Mirtazapine exposure in pregnancy and fetal safety: A nationwide cohort study.

OBJECTIVE: To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes. METHODS: A register-based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine-exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression. RESULTS: From a source population of 1,650,649 pregnancies, the propensity score-matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine-exposed) and 4485 pregnancies (897 mirtazapine-exposed) were included, respectively. Thirty-one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55-1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91-1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34-2.29) or neonatal death (HR = 0.60%, 95% CI 0.18-2.02). CONCLUSIONS: In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy.

Postoperative infections after non-elective cesarean section - a retrospective cohort study of prevalence and risk factors at a single center in Denmark administering prophylactic antibiotics after cord clamping.

BACKGROUND: Mothers giving birth by non-elective cesarean section have considerably higher risk of developing postoperative infection, than mothers giving birth by elective cesarean section. Meta-analyses have shown that the risk of infection is reduced when administering antibiotics at least 30 min prior to skin incision rather than after cord clamping. If given prior to incision, antibiotics are present in the neonatal bloodstream for up to 24 h after delivery, with early exposure to antibiotics potentially disturbing development of the gut microbiome. We aimed to retrospectively assess the prevalence of postoperative infection after non-elective cesarean section at a single labor ward administering antibiotics after cord clamping, additionally investigating risk factors for developing postoperative infections. METHODS: In this retrospective cohort study, we included a total of 2,725 women giving birth by non-elective cesarean section in 2010-2017 with a review of records for prenatal risk factors, labor management, and perinatal outcomes. The primary outcomes were a main composite infection of development of either endometritis, surgical-site infection, or sepsis in conjunction with a relevant antibiotic prescription. Secondary outcomes included infection of unknown focus, mastitis, urinary tract infection, and pneumonia. RESULTS: A total of 88 patients developed a main composite infection (3.2%). These infections subdivide into endometritis (n = 37/2725, 1.4%), surgical-site infection (n = 35/2725, 1.3%) and sepsis (n = 15/2725, 0.6%). We found a high body mass index (aOR = 3.38, 95%CI 1.93-5.92) and intrapartum fever (aOR = 2.26, 95%CI 1.22-4.59) to be independent risk-factors for developing postoperative infection after non-elective cesarean section. Furthermore, we found delivery by a more expedient emergency grade 2 cesarean section (aOR = 0.61 95%CI 0.37-0.998) compared to grade 3 to be a protective factor for developing postoperative infection after non-elective cesarean section. CONCLUSION: In a labor ward administering antibiotics after cord clamping at non-elective cesarean births, we find a low prevalence of main composite infections when compared to estimates from meta-analyses on the topic. We conclude that administration of prophylactic antibiotics after cord clamping appears to result in acceptable rates of postoperative infection and avoids transplacental-transmission of antibiotics to the infant.

A prospective cohort study of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy evaluating SARS-CoV-2 antibodies in maternal and umbilical cord blood and SARS-CoV-2 in vaginal swabs.

INTRODUCTION: Evidence about the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is rapidly increasing; however, data on antibody response and risk of transmission during pregnancy and delivery are still limited. The aim of this study was to evaluate if SARS-CoV-2 is detectable in vaginal swabs and whether antibodies against SARS-CoV-2 are present in maternal and umbilical cord blood of pregnant women with confirmed SARS-CoV-2. MATERIAL AND METHODS: A single-unit prospective cohort study in Denmark including pregnant women with SARS-CoV-2 infection confirmed by a pharyngeal swab between August 20, 2020, and March 1, 2021, who gave birth during the same period. All patients admitted to the maternity ward and antepartum clinic were screened for SARS-CoV-2 infection. A maternal blood sample and vaginal swabs were collected at inclusion. If included antepartum, these samples were repeated intrapartum when an umbilical cord blood sample was also collected. Swabs were analyzed for SARS-CoV-2 and blood samples were analyzed for SARS-CoV-2 total antibodies. Placental and neonatal swabs as well as placental histopathological examinations were performed on clinical indications. RESULTS: We included 28 women, of whom four had serious maternal or fetal outcomes including one case of neonatal death. Within the first 8 days after confirmed SARS-CoV-2 infection, SARS-CoV-2 was detectable in two vaginal swabs (2/28) and SARS-CoV-2 antibodies were detected in 1 of 13 women. From 16 days after confirmed infection, antibodies were observed in 19 of 21 of women. Antibodies in cord blood were not detected during the first 16 days after confirmed infection (n = 7). However, from 26 days, antibodies were present in 16 of 17 cord blood samples of seropositive mothers. Placental examination in two cases of severe fetal outcomes preceded by reduced fetal movements revealed SARS-CoV-2 in swabs and severe histopathological abnormalities. CONCLUSIONS: SARS-CoV-2 was detected in only 2 of 28 vaginal swabs within 8 days after confirmed infection in pregnant women. Our data suggest that maternal seroconversion occurs between days 8 and 16, whereas antibodies in cord blood of seropositive mothers were present in the majority from 26 days after confirmed infection. Additional data are needed regarding timing of seroconversion for the mother and appearance of antibodies in cord blood.

Relation Between Infant Microbiota and Autism?: Results from a National Cohort Sibling Design Study.

BACKGROUND: Hypotheses concerning adverse effects of changes in microbiota have received much recent attention, but unobserved confounding makes them difficult to test. We investigated whether surrogate markers for potential adverse microbiota change in infancy affected autism risk, addressing unobserved confounding using a sibling study design. METHODS: This is a population-based, prospective cohort study including all singleton live births in Denmark from 1997 to 2010. The exposure variables were cesarean delivery and antibiotic use in the first 2 years of life. The outcome was a subsequent autism diagnosis. We used the between- and within-sibling model and compared it with sibling-stratified Cox models and simpler standard Cox models that ignored sibship. RESULTS: Of our study population including 671,606 children, who were followed for up to 15 years (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted that both cesarean (compared with vaginal) delivery and antibiotics increased the risk of autism. In the sibling-stratified Cox model, only broader spectrum antibiotics were associated with increased risk of autism: hazard ratio (HR) = 1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18); and broader spectrum antibiotics HR = 1.05 (0.95, 1.16). CONCLUSIONS: The between-within model rendered more precise estimates than sibling-stratified Cox models, and we believe that it also provided more valid estimates. Results from these preferred models do not support a causal relation between antibiotic treatment during infancy, cesarean delivery, and autism. See video abstract at, http://links.lww.com/EDE/B432.

Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder.

BACKGROUND: Increasing attention deficit hyperactivity disorder (ADHD) incidence has been proposed to be caused by factors influencing microbiota in early life. We investigated the potential causality between ADHD and two surrogate markers for changes in children's microbiota: birth delivery mode and early childhood antibiotic use. METHOD: This population-based, prospective cohort study linked nationwide registers of data for native Danish singleton live births in Denmark from 1997 to 2010. Exposure variables were delivery mode and antibiotic use during the first 2 years of life. The main outcome measure was ADHD diagnosis or redeemed ADHD medication prescriptions. For statistical analysis, we used both advanced sibling models and a more traditional approach. RESULTS: We included 671,592 children, followed from their second birthday in the period 1999-2014 for 7,300,522 person-years. ADHD was diagnosed in 17,971. In total, 17.5% were born by cesarean delivery, and 72% received antibiotic treatment within their first 2 years of life. In the adjusted between-within sibling survival model, mode of delivery or antibiotics had no effect on ADHD when compared with vaginal delivery or no antibiotic treatment as hazard ratios were 1.09 (95% confidence interval 0.97-1.24) for intrapartum cesarean, 1.03 (0.91-1.16) for prelabor cesarean, 0.98 (0.90-1.07) for penicillin, and 0.99 (0.92-1.06) for broader spectrum antibiotics. In a sibling-stratified Cox regression, intrapartum cesarean was associated with increased ADHD risk, but other exposures were not. In a descriptive, nonstratified Cox model, we found increased risk for ADHD for all exposures. CONCLUSIONS: Detailed family confounder control using the superior between-within model indicates that cesarean delivery or use of antibiotics during the first 2 years of life does not increase ADHD risk. Therefore, our study suggests that changes in children's microbiota related to cesarean delivery or antibiotic use, do not cause ADHD.

Tibolone and risk of gynecological hormone sensitive cancer.

Risk of ovarian cancer with hormone therapy is associated with use of both unopposed estrogen therapy and combined estrogen-progestin therapy, whereas for endometrial cancer addition of continuous progestin decreases the estrogen induced increased risk. Less is known about risk with use of tibolone; a synthetic steroid with estrogenic, progestagenic and androgenic properties. We assessed these associations in a prospective cohort study, including all Danish women 50-79 years of age and followed 1995-2009. National Danish Registers captured individually updated exposure information, cancer cases including histology and confounding factors. Poisson regression analyses provided multiple adjusted incidence rate ratios (IRRs). More than 900,000 women were followed for 9.8 years on average; 4,513 were diagnosed with ovarian cancer and 6,202 with endometrial cancer. Compared to women never on postmenopausal hormone therapy, current users of tibolone had an increased IRR for ovarian cancer (1.42(95% confidence interval [CI], 1.01-2.00) and serous ovarian tumors (2.21(95%CI 1.48-3.32)). The risk increased with duration of use, particularly for serous ovarian tumors. Compared to never users, the IRR of endometrial cancer was 3.56(95%CI 2.94-4.32) among current users of tibolone and 3.80(95%CI 3.08-4.69) of Type I endometrial cancer. The steepest risk increase with duration of use was for Type I tumors. In conclusion, tibolone is associated with increased risk for ovarian and endometrial cancer overall; and particular the risk of serous ovarian tumors and Type I endometrial cancer. Because the associations are stronger with increasing durations of use - and for hormone sensitive tumors - the results seem indicative of causality.

Antibody status at delivery and pregnancy outcomes during the first Danish COVID-19 wave.

INTRODUCTION: We aimed to investigate the prevalence of SARS-CoV-2 infection and SARS-CoV-2 antibodies in parturient women and their newborns during the first Danish COVID-19 wave and to identify associations with maternal background characteristics, self-reported symptoms, and pregnancy outcomes. METHODS: In a single-centre, prospective cohort study from Denmark, we invited 1,883 women with singleton pregnancies giving live birth from 25 May 2020 to 2 November 2020. Hereof, 953 (50.6%) women were included. Nasopharyngeal swabs, maternal and umbilical cord blood samples, and questionnaires were collected. Medical records were available for participants and non-participants. RESULTS: SARS-CoV-2 antibodies were found in 1.3% of the women. All newborns of seropositive women had SARS-CoV-2 antibodies in cord blood. No association was found between SARS-CoV-2 antibodies and pregnancy outcomes. Self-reported loss of smell correlated with seropositivity (p less-than 0.001). No women were hospitalised due to COVID-19 during pregnancy or had a positive nasopharyngeal swab intrapartum. CONCLUSIONS: The prevalence of COVID-19 in pregnancy was low during the first wave. Maternal SARS-CoV-2 antibodies were associated with antibodies in cord blood, loss of smell and positive SARS-CoV-2 swab during pregnancy, but not with any adverse pregnancy outcomes. FUNDING: Ferring Pharmaceuticals funded part of the study. TRIAL REGISTRATION: The study was approved by the Regional Committee on Health Research Ethics (H-20028002) and the Danish Data Protection Agency (P-2020-264).

Reoccurrence of retained placenta at vaginal delivery: an observational study.

OBJECTIVE: To estimate the prevalence and validate the diagnosis of retained placenta in nulliparous women and the risk of reoccurrence at subsequent vaginal delivery. DESIGN: Nested cohort study. SETTING: Department of Gynecology and Obstetrics, university-affiliated teaching hospital. POPULATION: 10 334 nulliparous singleton pregnancies who delivered vaginally at the hospital during 2000-2009. METHODS: Data from a computerized database information system were used to identify 287 women who had an ICD-10 diagnosis of retained placenta and 572 randomly selected controls matched by the date of first delivery. At chart review the diagnosis was confirmed by: (1) excessive bleeding <30 minutes after delivery without placental separation, (2) placenta not separated 30 minutes after delivery or (3) confirmation of retained placental tissue >2 hours postpartum. MAIN OUTCOME MEASURES: Confirmation of the diagnosis and prevalence of retained placenta. Risk of reoccurrence in a subsequent vaginal delivery. RESULTS: The prevalence of retained placenta increased from 2.8 to 7.0% after confirmation according to the set criteria. Of the selected women, 48.4% had a subsequent vaginal delivery. Of these women, 25.3% (23/91) with a previous retained placenta and 5.3% (11/206) without previously retained placenta, experienced retained placenta in subsequent delivery. This corresponds to an adjusted odds ratio of 5.5 (95% confidence interval 2.6-12.7) in the multivariate analysis for recurrence of retained placenta in a subsequent vaginal delivery. CONCLUSIONS: The use of the ICD-10 diagnosis of retained placenta underestimated the prevalence. The risk of reoccurrence of retained placenta is significantly increased in a subsequent vaginal delivery.

Reorganising and improving quality of care for hyperemesis gravidarum in a Danish hospital: a quality improvement project.

BACKGROUND: Hyperemesis gravidarum (HG) is a pregnancy complication comprising severe nausea and vomiting in pregnancy. It is associated with adverse outcomes for both mother and child. Treatment consists primarily of antiemetics and intravenous fluids; however, support from healthcare professionals is also important. LOCAL PROBLEM: At the department of obstetrics at Nordsjællands Hospital, an increasing workload caused challenges regarding patient care and organisation for patients with HG, and exploring possibilities of reorganising HG care to release midwife resources was warranted. METHODS: Through input from staff and patients, possible improvements were identified. Plan-do-study-act cycles were conducted with staff and patients, resulting in adjustments in care and organisation and thus use of resources. The specific, measurable, attainable, realistic and timely aims included patient satisfaction and number of follow-ups conducted via phone. INTERVENTIONS: HG care was relocated to the department of gynaecology, where it was managed primarily by nurses. Staff and patients were actively involved in the process. RESULTS: HG care was successfully relocated without compromising patient satisfaction. Additionally, an option of patient-administered home treatment for selected patients was established. CONCLUSION: This quality improvement project describes the relocation and set-up of hospital care provided to patients with HG, resulting in high patient satisfaction. This project might serve as an inspiration to other departments of obstetrics and gynaecology.

Exclusive breastfeeding: Relation to gestational age, birth weight, and early neonatal ward admission. A nationwide cohort study of children born after 35 weeks of gestation.

OBJECTIVES: Prematurity, being small for gestational age and early neonatal ward admission are the major neonatal conditions that may interfere with breastfeeding supportive practices in infants born at gestational age ≥35+0 weeks. We aimed to investigate the associations between gestational age, small for gestational age, early neonatal ward admission and exclusive breastfeeding at one and four months. METHODS: A register-based cohort-study of all Danish singletons with gestational age ≥35+0 weeks born in 2014-2015. In Denmark, health visitors routinely conduct free home visits throughout infants' first year and thereby report breastfeeding data to The Danish National Child Health Register. These data were linked with data from other national registers. Logistic regression models estimated the odds ratio for exclusive breastfeeding at one and four months, adjusted for confounding variables. RESULTS: The study population comprised 106,670 infants. Compared to gestational age 40 weeks, the adjusted odds ratio for exclusive breastfeeding at one month showed a decreasing tendency from gestational age ≥42 (n = 2,282) (1.07; 95% confidence interval (CI) 0.97-1.17) to 36 weeks (n = 2,062) (0.80; 95% CI 0.73-0.88). Small for gestational age (n = 2,342) was associated with decreased adjusted odds ratio for exclusive breastfeeding at one month (0.84; 95% CI 0.77-0.92). Neonatal ward admission was associated with increased adjusted odds ratio for exclusive breastfeeding at one month among late preterm infants (gestational age 35-36 weeks; n = 3,139) (1.31; 95% CI 1.12-1.54), as opposed to among early term (gestational age 37-38 weeks; n = 19,171) (0.84; 95% CI 0.77-0.92) and term infants (gestational age >38 weeks; n = 84,360) (0.89; 95% CI 0.83-0.94). The associations seemed to persist at four months. CONCLUSIONS: Decreasing gestational age and small for gestational age were associated with decreased exclusive breastfeeding rates. Neonatal ward admission was associated with increased exclusive breastfeeding rates among late preterm infants, whereas the opposite was observed among early term and term infants.

Validation of Danish registry-cases of type 1 diabetes in women giving live birth using a clinical cohort as gold standard.

INTRODUCTION: The aim of this study was to validate type 1 diabetes in women giving live birth in the Danish national registries against a clinical cohort of confirmed cases (the Danish Diabetes Birth Registry [DDBR] cohort). METHODS: National registries including diagnosis codes, redeemed prescriptions and background data were combined. Three main algorithms were constructed to define type 1 diabetes in women giving live birth: (1) Any diabetes diagnosis registered before delivery and before age of 30, (2) a specific type 1 diabetes diagnosis registered before delivery regardless of maternal age and (3) a 'preexisting type 1 diabetes in pregnancy' diagnosis registered before delivery. In additional sub-algorithms, we added information on anti-diabetic medicine and gestational diabetes diagnosis. We calculated positive predictive value (PPV) and completeness using the DDBR cohort as gold standard. Since DDBR included between 75 and 93% of women with confirmed type 1 diabetes giving live birth, we used quantitative bias analysis to assess the potential impact of missing data on PPV and completeness. RESULTS: Main algorithm 2 had the highest PPV (77.4%) and shared the highest completeness (92.4%) with main algorithm 1. Information on anti-diabetic medicine and gestational diabetes increased PPV, on expense of completeness. All algorithms varied with PPV between 65.7 and 87.6% and completeness between 73.6 and 92.4%. The quantitative bias analysis indicated that PPV was underestimated, and completeness overestimated for all algorithms. For algorithm 2, corrected PPV was between 82.1 and 94.6% and corrected completeness between 84.7 and 91.2%. CONCLUSIONS: The Danish national registries can identify type 1 diabetes in women giving live birth with a reasonably high accuracy. The registries are a valuable source for future comparative outcome studies and may also be suitable for monitoring prevalence and incidence of type 1 diabetes in women giving live birth.

Using machine learning to identify quality-of-care predictors for emergency caesarean sections: a retrospective cohort study.

OBJECTIVES: Emergency caesarean sections (ECS) are time-sensitive procedures. Multiple factors may affect team efficiency but their relative importance remains unknown. This study aimed to identify the most important predictors contributing to quality of care during ECS in terms of the arrival-to-delivery interval. DESIGN: A retrospective cohort study. ECS were classified by urgency using emergency categories one/two and three (delivery within 30 and 60 min). In total, 92 predictor variables were included in the analysis and grouped as follows: 'Maternal objective', 'Maternal psychological', 'Fetal factors', 'ECS Indication', 'Emergency category', 'Type of anaesthesia', 'Team member qualifications and experience' and 'Procedural'. Data was analysed with a linear regression model using elastic net regularisation and jackknife technique to improve generalisability. The relative influence of the predictors, percentage significant predictor weight (PSPW) was calculated for each predictor to visualise the main determinants of arrival-to-delivery interval. SETTING AND PARTICIPANTS: Patient records for mothers undergoing ECS between 2010 and 2017, Nordsjællands Hospital, Capital Region of Denmark. PRIMARY OUTCOME MEASURES: Arrival-to-delivery interval during ECS. RESULTS: Data was obtained from 2409 patient records for women undergoing ECS. The group of predictors representing 'Team member qualifications and experience' was the most important predictor of arrival-to-delivery interval in all ECS emergency categories (PSPW 25.9% for ECS category one/two; PSPW 35.5% for ECS category three). In ECS category one/two the 'Indication for ECS' was the second most important predictor group (PSPW 24.9%). In ECS category three, the second most important predictor group was 'Maternal objective predictors' (PSPW 24.2%). CONCLUSION: This study provides empirical evidence for the importance of team member qualifications and experience relative to other predictors of arrival-to-delivery during ECS. Machine learning provides a promising method for expanding our current knowledge about the relative importance of different factors in predicting outcomes of complex obstetric events.

Microscopic Colitis in Denmark: Regional Variations in Risk Factors and Frequency of Endoscopic Procedures.

OBJECTIVE: Microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is an increasingly prevalent gastrointestinal disease with an unknown aetiology. Previous research has reported significant differences in the incidence of MC within Denmark, with the lowest incidence found in the most populated region [Capital Region of Denmark]. Our aim was to elucidate the causes of these regional differences. DESIGN: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] entered in The Danish Pathology Register between 2001 and 2016 were matched to 10 reference individuals [n = 142 481]. Information regarding drug exposure, including proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors [SSRIs], statins, and nonsteroidal anti-inflammatory drugs [NSAIDs], were retrieved from The Danish National Prescription Registry. Information regarding endoscopy rate, smoking-related diseases, and immune-mediated inflammatory diseases were acquired from The Danish National Patient Registry. RESULTS: Smoking, immune-mediated inflammatory diseases, exposure to PPIs, SSRIs, statins, and NSAIDs were significantly associated with MC in all Danish regions. The association between drug exposure and MC was weakest in the Capital Region of Denmark with an odds ratio of 1.8 (95% confidence interval [CI]: 1.61-2.01). The relative risk of undergoing a colonoscopy with biopsy was significantly increased in sex- and age-matched controls in all regions compared with controls from the Capital Region of Denmark, with the greatest risk found in the Region of Southern Denmark, 1.37 [95% CI: 1.26-1.50]. CONCLUSIONS: The cause of the regional differences in MC incidence in Denmark seems to be multifactorial, including variations in disease awareness and distribution of risk factors.

Occurrence of Colorectal Cancer and the Influence of Medical Treatment in Patients With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study, 1997 to 2015.

BACKGROUND: The risk of colorectal cancer (CRC) for patients with inflammatory bowel disease (IBD) has previously been investigated with conflicting results. We aimed to investigate the incidence and risk of CRC in IBD, focusing on its modification by treatment. METHODS: All patients with incident IBD (n = 35,908) recorded in the Danish National Patient Register between 1997 and 2015 (ulcerative colitis: n = 24,102; Crohn's disease: n = 9739; IBD unclassified: n = 2067) were matched to approximately 50 reference individuals (n = 1,688,877). CRC occurring after the index date was captured from the Danish Cancer Registry. Exposure to medical treatment was divided into categories including none, systemic 5-aminosalicylates, immunomodulators, and biologic treatment. The association between IBD and subsequent CRC was investigated by Cox regression and Kaplan-Meier estimates. RESULTS: Of the IBD patients, 330 were diagnosed with CRC, resulting in a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.03-1.28) as compared with the reference individuals. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the HR decreased to 0.80 (95% CI, 0.71-0.92). Patients with ulcerative colitis receiving any medical treatment were at significantly higher risk of developing CRC than patients with ulcerative colitis who were not given medical treatment (HR, 1.35; 95% CI, 1.01-1.81), whereas a similar effect of medical treatment was not observed in patients with Crohn's disease or IBD unclassified. CONCLUSIONS: Medical treatment does not appear to affect the risk of CRC in patients with IBD. The overall risk of developing CRC is significantly increased in patients with IBD as compared with the general population. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the elevated risk disappears.

Disease Activity Patterns, Mortality, and Colorectal Cancer Risk in Microscopic Colitis: A Danish Nationwide Cohort Study, 2001 to 2016.

BACKGROUND AND AIMS: The disease course of microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is not well known. In a Danish nationwide cohort, we evaluated the disease activity patterns as well as the risk of colorectal cancer [CRC] and mortality based on disease severity. METHODS: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] in the Danish Pathology Register, entered between 2001 and 2016, were matched to 10 reference individuals [n = 142 481]. Incident cases of CRC after the index date were captured from the Danish Cancer Registry. Mortality data were ascertained from the Danish Registry of Causes of Death, and information about treatment was obtained from the Danish National Prescription Registry. The risk of CRC and mortality analyses were investigated by Cox regression and Kaplan-Meier estimates. RESULTS: We identified a self-limiting or transient disease course in 70.6% of LC patients and in 59.9% of CC patients, p <0.001. Less than 5% of MC patients experienced a budesonide-refractory disease course and were treated with immunomodulators or biologic treatment. A total of 2926 [20.5%] MC patients and 24 632 [17.3%] reference individuals died during the study period. MC patients with a severe disease had a relative risk [RR] of mortality of 1.41 (95% confidence interval [CI]: 1.32-1.50) compared with reference individuals. Only 90 MC patients were diagnosed with CRC during follow-up, corresponding to an RR of 0.48 [95% CI: 0.39-0.60]. CONCLUSIONS: A majority of MC patients experience an indolent disease course with a lower risk of developing CRC compared with the background population.

Pregnant womens views on the timing of prophylactic antibiotics during caesarean delivery: A qualitative semi-structured interview study.

OBJECTIVE: To gain insight into pregnant women's preferences if given a choice between getting antibiotic prophylaxis before or after cord clamping during caesarean delivery. STUDY DESIGN: A qualitative semi-structured interview-study. The interviews were conducted at a Danish Hospital, with about 4000 deliveries a year. Fourteen individual semi-structured interviews were conducted with pregnant women, either considering or having a planned caesarean section, or scheduled for induction due to post-term gestational age. A systematic text condensation approach was used to analyze the transcribed interviews. RESULTS: Ten of the fourteen women favored antibiotic administration after cord clamping. Despite any adverse effects to the infant's microbiota and increased risk of long-term health outcomes were only hypothetical and the risk reduction in postpartum infections being well documented, they did not want to expose their offspring to antibiotics. Those who preferred antibiotic prophylaxis before cord clamping were concerned, if they would be able to care for the infant in case of a maternal infection. Three of the women preferring antibiotics after cord clamping said they would potentially change preference, if the maternal risk was higher. Most women preferred to be informed of the use of prophylactic antibiotic and that the timing has consequences for trans-placental exposure to the infant. CONCLUSIONS: With most of the interviewed women preferring antibiotic administration after cord clamping, we suggest patients should be involved in the decision regarding timing of prophylactic antibiotics before caesarean section.

Structured supervised exercise training or motivational counselling during pregnancy on physical activity level and health of mother and offspring: FitMum study protocol.

INTRODUCTION: A physically active lifestyle during pregnancy improves maternal and offspring health but can be difficult to follow. In Denmark, less than 40% of pregnant women meet physical activity (PA) recommendations. The FitMum study aims to explore strategies to increase PA during pregnancy among women with low PA and assess the health effects of PA. This paper presents the FitMum protocol, which evaluates the effects of structured supervised exercise training or motivational counselling supported by health technology during pregnancy on PA level and health of mother and offspring. METHODS AND ANALYSIS: A single-site three-arm randomised controlled trial that aims to recruit 220 healthy, pregnant women with gestational age (GA) no later than week 15 and whose PA level does not exceed one hour/week. Participants are randomised to one of three groups: structured supervised exercise training consisting of three weekly exercise sessions, motivational counselling supported by health technology or a control group receiving standard care. The interventions take place from randomisation until delivery. The primary outcome is min/week of moderate-to-vigorous intensity PA (MVPA) as determined by a commercial activity tracker, collected from randomisation until GA of 28 weeks and 0-6 days, and the secondary outcome is gestational weight gain (GWG). Additional outcomes are complementary measures of PA; clinical and psychological health parameters in participant, partner and offspring; analyses of blood, placenta and breastmilk samples; process evaluation of interventions; and personal understandings of PA. ETHICS AND DISSEMINATION: The study is approved by the Danish National Committee on Health Research Ethics (# H-18011067) and the Danish Data Protection Agency (# P-2019-512). Findings will be disseminated via peer-reviewed publications, at conferences, and to health professionals via science theatre performances. TRIAL REGISTRATION NUMBER: NCT03679130. PROTOCOL VERSION: This paper was written per the study protocol version 8 dated 28 August 2019.

[A ruptured ectopic pregnancy during early termination of pregnancy before ultrasound confirmation].

A new regimen for early termination of pregnancy does not require ultrasound confirmation of intrauterine pregnancy before mifepristone administration. This is a case report of a woman in her 30s, who was treated medically for unwanted pregnancy at five weeks and four days with a serum concentration of human chorionic gonadotropin of 859 U/l. As she was told to expect pain, she awaited follow-up appointment a week later, but before then she collapsed at home, and she was unconscious, when the emergency service arrived. In emergency surgery, 1.3 l of intra-abdominal blood and a right fallopian tube pregnancy were removed.

Incidence and Prevalence of Microscopic Colitis Between 2001 and 2016: A Danish Nationwide Cohort Study.

BACKGROUND AND AIMS: Epidemiological studies suggest an increasing global incidence of microscopic colitis, including collagenous colitis and lymphocytic colitis. We aimed to investigate the incidence and prevalence of microscopic colitis in Denmark. METHODS: In a nationwide cohort study, we included all incident patients with a recorded diagnosis of collagenous colitis or lymphocytic colitis in the Danish Pathology Register between 2001 and 2016. RESULTS: A total of 14 302 patients with microscopic colitis-8437 [59%] with collagenous and 5865 [41%] with lymphocytic colitis-were identified during the study period. The prevalence in December 2016 was estimated to be 197.9 cases per 100 000 inhabitants. Microscopic colitis was more prevalent among females (n = 10 127 [71%]), with a mean annual incidence of 28.8, compared with 12.3 per 100 000 person-years among males. The overall mean incidence during the study period was 20.7 per 100 000 person-years. Mean age at time of diagnosis was 65 years (standard deviation [SD]:14) for microscopic colitis, 67 [SD:13] for collagenous colitis, and 63 [SD:15] for lymphocytic colitis. The overall incidence increased significantly from 2.3 cases in 2001 to 24.3 cases per 100 000 person-years in 2016. However, the highest observed incidence of microscopic colitis was 32.3 cases per 100 000 person-years in 2011. Large regional differences were found, with the highest incidence observed in the least populated region. CONCLUSIONS: The incidence of microscopic colitis in Denmark has increased 10-fold during the past 15 years and has now surpassed that of Crohn's disease and ulcerative colitis. However, incidence has stabilised since 2012, suggesting that a plateau has been reached.