Danish Reference Research Articles

Impact of sarcopenia and muscle strength on postoperative complication risk following pancreatic resection

Background and aimsThe association between sarcopenia and postoperative complications has been widely reported in patients with cancer. Yet, the lack of standardized population-specific diagnostic cut-off points and assessments of muscle strength is hampering prospective clinical utilization. Therefore, we aimed to examine the impact of sarcopenia, defined by both regional and international cut-off points, along with various methods of measuring skeletal muscle and muscle strength, on the risk of postoperative complications following pancreatic resection. MethodsThe present prospective observational study enrolled patients scheduled for pancreatic resection. Body composition was assessed by DXA and CT prior to surgery. We applied the algorithm and cut-off points suggested by the European Working Group on Sarcopenia in Older People (EWGSOP) as well as cut-off points from a Danish normative reference population to classify patients as sarcopenic. Physical performance was assessed by usual gait speed while muscle strength was assessed by handgrip strength, leg extensor power, and 30-second sit-to-stand. Postoperative complications within 30 days following surgery were classified according to the Clavien-Dindo classification and the American College of Surgeons National Surgical Quality Improvement Program. Complications graded ≥3 according to Clavien-Dindo were considered major complications. ResultsA total of 134 patients with a mean age of 67 years (SD: 9) were enrolled of whom most underwent pancreaticoduodenectomy (64%). Using international cut-off points, eight patients (7%) were classified as sarcopenic using CT scans and sarcopenia was associated with an increased risk of major postoperative complications (RR 2.14 [1.33-3.43]). Using DXA, four patients (3%) were classified as sarcopenic, all of whom experienced a major complication. With regional cut-off points, 16 patients (13%) were classified as sarcopenic using CT scans, but sarcopenia was not associated with major complications (RR 1.39 [0.80-2.42]). Nine patients (7%) were classified as sarcopenic using DXA, but sarcopenia was not associated with major complications (RR 1.15 [0.54-2.48]). Across the different muscle strength assessment methods, handgrip strength consistently demonstrated a stronger association with postoperative complications. ConclusionSarcopenia defined according to the EWGSOP criteria and with international cut-off points is associated with an increased risk of postoperative complications following pancreatic resection. Using regionally based cut-off points, the prevalence of sarcopenia is higher, but it does not confer a higher postoperative complication risk. The use of different muscle strength assessment methods results in vastly different estimates of prevalence of low strength and associations with postoperative outcomes.

P-780 Bone health in Danish children aged 7-10 years born after assisted reproductive technology with frozen and fresh embryo transfer

Abstract Study question Is bone health in children conceived after frozen embryo transfer (FET) different from children conceived after fresh embryo transfer (fresh-ET) and natural conception (NC)? Summary answer FET-children had higher bone mineral density (BMD) and bone mineral content (BMC) compared to fresh-ET-children. Insulin-like-growth-factor-I (IGF-I) levels and lean bodymass were similar between groups. What is known already Children conceived after assisted reproductive technology (ART) with FET have a higher average birthweight (BW) and increased risk of being born large-for-gestational-age (LGA) while children born after fresh-ET are more often born small-for-gestational-age (SGA). In general, BW is a determinant of BMD and BMC in childhood with LGA being associated with higher BMD and BMC compared to children born appropriate-for-gestational-age. The relationship between BW and BMD and BMC may be mediated by IGF-I levels and lean bodymass as IGF-I is an important regulator of muscle and bone development. Bone health in children born after ART is scarcely explored. Study design, size, duration This study was part of the large Danish cohort study “Health in Childhood following Assisted Reproductive Technology” (HiCART) which included 606 singletons (292 boys) born in Denmark between 2009 and 2013. The children were conceived after FET (n = 200), fresh-ET (n = 203) and NC (n = 203) and matched for birth year and sex. The study examinations were performed from January 2019 to September 2021. Participants/materials, setting, methods The children underwent a clinical examination at 7-10 years of age with anthropometric measurements, pubertal staging, a fasting blood sample and a whole-body dual-energy x-ray absorptiometry-scan (DXA). Anthropometric measurements and circulating growth factors were converted to standard deviation scores (SDS) using Danish reference material. The study groups were compared pairwise using univariate linear regression and multiple linear regression adjusting for relevant confounders including sex, age, puberty, maternal pregestational BMI, breastfeeding and BW (SDS). Main results and the role of chance Children conceived after FET had significantly higher BW (SDS) (mean, SD: 0.20 SDS, 1.09) compared to children conceived after fresh-ET (-0.22 SDS, 1.00), mean difference: 0.42 SDS (95% CI: 0.21; 0.62) and NC (-0.16 SDS, 1.09), mean difference: 0.35 SDS (95% CI: 0.14; 0.57). In the adjusted model, children born after FET had significantly higher total BMD (g/cm2) (mean difference 0.01, 95% CI: 0.00; 0.03) and size-adjusted BMC (BMC/height, g/m) (mean difference 0.21, 95% CI: 0.01; 0.40) compared to children born after fresh-ET. There was no significant difference in total BMD or BMC/height when comparing FET and fresh-ET to NC children, respectively. There was a trend towards higher lean bodymass (g) in children born after FET and lower lean bodymass in children born after fresh-ET compared to NC children, however this did not reach the level of significance. IGF-I (SDS), IGF-binding-protein-3 (SDS) and serum calcium (mmol/L) levels were comparable between the groups. In the entire cohort, there was a significantly positive correlation between BW (SDS) and size-adjusted BMC (BMC/height, g/m) (b: 0.21, 95% CI: 0.14; 0.27) and total lean bodymass (g) (b: 755, 95% CI: 531; 978), while a significantly negative correlation with IGF-I (SDS) (b: -0.07, 95% CI: -0.13; -0.01). Limitations, reasons for caution The study was powered to detect a clinically relevant difference in BMI (SDS), the primary outcome. Hence, secondary analyses are exploratory by nature. We have no information regarding endometrial preparation protocol in the FET-cycles which may bias the results. Multiple testing may increase our risk of type I errors. Wider implications of the findings Reassuringly, BMD and size-adjusted BMC in children born after ART with FET and fresh-ET were comparable to NC children. Potential determinants of BMD and BMC (IGF-I and lean bodymass) were also similar. Increased BMD and size-adjusted BMC in FET compared to fresh-ET suggests that the different BW-profiles play a role. Trial registration number NCT03719703

Mental health and BMI in children and adolescents during one year in obesity treatment

BackgroundMental health plays a major role in children and adolescents with obesity. The aim of this study was (1) to compare mental health in children with obesity with the background population and (2) to investigate if mental health changed during one year in an obesity treatment program.MethodsData on self-reported mental health was collected in 107 children and adolescents (mean age 13.2 years) with obesity at first visit in an obesity treatment program and at one year follow-up (n = 47). Mental health was assessed by eight questions from the Danish Health Behaviour in School-aged Children (HBSC) questionnaire: (1) self-rated health (2) life satisfaction (3) feeling low (4) body-image (5) loneliness (6) self-esteem (7) self-efficacy and (8) social competence. Data was compared to a reference population based on HBSC data. BMI-SDS was based on Danish reference values.ResultsChildren and adolescents with obesity had significantly higher odds of reporting negative body image and feeling low and lower odds of reporting high self-rated health and high self-esteem compared to a reference population. There was no difference between the groups regarding life-satisfaction, social competence, self-efficacy or feeling lonely. There were no significant changes in mental health from first visit to one-year follow-up.ConclusionOur findings highlight the mental health difficulties in children and adolescents with obesity, and the importance of addressing these issues in obesity treatment. The results also indicate that children with obesity have psychosocial resources that should be exploited in treatment protocols.

Health-Related Quality of Life in Danish Cancer Survivors Referred to a Late Effects Clinic: A Prospective Cohort Study.

The Region of Southern Denmark has recently established four late effects clinics to help cancer survivors suffering from complex and severe late effects. This study aimed to capture and analyze the full range of physical, mental, and psychosocial issues using patient-reported outcomes. Moreover, we aimed to describe demographic data and the type and severity of the late effects. A prospective cohort study was conducted among cancer survivors referred to a late effects clinic. Before their first appointment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). We compared mean scores of the EORTC QLQ-SURV100 scales that were comparable to the scales/items from the EORTC QLQ-C30 questionnaire with norm data for the Danish population and EORTC reference values. All patients referred to the clinic within its first 2 years were included (n = 247). The mean age was 57 [23-85] years and 74% were females. The most common cancer diagnoses was breast cancer (39%). The five most commonly reported late effects were fatigue (66%), pain (51%), cognitive impairment (53%), sleep problems (42%), and neuropathy (40%). A total of 236 of the patients entering the clinic completed QLQ-SURV100. They reported significantly worse mean scores on all scales compared to the Danish norm population and EORTC reference values for pretreatment cancer patients, p < 0.001. Effect sizes were moderate or large for all scales. In this study, we collected demographic data and described the late effects presented by the patents referred to the clinic. Moreover, we captured and analyzed the full range of physical, mental, and psychosocial issues using QLQ-SURV100. Patients referred to the Late Effects Clinic (LEC) had a number of late effects and reported a significantly lower health-related quality of life compared to the general Danish population and patients who have just been diagnosed with cancer, suggesting the aim of helping patients suffering from late effects gain a better quality of life is in dire need.

Population curation: The construction of mutual obligation between individual and state in Danish precision medicine.

How do precision medicine initiatives (re)organize relations between individuals and populations? In this article, we investigate how the curation of national genomic populations enacts communities and, in so doing, constructs mutual obligation between individuals and the state. Drawing on ethnographic fieldwork in the Danish National Genome Center (DNGC), we show how members of advisory bodies negotiated the inclusion criteria for two different genomic populations: a patient genome population and an envisioned 'Danish' reference genome population. The patient genome population was curated through a politics of inclusion, of as many genomes as possible, whereas the reference genome was to be curated through a politics of exclusion, to include only the genomes of 'ethnic' Danes. These two data populations configure differently the community of 'Danish patients' who might benefit from precision medicine, and thereby prescribe different moral continuities between person, state, and territory. We argue that the DNGC's patient genome population reinforces reciprocal relations of obligations and responsibility between the Danish welfare state and all individuals, while the proposed Danish reference genome population privileges the state's commitment to individuals with biographical-territorial belonging to the nation-state. Drawing on scholarship on social and health citizenship, as well as data solidarity in the Nordics, the discussion shows how population curation in national precision medicine initiatives might both construct and stratify political obligation. Whereas STS scholarship has previously deconstructed the concept of 'population', in the context of the troubling and violent effects of the management of human populations, we point to the importance of population curation as a vehicle for making the individual legible as part of a community to which the state is responsible and for which it is committed to care.

DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design.

Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: The Odense Child Cohort

BackgroundSelenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. Methods719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. Results155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 μg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 μg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. ConclusionsThe results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

Climate data for moisture simulations: producing a Danish moisture reference year and comparison with previously used reference year locations

Buildings comprise of complex systems, and various materials in combination. Different materials have different expected service life, and degradation processes start as soon as a building is put into operation. Degradation processes are often accelerated with the presence of moisture. To build robust and moisture safe buildings, hygrothermal simulations are used to predict hygrothermal conditions in constructions, and especially areas of risk. Simulations are useful tools for prediction of moisture accumulation, and results can further help predict the risk of moisture damage, i.e., frost damage or mould growth. The external climate can therefore have a significant impact on the service life of constructions. Due to the lack of a sufficient Danish climate reference year, including precipitation, hygrothermal simulations of Danish constructions are currently performed with either Danish climate data without precipitation (primarily for energy and indoor climate conditions), or with climate data from closest locations in either Sweden or Germany which include rain. Therefore, a complete Danish reference year, including precipitation, will inevitably enhance the value of hygrothermal simulations of buildings in Denmark. This paper presents the method used to develop full climate datasets based on Danish conditions, including precipitation. To integrate the climate datasets in the hygrothermal simulation programs, the climate datasets contain the following parameters: temperature, relative humidity, wind direction and speed, solar radiation, rain, as well as estimations for cloud cover and longwave radiation based on the other climate parameters. The climate datasets generated and presented in this paper, represent a Typical Meteorological Year (TMY), without extreme events, generated according to EN ISO 15927-4:2006. The climate datasets are based on Danish climate data from the period 2001-2019, provided by the Danish Meteorological Institute, DMI. By prioritizing climate parameters, and through statistical analysis, representative 1-year reference climate datasets were generated based on Danish climate conditions. The climate parameters of the 1-year reference climate datasets are compared with the traditionally used Swedish and German datasets, and a Danish Design Reference Year (DRY) from 1995.

A randomized clinical trial of sex and population-specific troponin cutoffs for ruling out acute MI - the danish study of sex and population-specific cutoffs of troponin (DANSPOT)

Abstract Background Measurements of high-sensitivity cardiac troponin (cTn) T/I are used as the gold standard and are the preferred biomarkers to diagnose acute myocardial infarction (MI) in conjugation with symptoms and changes in the ECG. The URL is based on the 99th percentile of troponin concentrations in a healthy reference population. Currently, a sex-uniform manufacturer provided 99th percentile URL of troponin is utilized at Danish hospitals as a diagnostic cutoff for acute MI for both men and women. Reportedly, healthy men have twofold the troponin level compared to healthy women, suggesting that the use of a uniform URL for troponins may lead to the under-diagnostication of acute MI in women and potentially over-diagnostication in men. Purpose The purpose of the DANSPOT study is to evaluate the clinical effect on diagnosis, treatment and outcomes in men and women presenting with acute MI of implementing international guidelines recommended sex-specific 99th percentile URLs for troponin into clinical practice. Methods First, to determine the sex-specific 99th percentile URLs of troponins (table) based on a healthy Danish reference population, blood samples from Danish blood donors, were analyzed using five high-sensitivity (hs) cTn assays (Siemens Atellica and Vista hs-cTnI, Roche hs-cTnT, Abbott Alinity hs-cTnI and Orthos VITROS hs-cTnI). Second, the DANSPOT study is a nationwide cluster-randomized trial with "stepped-wedge" design (figure) with participation of 22 Danish hospital center. With one-month intervals, each of the 22 centers have been randomized to shift from the presently applied sex-uniform 99th percentile URL of troponin to the population and sex-specific 99th percentiles URLs. First center started implementing the new 99th percentiles URLs on April 1, 2022, and the last center is planned to enroll on January 1, 2024. Patients are followed up in Danish registries for 12 months after index admission. The primary endpoint is a composite of myocardial infarction, unplanned revascularization (after index admission) and all-cause mortality and is calculated for the cohort of women and men with ≥2 measurements of troponin within the first 24 hours of admission with maximal troponin level between the new sex-specific 99th percentile URLs and the old sex-uniform 99th percentile URL. Perspective The clinical significance of sex-specific 99th percentile URLs of troponin is poorly investigated and for the same reason not yet implemented in Denmark or many other countries. With the implementation of population and sex-specific 99th URLs of troponin, we expect to detect significantly more women with acute MI, theoretically resulting in a more accurate diagnosis and treatment of women and men with acute MI. This would be guideline-defining for implementing sex-specific cutoffs for troponin in Denmark as well as internationally as recommended in guidelines by professional cardiological societies.Schematic presentation of study designTable of the new 99th percentiles of cTn

Abstract 12724: High Health-Related Quality of Life Among Survivors of Out-of-Hospital Cardiac Arrest: A Nationwide Survey From 2001-2019

Background: Survival after out-of-hospital cardiac arrest has increased over the past two decades. However, little is known about the health-related quality of life of long-term survivors. Purpose: We conducted a nationwide survey to examine the long-term quality of life of out-of-hospital cardiac arrest survivors from 2001-2019. Methods: The study included all out-of-hospital cardiac arrest patients from the Danish Cardiac Arrest Registry between 2001-2019 who were alive in October 2020. Health-related quality of life was evaluated using the EuroQol health questionnaire (EQ-5D), SF-12 Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS). Results: Of the 4,545 survivors, 2,552 (56.1 %) completed the survey. Respondent and non-respondent age was comparable (67 vs. 68 years). The median EQ-index score for survivors who had been alive for 0-1 year was 0.8 (Q1-Q3: 0.7-1.0), while survivors who had been alive for 15-20 years had a median EQ-index score of 0.9 (0.8-1.0). These scores were comparable to a Danish reference population, whose mean EQ-index score was 0.9 (SD: 0.16). Mean standardized SF-12 physical health score was 40.6 (SD: 12.7) for 0-1 year survivors vs. 44.4 (SD: 11.8) for &gt;15-20-year survivors, and the SF-12 mental health score was 53.1 (SD: 8.4) vs. 54.1 (SD: 8.7), respectively. Both scores were comparable to a Danish reference population. In terms of symptoms of anxiety, 73% of survivors who had been alive for 0-1 year reported a normal score (score ≤ 8), compared to 89.3% of survivors who had been alive for 15-20 years. For symptoms of depression, the percentages were 79.7% and 87.5%, respectively (Figure 1). Health-related quality of life was similar for survivor groups &gt;1-2, &gt;2-4, &gt;4-6, &gt;6-8, &gt;8-10, and &gt;10-15 years after arrest. Conclusion: Short-term as well as long-term survivors of out-of-hospital cardiac arrest generally reported high health-related quality of life after the event, regardless of the time elapsed since the arrest.

The younger the better: importance of age in treatment of childhood obesity

Children living with obesity are prevalent worldwide. It is an established finding that many children who start a lifestyle intervention tend to leave prematurely. The aim of this study was to identify characteristics in children with obesity who prematurely leave a lifestyle intervention. The cohort study includes children living with obesity aged 4–17, treated in a Danish family-centered lifestyle intervention between 2014 and 2017. Data were collected from patient records. BMI-SDS was calculated using an external Danish reference population and multivariable regression analysis was used to answer the research question. Of the 159 children included, 64 children who left the intervention within the first 1.5 years were older compared to those who stayed in the intervention (10.2 years ± 2.9 vs 11.5 years ± 3.1, p = 0.005). Older participants (> 66.6th percentile) had a shorter treatment duration (489 days) compared to the youngest (190 days 95% CI: 60; 320, p = 0.005) and middle third (224 days 95% CI: 89; 358, p = 0.001). Additionally, an inverse association was found between duration of treatment and age at baseline (−31 days, 95% CI (−50; −13), p = 0.001). Conclusion: The risk of leaving a lifestyle intervention prematurely was primarily dependent on the age of the participants, emphasizing the importance of including children early in lifestyle interventions.What is Known:•Lifestyle interventions for childhood obesity that are shorter in duration often lead to short-term weight reductions only. Limited knowledge exists on why some children prematurely leave these interventions.What is New:•This study observes a solid inverse correlation and association between age and time spent in the interventions, when treating childhood obesity. We hereby suggest age as an important determinant for the adherence to lifestyle interventions and emphasize the importance of treatment early in life.

Long-Term Quality of Life After Out-of-Hospital Cardiac Arrest

Allocating resources to increase survival after cardiac arrest requires survivors to have a good quality of life, but long-term data are lacking. To determine the quality of life of survivors of out-of-hospital cardiac arrest from 2001 to 2019. This survey study used the EuroQol Health Questionnaire, 12-Item Short Form Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) to assess the health-related quality of life of all adult survivors of out-of-hospital cardiac arrest included in the Danish Cardiac Arrest Registry between June 1, 2001, and August 31, 2019, who were alive in October 2020 (follow-up periods, 0-1, >1-2, >2-4, >4-6, >6-8, >8-10, >10-15, and >15-20 years since arrest). The survey was conducted from October 1, 2020, through May 31, 2021. All patients who experienced an out-of-hospital cardiac arrest. Self-reported health was measured using the EuroQol Health Questionnaire index (EQ index) score and EQ visual analog scale. Physical and mental health were measured using the SF-12, and anxiety and depression were measured using the HADS. Descriptive statistics were used for the analysis. Of 4545 survivors, 2552 (56.1%) completed the survey, with a median follow-up since their event of 5.5 years (IQR, 2.9-8.9 years). Age was comparable between responders and nonresponders (median [IQR], 67 [58-74] years vs 68 [56-78] years), and 2075 responders (81.3%) were men and 477 (18.7%) women (vs 1473 male [73.9%] and 520 female [26.1%] nonresponders). For the shortest follow-up (0-1 year) and longest follow-up (>15-20 years) groups, the median EQ index score was 0.9 (IQR, 0.7-1.0) and 0.9 (0.8-1.0), respectively. For all responders, the mean (SD) SF-12 physical health score was 43.3 (12.3) and SF-12 mental health score, 52.9 (8.3). All 3 scores were comparable to a general Danish reference population. Based on HADS scores, a low risk for anxiety was reported by 73.0% (54 of 74) of 0- to 1-year survivors vs 89.3% (100 of 112) of greater than 15- to 20-year survivors; for symptoms of depression, these proportions were 79.7% (n = 59) and 87.5% (n = 98), respectively. Health-related quality of life was similar in survivor groups across all follow-up periods. Among this survey study's responders, who comprised more than 50% of survivors of out-of-hospital cardiac arrest in Denmark, long-term health-related quality of life up to 20 years after their event was consistently high and comparable to that of the general population. These findings support resource allocation and efforts targeted to increasing survival after out-of-hospital cardiac arrest.

O-200 Cardiometabolic health in Danish children aged 7-10 years born after assisted reproductive technology with frozen and fresh embryo transfer

Abstract Study question Is cardiometabolic health in children conceived after frozen embryo transfer (FET) different from children conceived after fresh embryo transfer (fresh-ET) and natural conception (NC)? Summary answer FET-children had similar anthropometrics, glucose- and lipid profile in childhood compared to fresh-ET and NC. Blood pressure was higher in FET-girls compared to fresh-ET-girls. What is known already Children conceived after assisted reproductive technology (ART) with FET are more often born large-for-gestational age (LGA) while children born after fresh-ET are at risk of being small-for-gestational age (SGA).In general, children born LGA or SGA are at increased risk of obesity, diabetes and cardiovascular disease later in life. Smaller studies on the whole ART-population have raised concerns about premature vascular aging, increased risk of insulin resistance and higher blood pressure. The long-term cardiometabolic health of children born after ART and especially FET is scarcely explored. Study design, size, duration This study was part of the large cohort study “Health in Childhood following Assisted Reproductive Technology” (HiCART) which included 606 singletons (292 boys) born between December 2009 and December 2013: 200 children were conceived after FET; 203 children were conceived after fresh-ET; and 203 children were conceived naturally and matched for birth year and sex. The study period lastet from January 2019 to September 2021. Participants/materials, setting, methods The children were 7-10 years of age at examination and underwent a clinical examination with anthropometric measurements, pubertal staging and blood pressure measurement. Furthermore a whole-body dual-energy x-ray absorptiometry-scan (DXA) was performed and a fasting blood sample was drawn. Anthropometric measurements and blood pressure were converted to standard deviation scores (SDS) using a Danish reference. The three study groups were compared pairwise using univariate linear regression model. Main results and the role of chance Data is presented as mean (SD). Children conceived after FET had significantly higher birth weight (SDS) (0.20 SDS (1.09)) compared to children conceived after fresh-ET (-0.22 SDS (1.00), mean difference: 0.42 SDS (95% CI: 0.21; 0.62)) and NC-children (-0.16 SDS (1.09), mean difference: 0.35 SDS (95% CI: 0.14; 0.57)). At 7-10 years height (SDS), weight (SDS) and BMI (SDS) were similar between the groups. Fat percentage (DXA) and waist-to-height ratio were also comparable between the groups. Markers of glucose metabolism were similar in the groups including fasting glucose, C-peptide, HbA1c and insulin resistance (HOMA-IR). Lipid profiles including, cholesterol, LDL and HDL were also similar. Blood pressure was comparable between the three groups, but stratified on sex girls conceived after FET had significantly higher systolic blood pressure (SDS) (0.75 SDS (0.84)) compared to girls concieved after fresh-ET (0.49 SDS (0.61), mean difference: 0.25 SDS (95% CI: 0.05; 0.45)) and significantly higher diastolic blood pressure (SDS) (FET: 0.54 SDS (0.57), fresh-ET: 0.38 (0.58), mean difference: 0.16 SDS (0.00; 0.31)). Puberty had started in 17% of the girls, equally distributed in the three groups. Limitations, reasons for caution As the participation rate was between 18-42% in the three groups, selection bias cannot be excluded. We currently do not have information regarding endometrial preparation protocol in the FET-cycles which may bias the results. Due to multiple testing type I errors cannot be excluded. Wider implications of the findings Higher birth weight in children conceived after FET did not translate into differences in anthropometrics, glucose- or lipid profile in children ages 7-10 years. However, the higher systolic- and diastolic blood pressure (SDS) found in girls concieved after FET compared to fresh-ET is of concern and should be further explored. Trial registration number NNF18OC0034092, NFF19OC0054340

Childhood BMI after ART with frozen embryo transfer.

Does BMI at 7-10 years of age differ in children conceived after frozen embryo transfer (FET) compared to children conceived after fresh embryo transfer (fresh-ET) or natural conception (NC)? BMI in childhood does not differ between children conceived after FET compared to children conceived after fresh-ET or NC. High childhood BMI is strongly associated with obesity and cardiometabolic disease and mortality in adulthood. Children conceived after FET have a higher risk of being born large for gestational age (LGA) than children conceived after NC. It is well-documented that being born LGA is associated with an increased risk of obesity in childhood, and it has been hypothesized that ART induces epigenetic variations around fertilization, implantation, and early embryonic stages, which influence fetal size at birth as well as BMI and health later in life. The study 'Health in Childhood following Assisted Reproductive Technology' (HiCART) is a large retrospective cohort study with 606 singletons aged 7-10 years divided into three groups according to mode of conception: FET (n = 200), fresh-ET (n = 203), and NC (n = 203). All children were born in Eastern Denmark from 2009 to 2013 and the study was conducted from January 2019 to September 2021. We anticipated that the participation rate would differ between the three study groups owing to variation in the motivation to engage. To reach the goal of 200 children in each group, we invited 478 in the FET-group, 661 in the fresh-ET-group, and 1175 in the NC-group. The children underwent clinical examinations including anthropometric measurements, whole-body dual-energy x-ray absorptiometry-scan, and pubertal staging. Standard deviation scores (SDS) were calculated for all anthropometric measurements using Danish reference values. Parents completed a questionnaire regarding the pregnancy and the current health of the child and themselves. Maternal, obstetric, and neonatal data were obtained from the Danish IVF Registry and Danish Medical Birth Registry. As expected, children conceived after FET had a significantly higher birthweight (SDS) compared to both children born after fresh-ET (mean difference 0.42, 95% CI (0.21; 0.62)) and NC (mean difference 0.35, 95% CI (0.14; 0.57)). At follow-up (7-10 years), no differences were found in BMI (SDS) comparing FET to fresh-ET, FET to NC, and fresh-ET to NC. Similar results were also found regarding the secondary outcomes weight (SDS), height (SDS), sitting height, waist circumference, hip circumference, fat, and fat percentage. In the multivariate linear regression analyses, the effect of mode of conception remained non-significant after adjusting for multiple confounders. When stratified on sex, weight (SDS), and height (SDS) were significantly higher for girls born after FET compared to girls born after NC. Further, FET-girls also had significantly higher waist, hip, and fat measurements compared to girls born after fresh-ET. However, for the boys the differences remained insignificant after confounder adjustment. The sample size was decided in order to detect a difference of 0.3 SDS in childhood BMI (which corresponds to an adult cardiovascular mortality hazard ratio of 1.034). Thus, smaller differences in BMI SDS may be overlooked. As the overall participation rate was 26% (FET: 41%, fresh-ET: 31%, NC: 18%), selection bias cannot be excluded. Regarding the three study groups, many possible confounders have been included but there might be a small risk of selection bias as information regarding cause of infertility is not available in this study. The increased birthweight in children conceived after FET did not translate into differences in BMI, however, for the girls born after FET, we observed increased height (SDS) and weight (SDS) compared to the girls born after NC, while for the boys the results remained insignificant after confounder adjustment. Since body composition in childhood is a strong biomarker of cardiometabolic disease later in life, longitudinal studies of girls and boys born after FET are needed. The study was funded by the Novo Nordisk Foundation (grant number: NNF18OC0034092, NFF19OC0054340) and Rigshospitalets Research Foundation. There were no competing interests. ClinicalTrials.gov identifier: NCT03719703.

Improved Real-Time Quaking Induced Conversion for Early Diagnostics of Creutzfeldt–Jakob Disease in Denmark

Cerebrospinal fluid-based real-time quaking-induced conversion (CSF RT-QuIC) is currently the most prominent method for early detection of sporadic Creutzfeldt-Jakob disease (sCJD), the most common prion disease. CSF RT-QuIC delivers high sensitivity (>90%) and specificity (100%), which has been demonstrated by large ring-trial studies testing probable and definitive sCJD cohorts. Following the inclusion of CSF RT-QuIC in the revised European CJD Surveillance Network diagnostic criteria for sCJD, it has become a standard diagnostic procedure in many prion disease reference or surveillance centers around the world. In this study, we present the implementation of the second-generation CSF RT-QuIC (commonly known as Improved QuIC or IQ) at the Danish Reference Center for Prion Diseases (DRCPD). The method's sensitivity and specificity were evaluated and validated by analyzing 63 CSF samples. These 63 samples were also analyzed at the National CJD Research and Surveillance Unit (NCJDRSU), based at the University of Edinburgh, UK; analysis was carried out using the first generation or previous CSF RT-QuIC method (PQ). The sensitivity and specificity of PQ during tests at the NCJDRSU were 92% and 100%, respectively. Using these 63 CSF samples, the agreement between the two RT-QuIC generations at DRCPD and NCJDRSU prion laboratories was 100%.

The Danish newborn standard and the International Fetal and Newborn Growth Consortium for the 21st Century newborn standard: a nationwide register-based cohort study

It is a matter of debate whether 1 universal standard, such as the International Fetal and Newborn Growth Consortium for the 21st Century standard, can be applied to all populations. The primary objective was to establish a Danish newborn standard based on the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard to compare the percentiles of these 2 standards. A secondary objective was to compare the prevalence and risk of fetal and neonatal deaths related to small for gestational age defined by the 2 standards when used in the Danish reference population. This was a register-based nationwide cohort study. The Danish reference population included 375,318 singletons born at 33 to 42 weeks of gestation in Denmark between January 1, 2008, and December 31, 2015. The Danish standard cohort included 37,811 newborns who fulfilled the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard. Birthweight percentiles were estimated using smoothed quantiles for each gestational week. The outcomes included birthweight percentiles, small for gestational age (defined as a birthweight of 3rd percentile), and adverse outcomes (defined as either fetal or neonatal death). At all gestational ages, the Danish standard median birthweights at term were higher than the International Fetal and Newborn Growth Consortium for the 21st Century standard median birthweights: 295g for females and 320 g for males. Therefore, the estimates of the prevalence rate of small for gestational age within the entire population were different: 3.9% (n=14,698) using the Danish standard vs 0.7% (n=2640) using the International Fetal and Newborn Growth Consortium for the 21st Century standard. Accordingly, the relative risk of fetal and neonatal deaths among small-for-gestational-age fetuses differed by SGA status defined by the different standards (4.4 [Danish standard] vs 9.6 [International Fetal and Newborn Growth Consortium for the 21st Century standard]). Our finding did not support the hypothesis that 1 universal standard birthweight curve can be applied to all populations.

Health and wellbeing in refugee families from Syria resettled in Denmark

AimsThe aim was to evaluate self-reported health status and wellbeing in a well-defined group of refugee families from Syria 2–4 years after resettlement in Denmark, and, where possible, compare it with a Danish reference population. The purpose was to determine the need for specialized health care to resettled refugees. MethodsThis cross-sectional study involved 90 individuals from Syria aged 13–56 years. We used questionnaire survey to assess the general health and wellbeing in the study population in relation to a Danish reference population. Objective measurements of selected health indicators like overweight, hypertension and levels of cholesterol and blood glucose (HbA1c) were also determined for the study population. ResultsMean wellbeing scores and the proportion of study participants rating their health as good were lower among the study participants compared with the Danish population for all age groups. The proportion of participants who reported often being alone against their will was significantly higher than among Danes, as was the proportion who had nobody to talk to when having problems. A significantly higher proportion of participants experienced various forms of pain or discomfort than in the Danish population. Overall, 23.6% and 3.4% of participants had elevated cholesterol and HbA1c levels, respectively, and the prevalence of overweight (BMI ≥ 25) was 70%. Hypertension was more frequent (16.2%) than in another refugee population in Denmark (9%). ConclusionsThe study demonstrated various mental and physical health challenges among the Syrian refugee families, and their health and wellbeing appeared to be substantially poorer as compared to the Danish reference population. The findings emphasize the need for systematic and specialized health care services at a municipality level to resettling refugees as a prerequisite for the refugees to become contributing citizens.

Proof of concept - using prospective hybrid MFA-LCA to evaluate the environmental implications of Circular Economy using a case study of wood

Consistent evaluations of impacts induced by implementation of Circular Economy (CE) design processes and solutions within the built environment, necessitates decision-support tool development/advancement, as CE does not allow for business-as-usual assessments only. A preliminary test of concept that seeks to quantify the environmental implications of CE on a case study of wood, is presented here.The core methodology is based on coupling of the Shared Socioeconomic Pathways (SSPs) with Material Flow Analysis (MFA) and consequential Life Cycle Assessment (cLCA). Applying this novel approach, a prospective consequential hybrid MFA-LCA analysis was initiated, to evaluate the mitigation challenges of CE design processes, through different formalized and generally accepted (i.e. consensus) scenarios.The case study is based on Danish reference buildings, meeting the current building regulations, designed to replace conventional building materials with wood. This “wood approach” for test of concept case study, is chosen due to the increasing interest in wood construction.The development and calibration of a prospective model for different building material consumptions will further illuminate the connection between the to-be generated emissions and the marginal productions of the materials in question, under specific sets of societal development scenarios.

Lung function in Lolland-Falster Health Study (LOFUS).

BackgroundCOPD prevalence in Denmark is estimated at 18% based on data from urban populations. However, studies suggest that using the clinical cut‐off for airway obstruction in population studies may overestimate prevalence. The present study aims to compare estimated prevalence of airway obstruction using different cut‐offs and to present lung function data from the Lolland‐Falster Health Study, set in a rural‐provincial area.MethodsDescriptive analysis of participant characteristics and self‐reported respiratory disease and of spirometry results in the total population and in subgroups defined by these characteristics. Airway obstruction was assessed using previously published Danish reference values and defined according to either FEV1/FVC below lower limit of normal (LLN) 5% (as in clinical diagnosis) or 2.5% (suggested for population studies), or as FEV1/FVC < 70%.ResultsUsing either FEV1/FVC < 70% or LLN 5% cut‐off, 19.0% of LOFUS participants aged 35 years or older had spirometry, suggesting airway obstruction. By the LLN 2.5% criterion, the proportion was considerably lower, 12.2%. The prevalence of airway obstruction was higher among current smokers, in participants with short education or reporting low leisure‐time physical activity and in those with known respiratory disease. Approximately 40% of participants reporting known respiratory disease had normal spirometry, and 8.7% without known respiratory disease had airway obstruction.ConclusionPrevalence of airway obstruction in this rural population was comparable to previous estimates from urban Danish population studies. The choice of cut‐off impacts the estimated prevalence, and using the FEV1/FVC cut‐off may overestimate prevalence. However, many participants with known respiratory disease had normal spirometry in this health study.

O-086 Assisted reproductive technology does not influence body mass index (BMI) in a cohort of 606 children aged 6-9 years

Abstract Study question Is BMI in children conceived after frozen embryo transfer different from children conceived after fresh embryo transfer and after natural conception? Summary answer BMI in children conceived after frozen embryo transfer was similar to BMI in children conceived after fresh embryo transfer or children born after natural conception. What is known already Children conceived after frozen embryo transfer (FET) have higher risk of being born large for gestational age (LGA) than children conceived after natural conception (NC). Generally, being born LGA increases the risk of obesity in childhood. Childhood BMI is strongly associated with obesity and cardiometabolic disease and mortality in adulthood. The long-term effects of ART on the metabolic health of the offspring and the underlying mechanisms are scarcely explored. However, it has been proposed that ART may induce epigenetic variations around fertilization, implantation, and early embryonic stages that may influence size at birth. Study design, size, duration The study “Health in Childhood following Assisted Reproductive Technology” (HiCART) includes 606 singletons (292 boys, 314 girls) – 200 conceived after FET; 203 after fresh-ET; and a random sample of 203 naturally conceived children matched for age and sex. All children were born in Eastern Denmark from 2009-2013 and had a clinical examination performed at the Copenhagen University Hospital - Rigshospitalet when they were 6-9 years of age. Participants/materials, setting, methods The children underwent a clinical examination with anthropometric measurements, whole-body dual-energy x-ray absorptiometry-scan (DXA), pubertal staging, and a blood sample. All anthropometric measurements were converted to standard deviation scores (SDS) using a Danish reference. Parents filled in a questionnaire regarding the pregnancy and the current health of the child and themselves. Maternal, obstetric and neonatal data from the national ART and birth registry were obtained. Main results and the role of chance Children conceived after FET had higher birthweight SDS (0.20SDS, 1.09SD) than children conceived after fresh-ET (-0.22SDS, 1.00SD), p &amp;lt; 0.001 and children conceived naturally (-0.16SDS, 1.09SD), p = 0.001. Mothers conceiving naturally were younger and had higher parity than mothers conceiving after ART. The three groups were similar regarding pregestational maternal BMI and gestational age. Puberty had started in 57 children (54 girls), evenly distributed among the groups. There were no differences in height SDS between FET (0.25SDS, 1.00SD) compared to fresh-ET (0.17SDS, 0.96SD), p = 0.50 and compared to NC (0.07 SDS, 1.06SD), p = 0.11 or in weight SDS between FET (0.22SDS, 1.07SD) compared to fresh-ET (0.10 SDS, 1.06SD), p = 0.22 and compared to NC (0.14SDS, 1.00SD), p = 0.43. Similarly, no differences were found in BMI SDS between FET (0.16SDS, 1.16SD) compared to fresh-ET (0.04SDS, 1.10SD), p = 0.25 and compared to NC (0.20SDS, 1.01SD), p = 0.80. Our primary endpoint BMI SDS remained non-significant after adjustment for child sex, age and birthweight SDS, parity, maternal BMI and smoking in pregnancy. Limitations, reasons for caution The sample size was decided to be able to detect a difference of 0.3 SDS in childhood BMI, corresponding to a 3.4% increased mortality hazard. Thus, smaller differences in BMI SDS may be overlooked. As the participation rate was between 18-42% in the three groups, selection bias cannot be excluded. Wider implications of the findings The increased birth weight in children conceived after FET did not translate into a difference in BMI in this large cohort. Since BMI in childhood is a strong biomarker of cardiometabolic disease later in life, the findings are reassuring and may reduce concerns associated with the long-term consequences of FET. Trial registration number NCT03719703