBD] but none have examined sexual function in a large population-based cohort. Methods To investigate the risk of sexual dysfunction in women with IBD, we used data from the Danish National Birth Cohort, a nationwide study of 92 274 pregnant women recruited during 1996–2002. We performed a cross-sectional study based on mothers who participated in the Maternal Follow-up in 2013–14. The outcome was self-reported sexual health. Information regarding demographics and IBD characteristics was retrieved from the Danish National Patient Register. Using regression models and adjusting for important confounders, we compared sexual function in women with and without IBD. Results The study population consisted of 38 011 women including 196 [0.5%] with Crohn’s disease [CD] and 409 [1.1%] with ulcerative colitis [UC]. Median age was 44 years. Compared to women without IBD, women with UC did not have significantly decreased sexual function, while women with CD had more difficulty achieving orgasm (adjusted odds ratio [aOR] 1.53; 95% confidence interval [CI] 1.02–2.30], increased dyspareunia [aOR 1.71; 95% CI 1.11–2.63] and deep dyspareunia [aOR 2.00; 95% CI 1.24–3.22]. The risk for difficulty achieving orgasm and deep dyspareunia was further increased within 2 years of an IBD-related contact/visit [aOR 1.81; 95% CI 1.11–2.95; and aOR 2.37; 95% CI 1.34–4.19]. Conclusions Women with CD have significantly increased difficulty achieving orgasm and increased dyspareunia. Physicians should be cognizant of and screen for sexual dysfunction in this group of patients.

Objective:We examined the causes of death amongst full term stillbirths and early neonatal deaths.Methods:Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE).Results:A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20–34 years and with a normal body mass index (BMI).Conclusion:Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

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., Graphical abstract Image 1

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.

Purpose Former studies have suggested that women with Crohn’s disease (CD) and ulcerative colitis (UC) have a decreased chance of a live born child after assisted reproductive technology (ART) treatment. It is debated whether corticosteroids before ART may improve outcomes, either by decreasing inflammatory bowel disease-related inflammation or increasing endometrial receptivity. We examined the efficacy of corticosteroids before embryo transfer in women with CD and UC. Patients and Methods Our cohort study is based on nationwide Danish health registries, comprising women with CD and UC receiving an embryo transfer (1 January 2006 through 2017). Exposed cohorts constituted women with CD and UC who had received corticosteroids within three months before embryo transfer, and the unexposed cohorts women with CD and UC who did not receive corticosteroids. Our primary outcome was live birth. We controlled for multiple covariates in the analyses. Results We examined 2408 embryo transfers. In patients with CD, 114 embryo transfers were preceded by a corticosteroid prescription, and 964 were not. The corresponding numbers in UC were 122 and 1208, respectively. The adjusted odds ratio (aOR) for live birth in women with CD receiving corticosteroids before embryo transfer, relative to women with CD not receiving corticosteroids, was 0.89 (95% CI 0.49–1.63). The corresponding aOR in UC was 0.98 (95% CI 0.55–1.74). Conclusion Corticosteroids prior to ART in women with CD and UC did not increase the chance of a live born child. The exact impact of corticosteroids prior to embryo transfer in patients with CD and UC still remains to be determined.

ObjectivesNo 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.MethodsOur 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.ResultsThe 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)).ConclusionsThe 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.

Backgroud: Women with inflammatory bowel disease (IBD) might have an increased tendency to choose an elective abortion due to a fear that their fetus could be harmed by use of medications, disease flares during pregnancy, or for genetic reasons. We examined the risk of elective abortions in women with ulcerative colitis (UC) and Crohn's disease (CD) compared with women without IBD.Methods: This nationwide cohort study, based on Danish health registries, comprises all registered pregnancies from 1996 through 2015. The 2 exposed groups constituted pregnancies of women with UC or CD, and the unexposed group constituted all pregnancies of women without IBD. Our outcome was elective abortion by maternal request up until the end of the 12th completed week of gestation. We used logistic regression models and calculated the odds ratio (OR) for an elective abortion, controlling for confounders.Results: The overall prevalence rates of elective abortions in women with UC and CD and without IBD were 12.4% (898 elective abortions/7250 pregnancies), 14.9% (978 elective abortions/6559 pregnancies), and 16.9% (285,251 elective abortions/1,691,857 pregnancies), respectively. In women with UC and CD, the adjusted ORs for an elective abortion (95% confidence interval) were 0.80 (0.74-0.86) and 0.96 (0.89-1.04), respectively.Conclusions: Pregnant women with IBD are not more likely to choose an elective abortion compared with women without IBD. These results are reassuring as they suggest that women with IBD are not so worried about a negative impact of their disease, disease activity, or medications that they would choose to terminate a pregnancy.

Aims To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer. Materials and methods The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment. Results In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54). Conclusions We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.

OBJECTIVES: The safety of paternal use of anti-tumor necrosis factor-α (TNF-α) agents immediately prior to conception is practically unknown. On the basis of nationwide data from Danish health registries, we examined the association between paternal use of anti-TNF-α agents within 3 months before conception and adverse birth outcomes.METHODS: This nationwide cohort study is based on data from all women who had a live born singleton child in Denmark from 1 January 2007 through 2013. Children fathered by men treated with anti-TNF-α agents within three months before conception constituted the exposed cohort (N=372), and children fathered by men not treated before conception constituted the unexposed cohort (N=399,498). The outcomes were congenital abnormalities (CAs), preterm birth, and small for gestational age (SGA). We adjusted for multiple covariates, and considered paternal underlying disease and concomitant medication.RESULTS: The adjusted risks of CAs and preterm birth were close to unity, and the adjusted odds ratio (OR) for SGA was 1.70 (95% confidence interval (CI): 0.94-3.09). Restricting our analysis to fathers with inflammatory bowel disease, we found no increased risk of CAs or SGA, and the adjusted OR for pretem birth was 1.42 (95% CI: 0.52-3.86). Restricting our analysis to fathers with rheumatologic/dermatological diseases, we found no increased risk of CAs or preterm birth, and the adjusted OR for SGA was 1.70 (95% CI: 0.74-3.89).CONCLUSIONS: Our results are overall reassuring regarding the safety of paternal preconceptional use of anti-TNF-α agents. The result regarding SGA should, however, be interpreted with caution as we found an increased risk, although not significantly increased.

OBJECTIVE: To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohn's disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments.METHODS: This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148 540 treatments in 52 489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes.RESULTS: The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62.CONCLUSIONS: Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.