Prenatal Exposure to Non-persistent Chemicals and Child neurodevelopment: an Epidemiological Study

This thesis investigates the relation between prenatal exposure to the non-persistent chemicals phthalates, bisphenols, and organophosphate pesticides, a

High critical temperature above Tg may contribute to the stability of biological systems

In this study, we characterized the molecular mobility around Tg in sugars, poly-L-lysine and dry desiccation-tolerant biological systems, using ST-EPR, 1H-NMR, and FTIR spectroscopy, to understand the nature and composition of biological glasses. Two distinct changes in the temperature dependence of the rotational correlation time (R) of the spin probe 3-carboxy-proxyl or the second moment (M2) were measured in sugars and poly-L-lysine. With heating, the first change was associated with the melting of the glassy state (Tg). The second change (Tc), at which R abruptly decreased over several orders of magnitude, was found to correspond with the so-called cross-over temperature, where the dynamics changed from solid-like to liquid-like. The temperature interval between Tg and Tc increased in the order of sucrose 50°C, implying that the stability above Tg improved in the same order. These differences in temperature-dependent mobilities above Tg suggest that proteins rather than sugars play an important role in the intracellular glass formation. The exceptionally high Tc of intracellular glasses is expected to provide excellent long-term stability to dry organisms, maintaining a slow molecular motion in the cytoplasm even at temperatures far above Tg

Organophosphate pesticides exposure in pregnant women and maternal and cord blood thyroid hormone concentrations

Background: Animal studies suggest that organophosphate (OP) pesticides exposure affects thyroid function, but evidence in humans remains sparse and inconclusive. Gestational exposure is of particular interest, since thyroid hormone is essential for fetal brain development. OP pesticides are able to cross the placental and blood-brain barrier and may interfere with fetal development processes regulated by thyroid hormone. Objective: To investigate the association of gestational OP pesticides exposure during pregnancy with maternal and cord blood thyroid hormone concentrations. Methods: This study was embedded within Generation R (Rotterdam, the Netherlands), a prospective population-based birth cohort. Mother-child pairs with OP pesticides assessment and maternal (N = 715) or cord blood (N = 482) thyroid hormone measurements were included. OP pesticides exposure was assessed at < 18, 18–25, and > 25 weeks gestation by measuring six urinary dialkylphosphate (DAP) metabolites. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in maternal and cord blood. Maternal measures also included total thyroxine (TT4) and TPO antibodies (TPOAbs). To study the association of creatinine-adjusted DAP metabolite concentrations with thyroid function and TPO antibodies, multivariable linear regression models including relevant confounders were used. Results: There was no association of DAP metabolites with maternal TSH, FT4, TT4 or TPOAb concentrations during pregnancy. Similarly, there was no association of DAP metabolites with cord blood TSH or FT4. Results did not change when DAP concentrations were analyzed at individual time points or as mean gestational exposure. Conclusion: Gestational OP pesticides exposure, as assessed by repeatedly measured urinary DAP metabolite concentrations in an urban population, was not associated with maternal or cord blood t

Determinants of organophosphate pesticide exposure in pregnant women: A population-based cohort study in the Netherlands

Background: In the Netherlands organophosphate (OP) pesticides are frequently used for pest control in agricultural settings. Despite concerns about the potential health impacts of low-level OP pesticides exposure, particularly in vulnerable populations, the primary sources of exposure remain unclear. The present study was designed to investigate the levels of DAP metabolites concentrations across pregnancy and to examine various determinants of DAP metabolite concentrations among an urban population of women in the Netherlands. Method: Urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined at 25 weeks of pregnancy in 784 pregnant women participating in the Generation R Study (between 2004 and 2006), a large population-based birth cohort in Rotterdam, the Netherlands. Questionnaires administered prenatally assessed demographic and lifestyle characteristics and maternal diet. Linear mixed models, with adjustment for relevant covariates, were used to estimate associations between the potential exposure determinants and DAP metabolite concentrations expressed as molar concentrations divided by creatinine levels. Results: The median DAP metabolite concentration was 311 nmol/g creatinine for the first trimester, 317 nmol/g creatinine for the second trimester, and 310 nmol/g creatinine for the third trimester. Higher maternal age, married/living with a partner, underweight or normal weight (BMI of <18.5 and 18.5-<25), high education, high income, and non-smoking were associated with higher DAP metabolite concentrations, and DAP metabolite concentrations tended to be higher during the summer. Furthermore, fruit intake was associated with increased DAP metabolite concentrations. Each 100 g/d difference in fruit consumption was associated with a 7% higher total DAP metabolite concentration across pregnancy. Other food groups were not associated with higher DAP metabolite concentrations. Conclusions: The DAP metabolite concentrations measured in the urine of pregnant women in the Netherlands were higher than those in most other studies previously conducted. Fruit intake was the main dietary source of exposure to OP pesticides in young urban women in the Netherlands. The extent to which DAP metabolite concentrations reflect exposure to the active parent pesticide rather than to less toxic metabolites remains unclear. Further research will be undertaken to investigate the possible effects of this relatively high level OP pesticides exposure on offspring health

Associations of physical activity and screen time with white matter microstructure in children from the general population

Physical activity and sedentary behaviors have been linked to a variety of general health benefits and problems. However, few studies have examined how physical activity during childhood is related to brain development, with the majority of work to date focusing on cardio-metabolic health. This study examines the association between physical activity and screen time with white matter microstructure in the general pediatric population. In a sample of 2532 children (10.12 ± 0.58 years; 50.04% boys) from the Generation R Study, a population-based cohort in Rotterdam, the Netherlands, we assessed physical activity and screen time using parent-reported questionnaires. Magnetic resonance imaging of white matter microstructure was conducted using diffusion tensor imaging. Total physical activity was positively associated with global fractional anisotropy (β = 0.057, 95% CI = 0.016, 0.098, p = 0.007) and negatively associated with global mean diffusivity (β = −0.079, 95% CI = −0.120, −0.038, p 0.05). This study provides new evidence that physical activity is modestly associated with white matter microstructure in children. In contrast, complementing other recent evidence on cognition, screen time was not associated with white matter microstructure. Causal inferences from these modest associations must be interpreted cautiously in the absence of longitudinal data. However, these data still offer a promising avenue for future work to explore to what extent physical activity may promote healthy white matter development