Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys.

Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov-Smirnov test, P-value<10-15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r S -values>-0.62), but in girls only 207 (41%) showed inverse correlation (r S -values>-0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.

Assessment of early-life lead exposure in rural Bangladesh.

Lead is a well-known neurotoxic metal and one of the most toxic chemicals in a child's environment. The aim of this study was to assess early-life lead exposure in a pristine rural area of Bangladesh. The exposure was expected to be very low because of the absence of vehicle traffic and polluting industries. Lead was measured in erythrocytes, urine, and breast milk of 500 randomly selected pregnant women, participating in a randomized food and micronutrient supplementation trial in Matlab (MINIMat). Lead was also measured in urine of their children at 1.5 and 5 years of age, and in rice, well water, cooking pots, and materials used for walls and roof. All measurements were performed using ICPMS. We found that the women had relatively high median erythrocyte lead levels, which increased considerably from early pregnancy to late lactation (81-136microg/kg), probably due to release from bone. Urinary lead concentrations were unchanged during pregnancy (median approximately 3.5microg/L) and non-linearly associated with maternal blood lead levels. Children, at 1.5 and 5 years of age, had a median urinary lead concentration of 4microg/L, i.e., similar to that in their mothers. Rice, the staple food in Matlab, collected from 63 homes of the study sample, contained 1-89microg/kg (median 13microg/kg) dry weight and seems to be an important source of lead exposure. Other sources of exposure may be cooking pots and metal sheet roof material, which were found to release up to 380 and 4200microg/L, respectively, into acidic solutions. Based on breast milk lead concentrations (median 1.3microg/L) a median daily intake of 1.2microg was estimated for 3 months old infants. However, alternatives to breast-feeding are likely to contain more lead, especially rice-based formula. To conclude, lead exposure in women and their children in a remote unpolluted area was found to be surprisingly high, which may be due to their living conditions.