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1.  Body Mass Index Development from Birth to Early Adolescence; Effect of Perinatal Characteristics and Maternal Migration Background in a Swedish Cohort 
PLoS ONE  2014;9(10):e109519.
Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring.
To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics.
A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data.
We observed a significant BMI change over time in children and time interaction with maternal migration status (P<0.0001). Estimated BMI over time adjusted for maternal and perinatal characteristics of offspring, showed slower BMI growth before age of 5, followed by an earlier plateau and steeper BMI growth after 5 years among children of immigrant mothers compared with children of Swedish mothers. These differences in BMI growth were more prominent among children with mothers from outside Europe.
Beside reinforcing early childhood as a crucial period in development of overweight, the observed slower BMI development at early childhood among children of immigrants followed by a steeper increase in BMI compared with children of Swedish mothers is important for further studies and for planning of preventive public health programs.
PMCID: PMC4193784  PMID: 25303283
2.  Effect of Parental Migration Background on Childhood Nutrition, Physical Activity, and Body Mass Index 
Journal of Obesity  2014;2014:406529.
Background. Poor nutrition, lack of physical activity, and obesity in children have important public health implications but, to date, their effects have not been studied in the growing population of children in Sweden with immigrant parents. Methods. We estimated the association between parental migration background and nutrition, physical activity, and weight in 8-year-old children born in Stockholm between 1994 and 1996 of immigrants and Swedish parents (n = 2589). Data were collected through clinical examination and questionnaires filled out by parents. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using multivariable logistic regression. Results. Children of immigrants complied more closely with Nordic Nutrition Recommendations compared with those of Swedes (OR = 1.35, 95% CI 1.11–1.64). They had higher intake of dietary fibre, vitamins C, B6, and E, folic acid, and polyunsaturated fatty acids (omega-3 and omega-6) reflecting higher consumption of foods of plant origin, but lower intake of vitamins A and D, calcium, and iron reflecting lower consumption of dairy products. Children of immigrants had higher intake of sucrose reflecting higher consumption of sugar and sweets. Furthermore, these children had a higher risk of having low physical activity (OR = 1.31, 95% CI 1.06–1.62) and being overweight (OR = 1.33, 95% CI 1.06–1.65) compared with children of Swedish parents. The odds of having low physical activity and being overweight were even higher in children whose parents were both immigrants. A low level of parental education was associated with increased risk of low physical activity regardless of immigration background. Conclusions. Culturally appropriate tools to capture the diverse range of ethnic foods and other lifestyle habits are needed. Healthcare professionals should be aware of the low levels of physical activity, increased weight, and lack of consumption of some important vitamins among children of immigrants.
PMCID: PMC4058807  PMID: 24991430
3.  Genomewide association study of the age of onset of childhood asthma 
Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children.
To identify genetic variants associated with earlier onset of childhood asthma.
We conducted the first genome-wide association study (GWAS) of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP), and used three independent cohorts from North America, Costa Rica, and Sweden for replication.
Two SNPs were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: : rs9815663 (Fisher’s P value=2.31 × 10−8) and rs7927044 (P=6.54 × 10−9). Of these two SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10−7 < P < 8.22 ×10−6). Having ≥1 risk allele of the two SNPs of interest (rs9815663 and rs7927044) was associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP.
We have identified two SNPs associated with earlier onset of childhood asthma in four independent cohorts.
PMCID: PMC3387331  PMID: 22560479
Asthma; pediatrics; age of onset; asthma genetics; C1orf100; genome-wide association study; pediatric asthma
4.  Environmental exposure assessment in European birth cohorts: results from the ENRIECO project 
Environmental Health  2013;12:8.
Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.
PMCID: PMC3564791  PMID: 23343014
Environment; Europe; Exposure assessment; Birth cohort; Review
5.  Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial 
Thorax  2011;67(3):215-221.
To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma.
Randomised, double-blind, placebo-controlled, parallel-group trial.
Nineteen European asthma clinics.
312 patients aged 7–70 with inadequately controlled persistent atopic asthma.
Main outcome measure
Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment.
TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of −7.1 ppb (−13.6 to −0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups.
Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma.
Trial registration number
Clinical Trials NCT00986323.
PMCID: PMC3282042  PMID: 22131290
Asthma; exposure control; temperature controlled laminar air flow; protexo; quality of life; allergic lung disease; paediatric physician; paediatric asthma; asthma pharmacology; aspergillus lung disease; copd mechanisms; eosinophil biology
6.  Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma 
Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.
To test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.
We genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.
Across the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.
TSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.
PMCID: PMC3032752  PMID: 21244681
7.  Birth anthropometric measures, body mass index and allergic diseases in a birth cohort study (BAMSE) 
Archives of Disease in Childhood  2007;92(10):881-886.
We aimed to assess increased birth weight or birth length in relation to allergic diseases at 4 years of age, taking body mass index (BMI) at age 4 as a covariate in the adjustment.
The parents of a large prospective birth cohort answered questionnaires on environmental factors and allergic symptoms when their children were 2 months and 1, 2 and 4 years old. Perinatal data on weight and length at birth were received from the child care health centres. The children were clinically examined at 4 years of age and height and weight recorded. Blood was drawn for analysis of specific IgE antibodies to common inhalant allergens. Risk associations between birth anthropometric measures and wheeze, allergic diseases or sensitisation were estimated in multivariate logistic regression analyses (n = 2869).
There were no clear overall associations between birth weight and allergic diseases at 4 years of age. Birth length ⩾90th percentile was inversely associated with any wheeze at age 4 (adjusted OR 0.64, 95% CI 0.44 to 0.92) but was significantly associated only with late‐onset wheeze (adjusted OR 0.40, 95% CI 0.21 to 0.77). No such associations were seen for persistent or transient wheeze, eczema, rhinitis or allergic sensitisation. Transient wheeze during the first 2 years of age tended to be associated with increased BMI at age 4.
Increased birth weight was not associated with wheeze or allergic disease. Increased birth length may play a protective role in late‐onset wheeze in early childhood.
PMCID: PMC2083245  PMID: 17475692
allergy; birth anthropometry; birth cohort; body mass index; wheeze
8.  MMP12, Lung Function, and COPD in High-Risk Populations 
The New England journal of medicine  2009;361(27):2599-2608.
Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups.
We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV1]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV1 and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD.
The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [−82A→G]) was positively associated with FEV1 in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2×10−6). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P = 0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P = 0.005) and among participants in a family-based study of early-onset COPD (P = 0.006).
The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers.
PMCID: PMC2904064  PMID: 20018959
9.  Interactions between Glutathione S-Transferase P1, Tumor Necrosis Factor, and Traffic-Related Air Pollution for Development of Childhood Allergic Disease 
Environmental Health Perspectives  2008;116(8):1077-1084.
Air pollutants may induce airway inflammation and sensitization due to generation of reactive oxygen species. The genetic background to these mechanisms could be important effect modifiers.
Our goal was to assess interactions between exposure to air pollution and single nucleotide polymorphisms (SNPs) in the β2-adrenergic receptor (ADRB2), glutathione S-transferase P1 (GSTP1), and tumor necrosis factor (TNF) genes for development of childhood allergic disease.
In a birth cohort originally of 4,089 children, we assessed air pollution from local traffic using nitrogen oxides (traffic NOx) as an indicator based on emission databases and dispersion modeling and estimated individual exposure through geocoding of home addresses. We measured peak expiratory flow rates and specific IgE for inhalant and food allergens at 4 years of age, and selected children with asthma symptoms up to 4 years of age (n = 542) and controls (n = 542) for genotyping.
Interaction effects on allergic sensitization were indicated between several GSTP1 SNPs and traffic NOx exposure during the first year of life (pnominal < 0.001–0.06). Children with Ile105Val/Val105Val genotypes were at increased risk of sensitization to any allergen when exposed to elevated levels of traffic NOx (for a difference between the 5th and 95th percentile of exposure: odds ratio = 2.4; 95% confidence interval, 1.0–5.3). In children with TNF-308 GA/AA genotypes, the GSTP1–NOx interaction effect was even more pronounced. We observed no conclusive interaction effects for ADRB2.
The effect of air pollution from traffic on childhood allergy appears to be modified by GSTP1 and TNF variants, supporting a role of genes controlling the antioxidative system and inflammatory response in allergy.
PMCID: PMC2516580  PMID: 18709160
ADRB2; air pollution; allergy; asthma; genetics; GSTP1; interaction; nitrogen oxides; polymorphism; TNF
10.  Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (BAMSE) 
Respiratory Research  2006;7(1):3.
Exposure to cigarette smoking during foetal and early postnatal life may have implications for lung health. The aim of this study was to assess the possible effects of such exposure in utero on lower respiratory disease in children up to two years of age.
A birth cohort of 4089 newborn infants was followed for two years using parental questionnaires. When the infant was two months old the parents completed a questionnaire on various lifestyle factors, including maternal smoking during pregnancy and after birth. At one and two years of age information was obtained by questionnaire on symptoms of allergic and respiratory diseases as well as on environmental exposures, particularly exposure to environmental tobacco smoke (ETS). Adjustments were made for potential confounders.
When the mother had smoked during pregnancy but not after that, there was an increased risk of recurrent wheezing up to two years' age, ORadj = 2.2, (95% CI 1.3 – 3.6). The corresponding OR was 1.6, (95% CI 1.2 – 2.3) for reported exposure to ETS with or without maternal smoking in utero. Maternal smoking during pregnancy but no exposure to ETS also increased the risk of doctor's diagnosed asthma up to two years of age, ORadj = 2.1, (95% CI 1.2 – 3.7).
Exposure to maternal cigarette smoking in utero is a risk factor for recurrent wheezing, as well as doctor's diagnosed asthma in children up to two yearsof age.
PMCID: PMC1360665  PMID: 16396689

Results 1-10 (10)