Objective: To develop a prediction model that quantifies the risk of being overweight at 10 years of age. Subjects/Methods: In total, 3121 participants from the GINIplus (German Infant Nutritional Intervention plus environmental and genetic influences on allergy development) and LISAplus (Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics) German birth cohorts were recruited. We predicted standardized body mass index (BMI) at 10 years of age using standardized BMIs from birth to 5 years. Parental education, family income and maternal smoking during pregnancy were considered as covariates. Linear and logistic regression models were used to evaluate the impact of risk factors on BMI and on being overweight at 10 years of age, respectively. Results: Birth weight, standardized BMI at 5 years (60–64 months) ( β =0.77; 95% confidence interval (CI): 0.73–0.81) and maternal smoking during pregnancy were positively associated with standardized BMI at 10 years of age. Standardized BMI and overweight at 5 years were strongest predictors of being overweight at 10 years. Conversely, high parental education conferred a protective effect ( β =−0.15; 95% CI: −0.29 to −0.01). Being overweight at 5 years (60–64 months) increased the risk of being overweight at 10 years of age with odds ratios above 10. Among children who were predicted to be overweight at 10 years, cross-validation results showed that 76.8% of female subjects and 68.1% of male subjects would be overweight at 10 years of age. Conclusion: BMI and being overweight at 5 years of age are strong predictors of being overweight at 10 years of age. The effectiveness of targeted interventions in children who are overweight at 5 years of age should be explored.

Numerous chronic diseases in childhood and adulthood have their origins in perinatal life and are potentially influenced by trans-generational epigenetic processes. Therefore, prospective birth cohorts can substantially contribute to our knowledge about the etiology of diseases including modifiable risk factors. The two population-based German birth cohorts GINIplus and LISAplus aim to describe the natural course of chronic diseases and intermediate phenotypes in childhood and its determinants, and to identify potential genetic effect modifications. In the mid-1990s, 5,991 (GINIplus) and 3,097 (LISAplus) healthy, term newborns were recruited for long-term follow-up in four regions of Germany. The follow-up rate for the first 10 years was about 55%. We analyzed the growth and development of overweight, infections and allergic diseases, mental and oral health, metabolic and inflammatory parameters and the role of potential risk factors including genetics. The results of these two birth cohorts substantially contribute to the current knowledge about the natural course of these health parameters. These data were included in many international projects and consortia for purposes of international comparisons of prevalence and consistency of findings, and to increase the power of the analyses.

GINIplus and LISAplus. Design and selected results of two German birth cohorts about natural course of atopic diseases and its determinants The increasing prevalence of asthma, hay fever and allergic sensitization in Western Germany after division in 1949 and the rapid increase in East German children after re-unification in 1990 are strong indications for the role of life-style and/or environmental factors for development of atopic diseases. Obviously the perinatal period is crucial for priming the immune system. Therefore, explorations of determinants of atopic diseases need pregnancy or birth cohorts as most appropriate epidemiological study designs. This review presents the design and selected results of the two German birth cohorts GINIplus and LISAplus. GINIplus and LISAplus recruited 5.991 and 3.097 healthy, term newborns from Munich, Wesel, Leipzig and Bad Honnef. Approximatly 55% could be followed for the first 10 years. We analyzed the natural course of atopic diseases and the role of life-style, environmental and genetic factors for disease onset, intermediate phenotypes and for genes involved in detoxification and oxidative stress. The results of these two large birth cohorts contributed substantially to the understanding of atopic diseases and its determinants.

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. (J Allergy Clin Immunol 2011;128:1235-41.)

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 filaggrin (FLG) mutations seem to play an important role. We hypothesized, that the dysfunction in skin barrier in children with FLG loss-of-function mutations may modulate the sibling-effect. Therefore we investigated the interaction between FLG mutations and the presence of elder siblings on the development of eczema in 2 independent birth cohorts. Materials and 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 between eczema, FLG-mutations and elder siblings was analysed longitudinally, using generalized estimating equations. Results: We found no protective effect of elder siblings on eczema development. On the contrary, the risk for eczema was significantly enhanced in children with FLG mutations if they had elder siblings. In LISAplus the ORs for the effect of elder siblings on eczema were 1.01 (CI: 0.74–1.37) for children without FLG mutations and 3.31 (CI: 1.21–9.04) for children with FLG mutations. In GINIplus the ORs were 1.00 (CI: 0.80–1.23) and 2.39 (CI: 1.09–5.28), respectively. The interaction between FLG mutations and elder siblings was significant in both cohorts. Conclusions: We observed that there was no protective effect of elder siblings on the development of eczema in children with FLG mutations. – In contrast elder siblings enhanced the effect of FLG mutations. Our findings give evidence for complex skin driven pathogenic mechanisms in eczema development taking gene-environment interactions into account.

BACKGROUND:Day care centre attendance is much more common in East than in West Germany. Although there is evidence that early day care might be protective against atopic diseases, several studies have shown a higher prevalence of childhood eczema in East Germany compared to West Germany.OBJECTIVES:To compare prevalence and cumulative incidence of eczema in a birth cohort study in East and West Germany and to identify risk factors that are associated with eczema, which might explain regional differences.METHODS:We used data from the ongoing population-based birth cohort 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. In 1997, 3097 children from study areas in East and West Germany were recruited. Cumulative incidence and 1-year prevalences of eczema up to the age of 6 years were determined from yearly questionnaires. Cox regression and generalized estimating equations/logistic regression were used to quantify regional differences and to identify risk factors that might explain them.RESULTS:Prevalence and incidence of eczema were higher in children living in East Germany than those living in West Germany. We identified 11 risk factors that showed significant regional differences. From these factors, only 'day care attendance during the first 2 years of life' was significantly associated with eczema (odds ratio 1.56, 95% confidence interval CI 1.31-1.86). The regional differences in eczema could be explained by differences in early day care utilization.CONCLUSION:Day care centre attendance is associated with an increased prevalence and incidence of eczema. Regional differences in eczema prevalence could be explained by regional differences in utilization of early day care.

Background: Early childhood influences are important for the development of the allergic phenotype. In East Germany, tremendous lifestyle changes took place after 1990 and it can be hypothesized that the allergic phenotypes in mothers and their children are less similar than in West Germany. This was investigated in our study done in mothers and their 6-year-old children from East and West Germany in the year 2000. Methods: 1,393 mother-child pairs participated. A subgroup of 774 pairs gave blood for the determination of specific IgE. Regional differences in mother-child correlations and in prevalence of mother-child combinations with respect to allergic sensitization and disease were examined by logistic regression analysis. Results: The adjusted association in positive allergic sensitization between mothers and their children was not significant in East Germany (OR 1.23, 95% CI: 0.68–2.24) but highly significant in West Germany (OR 2.89, 95% CI: 1.73–4.80). The probability for the combination of ‘negative’ mother and ‘positive’ child was significantly higher in East than in West Germany. Conclusions: Mother-child transmission of atopy predisposition can even be cancelled by environmental changes.