Exposure to endocrine-disrupting chemicals can alter normal physiology and increase susceptibility to non-communicable diseases like obesity. Especially the prenatal and early postnatal period is highly vulnerable to adverse effects by environmental exposure, promoting developmental reprogramming by epigenetic alterations. To obtain a deeper insight into the role of prenatal bisphenol A (BPA) exposure in children’s overweight development, we combine epidemiological data with experimental models and BPA-dependent DNA methylation changes. BPA concentrations were measured in maternal urine samples of the LINA mother-child-study obtained during pregnancy (n = 552), and BPA-associated changes in cord blood DNA methylation were analyzed by Illumina Infinium HumanMethylation450 BeadChip arrays (n = 472). Methylation changes were verified by targeted MassARRAY analyses, assessed for their functional translation by qPCR and correlated with children’s body mass index (BMI) z scores at the age of 1 and 6 years. Further, female BALB/c mice were exposed to BPA from 1 week before mating until delivery, and weight development of their pups was monitored (n ≥ 8/group). Additionally, human adipose-derived mesenchymal stem cells were treated with BPA during the adipocyte differentiation period and assessed for exposure-related epigenetic, transcriptional and morphological changes (n = 4). In prenatally BPA-exposed children two CpG sites with deviating cord blood DNA-methylation profiles were identified, among them a hypo-methylated CpG in the promoter of the obesity-associated mesoderm-specific transcript (MEST). A mediator analysis suggested that prenatal BPA exposure was connected to cord blood MEST promoter methylation and MEST expression as well as BMI z scores in early infancy. This effect could be confirmed in mice in which prenatal BPA exposure altered Mest promoter methylation and transcription with a concomitant increase in the body weight of the juvenile offspring. An experimental model of in vitro differentiated human mesenchymal stem cells also revealed an epigenetically induced MEST expression and enhanced adipogenesis following BPA exposure. Our study provides evidence that MEST mediates the impact of prenatal BPA exposure on long-term body weight development in offspring by triggering adipocyte differentiation.

Maternal perceived stress has been discussed to contribute to the development of childhood overweight. Our aim was to investigate the longitudinal relationship of early maternal perceived stress and BMI z-scores in preschool children (≤ five years). A longitudinal analysis was conducted in 498 mother-child pairs of the German prospective birth cohort LINA with information on maternal perceived stress during pregnancy, one and two years after birth. BMI z-scores were based on annual measurements of children’s weight/height and calculated based on WHO reference data. General estimation equations were applied to evaluate the impact of maternal stress on children’s longitudinal BMI z-scores. Potential stressors contributing to the perceived stress of the mother were assessed by linear regression models. Using mediation analyses we evaluated the relationship between stressors, maternal perceived stress, and children’s BMI z-score development. Postnatal maternal stress during the first year after birth had a positive longitudinal relationship with children’s BMI z-scores up to the age of five years. Gender-stratified analyses revealed that only girls showed this positive association while boy’s BMI z-scores were unaffected by maternal stress. We identified three neighborhood strains and two socio-demographic factors, which contributed to the maternal perceived stress level. Stressors themselves did not directly affect girl’s BMI z-scores but rather mediated their effect through the perceived stress level. While different stressors contribute to maternal stress, the perceived stress level - rather than the stressors themselves - is strongly positively associated with BMI z-score development in girls.

Background: Lifestyle and environmental factors are known to contribute to allergic disease development, especially very early in life. However, the link between diet composition and allergic outcomes remains unclear. Methods: In the present population-based cohort study we evaluated the dietary intake of 10-year-old children and analyses were performed with particular focus on atopic dermatitis or food allergy, allergic diseases known to be affected by dietary allergens. Dietary intake was assessed via semi-quantitative food frequency questionnaires. Based on these data, individual nutrient intake as well as children’s Dietary Inflammatory Index (C-DII™) scores were calculated. Information about atopic manifestations during the first 10 years of life and confounding factors were obtained from standardized questionnaires during pregnancy and annually thereafter. Results: Analyses from confounder-adjusted logistic regression models (n = 211) revealed that having atopic outcomes was associated with having a pro-inflammatory pattern at the age of 10 years: OR = 2.22 (95% CI: 1.14–4.31) for children with atopic dermatitis and OR = 3.82 (95% CI: 1.47–9.93) for children with food allergy in the first 10 years of life. Conclusion: A pro-inflammatory dietary pattern might worsen the atopic outcome and reduce the buffering capacity of the individual against harmful environmental exposures or triggers. For pediatricians it is recommended to test for the individual tolerance of allergenic foods and to increase the nutrient density of tolerable food items to avoid undesirable effects of eating a pro-inflammatory diet.