Maternal paraben exposure triggers childhood overweight development.

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother-child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation.

Environmental grass pollen levels in utero and at birth and cord blood IgE: Analysis of three birth cohorts.

BACKGROUND: Early life factors are associated with allergic respiratory diseases, but the role of high grass pollen concentrations during pregnancy and shortly after birth is not known. OBJECTIVE: To assess outdoor levels of grass pollen during the intrauterine period and at birth during peak pollen season on cord blood IgE in birth cohorts. METHODS: Three birth cohorts were included: MACS (n = 429), Australia; COPSAC2000 (n = 200), Denmark; and LISA (n = 1968), Germany. Cord blood IgE was categorized (<0.5 kU/L, 0.5-1 kU/L, >1 kU/L) and dichotomized (high IgE ≥ 0.5 kU/L). Birth during the grass pollen season months and cumulative exposure to outdoor grass pollen counts during pregnancy with cord blood IgE were analysed using multinomial regression and analysed in meta-analysis using binomial regression adjusted for potential confounders. RESULTS: Birth during the grass pollen season had higher pooled odds of cord blood IgE >0.5 kU/L 1.37 (95% CI 1.06, 1.77) in a meta-analysis with little heterogeneity between the three cohorts. Cumulative exposure to outdoor grass pollen counts during the entire pregnancy was associated with slightly lower pooled odds but significant (OR = 0.98, 95% CI: 0.96 to 0.99). CONCLUSIONS: Birth during grass pollen seasons were associated with increased risk of high cord blood IgE in cities from both hemispheres, but high pollen loads in the environment during the entire pregnancy appeared protective. As IgE responses develop during the first months of life, our study findings provide new insights into the mechanisms of grass pollen exposure at birth and shortly after on possible allergic respiratory diseases.

Complementary and Alternative Medicine Use Among Chronically Ill Adolescents from 2 German Birth Cohorts.

BACKGROUND: Pediatric use of complementary and alternative medicine (CAM) is popular in Europe, and utilization may be even more prevalent in chronically ill children/adolescents. This study's aim is to assess CAM use among adolescents with chronic conditions. METHODS: Data on drug utilization (past 4 weeks) and consultation with CAM providers (past year) were collected using a self-administered questionnaire from 4,677 adolescents from the German GINIplus/LISAplus birth cohorts. All reported drugs were classified into therapeutic categories (conventional drugs, homeopathy, herbal drugs, etc.). Additionally, participants were asked to list any chronic diseases (that were parent-reported, physician-verified diagnoses such as allergies, atopic dermatitis, asthma, or other chronic diseases) that they had had over the previous 5 years. RESULTS: Compared with the total sample, drug utilization in general (60.1% vs. 41.1%), homeopathy use (11.1% vs. 8.1%), and consultation with CAM providers (16.9% vs. 10.9%) was significantly more prevalent among chronically ill adolescents. However, chronically ill adolescents used relatively (proportion of the defined therapeutic category among all drugs used) more conventional drugs than healthy adolescents. CONCLUSION: Compared with healthy adolescents, CAM use is more prevalent among adolescents with chronic conditions. Nevertheless, CAM may predominantly be used as a complementary treatment option rather than substituting conventional drugs.

A longitudinal comparison of drug use among 10-year-old children and 15-year-old adolescents from the German GINIplus and LISAplus birth cohorts.

PURPOSE: The purpose of this study was to compare longitudinal data on drug utilization between 10-year-old children and 15-year-old adolescents and to analyse the association of drug use at the age of 15 years with drug use at the age of 10 years. METHODS: Based on the German GINIplus (German infant study on the Influence of Nutrition Intervention plus environmental and genetic influences on allergy development) and LISAplus (Influence of lifestyle factors on the immune system and allergies in East and West Germany plus the influence of traffic emissions and genetics) birth cohorts, data on drug utilization (past 4 weeks) were collected using a self-administered questionnaire for 3642 children (10-year follow-up) and 4677 adolescents (15-year follow-up). The drugs were classified by therapeutic categories (conventional drugs, homeopathic drugs, etc.) and by codes according to the anatomical therapeutic chemical (ATC) classification system. Associations of adolescents' drug use with gender, study area, maternal education, parental income, presence of chronic conditions, and prior drug use at the age of 10 years were analysed using a logistic regression model. RESULTS: The 4-week prevalence rates of overall drug use were similar for adolescents (41.1%) and children (42.3%). However, adolescents used noticeably more anti-inflammatory drugs, analgesics, and systemic antihistamines. Exactly 3194 children/adolescents participated in both follow-ups. Adolescents' use of anti-inflammatory drugs was predicted (OR = 3.37) by use of anti-inflammatory drugs as a child. In summary, the strongest predictor of adolescents' use of specific therapeutic categories or ATC groups was the previous use of the same therapeutic drug category or ATC group as a 10-year-old child. CONCLUSIONS: Despite similar prevalence rates of overall drug utilization among both age groups, there is a noticeable difference concerning the use of drugs from specific ATC groups. Drug use as a child may partly determine what they use as an adolescent.

Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation.

Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.

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.

Effect of fatty acid status in cord blood serum on children's behavioral difficulties at 10 y of age: results from the LISAplus Study.

BACKGROUND: Little is known about the effect of fatty acid (FA) concentrations in cord blood on long-term behavioral outcomes. OBJECTIVE: We assessed the effect of FAs in cord blood serum on children's behavioral difficulties at the age of 10 y. DESIGN: A longitudinal study of 416 children from the population-based Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood (LISAplus) birth cohort from Munich was conducted. Individual glycerophospholipid FAs in blood were analyzed in venous cord blood. Data on children's behavior were collected with a parent-reported Strength and Difficulties Questionnaire at 10 y of age. Zero-inflated Poisson regression models were applied and adjusted for sex, parental income, smoking during pregnancy, and dietary intake of arachidonic acid (AA) and DHA at 10 y. RESULTS: A 1% increase in DHA in cord blood serum was found to decrease total difficulties by (exp)ß(adj) = 0.93 (SE = 0.02, P < 0.0001) and hyperactivity or inattention by (exp)ß(adj) = 0.94 (SE = 0.03, P < 0.04). Higher long-chain (LC) PUFA concentrations in cord blood serum were associated with fewer emotional symptoms [(exp)ß(adj) = 0.95, SE = 0.03, P = 0.01], and similarly higher AA concentrations were associated with fewer emotional symptoms [(exp)ß(adj) = 0.94, SE = 0.03, P = 0.03]. CONCLUSION: Increased concentrations of DHA, LC-PUFAs, and AA in cord blood serum were associated with lower scores on a parent-completed behavioral screen. An appropriate FA supply to the developing fetus may be essential for optimal long-term behavioral outcomes 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.

Exposure to mycotoxins increases the allergic immune response in a murine asthma model.

RATIONALE: Epidemiological studies have shown that indoor molds are associated with increased prevalence and exacerbation of respiratory symptoms and asthma. Mycotoxins, secondary metabolites of molds, may contribute to these effects. OBJECTIVES: To investigate the adjuvant activity of mycotoxins on allergic airway inflammation. METHODS: Balb/c mice were exposed via the airways to gliotoxin and via the intestine to patulin, sensitized with ovalbumin (OVA), and then analyzed in acute and chronic murine asthma models. In addition, the effect of mycotoxin exposure on dendritic cell (DC) function was investigated using murine bone marrow-derived DCs. MEASUREMENTS AND MAIN RESULTS: Exposure of mice to both mycotoxins enhanced dose-dependently airway hyperreactivity, eosinophilic lung inflammation, and OVA-specific IgE serum levels compared with mice that received only the antigen. These findings correlated with increased Th2 cytokine levels and decreased IFN-gamma production. Long-term mycotoxin exposure exacerbated chronic airway inflammation and airway remodeling. In vitro or in vivo mycotoxin exposure inhibited IL-12 production in maturing DCs and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. Mycotoxin exposure enhanced OVA-induced lung lipid peroxidation and moderately increased isoprostane levels in naive mice. Treatment of mycotoxin-exposed DCs with the antioxidants N-acetylcysteine or glutathione ethyl ester restored IL-12 secretion and pretreatment of exposed mice with N-acetylcysteine prevented the mycotoxin-induced increase of airway inflammation and AHR. CONCLUSIONS: Our results demonstrate that gliotoxin and patulin increase the allergic immune response in mice by modulating the Th1/Th2 balance via direct effects on IL-12 secretion in DCs and by inducing oxidative stress.