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- Brew, Bronwyn K., et al.
(author)
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Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms
- 2022
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In: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047
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Research review (peer-reviewed)abstract
- It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
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2. |
- Rhedin, Samuel, et al.
(author)
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Risk factors for multisystem inflammatory syndrome in children – A population-based cohort study of over 2 million children
- 2022
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In: The Lancet Regional Health - Europe. - : Elsevier BV. - 2666-7762. ; 19
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Journal article (peer-reviewed)abstract
- Background: Although severe acute COVID-19 is rare in children, SARS-CoV-2 infection can trigger the novel post-infectious condition multisystem inflammatory syndrome in children (MIS-C). Increased knowledge on risk factors for MIS-C could improve our understanding of the pathogenesis of the condition and better guide targeted public health interventions. The aim of the study was to assess risk factors for MIS-C with the aim to identify vulnerable children. Methods: A register-based cohort study including all children and adolescents <19 years born in Sweden between March 1, 2001- December 31, 2020 was performed. Data on sociodemographic risk factors and comorbidities (sex, age, parental region of birth, parental education, asthma, autoimmune disease, chromosomal anomalies, chronic heart disease, chronic lung disease, obesity, life-limiting condition) were retrieved from national health and population registers. The outcome was MIS-C diagnosis according to the Swedish Pediatric Rheumatology Quality Register during March 1, 2020 – December 8, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis. Incidence rates per 100 000 person-years were calculated assuming a Poisson distribution. Findings: Among 2 117 443 children included in the study, 253 children developed MIS-C, corresponding to an incidence rate of 6·8 (95% CI: 6·0-7·6) per 100 000 person-years. Male sex (HR 1·65, 95% CI: 1·28-2·14), age 5-11 years (adjusted HR 1·44, 95% CI: 1·06-1·95 using children 0-4 years as reference), foreign-born parents (HR 2·53, 95% CI: 1·93-3·34), asthma (aHR 1·49, 95% CI: 1·00-2·20), obesity (aHR 2·15, 95% CI: 1·09-4·25) and life-limiting conditions (aHR 3·10, 95% CI: 1·80-5·33) were associated with MIS-C. Children 16-18 years had a reduced risk for MIS-C (aHR 0·45, 95% CI: 0·24-0·85). Interpretation: We report increased risks for MIS-C in children with male sex, age 5-11 years, foreign-born parents, asthma, obesity, and life-limiting condition. Knowing these risk populations might facilitate identification of children with MIS-C and potentially guide targeted public health interventions. Nevertheless, the absolute risks for MIS-C were very low. Funding: Financial support was provided from the Swedish Research Council (grant no 2018-02640), the Swedish Heart-Lung Foundation (grant no 20210416), the Asthma and Allergy Association, Ake Wiberg foundation, the Samariten Foundation, the Society of Child Care, and Region Stockholm.
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3. |
- Smew, Awad I.
(author)
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Epidemiological aspects of type 1 diabetes : early life origins, childhood comorbidities, and adult outcomes
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Type 1 diabetes is an autoimmune disease, often with onset during childhood, that requires lifelong insulin therapy due to the loss of pancreatic beta-cells. Several aspects of type 1 diabetes epidemiology remained to be explored and were the focus of this thesis. To begin, environmental risk factors in childhood play an important role in triggering the onset of disease, especially in genetically high-risk individuals but less was known of the early life origins related to maternal stress during pregnancy. Next, the comorbidity between type 1 diabetes and asthma or allergic diseases had long been debated but evidence stood inconclusive. Lastly, while many long-term outcomes of type 1 diabetes in adulthood had been demonstrated, the effect of glycaemic control on final adult height was not yet known. The aim of this thesis was therefore to address these knowledge gaps regarding epidemiological aspects of type 1 diabetes by investigating maternal depression or anxiety during pregnancy as a risk factor, furthering the understanding of the comorbidity with asthma or other allergic diseases, and examining the effect of glycaemic control on adult height. To study these associations on a population-based scale, linkages of healthcare and sociodemographic data from nationwide registers in Sweden were utilised alongside genetic information from the Swedish Twin Registry and clinical measurements from the National Diabetes Register. Paper I identified maternal depression or anxiety during pregnancy as a risk factor for offspring type 1 diabetes. The findings did not seem to be entirely explained by familial confounding from shared genes or environment. Paper II demonstrated the co-occurrence of asthma and type 1 diabetes in individuals, the importance of the sequential appearance of the diseases with previous asthma increasing the risk of subsequent type 1 diabetes, and the familial co-aggregation among full siblings and cousins pointing to the importance of shared familial factors. Paper III expanded on these findings by also displaying associations between type 1 diabetes and other allergic diseases (allergic rhinitis or eczema). Familial co-aggregation of allergic rhinitis and type 1 diabetes suggested a shared liability, in contrast to the lack of such associations for eczema. No signs of a large genetic overlap between type 1 diabetes and asthma or any other allergic disease were found. Paper IV uncovered differences in final adult height depending on glycaemic control in children and adolescents with type 1 diabetes. Having poor glycaemic control with a mean haemoglobin A1c >75 mmol/mol was associated with lower adult height in both males and females and an increased risk of short stature (adult height below -2 standard deviations) in males.
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4. |
- Smew, Awad I, et al.
(author)
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Limited association between markers of stress during pregnancy and fetal growth in 'Born into Life' : a new prospective birth cohort
- 2018
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In: Acta Paediatrica: Nurturing the Child. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 0803-5253 .- 1651-2227.
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Journal article (peer-reviewed)abstract
- Aims: We aimed to investigate the associations between perceived maternal stress or salivary cortisol levels during pregnancy and birthweight. Methods: In 2010-2012, we recruited 92 women living in Stockholm, Sweden, and followed them from before conception and through pregnancy and childbirth. Their Perceived Stress Scale (PSS) scores and salivary cortisol levels were collected at 26-28 gestational weeks. Birthweight was collected from medical records. Linear regression analyses and Pearson correlations were performed between the PSS scores or cortisol levels and birthweight, respectively, adjusted for gestational age. Results: No significant associations were found between PSS scores or cortisol levels and birthweight. There was a trend towards higher salivary cortisol levels among infants with lower birthweights, and this effect was attenuated after adjusting for gestational age. Morning cortisol levels (r = -0.31, p = 0.01), the decline in cortisol levels (r = -0.26, p = 0.03) and evening cortisol levels (r = -0.21, p = 0.09) were negatively correlated with PSS scores. Conclusion: Maternal stress during pregnancy was not associated with birthweight. The inverse correlation between PSS scores and cortisol levels may indicate other mechanisms for maternal stress on child outcomes than the previous explanation of hypothalamic-pituitary-adrenal axis activity.
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