Helena Skröder

Elevated childhood exposure to arsenic despite reduced drinking water concentrations--A longitudinal cohort study in rural Bangladesh.

OBJECTIVES The aim of this study was to evaluate the massive efforts to lower water arsenic concentrations in Bangladesh. METHODS In our large mother-child cohort in rural Matlab, we measured the arsenic concentrations (and other elements) in drinking water and evaluated the actual exposure (urinary arsenic), from early gestation to 10 years of age (n=1017). RESULTS Median drinking water arsenic decreased from 23 (2002-2003) to <2 μg/L (2013), and the fraction of wells exceeding the national standard (50 μg/L) decreased from 58 to 27%. Still, some children had higher water arsenic at 10 years than earlier. Installation of deeper wells (>50 m) explained much of the lower water arsenic concentrations, but increased the manganese concentrations. The highest manganese concentrations (~900 μg/L) appeared in 50-100 m wells. Low arsenic and manganese concentrations (17% of the children) occurred mainly in >100 m wells. The decrease in urinary arsenic concentrations over time was less apparent, from 82 to 58 μg/L, indicating remaining sources of exposure, probably through food (mean 133 μg/kg in rice). CONCLUSION Despite decreased water arsenic concentrations in rural Bangladesh, the children still have elevated exposure, largely from food. Considering the known risks of severe health effects in children, additional mitigation strategies are needed.

Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

BACKGROUND Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. OBJECTIVES To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. METHODS This cross-sectional study was part of the 4.5 years of age (range: 4.4-5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water was assessed by concentrations in childrens urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. RESULTS Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m(2), corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on childrens urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=-2.8; 95% CI: -5.5, -0.20; p=0.035), compared to those with higher selenium (B=-0.79; 95% CI: -3.0, 1.4; p=0.49). CONCLUSIONS Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young children in rural Bangladesh. Better selenium status appears to be protective. However, it is important to follow up these children to assess potential long-term consequences of these findings.

Selenium status during pregnancy: Influential factors and effects on neuropsychological development among Spanish infants

Selenium (Se) has been positively associated with neurodevelopment in early life. However, its margin of safety is rather narrow, and few prospective studies have evaluated its potential neurotoxic effects at intermediate levels. We aimed to explore the association between maternal Se concentrations and child neuropsychological development, including the genetic effect modification of the Se metabolizing gene INMT. Study subjects were 650 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2005). Infant neuropsychological development was assessed around 12months of age by the Bayley Scales of Infant Development. Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation. Se was measured in serum samples at the first trimester. The mean serum Se concentration was 79.7 (standard deviation=7.9) μg/L. In multivariate analysis, nonsignificant inverse linear associations were found between Se concentrations and standardized mental and psychomotor development scores (β (95% CI)=-0.13 (-0.29, 0.03) and β (95% CI)=-0.08 (-0.24, 0.07), respectively). Generalized additive models indicated inverted U-shaped relationships between Se concentrations and both scales. Using segmented regression, the turning point for the associations was estimated at 86μg/L for both scales. The association between Se and neuropsychological development was inverted U-shaped for children with the AG+AA genotype for rs6970396 INMT but a descending curve was suggested for the GG genotype. Further studies would be necessary in order to disentangle the complex equilibrium between the toxicity and benefits of Se exposure during the prenatal period.

Arsenite methyltransferase (AS3MT) polymorphisms and arsenic methylation in children in rural Bangladesh

Background: Arsenic methylation efficiency, a susceptibility factor for arsenic toxicity, is in adults partly explained by variation in arsenite methyltransferase (AS3MT) gene. Little is known about the role of AS3MT for childrens arsenic methylation. Objectives: Evaluating associations between AS3MT polymorphisms and childrens arsenic methylation efficiency. Methods: Bangladeshi childrens arsenic exposure (9‐years; n = 424) was assessed as sum urinary concentration of inorganic arsenic (iAs) and its metabolites (monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) using HPLC‐HG‐ICPMS. Arsenic methylation efficiency was assessed by the individual metabolite fractions (%). AS3MT polymorphisms (rs7085104, rs3740400, rs3740393 and rs1046778) were genotyped using TaqMan SNP genotyping assays. Results: We found higher %iAs and %MMA, and lower %DMA in urine, among rs1046778 TT carriers (median 8.8%, 9.6% and 81.1% for iAs, MMA and DMA, respectively), compared to CC carriers (median 7.0%, 8.3% and 84.9%). These associations were significant in multivariable‐adjusted linear regression models: B‐coefficients for TT vs CC were 1.26, 1.33 and −2.59 for iAs, MMA and DMA, respectively. Effect estimates were slightly stronger when restricting the analyses to children with urinary arsenic ≥58 &mgr;g/L (reducing the impact of ingested DMA). Estimates in girls were slightly stronger than in boys, although there were no significant differences between boys and girls. No clear associations were found for the other AS3MT polymorphisms. Conclusions: One out of four AS3MT polymorphisms, previously associated with arsenic methylation in adults, was associated with arsenic methylation in children. Thus, AS3MT variation seems to influence arsenic methylation efficiency in children to a lesser extent than in adults. HighlightsArsenic (As) methylation efficiency is a susceptibility factor for As toxicity.AS3MT rs1046778 was associated with As metabolite fractions in urine of children.AS3MT variation had less impact on As methylation in children than in adults.Sex‐differences on the effect of AS3MT on As methylation were inconclusive.

Predictors of selenium biomarker kinetics in 4–9-year-old Bangladeshi children

BACKGROUND Biomarker selenium concentrations vary greatly between studies. Concentrations in erythrocytes, urine, and hair vary even at similar plasma concentrations, suggesting that unknown factors influence the distribution of selenium between body compartments. OBJECTIVE To assess predictors of the different selenium biomarkers in children. DESIGN We used a mother-child cohort, nested in a population-based supplementation trial in rural Bangladesh (MINIMat), established for evaluation of arsenic toxicity. Selenium was measured in plasma (n = 223), erythrocytes, urine, and hair at 9 years (n = 395) and in erythrocytes and urine at 4.5 years (n = 259) using inductively coupled plasma mass spectrometry. We also measured concentrations of arsenic (all biospecimen) and cadmium (erythrocytes and urine). Genotyping for INMT, a methyltransferase involved in selenium metabolism, was performed using TaqMan probes. RESULTS At 9 years, the selenium concentrations ranged 51-139 μg/L in plasma, 128-281 μg/L in erythrocytes, 2.2-55 μg/L in urine, and 258-723 μg/kg in hair. Correlations (rS) between biomarkers ranged 0.12-0.37, and were strongest between blood compartments and between erythrocytes and hair (long-term markers). In multivariable-adjusted linear regression analyses, plasma selenium differed by sampling season (highest in food-secure pre-monsoon season) and was inversely associated with plasma arsenic (range < 0.0080-20 μg/L; B = -1.1, 95% CI: -1.8, -0.41). In contrast, erythrocyte selenium was positively associated with erythrocyte arsenic (range 0.95-50 μg/L; B = 0.58, 95% CI: 0.26, 0.91) and inversely associated with erythrocyte cadmium (range 0.27-3.1 μg/L; B = -12, 95% CI: -17, -6.9). These associations were similar at 4.5 years. Only selenium in hair and urine were influenced by INMT polymorphisms. Finally, chronic malnutrition seemed to increase selenium retention, measured as the ratio plasma/urinary selenium. CONCLUSIONS Selenium biomarkers seem to be influenced by malnutrition, genetics, and exposure to metal pro-oxidants. This might affect the evaluation of deficiency/sufficiency, normally assessed by selenium in plasma/serum.