Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions.

BACKGROUND: Childhood asthma is a result of a complex interaction of genetic and environmental components causing epigenetic and immune dysregulation, airway inflammation and impaired lung function. Although different microarray based EWAS studies have been conducted, the impact of epigenetic regulation in asthma development is still widely unknown. We have therefore applied unbiased whole genome bisulfite sequencing (WGBS) to characterize global DNA-methylation profiles of asthmatic children compared to healthy controls. METHODS: Peripheral blood samples of 40 asthmatic and 42 control children aged 5-15 years from three birth cohorts were sequenced together with paired cord blood samples. Identified differentially methylated regions (DMRs) were categorized in genotype-associated, cell-type-dependent, or prenatally primed. Network analysis and subsequent natural language processing of DMR-associated genes was complemented by targeted analysis of functional translation of epigenetic regulation on the transcriptional and protein level. RESULTS: In total, 158 DMRs were identified in asthmatic children compared to controls of which 37% were related to the eosinophil content. A global hypomethylation was identified affecting predominantly enhancer regions and regulating key immune genes such as IL4, IL5RA, and EPX. These DMRs were confirmed in n = 267 samples and could be linked to aberrant gene expression. Out of the 158 DMRs identified in the established phenotype, 56 were perturbed already at birth and linked, at least in part, to prenatal influences such as tobacco smoke exposure or phthalate exposure. CONCLUSION: This is the first epigenetic study based on whole genome sequencing to identify marked dysregulation of enhancer regions as a hallmark of childhood asthma.

Sleeping on animal fur is related to asthma outcomes in later childhood.

Animal furs might represent a "proxy" for high and diverse microbial exposures within a critical time window of immune development. We assessed whether sleeping on animal fur shortly after birth is associated with asthma and atopy up to the age of 10 years. LISAplus participants (n=2441) from Munich and Leipzig, Germany, were included in the analysis. Animal fur exposure, cofactors and health outcomes were obtained periodically up to 10 years of age by parental questionnaires. Information on specific IgE to aeroallergens was available at 10 years. Cytokine-producing peripheral T-cells were assessed in a subgroup of children at 2 and 3 years. Confounder-adjusted associations were evaluated using logistic regression analyses. Sleeping on animal fur was very common (55%). In adjusted logistic regression analyses, sleeping on animal fur was inversely associated with recurrent early wheezing at 4 years (adjusted OR 0.75, 95% CI 0.61-0.93) and current asthma at 6 years (adjusted OR 0.56, 95% CI 0.31-1.01). Furthermore, sleeping on animal fur during the first 3 months of life was significantly associated with a persistently stimulated interferon-γ response until the age of 3 years. Animal fur could be an effective measure of creating environments associated with higher microbial exposure.

Exposure to visible mould or dampness at home and sleep problems in children: Results from the LISAplus study.

BACKGROUND: Exposure to mould or dampness at home has been associated with adverse respiratory effects in all age groups. This exposure has also been related to insomnia in adults. We aimed to investigate the association between exposure to visible mould or dampness at home and sleep problems in children. METHODS: The study population consisted of 1719 10-year-old children from the German population-based birth cohort LISAplus with available data on current mould or dampness at home and sleep problems. The presence of visible mould or dampness at home was assessed by questionnaire. Parent-reported sleep problems of their child were analysed by four binary variables: presence of any sleep problems, problems to fall asleep, problems sleeping through the night and a 24h sleep time of less than 9h. Logistic regression models adjusted for study centre, sex, age and level of parental education were applied to examine the association between visible mould or dampness at home and sleep problems. Sensitivity analyses included a further adjustment for bedroom sharing and subgroup analyses in children without current allergic diseases. RESULTS: Thirteen percent of parents reported visible mould or dampness at home. We observed increased risks for all four sleep problem variables for children exposed to visible mould or dampness at home. Results were significant for any sleep problems (odds ratio (OR)=1.77 (95%-confidence interval (CI): 1.21-2.60), problems sleeping through the night (OR=2.52(1.27-5.00) and a short sleep time (OR=1.68(1.09-2.61)). While a further adjustment for bedroom sharing and the exclusion of children with asthma or eczema led to similar results, only the association with a short sleep time was still present in children without allergic rhinoconjunctivitis. CONCLUSION: Our data suggests that visible mould or dampness at home might negatively influence sleep in children. The influence of allergic rhinoconjunctivitis on this association needs to be investigated in future studies.

The association between physical activity and healthcare costs in children--results from the GINIplus and LISAplus cohort studies.

BACKGROUND: Physical inactivity in children is an important risk factor for the development of various morbidities and mortality in adulthood, physical activity already has preventive effects during childhood. The objective of this study is to estimate the association between physical activity, healthcare utilization and costs in children. METHODS: Cross-sectional data of 3356 children aged 9 to 12 years were taken from the 10-year follow-up of the birth cohort studies GINIplus and LISAplus, including information on healthcare utilization and physical activity given by parents via self-administered questionnaires. Using a bottom-up approach, direct costs due to healthcare utilization and indirect costs resulting from parental work absence were estimated for the base year 2007. A two-step regression model compared effects on healthcare utilization and costs for a higher (≥ 7 h/week) versus a lower (<7 h/week) level of moderate-to-vigorous physical activity (MVPA) adjusted for age, gender, BMI, education and income of parents, single parenthood and study region. Recycled predictions estimated adjusted mean costs per child and activity group. RESULTS: The analyses for the association between physical activity, healthcare utilization and costs showed no statistically significant results. Different directions of estimates were noticeable throughout cost components in the first step as well as the second step of the regression model. For higher MVPA (≥ 7 h/week) compared with lower MVPA (< 7 h/week) total direct costs accounted for 392 EUR (95% CI: 342-449 EUR) versus 398 EUR (95% CI: 309-480 EUR) and indirect costs accounted for 138 EUR (95% CI: 124-153 EUR) versus 127 EUR (95% CI: 111-146 EUR). CONCLUSIONS: The results indicate that childhood might be too early in life, to detect significant preventive effects of physical activity on healthcare utilization and costs, as diseases attributable to lacking physical activity might first occur later in life. This underpins the importance of clarifying the long-term effects of physical activity as it may strengthen the promotion of physical activity in children from a health economic perspective.

Cesarean delivery and risk of childhood obesity.

OBJECTIVE: To investigate whether birth by cesarean delivery rather than vaginal delivery is a risk factor for later childhood obesity. STUDY DESIGN: Healthy, full-term infants were recruited. Overweight and obesity were defined using measured weight and height according to World Health Organization reference data. Associations between cesarean delivery and being overweight or obese were investigated at age 2, 6, and 10 years (n = 1734, 1244, and 1170, respectively) by multivariate logistic regression models adjusted for socioeconomic status, child characteristics, and maternal prepregnancy characteristics. RESULTS: Mothers who gave birth by cesarean delivery (∼17%) had a higher mean prepregnancy body mass index (23.7 kg/m(2) vs 22.5 kg/m(2)), greater mean gestational weight gain (15.3 kg vs 14.5 kg), and shorter mean duration of exclusive breastfeeding (3.4 months vs 3.8 months) compared with those who delivered vaginally. The proportion of obese children was greater in the cesarean delivery group compared with the vaginal delivery group at age 2 years (13.6% vs 8.3%), but not at older ages. Regression analyses revealed a greater likelihood of obesity at age 2 years in the cesarean delivery group compared with the vaginal delivery group at age 2 years (aOR, 1.68; 95% CI, 1.10-2.58), but not at age 6 years (aOR, 1.49; 95% CI, 0.55-4.05) or age 10 years (aOR, 1.16; 95% CI, 0.59-2.29). CONCLUSION: Cesarean delivery may increase the risk of obesity in early childhood. Our results do not support the hypothesis that an increasing rate of cesarean delivery contributes to obesity in childhood.

Food intake and overweight in school-aged children in Germany: Results of the GINIplus and LISAplus studies.

OBJECTIVE: To investigate the cross-sectional association between food intake and overweight in children. METHODS: Height and weight were measured in 2,565 school-aged children. Intakes of 11 food groups were categorized (low, medium and high) using specific tertile cutoffs. Multivariate energy partition models were applied. Adjustment included energy intake from other food groups, city, family income, parental education and 'screen' time. Possible underreporters were identified and used in sensitivity analyses. RESULTS: Compared to low intake, high intakes of meat, fish, beverages and bakery products were associated with greater BMI z-scores [ß (95% CI) = 0.32 (0.21, 0.42), 0.13 (0.03, 0.24), 0.23 (0.11, 0.35) and 0.10 (-0.01, 0.20)] and increased risk of being overweight [odds ratio (OR) (95% CI) = 2.08 (1.58, 2.73), 1.39 (1.08, 1.80), 1.36 (1.01, 1.84) and 1.62 (1.24, 2.11)]. Conversely, medium and high intakes of confectionery were associated with smaller BMI z-scores [ß = -0.18 (-0.28, -0.07) and -0.22 (-0.33, -0.12)] and decreased risk of being overweight [OR = 0.64 (0.50, 0.83) and 0.53 (0.40, 0.68)]. These associations were robust to sensitivity analyses. CONCLUSIONS: Intakes of meat, fish, beverages and bakery products correlate with body weight status.

Serum 25(OH)D concentrations and atopic diseases at age 10: results from the GINIplus and LISAplus birth cohort studies.

BACKGROUND: Vitamin D is well recognized for its role in skeletal health and its involvement in the modulation of the immune system. In the literature, controversial results are reported for atopic diseases. Thus, we investigated the association between vitamin D status and the prevalence of atopic diseases. METHODS: Serum 25-hydroxy-vitamin D (25(OH)D) concentrations were measured in a sample of 2815 10-years old children from two German birth cohort studies. Self-reported physician-diagnosed eczema, hay fever or allergic rhinitis, and asthma were used as outcome variables as well as specific IgE positivity against common allergens. We applied logistic regression models, deriving adjusted odds ratio estimates (aOR) and 95% confidence intervals (CI). RESULTS: For asthma and hay fever or allergic rhinitis, no associations existed with serum 25(OH)D concentrations. We observed a significant positive relationship between serum 25(OH)D levels and eczema at age 10 (aOR = 1.09, CI = 1.01-1.17, per 10 nmol/l increase in serum 25(OH)D levels) and for the lifetime prevalence of eczema (aOR = 1.05, CI = 1.01-1.09). Specific IgE positivity for food allergens (aOR = 1.07, CI = 1.02-1.11) and aeroallergens (aOR = 1.05, CI = 1.01-1.08) at age 10, as well as lifetime prevalence, was significantly related to the vitamin D status. CONCLUSION: In this study we found no indication that higher blood 25(OH)D levels are associated with decreased risk for any of the atopic outcomes in children. However, we observed a positive association of serum 25(OH)D concentrations with eczema and detectable specific IgE. Due to the given limitations of our study, the clinical relevance of these findings needs further clarification.

Healthcare use and costs associated with children's behavior problems.

The objective of the study was to investigate associations between severity of behavior problems, specific symptom domains with healthcare use and costs in school-aged children. A cross-sectional study using data from the 10-year follow-up of two population-based birth cohorts was conducted on four rural and urban communities in Germany. There were 3,579 participants [1,834 boys (51%), 1,745 girls (49%)] on average aged 10.4 years. The severity levels (normal, at risk, abnormal) and symptom domains of behavioral problems were assessed by parent-reported strengths and difficulties questionnaire (SDQ).The outcomes were medical use categories (physicians, therapists, hospital, and rehabilitation), medical costs categories and total direct medical use and costs (calculated from parent-reported utilization of healthcare services during the last 12 months). Total direct medical costs showed a graded relationship with severity level (adjusted p < 0.0001). Average annual cost difference in total direct medical costs between at risk and normal total difficulties was Euro () 271 (SD 858), and 1,237 (SD 2,528) between abnormal and normal total difficulties. A significant increase in physician costs showed between children with normal and at risk total difficulties (1.30), and between normal and abnormal total difficulties (1.29; p < 0.0001). Between specific symptom domains, children with emotional symptoms showed highest costs for physicians, psychotherapist, and hospitalization as well as total direct medical costs. Children with hyperactivity/inattention showed highest costs for therapists and emergency room costs. Healthcare use and costs are related to the severity of child behavior problems. In general, children's costs for psychotherapy treatments have been low relative to general medical treatments which may indicate that some children with behavioral problems did not get appropriate care. To some degree, medical conditions may be attributable to some of the high hospitalization costs found in children with emotional symptom.

Body mass index trajectory classes and incident asthma in childhood: results from 8 European Birth Cohorts--a Global Allergy and Asthma European Network initiative.

BACKGROUND: The causal link between body mass index (BMI) or obesity and asthma in children is still being debated. Analyses of large longitudinal studies with a sufficient number of incident cases and in which the time-dependent processes of both excess weight and asthma development can be validly analyzed are lacking. OBJECTIVE: We sought to investigate whether the course of BMI predicts incident asthma in childhood. METHODS: Data from 12,050 subjects of 8 European birth cohorts on asthma and allergies were combined. BMI and doctor-diagnosed asthma were modeled during the first 6 years of life with latent growth mixture modeling and discrete time hazard models. Subpopulations of children were identified with similar standardized BMI trajectories according to age- and sex-specific "World Health Organization (WHO) child growth standards" and "WHO growth standards for school aged children and adolescents" for children up to age 5 years and older than 5 years, respectively (BMI-SDS). These types of growth profiles were analyzed as predictors for incident asthma. RESULTS: Children with a rapid BMI-SDS gain in the first 2 years of life had a higher risk for incident asthma up to age 6 years than children with a less pronounced weight gain slope in early childhood. The hazard ratio was 1.3 (95% CI, 1.1-1.5) after adjustment for birth weight, weight-for-length at birth, gestational age, sex, maternal smoking in pregnancy, breast-feeding, and family history of asthma or allergies. A rapid BMI gain at 2 to 6 years of age in addition to rapid gain in the first 2 years of life did not significantly enhance the risk of asthma. CONCLUSION: Rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years.

Association of atopic and non-atopic asthma with emotional symptoms in school children.

OBJECTIVE: To date, there is conflicting evidence whether the association between asthma and depression depends on the atopic or non-atopic asthma phenotype. This study investigates associations between emotional symptoms and atopic and non-atopic asthma in school-aged children. METHODS: Cross-sectional data on asthma and allergic diseases at the 10-year follow-up of two birth cohorts were collected by parent-reported physician diagnoses. Specific IgE levels including most common inhalant allergens (SX1) and food allergens (FX5) were measured by RAST-CAP FEIA. Atopic asthma was defined as asthma ever and positive specific IgE test, non-atopic asthma as asthma ever and no IgE sensitization. Emotional symptoms were assessed by parent-reported strength and difficulty questionnaire. Logistic regression modeling were applied to determine likelihood of emotional symptoms in children with atopic and non-atopic asthma controlling for socio-demographic factors, body mass index, atopic eczema, allergic rhinitis, and pubertal development. RESULTS: Non-atopic asthma was associated with about 3-fold higher likelihood of emotional symptoms compared to children with no asthma (ORadj = 2.90, CI95% = 1.46-5.73). Atopic asthma was not associated with emotional symptoms (ORadj = 1.35, CI95% = 0.81-2.26). CONCLUSIONS: Atopic and non-atopic asthma in children might have different etiologies, whereas for non-atopic asthma, emotional symptoms are relevant, this is not the case in atopic asthma. The relationship between the non-atopic asthma phenotype and emotional symptoms might be dependent on gender.

Traffic, asthma and genetics: combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution's impact on childhood asthma.

Associations between traffic-related air pollution and incident childhood asthma can be strengthened by analysis of gene-environment interactions, but studies have typically been limited by lack of study power. We combined data from six birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and candidate genes. Individual-level assessment of traffic-related air pollution exposure was estimated using land use regression or dispersion modeling. A total of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study; 6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1 rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for investigating the effect of genotype on the association between air pollution and childhood allergic disease.

Physical activity and its correlates in children: a cross-sectional study (the GINIplus & LISAplus studies).

BACKGROUND: Physical inactivity among children is an increasing problem that adversely affects children's health. A better understanding of factors which affect physical activity (PA) will help create effective interventions aimed at raising the activity levels of children. This cross-sectional study examined the associations of PA with individual (biological, social, behavioral, psychological) and environmental (East vs. West Germany, rural vs. urban regions) characteristics in children. METHODS: Information on PA and potential correlates was collected from 1843 girls and 1997 boys using questionnaires during the 10-year follow-up of two prospective birth cohort studies (GINIplus and LISAplus). Study regions represent urban and rural sites as well as East and West of Germany. Logistic regression modeling was applied to examine cross-sectional associations between individual as well as environmental factors and PA levels. RESULTS: Five of fourteen variables were significantly associated with PA. Among children aged 10, girls tended to be less active than boys, especially with respect to vigorous PA (OR = 0.72 for summer). Children who were not a member of a sports club showed a substantially reduced amount of PA in winter (OR = 0.15). Rural environments promote moderate PA, particularly in winter (OR = 1.88), whereas an increased time outdoors primarily promotes moderate PA in summer (OR = 12.41). Children with abnormal emotional symptoms exhibited reduced physical activity, particularly in winter (OR = 0.60). BMI, puberty, parental BMI, parental education, household income, siblings, TV/PC consumption, and method of arriving school, were not associated with PA. CONCLUSIONS: When considering correlates of PA from several domains simultaneously, only few factors (sex, sports club membership, physical environment, time outdoors, and emotional symptoms) appear to be relevant. Although the causality needs to be ascertained in longitudinal studies, variables which cannot be modified should be used to identify risk groups while modifiable variables, such as sports club activities, may be addressed in intervention programs.

Utilization and costs of conventional and alternative pharmaceuticals in children: results from the German GINIplus and LISAplus birth cohort studies.

PURPOSE: The socioeconomic determinants for drug utilization, especially in children, have not been investigated sufficiently so far. The study's aim was the estimation of prevalences and determinants of conventional, homeopathic and phytotherapeutic drugs and expenditures. METHODS: Population-based data on drug utilization of 3,642 children in two German birth cohorts (GINIplus and LISAplus, 10-year follow-up) were collected using a self-administered questionnaire. For analysis, the reported drugs (use within the last four weeks) were classified into the therapeutic categories of 'conventional medicine', 'homeopathy', 'phytotherapy' and 'others'. Drug costs were estimated using pharmaceutical identification numbers. RESULTS: In all, 42.3% of the children reported drug use; 24.1% of the drugs were homeopathic and 11.5% were phytotherapeutic. The proportion of children who took at least one homeopathic remedy was 14.3%. Drugs prescribed by physicians were dominated by conventional medicine (76.5%), whereas in non-prescribed drugs, both homeopathy and conventional medicine accounted for 37% each. Boys (OR = 0.78) used less homeopathy than girls. Income showed only a weak influence. Education had a strong effect on the use of phytotherapy such that children of mothers with higher school education (>10 years vs. <10 years) used more phytotherapy (OR = 2.01). If out-of-pocket payments arose (n = 613), the mean was €20. On average, total drug expenditures summed up to €39 in 4 weeks for drug users if only clearly identifiable prices for drugs were considered (58% of all data). CONCLUSIONS: Utilization of homeopathy is common in children from the analyzed cohort. User profiles of homeopathy and phytotherapy differ from each other and should be analyzed separately.

Food intake, diet quality and behavioral problems in children: results from the GINI-plus/LISA-plus studies.

BACKGROUND/AIMS: To assess the association between food intake and diet quality and behavioral problems at the 10-year follow-up of the two population-based birth cohorts of the studies German Infant Nutritional Intervention and 'Influences of lifestyle-related factors on the immune system and the development of allergies in childhood'. METHODS: Cross-sectional data on food intake over the past year were collected by a parent-reported food frequency questionnaire. Diet quality was based on reference values of food amounts of the optimized mixed diet. Behavioral problems were assessed by a parent-reported Strengths and Difficulties Questionnaire. Relationships between food category intake, diet quality and behavior problems were examined using multivariable regression modeling adjusted for gender, sociodemographic characteristics, body mass index, physical exercise, television viewing/PC use and total energy intake. A total of 3,361 children with complete data were analyzed. RESULTS: Children with increased intake of confectionery had increased odds of having emotional symptoms [adjusted odds ratio (OR(adj)) 1.19, 95% confidence interval (CI) 1.08-1.32] compared to children with low intake. A higher diet quality score was associated with lower likelihood of emotional symptoms (OR(adj) 0.89, 95% CI 0.80-0.98). The unadjusted significant relationship between diet quality and hyperactivity/inattention was attenuated by adjusting for several confounders to an OR(adj) of 0.92 (95% CI 0.82-1.03). CONCLUSIONS: Increased consumption of high-sugar products and lower diet quality are associated with a higher likelihood of emotional symptoms in children.

Exposure to second-hand smoke and direct healthcare costs in children - results from two German birth cohorts, GINIplus and LISAplus.

BACKGROUND: Although the negative health consequences of the exposure to second hand tobacco smoke during childhood are already known, evidence on the economic consequences is still rare. The aim of this study was to estimate excess healthcare costs of exposure to tobacco smoke in German children. METHODS: The study is based on data from two birth cohort studies of 3,518 children aged 9-11 years with information on healthcare utilisation and tobacco smoke exposure: the GINIplus study (German Infant Study On The Influence Of Nutrition Intervention Plus Environmental And Genetic Influences On Allergy Development) and the LISAplus study (Influence of Life-Style Factors On The Development Of The Immune System And Allergies In East And West Germany Plus The Influence Of Traffic Emissions And Genetics). Direct medical costs were estimated using a bottom-up approach (base year 2007). We investigated the impact of tobacco smoke exposure in different environments on the main components of direct healthcare costs using descriptive analysis and a multivariate two-step regression analysis. RESULTS: Descriptive analysis showed that average annual medical costs (physician visits, physical therapy and hospital treatment) were considerably higher for children exposed to second-hand tobacco smoke at home (indoors or on patio/balcony) compared with those who were not exposed. Regression analysis confirmed these descriptive trends: the odds of positive costs and the amount of total costs are significantly elevated for children exposed to tobacco smoke at home after adjusting for confounding variables. Combining the two steps of the regression model shows smoking attributable total costs per child exposed at home of €87 [10-165] (patio/balcony) and €144 [6-305] (indoors) compared to those with no exposure. Children not exposed at home but in other places showed only a small, but not significant, difference in total costs compared to those with no exposure. CONCLUSIONS: This study shows adverse economic consequences of second-hand smoke in children depending on proximity of exposure. Tobacco smoke exposure seems to affect healthcare utilisation in children who are not only exposed to smoke indoors but also if parents reported exclusively smoking on patio or balcony. Preventing children from exposure to second-hand tobacco smoke might thus be desirable not only from a health but also from an economic perspective.

Predictive value of food sensitization and filaggrin mutations in children with eczema.

BACKGROUND: It was reported that in infants with eczema and food sensitization, the presence of a filaggrin (FLG) null mutation predicts future asthma with a specificity and positive predictive value of 100%. OBJECTIVES: We sought to evaluate the predictive value of food sensitization and food allergy, FLG haploinsufficiency, and their combination in infants with early-onset eczema for persistent eczema and childhood asthma. METHODS: The German Infant Nutritional Intervention (GINI) and Influence of Lifestyle-related Factors on the Immune System and the Development of Allergies in Childhood (LISA) birth cohorts, as well as a collection of 65 cases of early-onset eczema with and without food allergy were investigated. RESULTS: The risk for asthma was significantly increased by food sensitization (positive diagnostic likelihood ratios [PLRs] of 1.9 [95% CI, 1.1-3.4] in the GINI cohort and 5.5 [95% CI, 2.8-10.8] in the LISA cohort) and the presence of an FLG mutation (PLRs of 2.9 [95% CI, 1.2-6.6] in the GINI cohort and 2.8 [95% CI, 1.0-7.9] in the LISA cohort) with a rather high specificity (79.1% and 92.9% in the GINI cohort and 89.0% and 91.7% in the LISA cohort, respectively) but low sensitivity (40.0% and 39.3% in the GINI cohort and 31.6% and 23.5% in the LISA cohort, respectively). Likewise, the risk for persistent eczema was increased. In the clinical cases neither food allergy nor FLG mutations had a significant effect. The combination of both parameters did not improve prediction and reached positive predictive values of 52.3% (GINI cohort), 66.9% (LISA cohort), and 30.6% (clinical cases), assuming an asthma prevalence in children with early eczema of 30%. CONCLUSION: Early food sensitization and the presence of an FLG mutation in infants with early eczema increase the risk for later asthma, but the combination of the 2 factors does not represent a clinically useful approach to reliably identify children at risk.

Passive smoking and behavioural problems in children: results from the LISAplus prospective birth cohort study.

OBJECTIVE: To analyse the association between pre- and postnatal exposure to tobacco smoke and child behavioural problems and to further investigate the influence of trimester-specific exposure to maternal smoking and the impact of paternal smoking at home on the same outcome. METHODS: Data of 3097 German children recruited at birth for a population-based, prospective study were used. Detailed information on children's tobacco smoke exposure was collected by self-administered questionnaires at each follow-up. Behavioural outcomes were measured by the Strengths and Difficulties Questionnaire applied at 10-year follow-up. RESULTS: Children exposed to environmental tobacco smoke at home showed increased risks of hyperactivity/inattention problems. Only smoking during the entire pregnancy increased the risk for conduct and hyperactivity/inattention problems (proportional odds ratio (pOR)=1.58, 95% confidence interval (CI)=1.06-2.37 and pOR=1.67, CI=1.03-2.72). Pre- and postnatal exposure to paternal smoking was associated with hyperactivity/inattention problems in children of non-smoking mothers (pOR=1.97, CI=1.06-3.65). Effect estimates were adjusted for study centre, sex, parental educational level, mother's age at birth, having a single parent and time spent in front of a screen. CONCLUSIONS: Not only maternal smoking during pregnancy but also paternal smoking at home should be considered as a risk for hyperactivity/inattention problems in children.

Regional and socio-economic differences in food, nutrient and supplement intake in school-age children in Germany: results from the GINIplus and the LISAplus studies.

OBJECTIVE: To describe regional differences between eastern and western Germany with regard to food, nutrient and supplement intake in 9-12-year-old children, and analyse its association with parental education and equivalent income. DESIGN: Data were obtained from the 10-year follow-up of the two prospective birth cohort studies - GINIplus and LISAplus. Data on food consumption and supplement intake were collected using an FFQ, which had been designed for the specific study population. Information on parental educational level and equivalent income was derived from questionnaires. Logistic regression modelling was used to analyse the effect of parental education, equivalent income and region on food intake, after adjusting for potential confounders. SETTING: Germany. SUBJECTS: A total of 3435 children aged 9-12 years. RESULTS: Substantial regional differences in food intake were observed between eastern and western Germany. Intakes of bread, butter, eggs, pasta, vegetables/salad and fruit showed a significant direct relationship with the level of parental education after adjusting for potential confounders, whereas intakes of margarine, meat products, pizza, desserts and soft drinks were inversely associated with parental education. Equivalent income had a weaker influence on the child's food intake. CONCLUSIONS: Nutritional education programmes for school-age children should therefore account for regional differences and parental education.

Elder siblings enhance the effect of filaggrin mutations on childhood eczema: results from the 2 birth cohort studies LISAplus and GINIplus.

BACKGROUND: Several studies showed a protective effect of elder siblings on eczema development, which is in line with the hygiene hypothesis. However, findings are not consistent, and there might exist different causal pathways for the development of eczema. Especially barrier disturbances as found in children with mutations in the filaggrin gene (FLG) seem to play an important role. OBJECTIVES: To investigate the interaction between FLG mutations and the presence of elder siblings on the development of eczema in 2 independent birth cohorts. METHODS: We used data from 2 German birth cohorts (LISAplus, GINIplus) up to the age of 6 years. Genotyping for FLG mutations (R501X, 2282del4) was performed in 1039 (LISAplus) and 1828 (GINIplus) children. Data on eczema (diagnosis and symptoms) and elder siblings were obtained by parental questionnaires. The association among eczema, FLG mutations, and elder siblings was analyzed longitudinally by using generalized estimating equations. RESULTS: We found no protective effect of elder siblings on eczema development. On the contrary, children with FLG mutations had a significantly higher risk for eczema if they had elder siblings. Attending day care centers lessened this effect. After excluding 303 children who attended early day care, the odds ratio for interaction between FLG mutations and elder siblings was 3.27 (95% CI, 1.14-9.36) in LISAplus and 2.41 (95% CI, 1.06-5.48) in GINIplus. CONCLUSION: Our findings did not confirm a protective sibling effect. The prevalence of eczema in children with filaggrin deficiency was higher if elder siblings were present. Our results give evidence for complex skin-driven pathogenic mechanisms that might be different depending on children's genetic backgrounds.