Publications by authors named "Beate Schaaf"

41 Publications

Longitudinal trends of serum IgE and IL5RA expression throughout childhood are associated with asthma but not with persistent wheeze.

Allergy 2019 10 21;74(10):2002-2006. Epub 2019 May 21.

Molecular Epidemiology Unit, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, associated partner of the German Center for Lung Research (DZL), Berlin, Germany.

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http://dx.doi.org/10.1111/all.13837DOI Listing
October 2019

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

BMC Public Health 2015 Apr 29;15:437. Epub 2015 Apr 29.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1186/s12889-015-1721-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423115PMC
April 2015

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

Eur Respir J 2015 Jul 2;46(1):107-14. Epub 2015 Apr 2.

Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1183/09031936.00204914DOI Listing
July 2015

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

Environ Res 2015 Feb 17;137:357-63. Epub 2015 Jan 17.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.envres.2014.11.023DOI Listing
February 2015

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

BMC Pediatr 2014 Nov 25;14:286. Epub 2014 Nov 25.

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.
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http://dx.doi.org/10.1186/s12887-014-0286-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251945PMC
November 2014

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

Ann Nutr Metab 2014 22;64(1):60-70. Epub 2014 May 22.

Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

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 [β (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 [β = -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.
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http://dx.doi.org/10.1159/000362694DOI Listing
February 2015

Cesarean delivery and risk of childhood obesity.

J Pediatr 2014 May 5;164(5):1068-1073.e2. Epub 2014 Feb 5.

Division of Pediatric, Gastroenterology, and Hepatology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpeds.2013.12.044DOI Listing
May 2014

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

Eur Child Adolesc Psychiatry 2014 Aug 11;23(8):701-14. Epub 2013 Dec 11.

Institute of Epidemiology I, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany,

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.
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http://dx.doi.org/10.1007/s00787-013-0504-9DOI Listing
August 2014

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.

Eur J Epidemiol 2013 Jul 24;28(7):597-606. Epub 2013 Jul 24.

School of Population and Public Health, University of British Columbia, 2206 East Mall, Vancouver, BC, V6T1Z3, Canada.

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.
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http://dx.doi.org/10.1007/s10654-013-9828-5DOI Listing
July 2013

Children with ADHD symptoms have a higher risk for reading, spelling and math difficulties in the GINIplus and LISAplus cohort studies.

PLoS One 2013 27;8(5):e63859. Epub 2013 May 27.

Max Planck Institute of Psychiatry, Munich, Germany.

Attention-deficit/hyperactivity disorder (ADHD) and dyslexia belong to the most common neuro-behavioral childhood disorders with prevalences of around 5% in school-aged children. It is estimated that 20-60% of individuals affected with ADHD also present with learning disorders. We investigated the comorbidity between ADHD symptoms and reading/spelling and math difficulties in two on-going population-based birth cohort studies. Children with ADHD symptoms were at significantly higher risk of also showing reading/spelling difficulties or disorder (Odds Ratio (OR) = 2.80, p = 6.59×10⁻¹³) as compared to children without ADHD symptoms. For math difficulties the association was similar (OR = 2.55, p = 3.63×10⁻⁰⁴). Our results strengthen the hypothesis that ADHD and learning disorders are comorbid and share, at least partially, the same underlying process. Up to date, it is not clear, on which exact functional processes this comorbidity is based.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063859PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664565PMC
November 2013

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

Pediatr Allergy Immunol 2013 May;24(3):230-6

Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1111/pai.12056DOI Listing
May 2013

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

BMC Public Health 2013 Apr 16;13:349. Epub 2013 Apr 16.

Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany.

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.
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http://dx.doi.org/10.1186/1471-2458-13-349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641958PMC
April 2013

No cross-sectional and longitudinal association of ferritin and symptoms of attention-deficit-/hyperactivity disorder in a large population-based sample of children: results from the GINIplus and LISAplus studies.

Atten Defic Hyperact Disord 2013 Sep 13;5(3):313-20. Epub 2013 Apr 13.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Clinic of Munich, Nußbaumstr. 5 a, 80336 Munich, Germany.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with alterations in iron metabolism, and low ferritin concentrations in peripheral blood have inconsistently been reported in clinically referred samples of children with ADHD. This study examined whether higher peripheral concentrations of ferritin, the major iron storage protein, are associated with decreased symptoms of ADHD in 2,805 children aged 10 years participating in two large population-based birth cohorts (GINIplus and LISAplus). Whether high ferritin concentrations at age 4 months predict lower ADHD symptoms at age 10 years was also investigated using a longitudinal approach in a subsample of 193 children. No indications for an association between peripheral ferritin concentrations and ADHD symptoms were found in this large population-based study. Re-evaluating iron substitution as a therapeutic measure for ADHD may be warranted.
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http://dx.doi.org/10.1007/s12402-013-0108-8DOI Listing
September 2013

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

J Allergy Clin Immunol 2013 Jun 10;131(6):1528-36. Epub 2013 Feb 10.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1016/j.jaci.2013.01.001DOI Listing
June 2013

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

BMC Health Serv Res 2012 Oct 2;12:344. Epub 2012 Oct 2.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Member of the German Center for Lung Research, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1186/1472-6963-12-344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506539PMC
October 2012

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

Pharmacoepidemiol Drug Saf 2012 Oct 1;21(10):1102-11. Epub 2012 Aug 1.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1002/pds.3323DOI Listing
October 2012

Genetic association between obstructive bronchitis and enzymes of oxidative stress.

Metabolism 2012 Dec 26;61(12):1771-9. Epub 2012 Jun 26.

UFZ-Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Leipzig, Germany.

Objective: Obstructive respiratory diseases, mainly the chronic obstructive pulmonary disease (COPD) and asthma, are associated with functional polymorphisms of xenobiotic-metabolizing enzymes (XMEs). To date, association for obstructive bronchitis has not been described.

Material/methods: In this study, we investigated the genotypes from 26 functional polymorphisms of 20 XMEs in children (n, 1028) at the age of 6 years from the German prospective birth cohort study (LISAplus) and analyzed the associations between genotypes and obstructive bronchitis.

Results: For the first time, we found noteworthy gene-disease associations for the functional PON1 M55L and EPHX1 H139R polymorphisms and gene-environment associations for the functional COMT V158M and NQO1 P187S polymorphisms after stratification for maternal active smoking behaviour during pregnancy. The noteworthy associations were substantiated by the biological findings that all the risk genotypes belong to genes involved in oxidative stress and code for proteins with a fast enzymatic activity or concomitantly appear in common estrogene-metabolizing pathway (COMT, NQO1).

Conclusion: The oxidative stress has to be taken into account in mechanism of the obstructive bronchitis in early childhood. The risk genotypes may serve as risk factors for respiratory obstruction rather than for signs of COPD or asthma.
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http://dx.doi.org/10.1016/j.metabol.2012.05.013DOI Listing
December 2012

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

Ann Nutr Metab 2012 1;60(4):247-56. Epub 2012 Jun 1.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1159/000337552DOI Listing
November 2012

FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children: results from the GINIplus and LISAplus studies.

PLoS One 2012 21;7(5):e37780. Epub 2012 May 21.

Institute of Epidemiology I, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.

Background: Elevated cholesterol levels in children can be a risk factor for cardiovascular diseases in later life. In adults, it has been shown that blood lipid levels are strongly influenced by polymorphisms in the fatty acid desaturase (FADS) gene cluster in addition to nutritional and other exogenous and endogenous determinants. Our aim was to investigate whether lipid levels are determined by the FADS genotype already in children and whether this association interacts with dietary intake of n-3 fatty acids.

Methods: The analysis was based on data of 2006 children from two German prospective birth cohort studies. Total cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped. Dietary n-3 fatty acid intake was assessed by food frequency questionnaire. Linear regression modeling was used to assess the association between lipid levels, n-3 fatty acid intake and FADS genotype.

Results: Individuals carrying the homozygous minor allele had lower levels of total cholesterol [means ratio (MR) ranging from 0.96 (p = 0.0093) to 0.98 (p = 0.2949), depending on SNPs] and LDL [MR between 0.94 (p = 0.0179) and 0.97 (p = 0.2963)] compared to homozygous major allele carriers. Carriers of the heterozygous allele showed lower HDL levels [β between -0.04 (p = 0.0074) to -0.01 (p = 0.3318)] and higher triglyceride levels [MR ranging from 1.06 (p = 0.0065) to 1.07 (p = 0.0028)] compared to homozygous major allele carriers. A higher n-3 PUFA intake was associated with higher concentrations of total cholesterol, LDL, HDL and lower triglyceride levels, but these associations did not interact with the FADS1 FADS2 genotype.

Conclusion: Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037780PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357401PMC
December 2012

Peak growth velocity in infancy is positively associated with blood pressure in school-aged children.

J Hypertens 2012 Jun;30(6):1114-21

Helmholtz Zentrum Munich, Center for Environment and Health, Institute of Epidemiology I, Neuherberg, Germany.

Objectives: Rapid growth velocity in early life may be a risk factor for obesity, elevated blood pressure, and adverse metabolic markers in childhood, but results are not consistent. We analysed the association between peak growth velocity during the first 2 years of life and blood pressure, fasting glucose and insulin at 10 years of age.

Methods: A prospective German birth cohort (LISAplus) provided data on growth, blood pressure, glucose, and insulin for 1127 children up to the age of 10 years. All children had a birth weight of at least 2500 g. Growth was modelled using nonlinear mixed-effect Reed1 models. Associations between peak growth velocities and metabolic outcomes were calculated with linear regression models. Potential confounders were sequentially adjusted for.

Results: Higher peak height velocity (PHV) and peak weight velocity (PWV) in infancy were associated with significant increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in children at 10 years. For each 10.2 cm/year [2 standard deviation (SD)] increase in PHV, SBP increased by 2.94 mmHg [95% confidence interval (CI) 1.34, 4.54] after adjustment for potential confounders including birth weight and body mass index. A 5.1 kg/year (2 SD) higher PWV was associated with a 2.13 mmHg (95% CI 0.51, 3.74) increase in SBP and a 1.91 mmHg (95% CI 0.52, 3.30) increase in DBP. No consistent associations were found between PHV or PWV and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index after multiple adjustments.

Conclusions: Blood pressure and metabolic outcomes at school age may be associated with growth patterns in early life, regardless of relative weight during school age.
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http://dx.doi.org/10.1097/HJH.0b013e328352d699DOI Listing
June 2012

Indoor factors and behavioural problems in children: the GINIplus and LISAplus birth cohort studies.

Int J Hyg Environ Health 2013 Mar 7;216(2):146-54. Epub 2012 Apr 7.

Centre for Research in Environmental Epidemiology, Spain.

Indoor microbial agents exposure is associated to depressive symptoms in adults and persistent exposure to indoor mould is associated to poorer cognitive function in children. In our study, we aimed to assess the effects of the exposure to indoor factors associated with increased microbial exposure (mould, dampness and pets) on behavioural problems in children aged 10 years, participating in two German birth cohorts. A total of 4860 children were followed until the age of 10 years, and the strengths and difficulties questionnaire (SDQ) was administered to the parents. Indoor factors were assessed through parental reported questionnaires in periodical surveys. Logistic and multinomial regressions adjusting for potential confounders were performed. Prevalences of borderline/abnormal total scores in the SDQ at 10 years of age were higher in children exposed to mould (aOR=1.23, 95%CI=1.00-1.56), dampness (aOR=1.51, 95%CI=1.10-2.07), and pets (aOR=1.48, 95%CI=1.20-1.94). The dimension "emotional symptoms" showed statistically significant risk estimates for mould and pets, meanwhile "conduct problems" and "hyperactivity/inattention" dimensions only did for pets. No significant associations were found for the "peer relationship problems" dimension. We found a significant strong interaction between dampness and pet, the risk of borderline/abnormal scores in the "total difficulties" scale and the "emotional symptoms" dimension for pets' was at least twice the risk in children with reported dampness than in children without. Our findings point to a potential effect of microbial exposure on children's behavioural problems, especially on emotional disorders, probably mediated through neurotoxicity and immune system activation.
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http://dx.doi.org/10.1016/j.ijheh.2012.03.006DOI Listing
March 2013

The hygiene hypothesis does not apply to atopic eczema in childhood.

Chem Immunol Allergy 2012 13;96:15-23. Epub 2012 Mar 13.

There is evidence that environmental factors are important for the development of eczema. Different mechanisms have been discussed in the literature, the best known of which is the hygiene hypothesis. However, epidemiological data give reason for questioning this hypothesis with regard to childhood eczema. We present results from two German birth cohort studies (LISAplus and GINIplus) concerning regional prevalence patterns of eczema and the association of eczema with day care center attendance and older siblings. Our findings are not in line with the hygiene hypothesis and question its validity with regard to eczema. It seems reasonable to assume that the effect of environmental factors is somehow disease-specific.
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http://dx.doi.org/10.1159/000331805DOI Listing
July 2012

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

J Allergy Clin Immunol 2011 Dec 26;128(6):1235-1241.e5. Epub 2011 Oct 26.

Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

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.
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http://dx.doi.org/10.1016/j.jaci.2011.09.014DOI Listing
December 2011

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

Environ Res 2011 Nov 20;111(8):1173-9. Epub 2011 Jul 20.

Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology I, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.

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.
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http://dx.doi.org/10.1016/j.envres.2011.06.011DOI Listing
November 2011

Prenatal and postnatal tobacco smoke exposure and development of insulin resistance in 10 year old children.

Int J Hyg Environ Health 2011 Sep 12;214(5):361-8. Epub 2011 May 12.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Neuherberg, Germany.

In this study, we evaluated the association between prenatal and postnatal exposure to environmental tobacco smoke and the development of insulin resistance in 10 year old children. Fasting blood samples were collected from 470 children participating in two prospective birth cohorts. Of those 276 were selected population based and enriched with 194 children exceeding the 85th percentile of body mass index in this age group. Children already having diabetes type 1 or 2 at the age of 10 years were excluded. Fasting blood insulin and glucose levels and calculated HOMA index for insulin resistance assessment were analysed using generalised additive models. Potential confounders were adjusted for. Insulin resistance was increased by 24% in children frequently exposed to environmental tobacco smoke during childhood (MR(adj) = 1.24, p = 0.001), while glucose levels were not. Exclusion of prenatally exposed children did not attenuate the association (MR(adj) = 1.25, p = 0.006). After stratification, the effect sizes were identical within overweight children and the population based sample of children. Insulin resistance and fasting insulin levels were increasing with increasing numbers of cigarettes smoked in children's home. Maternal smoking during the third trimester of pregnancy increased children's insulin levels (MR(adj) = 1.19, p = 0.037), and even more so, if children were exclusively breastfed after birth (MR(adj) = 1.31, p = 0.016). Increased mean ratios were found for smoking of a third person in addition to maternal smoking. Positive dose-dependent associations and independent effects of postnatal exposure suggest involvement of environmental tobacco smoke in the risk for development of insulin resistance in children.
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http://dx.doi.org/10.1016/j.ijheh.2011.04.004DOI Listing
September 2011

Relative weight-related costs of healthcare use by children--results from the two German birth cohorts, GINI-plus and LISA-plus.

Econ Hum Biol 2011 Jul 2;9(3):302-15. Epub 2011 Mar 2.

Helmholtz Zentrum München - German Research Center for Environmental Health - Institute of Health Economics and Health Care Management, Munich, Germany.

Obesity among children and adolescents is a growing public health burden. According to a national reference among German children and adolescents aged 3-17 years, 15% are overweight (including obese) and 6.3% are obese. This study aims to assess the economic burden associated with overweight and obesity in children based on a cross-sectional survey from two birth cohort studies: the GINI-plus - German Infant Nutritional Intervention plus Non-Intervention study (3287 respondents aged 9 to <12 years) and the LISA-plus study - Influence of life-style factors on the development of the immune system and allergies in East and West Germany (1762 respondents aged 9 to <12 years). Using a bottom-up approach, we analyse direct costs induced by the utilisation of healthcare services and indirect costs emerging from parents' productivity losses. To investigate the impact of Body Mass Index (BMI) on costs, we perform various descriptive analyses and estimate a two-part regression model. Average annual total direct medical costs of healthcare use are estimated to be €418 (95% CI [346-511]) per child, split between physician (22%), therapist (29%), hospital (41%) and inpatient rehabilitation costs (8%). Bivariate analysis shows considerable differences between BMI groups: €469 (severely underweight), €468 (underweight), €402 (normal weight), €468 (overweight) and €680 (obese). Indirect costs make up €101 per year on average and tend to be higher for obese children, although this was not statistically significant. Drawing on these results, differences in healthcare costs between BMI groups are already apparent in children.
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http://dx.doi.org/10.1016/j.ehb.2011.02.001DOI Listing
July 2011

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.

Public Health Nutr 2011 Oct 31;14(10):1724-35. Epub 2011 Jan 31.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.

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.
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http://dx.doi.org/10.1017/S1368980010003575DOI Listing
October 2011

Early-life otitis media and incident atopic disease at school age in a birth cohort.

Pediatr Infect Dis J 2010 Dec;29(12):e96-9

Institute of Epidemiology, German Research Centre for Environmental Health, Neuherberg, Germany.

Background: Otitis media is a common and costly disease that peaks in early childhood. Recent reviews concluded that the relationship between otitis media and atopy is not well understood, and that further research is warranted.

Methods: Logistic regression was used to analyze data from a German Birth Cohort (n = 1690; born 1997–1999). Parental questionnaires were used to assess children for physician-diagnosed otitis media throughout the first 2 years of life and for incident atopic disease (asthma, allergic rhinitis, and eczema) during the sixth year of life. Odds ratios were adjusted for gender, older siblings, city, parental education, breast-feeding, and daycare. Parallel analyses were completed for the full birth cohort and for a population subset with atopic mothers.

Results: The adjusted odds of asthma were elevated for children with early-life otitis media, but were statistically significant only for those children with at least 3 episodes (adjusted odds ratio: 4.26 [95% confidence interval: 1.34–13.6]). Associations between early-life otitis media and allergic rhinitis were largely inconsistent. There was a positive association between early-life otitis media and late-onset allergic eczema (≥2 episodes: 2.68 [1.35–5.33], ≥3 episodes: 3.84 [1.80–8.18]). Similar results were found for the maternal atopy subgroup but with greater effect estimates.

Conclusions: Children diagnosed with otitis media during infancy were at greater risk for developing late-onset allergic eczema and asthma during school age, and associations were stronger for frequent otitis. These results indicate that frequent otitis media during infancy may predispose children to atopic disease in later life.
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http://dx.doi.org/10.1097/inf.0b013e3181fcd9e8DOI Listing
December 2010

Associations between BMI and the FTO gene are age dependent: results from the GINI and LISA birth cohort studies up to age 6 years.

Obes Facts 2010 Jun 28;3(3):173-80. Epub 2010 May 28.

Institute of Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.

Objective: The association between polymorphisms in intron 1 of the fat mass and obesity associated gene (FTO) and obesity-related traits is one of the most robust associations reported for complex traits and is established both in adults and children. However, little is known about the longitudinal dynamics of these polymorphisms on body mass index (BMI), overweight, and obesity.

Methods: This study is based on the 2,732 full-term neonates of the German GINI-plus and LISA-plus birth cohorts, for whom genotyping data on the FTO variants rs1558902 (T>A) or rs9935401 (G>A) were available. Children were followed from birth up to age 6 years. Up to 9 anthropometric measurements of BMI were obtained. Fractional-Polynomial-Generalized-Estimation-Equation modeling was used to assess developmental trends and their potential dependence on genotype status.

Results: We observed no evidence for BMI differences between genotypes of both variants for the first 3 years of life. However, from age 3 years onwards, we noted a higher BMI for the homozygous minor alleles carriers in comparison to the other two genotype groups. However, evidence for statistical significance was reached from the age of 4 years onwards.

Conclusions: This is one of the first studies investigating in detail the development of BMI depending on FTO genotype between birth and the age of 6 years in a birth cohort not selected for the phenotype studied. We observed that the association between BMI and FTO genotype evolves gradually and becomes descriptively detectable from the age of 3 years onwards.
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http://dx.doi.org/10.1159/000314612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452146PMC
June 2010

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

J Allergy Clin Immunol 2010 Jun;125(6):1254-1260.e5

IUF-Institut für Umweltmedizinische Forschung, Düsseldorf, Germany.

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.
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http://dx.doi.org/10.1016/j.jaci.2010.03.036DOI Listing
June 2010