Prenatal and early life exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls may influence dehydroepiandrosterone sulfate levels at prepubertal age: results from the Duisburg birth cohort study.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and polychlorinated biphenyls (PCB) are postulated to act as endocrine disrupters. In the ongoing Duisburg birth cohort study, started in 2000-2002, influence of persistent organic pollutants (POP) on child development was monitored. For the first time, associations were reported between prenatal and postnatal PCDD/F and PCB exposures and early endocrinological changes concerning adrenarchal development. PCDD/F and PCB concentrations were measured in blood samples taken in wk 32 of pregnancy and in breast milk using gas chromatography and high-resolution mass spectrometry (GC/HRMS). At the age of 6-7 and 8-9 yr, serum samples were collected from 111 children. The samples were assayed for the sex hormones testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), and 17-OH-progesterone (17-OHP) by using an automated chemiluminescence assay system. Analyses of repeated measurements of DHEA-S serum levels were performed by linear regression analysis using generalized estimating equations (GEE). Linear regression analysis showed a positive association between DHEA-S and breast milk levels of PCDD/F and PCB expressed as toxicity equivalents according to toxicity equivalent factors published by the World Health Organization (WHO) in 2005 (WHO(2005)-TEq) (increase of 29%, geometric mean ratio, GMR: 1.29, 95% CI 1.06-1. 58 per doubling of PCDD/F + PCB WHO(2005)-TEq levels). Results for the association with the WHO(2005)-TEq levels in blood of mothers were in the same direction (increase of 15%, GMR 1.15, 95% CI 0.93-1.42 per doubling of PCDD/F + PCB WHO(2005)-TEq levels), but not significant. Data indicate that PCDD/F and PCB exposure in infancy may influence DHEA-S serum levels in prepubertal children. Increased DHEA-S serum levels are considered to indicate acceleration of the adrenal maturation.

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.

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.

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

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.