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51.
  • Fall, Tove, et al. (författare)
  • Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma
  • 2015
  • Ingår i: JAMA pediatrics. - Stockholm : American Medical Association. - 2168-6203 .- 2168-6211. ; 169:11
  • Tidskriftsartikel (refereegranskat)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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52.
  • Fall, Tove, 1979-, et al. (författare)
  • Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay
  • 2019
  • Ingår i: Clinical Laboratory. - 1433-6510. ; 65:7, s. 1293-1297
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values.METHODS: Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent.RESULTS: The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times.CONCLUSIONS: The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.
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53.
  • Fang, Fang, et al. (författare)
  • Maternal bereavement and childhood asthma-analyses in two large samples of Swedish children
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11, s. e27202-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1-4 (n = 426 334) and 7-12 (n = 493 813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1-4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7-12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1-4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7-12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant. CONCLUSIONS/SIGNIFICANCE: Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.
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54.
  • Ferreira, Manuel A R, et al. (författare)
  • Eleven loci with new reproducible genetic associations with allergic disease risk.
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
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55.
  • Flanigan, Catherine, et al. (författare)
  • Prenatal maternal psychosocial stress and offspring’s asthma and allergic disease : a systematic review and meta-analysis
  • 2018
  • Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic-pituitary-axis (HPA), leading to Th2-biased cell differentiation in the fetus. We undertook a systematic review and meta-analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring. METHODS: We searched 11 electronic databases from 1960 to 2016, search the grey literature, and contacted experts in the field. Type of stress indicator included mood disorders, anxiety, exposure to violence, bereavement and socio-economic problems occurring during pregnancy, both objectively or subjectively measured. We included all possible asthma and IgE-mediated allergy outcomes. We conducted random-effects meta-analyses to synthesize the data. RESULTS: We identified 9,779 papers of which 30 studies (enrolling >6 million participants) satisfied inclusion criteria. The quality of 25 studies was moderate, four were strong, and one was weak. Maternal exposure to any type of stressors was associated with an increased risk of offspring atopic eczema/dermatitis (OR 1.34, 95%CI 1.22-1.47), allergic rhinitis (OR 1.30, 95%CI 1.04-1.62), wheeze (OR 1.34, 95%CI 1.16-1.54) and asthma (OR 1.15, 95%CI 1.04-1.27). Exposure to anxiety and depression had strongest effect compared to other stressors. Exposure during the third trimester had the greatest impact compared to first and second trimesters. The increased risk was stronger for early-onset and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95%CI 1.10-1.48) or a spouse (HR 1.40, 95%CI 1.03-1.90) increased the risk of offspring asthma. CONCLUSIONS: Exposure to prenatal maternal psychosocial stress was associated with increased risk, albeit modestly, of asthma and allergy in the offspring. The pronounced risk during the third trimester may represent cumulative stress exposure throughout pregnancy rather than trimester-specific effect. Our findings may represent a causal effect or a result of inherent biases in studies, particularly residual confounding.
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56.
  • Fraser, Abigail, et al. (författare)
  • Maternal diabetes in pregnancy and offspring cognitive ability : sibling study with 723,775 men from 579,857 families
  • 2014
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 57:1, s. 102-109
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: The aim of this study was to investigate the association between maternal diabetes in pregnancy and offspring cognitive ability and also to assess whether the association was due to intrauterine mechanisms or shared familial characteristics.METHODS: We linked national registers and conducted a prospective cohort study of singleton Swedish-born men to explore associations between maternal pregnancy diabetes and educational achievement at age 16 years, the age of completing compulsory education in Sweden (n = 391,545 men from 337,174 families, graduating in 1988-1997 and n = 326,033 men from 282,079 families, graduating in 1998-2009), and intelligence quotient (IQ) at the mandatory conscription examination at 18 years of age (n = 664,871 from 543,203 families).RESULTS: Among non-siblings, maternal diabetes in pregnancy was associated with lower offspring cognitive ability even after adjustment for maternal age at birth, parity, education, early-pregnancy BMI, offspring birth year, gestational age and birthweight. For example, in non-siblings, the IQ of men whose mothers had diabetes in their pregnancy was on average 1.36 points lower (95% CI -2.12, -0.60) than men whose mothers did not have diabetes. In comparison, we found no such association within sibships (mean difference 1.70; 95% CI -1.80, 5.21).CONCLUSIONS/INTERPRETATION: The association between maternal diabetes in pregnancy and offspring cognitive outcomes is likely explained by shared familial characteristics and not by an intrauterine mechanism.
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57.
  • Furuhjelm, Catrin (författare)
  • Can fish oil in pregnancy and lactation alter maternal and infant immunological responses and prevent allergy in the offspring?
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: A connection has been proposed between the increase of allergic disease and the altered composition of fatty acids in the diet in the westernised world. Less oily fish and more vegetable oil are consumed today compared to 50-100 years ago. Programming of the immune responses takes place very early in life and environmental factors, such as fish in the diet, have been suggested to protect from infant allergy.Aim: The general aim of this thesis was to assess the effects of maternal dietary supplementation with ω-3 long chain polyunsaturated fatty acids (LCPUFA), i.e. fish oil, in pregnancy and lactation on the development of allergic symptoms and sensitisation in the infants as well as some immunological markers in mothers and infants.Subjects and methods: This thesis is based on the results from a prospective double-blind placebo-controlled multi-centre trial comprising 145 families. Pregnant women, at risk of having an allergic infant, were recruited at the antenatal clinics and randomised to daily supplementation with 1.6 g eicosapentaenoic acid (EPA, C20:5ω-3) and 1.1 g docosahexaenoic acid (DHA, C22:6ω-3) or placebo, starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Phospholipid fatty acids in maternal and infant plasma were analysed to assess compliance. Maternal prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and cytokines along with infant vaccine induced responses and chemokines were analysed with ELISA and Luminex techniques. Clinical outcomes were allergic disease and positive skin prick test/detectable circulating IgE antibodies to common allergens.Results: Phospholipid proportions of ω-3 LCPUFA increased significantly in the ω-3 supplemented women and their infants. Lipopolysaccharide-induced PGE2 secretion from whole blood culture supernatants decreased in a majority of the ω-3-supplemented mothers (p<0.01). The decrease in PGE2 production was more pronounced among non-atopic than atopic mothers. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE associated eczema and IgE mediated food allergy was though reduced in the ω-3 group during the first two years (OR=0.2 and 0.3 compared to placebo, p<0.05 for both). The cumulative incidence of any IgE associated disease during the first two years of life was 13% in the ω-3 supplemented group compared to 30% in the placebo group (p=0.01, OR 0.3, p<0.05). This effect was most evident in infants of non-allergic mothers. Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05), in a dose dependent manner. In addition, no allergic symptoms as compared to multiple allergic symptoms in the infants, regardless of sensitisation, were related to higher maternal and infant ω-3 LCPUFA status (p<0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CC-chemokine ligand 17 (CCL17)/ CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p<0.05). Furthermore in non-allergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p<0.05), as well as increased IgG titres to diphtheria (p=0.01) and tetanus (p=0.05) toxins.Conclusions: A decreased cumulative incidence of IgE associated disease in the infants was found after maternal ω-3 LCPUFA supplementation as well as a reverse dose response relationship between maternal ω-3 LCPUFA status and infant IgE associated disease. Higher plasma proportions of DHA and EPA in were also associated to less severe allergic disease. A tendency towards strengthened Th1 associated response after maternal ω-3 LCPUFA supplementation was indicated in the analysis of maternal and infant immunological markers. These effects, as well as the clinical outcomes, were more pronounced in non-allergic individuals, suggesting gene-by-environment interactions.
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58.
  • Garden, Frances L, et al. (författare)
  • Infant and early childhood dietary predictors of overweight at age 8 years in the CAPS population
  • 2011
  • Ingår i: European Journal of Clinical Nutrition. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1476-5640 .- 0954-3007.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/OBJECTIVES: Programs to address obesity are a high priority for public policy especially for young children. Research into dietary determinants of obesity is challenging but important for rational planning of interventions to prevent obesity, given that both diet and energy expenditure influence weight status. We investigated whether early life dietary factors were predictive of weight status at 8 years in a cohort of Australian children. SUBJECTS/METHODS: We used data from the Childhood Asthma Prevention Study-a birth cohort at high risk of asthma. Dietary data (3-day weighed food records) were collected at 18 months and height, weight and waist circumference were collected at 8 years. We assessed the relationship between dietary predictor variables and measures of adiposity using linear regression. RESULTS: Intakes of protein, meat and fruit at age 18 months were positively associated with measures of adiposity at age 8 years, namely, body mass index and/or waist circumference. We also showed a significant negative relationship between these measures of adiposity at 8 years and intake at 18 months of dairy foods as a percent of total energy, and intake of energy dense cereal-based foods such as cookies and crackers. CONCLUSIONS: This birth cohort study with rigorous design, measures and analyses, has shown a number of associations between early dietary intake and subsequent adiposity that contribute to the growing evidence base in this important field.
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59.
  • Ginsberg, Ylva, et al. (författare)
  • Maternal infection requiring hospitalization during pregnancy and attention-deficit hyperactivity disorder in offspring : a quasi-experimental family-based study
  • 2019
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 60:2, s. 160-168
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Maternal infection during pregnancy (IDP) has been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. However, infection is associated with social adversity, poor living conditions and other background familial factors. As such, there is a need to rule out whether the observed association between maternal IDP and ADHD might be attributed to such confounding.METHODS: This nationwide population-based cohort study using a family-based, quasi-experimental design included 1,066,956 individuals born in Sweden between 1992 and 2002. Data on maternal IDP (bacterial or viral) requiring hospitalization and ADHD diagnosis in offspring were gathered from Swedish National Registers, with individuals followed up through the end of 2009. Ordinary and stratified Cox regression models were used for estimation of hazard ratios (HRs) and several measured covariates were considered. Cousin- and sibling-comparisons accounted for unmeasured genetic and environmental factors shared by cousins and siblings.RESULTS: In the entire population, maternal IDP was associated with ADHD in offspring (HR = 2.31, 95% CI = 2.04-2.61). This association was attenuated when accounting for measured covariates (HR = 1.86, 95% CI = 1.65-2.10). The association was further attenuated when adjusting for unmeasured factors shared between cousins (HR = 1.52, 95% CI = 1.12-2.07). Finally, the association was fully attenuated in sibling comparisons (HR = 1.03, 95% CI = 0.76-1.41).CONCLUSIONS: This study suggests that the association between maternal IDP and offspring ADHD is largely due to unmeasured familial confounding. Our results underscore the importance of adjusting for unobserved familial risk factors when exploring risk factors for ADHD.
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60.
  • Gong, Tong, et al. (författare)
  • Exposure to air pollution from traffic and neurodevelopmental disorders in Swedish twins.
  • 2014
  • Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:6, s. 553-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have reported associations between air pollution exposure and neurodevelopmental disorders in children, but the role of pre- and postnatal exposure has not been elucidated.
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