LifeLines is a large prospective population-based three generation cohort study in the north of the Netherlands. Different recruitment strategies were adopted: recruitment of an index population via ...general practitioners, subsequent inclusion of their family members, and online self-registration. Our aim was to investigate the representativeness of the adult study population at baseline and to evaluate differences in the study population according to recruitment strategy.
Demographic characteristics of the LifeLines study population, recruited between 2006-2013, were compared with the total adult population in the north of the Netherlands as registered in the Dutch population register. Socioeconomic characteristics, lifestyle, chronic diseases, and general health were further compared with participants of the Permanent Survey of Living Conditions within the region (2005-2011, N = 6,093). Differences according to recruitment strategy were assessed.
Compared with the population of the north of the Netherlands, LifeLines participants were more often female, middle aged, married, living in a semi-urban place and Dutch native. Adjusted for differences in demographic composition, in LifeLines a smaller proportion had a low educational attainment (5% versus 14%) or had ever smoked (54% versus 66%). Differences in the prevalence of various chronic diseases and low general health scores were mostly smaller than 3%. The age profiles of the three recruitment groups differed due to age related inclusion criteria of the recruitment groups. Other differences according to recruitment strategy were small.
Our results suggest that, adjusted for differences in demographic composition, the LifeLines adult study population is broadly representative for the adult population of the north of the Netherlands. The recruitment strategy had a minor effect on the level of representativeness. These findings indicate that the risk of selection bias is low and that risk estimates in LifeLines can be generalized to the general population.
The LifeLines Cohort Study is a large population-based cohort study and biobank that was established as a resource for research on complex interactions between environmental, phenotypic and genomic ...factors in the development of chronic diseases and healthy ageing. Between 2006 and 2013, inhabitants of the northern part of The Netherlands and their families were invited to participate, thereby contributing to a three-generation design. Participants visited one of the LifeLines research sites for a physical examination, including lung function, ECG and cognition tests, and completed extensive questionnaires. Baseline data were collected for 167 729 participants, aged from 6 months to 93 years. Follow-up visits are scheduled every 5 years, and in between participants receive follow-up questionnaires. Linkage is being established with medical registries and environmental data. LifeLines contains information on biochemistry, medical history, psychosocial characteristics, lifestyle and more. Genomic data are available including genome-wide genetic data of 15 638 participants. Fasting blood and 24-h urine samples are processed on the day of collection and stored at -80 °C in a fully automated storage facility. The aim of LifeLines is to be a resource for the national and international scientific community. Requests for data and biomaterials can be submitted to the LifeLines Research Office LLscience@umcg.nl.
We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood.
First, we used cord blood ...of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals false-discovery rate (FDR) < 0.05. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis.
We found 35 differentially methylated CpGs (FDR < 0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P < 1 × 10(-7)). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P < 0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity.
Maternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system.
PurposeThere is a critical need for population-based prospective cohort studies because they follow individuals before the onset of disease, allowing for studies that can identify biomarkers and ...disease-modifying effects, and thereby contributing to systems epidemiology.ParticipantsThis paper describes the design and baseline characteristics of an intensively examined subpopulation of the LifeLines cohort in the Netherlands. In this unique subcohort, LifeLines DEEP, we included 1539 participants aged 18 years and older.Findings to dateWe collected additional blood (n=1387), exhaled air (n=1425) and faecal samples (n=1248), and elicited responses to gastrointestinal health questionnaires (n=1176) for analysis of the genome, epigenome, transcriptome, microbiome, metabolome and other biological levels. Here, we provide an overview of the different data layers in LifeLines DEEP and present baseline characteristics of the study population including food intake and quality of life. We also describe how the LifeLines DEEP cohort allows for the detailed investigation of genetic, genomic and metabolic variation for a wide range of phenotypic outcomes. Finally, we examine the determinants of gastrointestinal health, an area of particular interest to us that can be addressed by LifeLines DEEP.Future plansWe have established a cohort of which multiple data levels allow for the integrative analysis of populations for translation of this information into biomarkers for disease, and which will offer new insights into disease mechanisms and prevention.
This article—published in the Journal Gruppe. Interaktion. Organisation.— presents a systematic overview of the current empirical evidence of the effectiveness of the systemic constellation method ...when applied in organisations.
Although the systemic constellation method is increasingly used for team coaching, organisational development and transformation processes, among others, scientific evidence on the effectiveness and quality of this method is still scarce. This may hamper the broader implementation of a potentially useful approach. Altogether, ten electronic databases were searched up to January, 2020. Multiple languages, qualitative and quantitative designs, and academic and grey literature were included. The search resulted in the identification of 79 potentially relevant publications, seven of which were prospective and 13 were retrospective effectiveness studies in terms of organisational outcomes. Only two of the seven prospective studies used a controlled design. This review concludes that the empirical evidence on the systemic organisational constellation method points toward a potentially effective intervention in the organisational context. However, it is too early to make firm conclusions as the number of studies was small and quality of the studies was low in general.
The present systematic review summarises the literature on the systemic constellation method applied in organisations. It offers coaches and consultants insights into the method from a scientific perspective and describes potential mechanisms of action regarding the intervention. The results of the review provide a solid basis for future research and give directions for new studies to support quality improvement and help us better understand the factors influencing effectiveness.
Background Asthma may be more prevalent in overweight children. However, how early overweight and changes in weight status during childhood affect the asthma risk is unclear. Objectives To ...investigate overweight and changes in overweight status in children age 1 to 8 years in relation to asthma symptoms in childhood. Methods We studied 3756 children who participated in a large birth cohort study. The parents reported their children's weight and height, and wheeze, dyspnea, and prescription of inhaled corticosteroids in yearly questionnaires. Sensitization to inhalant allergens and bronchial hyperresponsiveness (BHR) were determined at 8 years. Results At 8 years, 275 children (7.3%) wheezed, 361 (9.6%) had dyspnea, and 268 (7.1%) had a prescription of inhaled corticosteroids in the preceding year. Children who had a persistent high body mass index (BMI, weight/height2 ) during childhood or a high BMI at 6 to 7 years had a significantly increased risk of dyspnea (adjusted odds ratio, 1.68; 95% CI, 1.18-2.39, for a high BMI at 6-7 years) and measured BHR (adjusted odds ratio, 1.66; 95% CI, 1.10-2.52) at 8 years. Children with a high BMI at a young age, but who developed a normal BMI at 6 to 7 years, did not have an increased risk of dyspnea or BHR at 8 years. BMI was not associated with sensitization. Conclusion Children with a current high BMI are at increased risk to have dyspnea and BHR at 8 years. A high BMI at an earlier age is not related to an increased risk if the child has become normal weight at 6 to 7 years.
There is ample evidence that childhood overweight is associated with increased risk of chronic disease in adulthood. The aim of this study was to investigate associations between childhood overweight ...and common childhood health problems.
Data were used from a general population sample of 3960 8-year-old children, participating in the Dutch PIAMA birth cohort study. Weight and height, measured by the investigators, were used to define BMI status (thinness, normal weight, moderate overweight, obesity). BMI status was studied cross-sectionally in relation to the following parental reported outcomes: a general health index, GP visits, school absenteeism due to illness, health-related functional limitations, doctor diagnosed respiratory infections and use of antibiotics.
Obesity was significantly associated with a lower general health score, more GP visits, more school absenteeism and more health-related limitations, (adjusted odds ratios around 2.0 for most outcomes). Obesity was also significantly associated with bronchitis (adjusted odds ratio (aOR) and 95% confidence intervals (95%CI): 5.29 (2.58;10.85) and with the use of antibiotics (aOR (95%CI): 1.79 (1.09;2.93)). Associations with flu/serious cold, ear infection and throat infection were positive, but not statistically significant. Moderate overweight was not significantly associated with the health outcomes studied.
Childhood obesity is not merely a risk factor for disease in adulthood, but obese children may experience more illness and health related problems already in childhood. The high prevalence of the outcomes studied implies a high burden of disease in terms of absolute numbers of sick children.
HbA1c is associated with cardiovascular risk in persons without diabetes and cardiovascular risk accumulates over the life course. Therefore, insight in factors determining HbA1c from childhood ...onwards is important. We investigated (lifestyle) determinants of HbA1c at age 12 years and the effects of growth on change in HbA1c and the tracking of HbA1c between the age of 8 and 12 years.
Anthropometric measurements were taken and HbA1c levels were assessed in 955 children without diabetes aged around 12 years participating in the PIAMA birth cohort study. In 363 of these children HbA1c was also measured at age 8 years. Data on parents and children were collected prospectively by questionnaires.
We found no significant association between known risk factors for diabetes and HbA1c at age 12 years. Mean(SD) change in HbA1c between ages 8 and 12 years was 0.6(0.7) mmol/mol per year (or 0.1(0.1) %/yr). Anthropometric measures at age 8 and their change between age 8 and 12 years were not associated with the change in HbA1c. 68.9% of the children remained in the same quintile or had an HbA1c one quintile higher or lower at age 8 years compared to age 12 years.
The lack of association between known risk factors for diabetes and HbA1c suggest that HbA1c in children without diabetes is relatively unaffected by factors associated with glycaemia. HbA1c at age 8 years is by far the most important predictor of HbA1c at age 12. Therefore, the ranking of HbA1c levels appear to be fairly stable over time.
Childhood obesity is a worldwide public health concern. Recent studies from high income countries have demonstrated associations between maternal smoking during pregnancy and children’s excess body ...weight. We examine associations between maternal smoking during pregnancy and children’s overweight or obesity, in six countries in the less affluent Central/Eastern European region. Questionnaire data were analysed, for 8,926 singleton children aged 9–12 years. Country-specific odds ratios for effects of maternal smoking during pregnancy on being overweight, and on obesity, were estimated using logistic regression. Heterogeneity between country-specific results, and mean effects (allowing for heterogeneity) were estimated. Positive associations between maternal smoking and overweight were seen in all countries but Romania. While not individually statistically significant, the mean odds ratio was 1.26 (95% CI 1.03–1.55), with no evidence of between-country heterogeneity. Obese children were few (2.7%), and associations between obesity and maternal smoking during pregnancy were more heterogeneous, with odds ratios ranging from 0.71 (0.32–1.57) in Poland to 5.49 (2.11–14.30) in Slovakia. Between-country heterogeneity was strongly related to average persons-per-room, a possible socioeconomic indicator, with stronger associations where households were less crowded. Estimates of dose–response relationships tended to be small and non-significant, even when pooled. Our results provide evidence of a link between maternal smoking in pregnancy and childhood overweight. Associations with obesity, though strong in some countries, were less consistent. Maternal smoking may confer an addition to a child’s potential for obesity, which is more likely to be realised in affluent conditions.
The long-chain PUFA (LCPUFA) content of an infant's diet might affect early weight gain. In early trials on supplementation of formula feeding n-3 LCPUFA affected weight gain adversely. n-6 LCPUFA ...are thought to promote adipose tissue development and might be associated with higher weight gain. We studied the association between the natural n-3 and n-6 LCPUFA content of breast milk of Dutch women and weight and BMI gain of their breast-fed infants in the first year of life. The children in this study were enrolled in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and were born in 1996-1997 in the Netherlands. Parents reported their child's weight and length in a questionnaire. Of a subgroup of the total population breast-milk samples were collected (n 244). The fatty acid composition of breast milk was determined by GLC and expressed as weight percentages. Linear regression was used for data analysis. Mean gain in weight, length and BMI per week from birth to 1 year of age was 119·5 (sd 16·1) g, 0·48 (sd 0·05) cm and 0·06 (sd 0·03) kg/m2, respectively. The associations between n-6 and n-3 LCPUFA in breast milk, and infant weight, length and BMI gain were weak and inconsistent. The n-3 and n-6 LCPUFA content in breast milk did not affect weight or BMI gain in the first year of life in breast-fed term infants.