| 1. |
- Fall, Tove, et al.
(author)
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Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma
- 2015
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In: JAMA pediatrics. - Stockholm : American Medical Association. - 2168-6203 .- 2168-6211. ; 169:11
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Journal article (peer-reviewed)abstract
- IMPORTANCE: The association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results.OBJECTIVE: To determine whether exposure to dogs and farm animals confers a risk of asthma.DESIGN, SETTING AND PARTICIPANTS: In a nationwide cohort study, the association between early exposure to dogs and farm animals and the risk of asthma was evaluated and included all children born in Sweden from January 1, 2001, to December 31, 2010 (N = 1 011 051), using registry data on dog and farm registration, asthma medication, diagnosis, and confounders for parents and their children. The association was assessed as the odds ratio (OR) for a current diagnosis of asthma at age 6 years for school-aged children and as the hazard ratio (HR) for incident asthma at ages 1 to 5 years for preschool-aged children. Data were analyzed from January 1, 2007, to September 30, 2012.EXPOSURES: Living with a dog or farm animal.MAIN OUTCOMES AND MEASURES: Childhood asthma diagnosis and medication used.RESULTS: Of the 1 011 051 children born during the study period, 376 638 preschool-aged (53 460 [14.2%] exposed to dogs and 1729 [0.5%] exposed to farm animals) and 276 298 school-aged children (22 629 [8.2%] exposed to dogs and 958 [0.3%] exposed to farm animals) were included in the analyses. Of these, 18 799 children (5.0%) in the preschool-aged children's cohort experienced an asthmatic event before baseline, and 28 511 cases of asthma and 906 071 years at risk were recorded during follow-up (incidence rate, 3.1 cases per 1000 years at risk). In the school-aged children's cohort, 11 585 children (4.2%) experienced an asthmatic event during the seventh year of life. Dog exposure during the first year of life was associated with a decreased risk of asthma in school-aged children (OR, 0.87; 95% CI, 0.81-0.93) and in preschool-aged children 3 years or older (HR, 0.90; 95% CI, 0.83-0.99) but not in children younger than 3 years (HR, 1.03; 95% CI, 1.00-1.07). Results were comparable when analyzing only first-born children. Farm animal exposure was associated with a reduced risk of asthma in both school-aged children and preschool-aged children (OR, 0.48; 95% CI, 0.31-0.76, and HR, 0.69; 95% CI, 0.56-0.84), respectively.CONCLUSIONS AND RELEVANCE: In this study, the data support the hypothesis that exposure to dogs and farm animals during the first year of life reduces the risk of asthma in children at age 6 years. This information might be helpful in decision making for families and physicians on the appropriateness and timing of early animal exposure.
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| 2. |
- Wernroth, Lisa, et al.
(author)
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Development of gut microbiota during the first 2 years of life
- 2022
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In: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
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| 3. |
- Wernroth, Lisa, et al.
(author)
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Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes : A Nationwide Register-Based Study With Sibling Analysis
- 2020
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:5, s. 991-999
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The effect of early life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis.RESEARCH DESIGN AND METHODS: = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings.RESULTS: for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00-1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations.CONCLUSIONS: Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10, most prominently in children delivered by cesarean section.
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| 4. |
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| 5. |
- Wernroth, Mona-Lisa, et al.
(author)
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Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood
- 2017
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In: JAMA pediatrics. - : AMER MEDICAL ASSOC. - 2168-6203 .- 2168-6211. ; 171:7, s. 663-669
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Journal article (peer-reviewed)abstract
- IMPORTANCE The association between early exposure to animals and type 1 diabetes in childhood is not clear. OBJECTIVE To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. DESIGN, SETTING, AND PARTICIPANTS A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. EXPOSURES Having a parent who was registered as a dog owner during the child's first year of life. MAIN OUTCOMES AND MEASURES Childhood-onset type 1 diabetes. RESULTS Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; >= 3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0.43-1.17) for dog exposure. CONCLUSIONS AND RELEVANCE In a nationwide study, no evidence supporting an association of register-derived measures of dog exposure with childhood type 1 diabetes was identified.
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| 6. |
- Wernroth, Mona-Lisa
(author)
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Type l diabetes in childhood and adolescence, environmental exposures and gut microbiota
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Environmental factors leading to disturbances in the gut microbiota might play an important role as triggers for, and/or contributing factors in, the development of type 1 diabetes (T1D). The overall aim of the research underlying this thesis was to study the influence of environmental factor exposure on the risk of T1D in childhood and adolescence, and gut microbiota composition in early childhood.In this project, national registers provided information about T1D onset and exposure to animals, antibiotics, caesarean section and severe stress, defined as death of a first degree relative. In the first study (1,999 T1D events), no evidence supported an association between early exposure to dog or farm animals and T1D in childhood. In the second study (1,297 T1D events), dispensed prescriptions of antibiotics in the first year of life was found to be associated with T1D during childhood. Sibling analysis did not indicate confounding from familial factors. Furthermore, the effect estimate for the association between antibiotics and T1D was largest in children delivered by caesarean section. In the third study (10,789 T1D events), death of a close relative was associated with an increased risk for T1D within the first years following the loss, and when the loss occurred during the teenage years. The fourth study was a longitudinal study using 16S rRNA sequencing to analyse faecal samples from 83 children to study the gut microbiota development from birth to 2 years of age. Having a furry pet in the household was associated with a lower abundance of a bacterial species belonging to the genus Bifidobacterium. The overall gut microbiota composition was associated with prenatal exposure to antibiotics and caesarean section. Finally, caesarean section was associated with a lower abundance of Bacteroidetes and a higher abundance of Firmicutes.In conclusion, no evidence was found in the present study to support the association of exposure to animals to lowered risk of T1D in the general population. Although exposure to antibiotics was associated with T1D, it is likely to only make a small contribution to the overall risk of T1D. Our findings support the hypothesis that severe stress might accelerate T1D onset during certain time periods. Furthermore, our findings add to the body of research showing that exposure to animals, prenatal antibiotics and caesarean section account for some of the inter-individual variation in early childhood microbiota development.
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| 7. |
- Chen, Ruoqing, et al.
(author)
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Childhood injury after a parental cancer diagnosis
- 2015
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In: eLIFE. - Stockholm : eLife Sciences Publications Ltd. - 2050-084X. ; 4
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Journal article (peer-reviewed)abstract
- A parental cancer diagnosis is psychologically straining for the whole family. We investigated whether a parental cancer diagnosis is associated with a higher-than-expected risk of injury among children by using a Swedish nationwide register-based cohort study. Compared to children without parental cancer, children with parental cancer had a higher rate of hospital contact for injury during the first year after parental cancer diagnosis (hazard ratio [HR]=1.27, 95% confidence interval [CI]=1.22-1.33), especially when the parent had a comorbid psychiatric disorder after cancer diagnosis (HR=1.41, 95% CI=1.08-1.85). The rate increment declined during the second and third year after parental cancer diagnosis (HR=1.10, 95% CI=1.07-1.14) and became null afterwards (HR=1.01, 95% CI=0.99-1.03). Children with parental cancer also had a higher rate of repeated injuries than the other children (HR=1.13, 95% CI= 1.12-1.15). Given the high rate of injury among children in the general population, our findings may have important public health implications.
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| 8. |
- Chen, Ruoqing, et al.
(author)
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Parental cancer diagnosis and child mortality : a population-based cohort study in Sweden
- 2015
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In: Cancer Epidemiology. - Stockholm : American Diabetes Association. - 1877-7821 .- 1877-783X. ; 39:1, s. 79-85
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Journal article (peer-reviewed)abstract
- 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 socioeconomic 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 112), 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. (C) 2014 Elsevier Ltd. All rights reserved.
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| 9. |
- Li, Yuchen, et al.
(author)
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Associations of parental and perinatal factors with subsequent risk of stress-related disorders : a nationwide cohort study with sibling comparison
- 2022
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 27, s. 1712-1719
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Journal article (peer-reviewed)abstract
- Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity >= 4, mothers with BMI >= 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.
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| 10. |
- Song, Huan, et al.
(author)
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Association of Stress-Related Disorders With Subsequent Autoimmune Disease
- 2018
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 319:23, s. 2388-2400
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Journal article (peer-reviewed)abstract
- Importance: Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear.Objective: To determine whether there is an association between stress-related disorders and subsequent autoimmune disease.Design, Setting, and Participants: Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients.Exposures: Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions.Main Outcomes and Measures: Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors.Results: The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ≤33, 34-41, 42-50, and ≥51 years, respectively; P for interaction < .001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration ≤179, 180-319, and ≥320 days, respectively; P for trend = .03).Conclusions and Relevance: In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.
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