CONTEXT:An increased risk of birth defects in children born to mothers with hyperthyroidism has been found, and uncertainties prevail on the role of maternal thyroid function and thyroid autoimmunity. OBJECTIVE:To evaluate the association between maternal thyroid function, thyroid autoantibodies, and birth defects. METHODS:Retrospective cohort study of 20 399 pregnant women with no known thyroid disease and their children from the Danish National Birth Cohort and the North Denmark Region Pregnancy Cohort. Blood samples from early pregnancy (median week 10) were assessed for maternal TSH and free T4 in both cohorts and for thyroid peroxidase antibodies and thyroglobulin antibodies as well as TSH receptor antibodies and thyroid stimulating immunoglobulin in the North Denmark Region Pregnancy Cohort. Information on birth defects was retrieved from hospital diagnoses. RESULTS:Altogether 702 children (3.4%) had birth defects, and maternal median TSH (no birth defects: 1.13 mIU/L; birth defects: 1.19 mIU/L; P = .1) and free T4 (no birth defects: 15.5 pmol/L; birth defects: 15.7 pmol/L; P = .3) did not differ by outcome of birth defect. The prevalence of birth defects was similar in children born to mothers who were thyroid peroxidase antibodies- or thyroglobulin antibodies-positive (4.3%) or negative (4.0%; P = .6) but higher (9.5%) when the mother was positive for TSH receptor antibodies or thyroid stimulating immunoglobulin (P = .003). CONCLUSION:In a large Danish pregnancy cohort, no evidence was found that maternal thyroid function in early pregnancy is associated with a risk of birth defects. A possible link with maternal thyroid stimulating antibodies warrants further investigation.

INTRODUCTION:Brown adipose tissue (BAT) thermogenesis is mediated by sympathetic nervous system activation and enhanced by thyroid hormones via upregulation of uncoupling protein 1. Studying thyroid hormone response to cooling in populations with habitual cold exposure may give new insights to the role of thyroid hormones in non-shivering thermogenesis. METHODS:Twenty-one participants (11 Greenlanders, 10 Danes) underwent a cross-over protocol with experimental sessions of cooling and thermal comfort, followed by [18F]FDG positron emission tomography/computed tomography scans. Serial blood samples were collected to assess thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4), and thyroglobulin (Tg) before, during, and after cooling. RESULTS:Cooling induced an increase in TSH (Danes: 0.24 mIU/L, P < .001; Greenlanders: 0.15 mIU/L, P = .009). TT3 also increased in response to cooling (Danes: 0.15 nmol/L, Greenlanders: 0.09 nmol/L, Pboth < .001). Greenlanders had lower TSH and higher TT3 levels compared to Danes (baseline 0.27 nmol/L, P = .009) with an attenuated TT3 response to cooling (-0.07 nmol/L, P  =  .009). The T3/T4 ratio was elevated during cold exposure compared to thermoneutral conditions in both Danes (P < .001) and Greenlanders (P = .022), and Greenlanders had consistently higher T3/T4 ratios compared to Danes (baseline, P = .001; after cooling, P = .023). Finally, Tg levels were higher in participants with low- compared to high-BAT volume (7.27 µg/L, P = .008). CONCLUSION:Serial measurements of thyroid hormones and thyroglobulin with gold-standard detection of BAT activity documented distinct thyroid responses to cooling. The findings suggested a physiological preparedness to acute cold exposure in individuals with cold adaptation, irrespective of origin.

CONTEXT:Brown adipose tissue (BAT) is a thermogenic tissue that converts energy into heat in response to cold exposure, and is therefore a promising target for improving cardiometabolic health. Habitually cold-exposed Arctic people represent a unique model of metabolic adaptation to cold. OBJECTIVE:We investigated cold-induced BAT activation in Greenlanders in comparison to Danes. METHODS:A comparative crossover study was conducted of 13 Greenlanders and 11 Danes, with 2 experimental sessions conducted 2 weeks apart: A, a thermoneutral session; and B, a cooling session. BAT volume and activity were assessed using 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging. Serial measurement of metabolic markers associated with BAT activity was performed by blood sampling. RESULTS:Both for Greenlanders and Danes, core temperature decreased 0.5 °C during cooling, and the volume of active BAT increased, yet with a higher increase in active BAT volume of 16 917% in Greenlanders compared to 4541% in Danes (P = .046). Marked differences in glucose levels were seen in Greenlanders and Danes in response to cooling (Danes: 0.30 mmol/L, P = .013; Greenlanders: 0.16 mmol/L, P = .12), insulin (Danes: 2.43 pmol/L, P = .32; Greenlanders: 6.65 pmol/L, P = .001), triglycerides (Danes: -0.59 mmol/L, P < .001; Greenlanders: -0.16 pmol/L, P = .21), and total cholesterol (Danes: 0.39 mmol/L, P < .001; Greenlanders: 0.02 mmol/L, P = .89). CONCLUSION:The larger increase in BAT activity in response to cooling and the dampened response in metabolic parameters in Greenlanders compared to Danes leads to a hypothesis of preparedness for rapid thermogenic response to cold exposure in populations with active BAT.

Context Hyperthyroidism caused by Graves' disease (GD) should be treated in pregnancy to prevent maternal and fetal complications; however, side effects observed with antithyroid drugs (ATDs) may complicate current clinical management. Objective To investigate current treatment practices for hyperthyroidism during pregnancy in Denmark and the characteristics of women receiving ATDs. Methods The Danish multicenter study PRETHYR (Pregnancy Investigations on Thyroid Disease) included women with GD and women treated with ATDs in pregnancy. Maternal characteristics, preconception measurements of TSH, total T3, and TSH-receptor antibodies, and information on the clinical management and treatment before and during pregnancy, were obtained through patient questionnaires and review of the medical record. Results Of the 121 women included, 97.5% had GD. Among the 102 women with known thyroid disease preconceptionally and no prior definitive treatment, 58.8% (n = 60) received ATDs in pregnancy. These women were more often managed by endocrinologist at conception, had lower preconception TSH, and higher total T3 and TSH-receptor antibodies compared to women not treated with ATDs. Treatment was predominantly confined to the first half of the first trimester and generally discontinued by the second or third trimester. Before conception, 59.1% of women treated with methimazole were switched to propylthiouracil, and 10.7% were switched from propylthiouracil to methimazole. Conclusion This is the first report from a multicenter study on pregnant women with GD and women treated with ATDs during pregnancy. The results provide insight into the current clinical treatment practices of hyperthyroidism in Denmark.

OBJECTIVE:Hypothyroidism may be detrimental when left undiagnosed, but universal testing of pregnant women is hitherto not implemented. We studied the implementation of a laboratory-guided universal screening model to detect hypothyroidism in pregnant women. DESIGN:A prospective implementation study in the North Denmark Region during a 2-year period (2022-2024). SETTING:Serum residues of blood samples drawn from Danish pregnant women as part of prenatal screening for chromosomal anomalies in early pregnancy (median the 10th week) were used for measurement of thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase, and thyroglobulin antibodies (TPO-Ab and Tg-Ab) upon arrival in the laboratory. Results were clinically reported only if maternal TSH in the sample was above 6 mIU/L, and thyroid disease was not known. Overt/subclinical hypothyroidism was defined by fT4 below/within the method- and trimester-specific reference interval (10.2-15.2 pmol/L). RESULTS:A total of 11 841 samples were screened from 10 403 pregnant women (median age of 30 years). Unknown maternal TSH above 6 mIU/L was identified in 41 women (0.39%) of whom 32 had overt and 9 had subclinical hypothyroidism. Thyroid-stimulating hormone ranged from 6.1 to 59.4 mIU/L and was above 10 mIU/L in 19 women. All screen-positive cases had detectable TPO-Ab and/or Tg-Ab, and the general practitioner was immediately informed for specialist referral and treatment. CONCLUSIONS:This prospective study tested implementation of a universal screening model to detect maternal hypothyroidism in pregnancy. Clinical implementation was feasible, and 0.4% of Danish pregnant women were found to be screen positive, all with detectable thyroid autoantibodies, indicative of autoimmune hypothyroidism.

OBJECTIVE:Subacute thyroiditis (SAT) is a differential diagnosis in the clinical care of hypo- and hyperthyroid patients, but large-scale population data on the incidence, patient characteristics, and outcome are limited. Thus, the aim was to determine the incidence of SAT in the Danish population and to characterise patient demographics and the risk of permanent hypothyroidism. DESIGN:Retrospective cohort study based on Danish nationwide health registers. PATIENTS:Individuals diagnosed with SAT at Danish hospitals from 1995 to 2016, covering the years before and after the implementation of mandatory iodine fortification in Denmark as of July 2000. MEASUREMENTS:Annual incidence rates of SAT were calculated overall and by geographical region (East and West Denmark). The development of permanent hypothyroidism following SAT was evaluated based on redeemed prescriptions of levothyroxine (L-T4) within a 4-year follow-up period. RESULTS:A total of 1763 individuals were identified with a diagnosis of SAT among 1,747,168 individuals at risk. The overall nationwide incidence increased from 3.3/100,000 individuals (95% confidence interval (CI): 2.5-4.4) in 1995 to 6.2/100,000 individuals (95% CI: 5.1-7.6) in 2016, with no regional difference (p = 0.18). Follow-up showed that 459 of 1763 patients with SAT (26.0%) started treatment with L-T4, and in 224 of these patients (48.7%), the duration of L-T4 treatment exceeded 36 months. CONCLUSIONS:In a Danish nationwide cohort, the incidence of SAT increased during a 22-year period without geographical difference. Notably, the frequency of long-term L-T4 treatment was high, emphasising a focus on the post-diagnosis management of patients with SAT.

Background:Dehydration-specifically hyperosmolar dehydration (HD)-in adults is a common clinical condition affecting an estimated 25%-58% of adults admitted to the hospital, depending on the method used to assess HD and the patient group. HD is defined as low total body water and increased serum osmolality over 300 mOsm/kg. Hypernatremia, increased blood urea nitrogen (BUN)/creatinine ratio, and calculated serum osmolarity are often used as proxy markers. The condition is associated with an increased risk of a range of complications, including increased morbidity and mortality. Despite the high prevalence, current treatment guidelines often fail to distinguish HD from hypovolemia. As a result, HD is often treated like hypovolemia with fluids containing isotonic saline rather than hypotonic fluids. Objective:The objective of this review is to identify and summarize existing studies on the treatment of HD in adults and to map the current evidence, highlight gaps in the literature and guide future research. Methods:The planned review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search will be conducted in MEDLINE (PubMed), Embase (Ovid), Scopus, and the Cochrane Central Register of Controlled Trials, with additional examination of reference lists and citations (backward snowballing) and a search for completed trials based on found protocols (forward snowballing). Original studies of any design focusing on adult patients with a suspected low total body water and biochemically-confirmed HD receiving treatment for HD will be included. Studies will be excluded if: conducted on a non-adult population, no diagnoses of HD, focusing solely on hypovolaemia, or conducted in a non-hospital setting. Data charting will contain study characteristics, participant demographics, details of HD diagnosis, treatment approaches, and reported outcomes. Relevant information from the included studies will be reported in a narrative summary, supported by descriptive analyses of quantitative data where appropriate. Results:The primary search was completed in September 2025. An updated search will be performed before the completion of the review. As of April 2026, data extraction using Covidence on the relevant studies found in the primary search has been completed. Conclusions:This scoping review will provide an overview of the current evidence on the treatment of HD in patients referred to hospital, identifying key insights and evidence gaps to inform future research.

The global population is ageing, contributing to an increase in frailty and increasing pressure on healthcare and rehabilitation systems. The Clinical Frailty Scale (CFS) may be used as a triage tool to guide important clinical decisions and to set goals for care. This study aimed to translate and test the inter-rater reliability and feasibility of CFS for Greenland (CFS-GL), including its relation to demographic factors. CFS-GL was developed under The International Society for Pharmacoeconomics and Outcomes Research guidelines (ISPOR) to ensure conceptual, cultural and linguistic equivalence with translation. The inter-rater reliability was tested using two independent Greenlandic healthcare professionals and a Danish healthcare professional. The data were evaluated using Cohen's kappa and ANOVA. CFS-GL was assessed among 169 participants with a median age of 73 years (interquartile range [IQR] 14). The participants' residences were scattered across Greenland. Inter-rater reliability was very high, with a combined Cohen's kappa of 0.98 (95% CI 0.97-0.99). The median CFS-GL score was 3.9. CFS-GL was associated with residential living, marital status, alcohol intake, outdoor activity, number of medications taken and chronic diseases but was only moderately associated with age. In conclusion, CFS-GL is now available and reliable for Greenland. Future contextual adaptations could improve CFS-GL by detailing Greenlandic activities.

Background : Low physical activity levels and sedentary behaviour during hospitalisation increase risk of functional decline, and adverse outcomes for medical inpatients. Increasing inpatients’ physical activity and reducing sedentary behaviour can be challenging in a busy hospital setting. Digital nudging and feedback using real-time data from wearable accelerometers may help promote in-hospital activity and improve recovery for patients. Aim : To determine whether a digital nudging intervention, targeting patients and staff, increases daily average physical activity (minutes/day) among adult medical inpatients compared with usual care. Secondly, an embedded qualitative study aims to explore the healthcare staff’s experience with the intervention and explore their perspectives on its usability in and impact on practice. Methods : This trial will be a stepped wedge cluster randomised multicentre trial, in which medical inpatients from four hospital clusters, across the Kingdom of Denmark, sequentially will receive a digital nudging intervention. All participants’ activity levels (control and intervention group) will be measured with wearable accelerometers. The intervention involves real-time activity feedback to patients and staff regarding patients’ physical activity levels during hospitalisation. In the qualitative study, healthcare staff from all four sites will attend focus group interviews. The primary outcome is daily average minutes of physical activity. Secondary outcomes include daily minutes of sedentary behaviour, readmission, and length of stay. Target sample size is 400 patients, powered to detect a between-group difference of ≥38 minutes activity/day. Data will be collected at enrolment (<48 hours of admission to ward), during hospitalisation, at discharge, and 90 days post-discharge. Discussion : By testing a digital intervention on a multicentre scale, this trial seeks to change the paradigm of inactivity during hospitalisation, making physical activity and reduction of sedentary behaviour integral to hospital care. We aim to address multiple factors, that are known to impact inpatient mobilisation, by implementing a relatively simple digital intervention aimed at both patients and staff. The findings will inform best practices for patientcare and culture regarding inpatient physical activity in medical wards. Trial registration : Clinicaltrials.gov: NCT06983977. Prospectively registered May 14 th , 2025. Date of first recruitment: May 19 th , 2025. Ethics approvals have been obtained in all three countries.

BACKGROUND:Evidence regarding thyroid function changes with ageing remains inconsistent and the implications of potential changes are unclear. We aimed to investigate ageing-related thyroid function changes and their associations with mortality. METHODS:In this individual participant data (IPD) analysis, prospective population-based cohorts were eligible for inclusion when data on thyroid function measurements and mortality were available in individuals aged 18 years and older. Eligible datasets were identified through a systematic search of PubMed. We excluded cohorts of participants with only thyroid disease or thyroid-altering medications, or pregnant individuals. We requested data from all eligible cohorts that agreed to participate in the study. Linear mixed models were used to investigate associations between age and thyroid function, stratified for sex and regional iodine status. Annual changes in thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were estimated per individual and categorised into quintiles, with the highest and lowest quintiles defined as increasing and decreasing, respectively, and the rest as stable. Patterns of thyroid function change were identified based on combined TSH and FT4 evolution. We used cohort-stratified Cox models to assess associations between changing patterns and all-cause mortality. This study is registered with PROSPERO, CRD42023408086. FINDINGS:In this IPD analysis, we analysed data collected between Jan 1, 2011, and Oct 13, 2022, from 31 cohorts across Europe (n=19), the USA (n=5), Asia (n=3), Brazil (n=2), and Australia (n=2; 137 488 participants; 68 322 [49·7%] were female and 69 166 [50·3%] were male; median age 60 years [range 18-106]). Cross-sectionally, older age was associated with higher TSH in iodine-sufficient regions and with lower TSH in iodine-insufficient regions. Longitudinal analyses showed that TSH increased with increasing age regardless of iodine status. The overall increase in TSH from age 18 years to 100 years was 0·61 mIU/L (0·52 SD) for female participants and 0·99 mIU/L (0·76) for male participants from iodine-sufficient regions. Greater variability in population distribution and longitudinal TSH changes was observed in adults aged 65 years or older. Higher FT4 with older age was suggested cross-sectionally, but longitudinally FT4 increased in iodine-sufficient regions and decreased in iodine-insufficient regions. Compared with stable thyroid function, all changing patterns were associated with increased all-cause mortality: hazard ratios of 1·80 (95% CI 1·57-2·06) for increasing TSH with stable or decreasing FT4; 2·45 (2·01-2·97) for increasing TSH and increasing FT4; 2·45 (1·99-3·01) for decreasing TSH with decreasing FT4; and 1·94 (1·68-2·24) for decreasing TSH with stable or increasing FT4. INTERPRETATION:Ageing-related changes in thyroid function varied by sex and iodine status. Most individuals had stable thyroid function during ageing with a slight increase in TSH, although older adults displayed greater variability. Patterns of changing thyroid function were associated with an increased all-cause mortality risk, warranting further exploration of the underlying mechanisms and clinical management. FUNDING:None.

Thyroid hormones are involved in the regulation of haemostasis, and it has been hypothesised that abnormal levels of thyroid hormones are associated with an increased risk of excessive bleeding. However, this association is yet to be investigated in pregnant women. We performed a retrospective nationwide cohort study of Danish pregnant women from 1999 to 2015. Information on maternal hyperthyroidism and hypothyroidism diagnosed before/during or after the pregnancy, as well as outcomes of bleeding in early and late pregnancy, was collected via the Danish nationwide health registers on hospital diagnoses and drug prescriptions. Multivariate logistic regression was used to calculate adjusted odds ratio (aOR) with a 95

PURPOSE:Dehydration is common among those admitted to hospital with delirium or dementia and may itself contribute to cognitive impairment. Agitated behaviors are also common in such patients and may lead to difficulty in maintenance of peripheral IV cannulas. In this paper, we examine the potential advantages and drawbacks of subcutaneous (SC) compared with intravenous (IV) hydration in patients with cognitive impairment and mild-to-moderate dehydration. METHODS:We reviewed and summarized the available literature on SC versus IV hydration in patients with cognitive impairment and the impact on agitation and cannula maintenance in particular. RESULTS:Compared with IV hydration, SC hydration is faster to establish and associated with fewer adverse effects. A meta-analysis of randomized controlled trials found that SC hydration in patients with cognitive impairment results in a lower risk of agitation (relative risk 0.40 [95% CI 0.22-0.72]) compared with IV hydration. Furthermore, there is an 80% reduced risk of catheter dislodgment. It is likely that the reduced risk of agitation and catheter dislodgment is causally related to the fact that subcutaneous access is less traumatic approach for a population at high risk for agitation. CONCLUSION:SC hydration has many advantages and few disadvantages for those with mild-to-moderate dehydration and cognitive impairment who need parenteral hydration. It should, in our opinion, always be considered in this population. It is important, however, that ease of use does not lead to overuse, especially where low-intake dehydration may represent part of the natural course of advanced illness.

OBJECTIVES:To evaluate the efficacy of perturbation-based balance training (PBT) in reducing falls, injurious falls, and fall risk factors in older adults. DESIGN:Systematic review and meta-analysis. SETTING AND PARTICIPANTS:Community-dwelling older adults (aged 65 years and older). METHODS:PubMed, CINAHL, EMBASE, and Cochrane databases were searched from inception to June 2024. Randomized controlled trials assessing the effects of PBT on falls or fall risk factors, including reactive balance via laboratory-induced perturbations, were included. Two reviewers independently screened studies and extracted data. Meta-analyses were conducted using a random-effects model, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS:PBT significantly reduced fall rates by 23% (rate ratio, 0.77; 95% CI, 0.60-0.99; I2 = 57%, low certainty) and injurious falls by 24% (rate ratio, 0.76; 95% CI, 0.58-0.98; I2 = 0%) compared with controls. PBT improved reactive balance (eg, lab-induced falls) but had limited effects on other fall risk factors (eg, gait). In the dosage subgroup analysis, only PBT programs for at least 6 hours reduced falls by 33%. CONCLUSIONS AND IMPLICATIONS:PBT reduces falls and related injuries, likely through enhanced reactive balance rather than physical improvements. While most PBT programs are low doses (∼2 hours), higher doses (6+ hours) likely offer greater fall protection. Further high-quality trials using accessible PBT methods are required to inform policy and guideline development and support scalable implementation of PBT in fall-prevention strategies.

Immune checkpoint inhibitor (ICI) therapy is used in the management of advanced malignancies. Thyroid function abnormalities have been reported, but more evidence is needed to substantiate the subtypes and course of thyroid disease associated with this treatment. A 51-year-old woman with metastatic pancreatic cancer and no previous history of autoimmune disease was referred to the Endocrine Department six days after the initiation of combined treatment with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). At the initial endocrinologic assessment, the patient had biochemical overt thyrotoxicosis with suppressed thyroid stimulating hormone < 0.01 mIU/L (reference range (RR), 0.3–4.5 mIU/L), elevated total thyroxine (TT4) > 309 nmol/L (> 24.0 µg/dL) (RR, 60–140 nmol/L; 4.7–10.9 µg/dL), and total triiodothyronine (TT3) 7.0 nmol/L (454.5 ng/dL) (RR, 1.1–2.5 nmol/L; 71.4–162.3 ng/dL). Despite marked biochemical thyrotoxicosis, the patient presented with few symptoms. TSH-receptor antibodies (TRAb) were negative, as were thyroid peroxidase antibodies, whereas elevated levels of thyroglobulin antibodies were found. Thyroid ultrasound revealed an enlarged, heterogeneous hypoechoic gland with increased vascularity. High-dose antithyroid drug (ATD) therapy were followed by a decline in thyroid hormone levels (after one week of treatment: TT4: >309 nmol/L (> 24.0 µg/dL); TT3: 1.8 nmol/L (116.9 ng/dL); after two weeks: TT4: 164 nmol/L (12.7 µg/dL); TT3: 0.9 nmol/L (58.4 ng/dL)). After five weeks, the patient developed biochemical hypothyroidism. Thus, ATD therapy was discontinued, and levothyroxine was initiated. This case report illustrates with a short time frame from the initiation of ICI therapy the onset of thyrotoxicosis, followed by the development of thyroid insufficiency. This case highlights the challenges associated with subtyping the cause of thyroid dysfunction in patients treated with ICIs. Further, this case highlights the importance of clinical awareness and close monitoring of thyroid function in patients receiving immunotherapy.

Dehydration—specifically hyperosmolar dehydration (HD)—in adults is a common clinical condition associated with increased morbidity, mortality, and hospital admissions. Despite these alarming statistics, current treatment guidelines often fail to distinguish HD from other types of low body fluid status (e.g. hypovolaemia). This review aims to explore the existing evidence on treatment and to identify gaps in the evidence to guide future research The objective is to identify and summarize existing studies on treatment of dehydration in adults and to map the current evidence, highlight gaps in the literature and guide future research. The planned review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search will be performed across major peer-reviewed databases, with additional examination of reference lists and citations. Original studies of any design concerning treatment for HD in adults, specifically involving treatment with oral, subcutaneous, or intravenous fluids for dehydration, will be included. Data charting will contain study characteristics, participant demographics, details of HD diagnosis, treatment approaches, and reported outcomes. The findings from the included studies will be reported through a narrative summary, supported by descriptive analysis of quantitative data if suitable. This scoping review will provide an overview of the current evidence on the treatment of HD in patients referred to hospital, identifying key insights and evidence gaps to inspire future research areas. The protocol will be registered at Open Science Framework? https://osf.io/ym65x

Brown adipose tissue (BAT) is essential for non-shivering thermogenesis, a key survival mechanism for Arctic populations exposed to chronic cold. As BAT dissipates energy as heat, it presents a potential target for improving cardiometabolic health and treating obesity. The Arctic Inuit represents a unique metabolic model due to distinct genetic and environmental adaptations. This study advances methods in cardiometabolic research by investigating BAT activation in Arctic Inuit and ethnic Danes under cold exposure. A comparative crossover study of 20 Inuit and Danes includes two sessions: (A) thermal comfort and (B) 2 hours of individualised cooling. Each session concludes with fat biopsies and [18F]FDG-PET/CT scans to quantify BAT activity and volume. Additional measures include blood sampling and infrared thermography (IRT). The cooling protocol and biological sampling are designed to capture key metabolic signatures of BAT activation, enabling detailed insight into thermogenic function and its cardiometabolic implications. PET/CT scans contribute valuable insights into metabolic processes and the ethical considerations balance the benefit of unique insight against radiation risk. Given limitations in accessibility and radiation exposure, this study also evaluates IRT as a low-risk, accessible alternative to PET/CT scans. This methodological advancement supported approval by the North Denmark Region ethics committee (N-20220042). As [18 F]FDG-PET/CT is not available in Arctic Greenland, data collection was conducted in Denmark with an accessible Inuit population. The study forms part of a broader study on climate and health, approved by the ethics committee for Greenland.

Objective:Hypothyroidism in pregnant women has been linked to deviations in birth weight, but associations are not consistent and the role of confounding factors, including maternal body mass index (BMI), is not clear. This study aimed to evaluate the association between maternal hypothyroidism, birth weight of the child, and placental weight. Methods:This was a retrospective register-based study of singleton live births in Denmark from 2004 to 2015 (n = 694,734). Small for gestational age (SGA) (<10th percentile), large for gestational age (LGA) (>90th percentile), and placental weight Z-scores were defined according to gestational week at birth and sex of the child. Associations were evaluated using logistic and linear regression, adjusting for potential confounders, which included maternal BMI. Results:Altogether, 9.8 and 9.9% of pregnant women with no diagnosis of hypothyroidism gave birth to SGA and LGA children. The frequency of SGA was higher among children whose mothers were newly diagnosed with hypothyroidism in pregnancy (12.4%; adjusted odds ratio (aOR) = 1.16 (95% confidence interval (CI): 1.00-1.34)), but not LGA (9.3%; aOR = 1.03 (95% CI: 0.87-1.21)). Children born to mothers with treated hypothyroidism in pregnancy did not have higher frequencies of SGA (aOR = 0.94 (95% CI: 0.86-1.03)) or LGA (aOR = 1.06 (95% CI: 0.98-1.14)). No association between maternal hypothyroidism and placental weight Z-score was found (adjusted beta coefficient: 0.004 (95% CI: -0.016; 0.024)). Conclusions:The findings from a large Danish cohort point toward an association between hypothyroidism in pregnancy and lower birth weight of the child, whereas no association with placental weight was found.