Pre-eclampsia and risk of early-childhood asthma: A register study with sibling comparison and an exploration of intermediate variables

Background: We aimed to study whether pre-eclampsia is associated with childhood asthma, allergic and non-Allergic asthma, accounting for family factors and intermediate variables. Methods: The study population comprised 779 711 children born in 2005-2012, identified from Swedish national health registers (n = 14 823/7410 exposed to mild/moderate and severe pre-eclampsia, respectively). We used Cox regression to estimate the associations of mild/moderate and severe pre-eclampsia with incident asthma, before and after age 2 years. Cox regressions were controlled for familial factors using sibling comparisons, then stratified on high and low risk for intermediate variables: caesarean section, prematurity and small for gestational age. We used logistic regression for allergic and non-Allergic prevalent asthma at 6 years as a measure of more established asthma. Results: The incidence of asthma in children was 7.7% (n = 60 239). The associations varied from adjusted hazard ratio (adjHR) 1.11, 95% confidence interval (CI): 1.00, 1.24 for mild/moderate pre-eclampsia and asthma at >2 years age, to adjHR 1.78, 95% CI: 1.64, 1.95 for severe pre-eclampsia and asthma at <2 years age. Sibling comparisons attenuated most estimates except for the association between severe pre-eclampsia and asthma at <2 years age (adjHR 1.45, 95% CI: 1.10, 1.90), which also remained when stratifying for the risk of intermediates. Mild/moderate and severe pre-eclampsia were associated with prevalent non-Allergic (but not allergic) asthma at 6 years, with adjusted odds ratio (adjOR) 1.17, 95% CI: 1.00, 1.36 and adjOR 1.51, 95% CI: 1.23, 1.84, respectively. Conclusions: We found evidence that severe, but not mild/moderate, pre-eclampsia is associated with asthma regardless of familial factors and confounders

Hypospadias as a novel feature in spinal bulbar muscle atrophy

Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA phenotype consists of slowly progressive neuromuscular symptoms and undermasculinization features as the result of malfunction of the AR. The latter mainly includes gynecomastia and infertility. Hypospadias is also a feature of undermasculinization with an underdeveloped urethra and penis; it has not been described as part of the SBMA phenotype but has been suggested to be associated with a prolonged CAG repeat in the AR gene. This study includes the first epidemiologic description of the co-occurrence of hypospadias and SBMA in subjects and their male relatives in Swedish population-based health registers, as well as an additional clinical case. One boy with severe hypospadias was screened for mutations in the AR gene and was found to have 42 CAG repeats in it, which is in the full range of mutations causing SBMA later in life. We also detected a maximum of four cases displaying the combination of SBMA and hypospadias in our national register databases. This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life. Our findings suggest that hypospadias may be an under diagnosed feature of the SBMA phenotype and we propose that neurologists working with SBMA further investigate and report the true prevalence of hypospadias among patients with SBMA.Swedish Research Council, K2012-64X-14506-10-5Stockholm City CouncilFoundation Frimurare Barnhuset in StockholmSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM), 340-2013-5867Accepte

Similar familial risk in multiple sclerosis subgroups Introduction

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Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Context: Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. Objective: To study mortality and causes of death in CAH. Design, Setting and Participants: We studied patients with CAH (21-hydroxylase deficiency, n=588; CYP21A2 mutations known, >80%), and compared them with controls (n=58800). Data were derived through linkage of national population-based registers. Main Outcome Measures: Mortality and causes of death. Results: The mean age of death was 41.2±26.9 years in CAH patients and 47.7±27.7 years in controls (P<0.001). Among CAH patients 23 (3.9%) had deceased compared to 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3(1.2-4.3) in CAH males and 3.5(2.0-6.0) in CAH females. Including only patients born 1952-2009, gave similar total results but only patients with salt-wasting or with unclear phenotype had an increased mortality. The causes of death in CAH patients were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter all except one were deceased before the introduction of neonatal screening in 1986 and most of them in the first weeks of life, probably in an adrenal crisis. Conclusions: CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The salt-wasting phenotype seemed to have worse outcome also in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.NonePublishe

Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings

Background: To assess the risk of psychiatric disorders in Ehlers-Danlos syndrome (EDS) and hypermobility syndrome. Methods: Nationwide population-based matched cohort study. EDS, hypermobility syndrome and psychiatric disorders were identified through Swedish national registries. Individuals with EDS (n = 1,771) were matched with comparison individuals (n = 17,710). Further, siblings to individuals with EDS who did not have an EDS diagnosis themselves were compared with matched comparison siblings. Using conditional logistic regression, risk of autism spectrum disorder (ASD), bipolar disorder, attention deficit hyperactivity disorder (ADHD), depression, attempted suicide, suicide and schizophrenia were estimated. The same analyses were conducted in individuals with hypermobility syndrome (n = 10,019) and their siblings. Results: EDS was associated with ASD: risk ratio (RR) 7.4, 95 % confidence interval (95 % CI) 5.2–10.7; bipolar disorder: RR 2.7, CI 1.5–4.7; ADHD: RR 5.6, CI 4.2–7.4; depression: RR 3.4, 95 % CI 2.9–4.1; and attempted suicide: RR 2.1, 95 % CI 1. 7–2.7, but not with suicide or schizophrenia. EDS siblings were at increased risk of ADHD: RR 2.1, 95 % CI 1.4–3.3; depression: RR 1.5, 95 % CI 1.1–1.8; and suicide attempt: RR 1.8, 95 % CI 1.4–2.3. Similar results were observed for individuals with hypermobility syndrome and their siblings. Conclusions: Individuals with EDS and hypermobility syndrome are at increased risks of being diagnosed with psychiatric disorders. These risk increases may have a genetic and/or early environmental background as suggested by evidence showing that siblings to patients have elevated risks of certain psychiatric disorders.NonePublishe

A scientific perspective on reducing ski-snow friction to improve performance in Olympic Cross-Country Skiing, the Biathlon and Nordic Combined

Of the medals awarded at the 2022 Winter Olympics in Beijing, 24% were for events involving cross-country skiing, the biathlon and Nordic combined. Although much research has focused on physiological and biomechanical characteristics that determine success in these sports, considerably less is yet known about the resistive forces. Here, we specifically describe what is presently known about ski-snow friction, one of the major resistive forces. Today, elite ski races take place on natural and/or machine-made snow. Prior to each race, several pairs of skis with different grinding and waxing of the base are tested against one another with respect to key parameters, such as how rapidly and for how long the ski glides, which is dependent on ski-snow friction. This friction arises from a combination of factors, including compaction, plowing, adhesion, viscous drag, and water bridging, as well as contaminants and dirt on the surface of and within the snow. In this context the stiffness of the ski, shape of its camber, and material composition and topography of the base exert a major influence. An understanding of the interactions between these factors, in combination with information concerning the temperature and humidity of both the air and snow, as well as the nature of the snow, provides a basis for designing specific strategies to minimize ski-snow friction. In conclusion, although performance on "narrow skis" has improved considerably in recent decades, future insights into how best to reduce ski-snow friction offer great promise for even further advances

Parental cancer diagnosis and child mortality : a population-based cohort study in Sweden

OBJECTIVE: Cancer diagnosis is known to induce severe psychological stress for the diagnosed patients; however, how it affects the next-of-kin is less well documented. This study aimed to assess the impact of parental cancer on the risk of childhood death. METHODS: A population-based cohort study was conducted using the Swedish national registries, including 2,871,242 children followed during the period of 1991-2009. Parental cancer diagnosis was defined as a time-varying exposure. We used Cox proportional hazards regression to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) as an estimate of the association between parental cancer and childhood mortality. We adjusted for attained age, sex, gestational age, mode of delivery and birth weight of the child, maternal age at child's birth, as well as educational level and socio-economic classification of the parents in the analyses. RESULTS: Among 113,555 children with parental cancer, 127 deaths occurred during 561,198 person-years of follow-up. A parental cancer diagnosis was associated with an increased rate of death among children at the age of 1-18 (HR for all-cause death: 1.39; 95% CI: 1.16-1.66). For young children (aged 1-12), an increased rate was only noted for death due to cancer (HR: 2.06; 95% CI: 1.13-3.75) after parental cancer diagnosis. Among adolescents (aged 13-18), an increased rate was noted for all-cause death (HR: 1.52; 95% CI: 1.25-1.86), and for both non-cancer-related (HR: 1.43; 95% CI: 1.14-1.79) and cancer-related (HR: 2.07; 95% CI: 1.33-3.24) death in the exposed children. CONCLUSION: Children have an increased rate of death if they have a parent diagnosed with cancer as compared to children without such experience; this association appears to be slightly stronger among adolescents.Swedish Research CouncilSwedish Research Council for Health Working Life & Welfare (Forte), 2012-0498Swedish Research Council SIMSAM, 80748301, 340-2013-5867China Scholarship Council, 201206100002Swedish Society for Medical Research (SSMF)Karolinska InstitutetPublishe

Early-Life Adversity Due to Bereavement and Inflammatory Diseases in the Next Generation: A Population Study in Transgenerational Stress Exposure

Emerging evidence suggests that trauma experienced in childhood has negative transgenerational implications for offspring mental and physical health. We aimed to investigate whether early-life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included 3 generations of Swedish families with a base population of 453,516 children (generation 3) born in 2001-2012. Exposure was defined as the middle generation's (generation 2) experiencing bereavement in childhood due to the death of a parent (generation 1). Outcomes in generation 3 included 2 diagnoses of inflammatory diseases, including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways, including investigation of mediation by generation 2 mood disorders and socioeconomic status (SES). We found that early-life bereavement experienced by women was associated with early-onset offspring asthma (hazard ratio = 1.15, 95% confidence interval: 1.08, 1.23); mediation analysis revealed that 28%-33% of the association may be mediated by SES and 9%-20% by mood disorders. Early-life bereavement experienced by men was associated with autoimmune diseases in offspring (hazard ratio = 1.31, 95% confidence interval: 1.06, 1.62), with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk of inflammatory diseases which is partly mediated by mood disorders and SES

antidiabetics statins and the risk of amyotrophic lateral sclerosis

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Registers of the Swedish total population and their use in medical research

The primary aim of the Swedish national population registration system is to obtain data that (1) reflect the composition, relationship and identities of the Swedish population and (2) can be used as the basis for correct decisions and measures by government and other regulatory authorities. For this purpose, Sweden has established two population registers: (1) The Population Register, maintained by the Swedish National Tax Agency ("Folkbokforingsregistret"); and (2) The Total Population Register (TPR) maintained by the government agency Statistics Sweden ("Registret over totalbefolkningen"). The registers contain data on life events including birth, death, name change, marital status, family relationships and migration within Sweden as well as to and from other countries. Updates are transmitted daily from the Tax Agency to the TPR. In this paper we describe the two population registers and analyse their strengths and weaknesses. Virtually 100 % of births and deaths, 95 % of immigrations and 91 % of emigrations are reported to the Population Registers within 30 days and with a higher proportion over time. The over-coverage of the TPR, which is primarily due to underreported emigration data, has been estimated at up to 0.5 % of the Swedish population. Through the personal identity number, assigned to all residents staying at least 1 year in Sweden, data from the TPR can be used for medical research purposes, including family design studies since each individual can be linked to his or her parents, siblings and offspring. The TPR also allows for identification of general population controls, participants in cohort studies, as well as calculation of follow-up time.NonePublishe