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- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Theuns, J., et al.
(författare)
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Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease
- 2014
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 83:21, s. 13-1906
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort. METHODS: C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia. RESULTS: A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.055%), all with a positive family history of neurodegenerative dementia, amyotrophic lateral sclerosis, or atypical parkinsonism, while no carriers were detected with typical sporadic or familial PD. Meta-analysis revealed a small increase in risk of PD with an increasing number of (G4C2)n repeats; however, we could not detect a robust association between the C9orf72 (G4C2)n repeat and PD, and the population attributable risk was low. CONCLUSIONS: Together, these findings indicate that expansions in C9orf72 do not have a major role in the pathogenesis of PD. Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease.
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- Madireddy, L, et al.
(författare)
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A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2236-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.
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33. |
- Gwozdz, W., et al.
(författare)
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Maternal employment and childhood obesity - A European perspective
- 2013
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Ingår i: Journal of Health Economics. - : Elsevier BV. - 0167-6296 .- 1879-1646. ; 32:4, s. 728-742
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Tidskriftsartikel (refereegranskat)abstract
- The substantial increase in female employment rates in Europe over the past two decades has often been linked in political and public rhetoric to negative effects on child development, including obesity. We analyse this association between maternal employment and childhood obesity using rich objective reports of various anthropometric and other measures of fatness from the IDEFICS study of children aged 2-9 in 16 regions of eight European countries. Based on such data as accelerometer measures and information from nutritional diaries, we also investigate the effects of maternal employment on obesity's main drivers: calorie intake and physical activity. Our analysis provides little evidence for any association between maternal employment and childhood obesity, diet or physical activity. (c) 2013 Elsevier B.V. All rights reserved.
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- Hebestreit, A., et al.
(författare)
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Cross-sectional and longitudinal associations between energy intake and BMI z-score in European children
- 2016
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for the effect of dietary energy on BMI z-scores in young children is limited. We aim to investigate cross-sectional and longitudinal effects of daily energy intake (EI) on BMI z-scores of European boys and girls considering growth-related height dependencies of EI using residual EI. Methods: To investigate cross-sectional and longitudinal effects of daily energy intake (EI) on BMI z-scores of European boys and girls considering growth-related height dependencies of EI using residual EI. Methods: Subjects were children aged 2-< 10 y old (N = 2753, 48.2 % girls) participating in the IDEFICS (Identification and prevention of Dietary-and lifestyle-induced health EFfects In Children and infantS) baseline and follow-up examination. Usual EI (kcal/day) was calculated based on the National Cancer Institute-method excluding subjects with implausible reported EI. Effect of age, height and sex-adjusted residuals of EI on BMI z-score was investigated stratified by baseline age-group (2-< 4 y, 4-< 6 y, 6-< 8 y and 8-< 10 y) cross-sectionally using linear regression models adjusted for relevant confounders (crude model: age, sex, country; fully adjusted model: plus parental ISCED level, parental BMI, screen time; subgroup analysis: plus objectively measured physical activity). Longitudinal associations were estimated between changes in (Delta) residual EI per year and Delta BMI z-score per year with adjustments analogously to the cross-sectional models but with additional adjustment for residual EI at baseline. Results: Cross-sectionally, positive associations were observed between residual EI and BMI z-score for the full study sample, for boys and in older (>= 6 years) but not in younger children in the crude and fully adjusted model. Longitudinally, small positive associations were observed between Delta residual EI per y on Delta BMI z-score per y for the full study sample and in 4-< 6 y olds in the crude and fully adjusted model. Conclusion: In conclusion, EI above the average intakes for a certain sex, age and height are weakly associated with BMI z-scores in European children. Residual EI may be considered as a useful exposure measure in children as it accounts for growth-related changes in usual EI during childhood.
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35. |
- Heckman, Michael G., et al.
(författare)
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Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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- Moustafa, J. S. E., et al.
(författare)
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Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:16, s. 3727-3738
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Tidskriftsartikel (refereegranskat)abstract
- Variable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (P-empirical 8.9 10(8) and P 3.1 10(3), respectively) which we estimate explains approximate to 0.8 of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46 of the variance (P-combined 1.6 10(3)). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P 0.027) and both VNTRs (P-empirical 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies.
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- Papoutsou, S., et al.
(författare)
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Timing of solid food introduction and association with later childhood overweight and obesity: The IDEFICS study
- 2018
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Ingår i: Maternal and Child Nutrition. - : Wiley. - 1740-8695. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated associations between timing of solid food introduction and childhood obesity and explored maternal characteristics influencing early feeding practices. Cross-sectional data from children 2-9years (n=10,808; 50.5% boys) residing in 8 European countries of the IDEFICS study (2007-2008) were included. Late solid food introduction (7months of age) was associated with an increased prevalence of later childhood overweight/obesity among exclusively breastfed children (OR [odds ratio]: 1.38, 95% CI [confidence interval] [1.01, 1.88]). In contrast, early solid food introduction (<4months of age) was associated with lower prevalence of overweight/obesity among children that ceased exclusive breastfeeding earlier than 4 months (OR: 0.63, 95% CI [0.47, 0.84]). Children that were introduced to solids right after 6months exclusive breastfeeding and continued to receive breastmilk (12months) were less likely to become overweight/obese (OR: 0.67, 95% CI [0.51, 0.88]) compared to children that discontinued to receive breastmilk. Analyses were adjusted for age, sex, country, birth weight, parental education level, parental body mass index, tobacco use in pregnancy, gestational weight gain, and gestational diabetes. Underweight mothers, overweight mothers, mothers who reported daily smoking during pregnancy, and low-educated mothers were less likely to follow recommendations on breastfeeding and timely solids introduction. Future studies should examine whether guidelines for solid food introduction timing have to distinguish between exclusively breastfed, formula fed, and too early exclusive breastfeeding-ceased infants. There is also need for more prospective studies; recall bias was an important current limitation. In conclusion, health professionals should emphasize benefits of breastfeeding and appropriate solid food introduction, especially to mothers that are less likely to follow recommendations.
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- Ross, Owen A., et al.
(författare)
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Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
- 2011
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Ingår i: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
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Tidskriftsartikel (refereegranskat)abstract
- Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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- Verbestel, V., et al.
(författare)
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Effectiveness of the IDEFICS intervention on objectively measured physical activity and sedentary time in European children
- 2015
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:Suppl. 2, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThis paper reports on the effectiveness of the prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) intervention on objectively measured physical activity (PA) and sedentary time (ST) in 2- to 9.9-year-old European boys and girls. MethodsThe intervention was evaluated after 2years through a non-randomized cluster-controlled trial in eight European countries (one control and one intervention community per country). All children in the intervention group received a culturally adapted childhood obesity prevention programme through the community, schools/kindergartens and family. A random sub-sample of children participating in the IDEFICS study wore an accelerometer at baseline and follow-up for at least 3days (n=9,184). Of this sample, 81% provided valid accelerometer data at baseline (n=7,413; 51% boys; 6.211.76years; boys: 617170cpmday(-1); girls 556 +/- 156cpmday(-1)) and 3,010 children provided valid accelerometer data at baseline and during the follow-up survey 2years later. ResultsIn boys and girls, no significant differences in PA and ST were found between intervention and control groups over 2years. Strong temporal effects were found in the total sample of boys and girls: the percentage of time spent in light PA per day decreased by 4 percentage points in both boys and girls between baseline and follow-up (both: p<0.001), while time spent in ST per day increased by 4 percentage points in both sexes over time (both: p<0.001). Percentage of time spent in moderate-to-vigorous PA per day remained stable over time in boys and girls. ConclusionDespite the socio-ecological approach and implementation of a culturally adapted intervention in each country, no effects of the IDEFICS intervention were found on children's objectively measured PA and ST. Behavioural interventions for children may need to enhance specificity and intensity at the family level using other behaviour change techniques and more direct strategies to reach parents. (c) 2015 World Obesity
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