Association of Maternal Body Mass Index During Early Pregnancy With Offspring Lower Respiratory Infections: A Nationwide Cohort Study.

OBJECTIVE: To assess whether or to what extent maternal obesity during early pregnancy could increase the risk of offspring lower respiratory infections (LRI). STUDY DESIGN: This population-based cohort included 688,457 live singleton births born in Denmark between 2004 and 2016. The exposure was maternal body mass index (BMI) during early pregnancy, and the outcome was LRI in offspring. Cox regression models were used to estimate hazard ratios with their 95% confidence intervals (CI) for the association. We also performed subanalysis stratified by the LRI onset age, number of infection episodes before the age of 3, infection pathogens, infection sites, duration of hospital stay due to LRI and allergic constitution of children. RESULTS: A total of 64,725 LRIs in offspring were identified during follow-up. Maternal overweight (BMI 25.0-29.9 kg/m 2 ), moderate or severe obesity (BMI 30.0-39.9 kg/m 2 ) and very severe obesity (BMI ≥40 kg/m 2 ) were associated with a 7% (95% CI: 5%-9%), 16% (95% CI: 14%-19%) and 21% (95% CI: 13%-28%) increased risk of LRI in offspring, respectively. Higher maternal BMI was positively associated with earlier onset age, more episodes before the age of 3, and longer hospital stay of LRI in offspring. In addition, allergic constitution of offspring significantly enhanced the effect of maternal BMI on offspring LRI (44% increased risk, 95% CI: 5%-97% for very severe obesity). CONCLUSIONS: Maternal BMI during early pregnancy might be a risk factor for offspring LRI, especially in children with allergic constitution.

Social well-being and problematic school absence among Danish adolescents: A nationwide cross-sectional study.

AIM: Adolescents' well-being and school absence are important factors for public health. The aim of this study was to examine the association between social well-being and problematic school absence among Danish adolescents in the ninth grade, as well as to examine potential sex differences, using a large cohort of adolescents. METHODS: In this cross-sectional study, information on social well-being was obtained from the yearly Danish National Well-being Questionnaire mandatory in compulsory school. Data on school absence was obtained from the Ministry of Children and Education. The study population comprised 203,570 adolescents in the school years 2014/2015 to 2019/2020. The association between social well-being and problematic school-absence was analysed using logistic regression. A stratified analysis was made to investigate potential sex differences. RESULTS: A total of 17,555 (9.16%) adolescents had problematic school absence, defined as >10% illegal absence and/or sickness absence in the ninth grade. Adolescents with low social well-being had higher odds for having problematic school absence compared with adolescents with high social well-being, adjusted odds ratio=2.22 (95% confidence interval 2.10-2.34). When stratifying for sex, the association was strongest for girls. The results remained after adjustment for parents' educational level and family structure. CONCLUSIONS: Associations between adolescents' social well-being and problematic school absence were found, where girls had the strongest association. These findings might provide knowledge about social well-being as an important factor for problematic school absence, while underlining the importance of early focus and prevention, which is of importance for both the adolescents and society.

Association of intellectual disability with overall and type-specific cardiovascular diseases: a population-based cohort study in Denmark.

BACKGROUND: Individuals with mental health problems have been shown to have an increased risk of cardiovascular disorder (CVD), but little is known about the risk of early-onset CVD among those with intellectual disability. We aimed to investigate the association between intellectual disability and subsequent CVD, taking into consideration the severity of intellectual disability and neurodevelopmental and neurologic comorbidity. METHODS: This population-based cohort study used individual-level linked data from Danish national health registries. Participants were all live-born singletons born in Denmark during 1978-2016 (n = 2,288,393). Follow-up began from birth and continued until the onset of CVD, death, emigration, or December 31, 2018, whichever came first. Clinical diagnosis of any CVD or type-specific CVDs was identified in the Danish National Patient Register. Time-varying Cox regression analyses were used to estimate the hazard ratio (HR) of intellectual disability associated with overall and type-specific CVDs. RESULTS: A total of 11,954 individuals received a diagnosis of intellectual disability (7434 males and 4520 females). During a median follow-up time of 18.5 years (interquartile range, 18.1 years), 652 individuals with intellectual disability (5.5%) received a diagnosis of CVD (incidence rate, 2.4 per 1000 person-years), compared with 78,088 (3.4%) CVD cases in individuals without intellectual disability (incidence rate, 1.9 per 1000 person-years), corresponding to a HR of 1.24 (95% CI, 1.15-1.34). Increased risks of CVD were similar in both childhood (HR, 1.24; 95% CI, 1.08-1.43) and early adulthood (HR, 1.25; 95% CI, 1.14-1.38). For type-specific CVDs, intellectual disability was significantly associated with cerebrovascular disease (HR, 2.50; 95% CI, 2.02-3.10), stroke (HR, 2.20; 95% CI, 1.69-2.86), heart failure (HR, 3.56; 95% CI, 2.37-5.35), hypertensive disease (HR, 1.30; 95% CI, 1.22-1.39), and deep vein thrombosis (HR, 2.10; 95% CI, 1.60-2.75). Stratified HRs of overall CVD were 1.14 (95% CI, 1.01-1.30) for borderline/mild intellectual disability, 1.25 (95% CI, 1.01-1.54) for moderate intellectual disability, and 1.91 (95% CI, 1.47-2.48) for severe/profound intellectual disability. After the exclusion of individuals with neurodevelopmental and neurologic comorbidity, intellectual disability remained significantly associated with increased risks of CVD. CONCLUSIONS: Individuals with intellectual disability had increased risks of early-onset CVD, in particular, for cerebrovascular disease, stroke, heart failure, and deep vein thrombosis, and the risks also increased with the severity of intellectual disability. Our findings highlight the awareness of increased risks of CVD in intellectual disability patients.

Risk of malignancy following exposure to Epstein-Barr Virus associated infectious mononucleosis: A nationwide population-based cohort study.

Purpose: Epstein-Barr virus (EBV) infection has been shown to contribute to oncogenesis and often causes acute clinical manifestation of Infectious mononucleosis (IM). It is unknown whether IM could increase the risk of subsequent malignancies. We aimed to evaluate the association of IM caused by EBV (EBV-IM) with overall and subtypes of malignancy in a large population-based cohort study. Methods: This study included 1,419,407 individuals born in Denmark between 1973 and 2016 identified from national registers and 23,057 individuals had IM. The 5,394 of them had confirmed EBV-IM and they were birth date- and sex- matched (1:63) to 1,396,350 non-IM individuals. Cox regression was used to examine the associations of EBV-IM with malignancy. Results: Individuals with a history of confirmed EBV-IM had an 88% increased overall risk of malignancy (hazard ratio [HR]:1·88, 95% confidence interval [CI]: 1·42-2·49) and a five-fold risk of hematologic malignancies (HR 5·04, 95% CI: 3·07-8·25), compared to those without IM. Similar estimates were observed in the sibling analysis. The overall risk of malignancy was greater for EBV-IM with complications (HR 8·93, 95% CI: 3·35-23·81) than that for EBV-IM without complications (HR 1·35, 95% CI: 1·20-1·53). EBV-IM duration was related to increased risk of malignancy in a dose-response way. Notably, the significant elevated risk of overall malignancy was observed in the first two years after EBV-IM onset (rate ratio [RR] 4·44, 95% CI: 2·75-7·17) and attenuated thereafter. Conclusion: EBV-IM was associated with an increased risk in malignancy, particularly hematologic malignancies and in the first two years following IM exposure. Our findings suggest an important time-window for early screening of the EBV-attributed malignancy.

The association of asthma, atopic dermatitis, and allergic rhinitis with peripartum mental disorders.

BACKGROUND: Atopic diseases are characterized by dysregulated inflammatory response, which may incur the onset of peripartum mental disorders, but the impact remains unknown. This study examined whether and to what extent the history of atopic diseases is associated with newly onset peripartum mental disorders. METHODS: Using population-based registries, we identified all primiparous women who gave birth to live singletons in Denmark during 1978-2016 (n = 937,422). The exposure was hospital contact due to the three major types of atopic diseases-asthma, atopic dermatitis, and allergic rhinitis-before conception. The primary outcome was any hospital contact for mental disorder during pregnancy and 1-year postpartum, which was further classified into affective disorders, neurotic, stress-related and somatoform disorders, and substance abuse. The follow-up started from the date of conception and ended at the date of the first diagnosis of mental disorders, 1-year postpartum, death, emigration, or December 31, 2016, whichever came first. Cox regression was used, adjusted for calendar year, age at childbirth, education, residence, and Charlson comorbidity index. RESULTS: A total of 24,016 (2.6%) women received diagnosis of at least one of the three atopic diseases before conception (asthma, 1.7%; atopic dermatitis, 0.6%; and allergic rhinitis, 0.8%). Exposure to asthma, atopic dermatitis, or allergic rhinitis was associated with a 37% increased overall risk of peripartum mental disorders (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.27-1.49). Higher risks were observed among women with more frequent hospital contacts for atopic disease (HR, 1.80; 95% CI, 1.37-2.35; ≥5 times), and with recent hospital contacts for atopic disease (HR, 1.74; 95% CI, 1.48-2.06; within 2 years before conception). Specific associations were observed between asthma and neurotic, stress-related and somatoform disorders (HR, 1.40; 95% CI, 1.21-1.62), and between atopic dermatitis and substance abuse (HR, 1.62; 95% CI, 1.12-2.34). CONCLUSIONS: History of asthma, atopic dermatitis, and allergic rhinitis before conception was associated with increased risks of peripartum mental disorders. Women who have atopic diseases before pregnancy may benefit from systematic mental health monitoring.

Toward Machine-Learning-Based Decision Support in Diabetes Care: A Risk Stratification Study on Diabetic Foot Ulcer and Amputation.

Diabetes mellitus is associated with serious complications, with foot ulcers and amputation of limbs among the most debilitating consequences of late diagnosis and treatment of foot ulcers. Thus, prediction and on-time treatment of diabetic foot ulcers (DFU) are of great importance for improving and maintaining patients' quality of life and avoiding the consequent socio-economical burden of amputation. In this study, we use Danish national registry data to understand the risk factors of developing diabetic foot ulcers and amputation among patients with diabetes. We analyze the data of 246,705 patients with diabetes to assess some of the main risk factors for developing DFU/amputation. We study the socioeconomic information and past medical history of the patients. Factors, such as low family disposable income, cardiovascular disorders, peripheral artery, neuropathy, and chronic renal complications are among the important risk factors. Mental disorders and depression, albeit not as pronounced, still pose higher risks in comparison to the group of people without these complications. We further use machine learning techniques to assess the practical usefulness of such risk factors for predicting foot ulcers and amputation. Finally, we outline the limitations of working with registry data sources and explain potentials for combining additional public and private data sources in future applications of artificial intelligence (AI) to improve the prediction of diabetic foot ulcers and amputation.

Danish norms for the Strengths and Difficulties Questionnaire.

INTRODUCTION: The Strengths and Difficulties Ques-tion-naire (SDQ) is a brief well-validated psychometric instrument for assessment of developmental, behavioural and emo-tional problems in children and adolescents. Versions of the questionnaire covering the 2-17-year age range are an-swered by parents and by pedagogues or teachers. Also, a self-report version can be used from the age of 11 years. The SDQ is well-accepted by informants and is increasingly preferred both internationally and in Denmark for research and evaluation purposes. The questionnaire is also well-suited for clinical use, especially in the primary sector. However, no comprehensive set of Danish norms has been available before this study. METHODS: Data from an extensive survey in a Danish municipality was used to generate national norms for SDQ scores. These norms were compared with British and Nordic population data. RESULTS: Across informants, threshold values show some variation with age and often differ between sexes. Therefore, norms are provided both with and without gender stratification. Similarities as well as differences were found between the Danish norms and materials from other countries. The differences may, to some extent, be attributable to methodological issues. CONCLUSION: We expect that the availability of Danish SDQ norms will further stimulate the use of the instrument. FUNDING: TrygFonden provided financial support for the development of Danish SDQ norms. TRIAL REGISTRATION: not relevant.