Margaretha Grandér

Breast-feeding protects against arsenic exposure in Bangladeshi infants.

Background Chronic arsenic exposure causes a wide range of health effects, but little is known about critical windows of exposure. Arsenic readily crosses the placenta, but the few available data on postnatal exposure to arsenic via breast milk are not conclusive. Aim Our goal was to assess the arsenic exposure through breast milk in Bangladeshi infants, living in an area with high prevalence of arsenic-rich tube-well water. Methods We analyzed metabolites of inorganic arsenic in breast milk and infant urine at 3 months of age and compared them with detailed information on breast-feeding practices and maternal arsenic exposure, as measured by concentrations in blood, urine, and saliva. Results Arsenic concentrations in breast-milk samples were low (median, 1 μg/kg; range, 0.25–19 μg/kg), despite high arsenic exposures via drinking water (10–1,100 μg/L in urine and 2–40 μg/L in red blood cells). Accordingly, the arsenic concentrations in urine of infants whose mothers reported exclusive breast-feeding were low (median, 1.1 μg/L; range, 0.3–29 μg/L), whereas concentrations for those whose mothers reported partial breast-feeding ranged from 0.4 to 1,520 μg/L (median 1.9 μg/L). The major part of arsenic in milk was inorganic. Still, the infants had a high fraction (median, 87%) of the dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated with arsenic in maternal blood, urine, and saliva. Conclusion Very little arsenic is excreted in breast milk, even in women with high exposure from drinking water. Thus, exclusive breast-feeding protects the infant from exposure to arsenic.

High concentrations of essential and toxic elements in infant formula and infant foods – A matter of concern

This study assessed concentrations in and intake of toxic and essential elements from formulas and foods intended for infants during their first 6months of life. Concentrations of the essential elements Ca, Fe, Zn, Mn and Mo were significantly higher in most formulas than in breast milk. Daily intake of Mn from formula varies from ten up to several hundred times the intake of the breast fed infant, levels that may be associated with adverse health effects. One portion of infant food provided significantly more Fe, Mn, Mo, As, Cd, Pb and U than one feeding of breast milk, but less Ca, Cu and Se. Rice-based products in particular contained elevated As concentrations. Drinking water used to mix powdered formula may add significantly to the concentrations in the ready-made products. Evaluation of potentially adverse effects of the elevated element concentrations in infant formulas and foods are warranted.

Arsenic methylation efficiency increases during the first trimester of pregnancy independent of folate status.

Exposure to inorganic arsenic during pregnancy may negatively influence the offspring, though efficient metabolism of arsenic to dimethylarsinic acid (DMA) likely reduces the health risks. This study aimed to evaluate methylation of arsenic over the entire pregnancy and the influence of nutritional status. We studied longitudinally the arsenic metabolite pattern in the urine of 324 pregnant women exposed to arsenic via drinking water and food in rural Bangladesh. Metabolism of arsenic to DMA increased markedly over the course of pregnancy, with the greatest improvement occurring in the first trimester, along with a marked decrease in the most risk-associated monomethylated metabolite. This improvement in methylation was not associated with nutritional status, including vitamin B(12) and folate. Efficient methylation to DMA was associated with improved urinary excretion of arsenic, relative to blood arsenic concentrations, indicating that micronutrient-independent up-regulation of arsenic metabolism already in early pregnancy may provide protection for the fetus.

High-level exposure to lithium, boron, cesium, and arsenic via drinking water in the Andes of Northern Argentina.

Elevated concentrations of arsenic in drinking water are common worldwide, however, little is known about the presence of other potentially toxic elements. We analyzed 31 different elements in drinking water collected in San Antonio de los Cobres and five surrounding Andean villages in Argentina, and in urine of the inhabitants, using ICP-MS. Besides confirmation of elevated arsenic concentrations in the drinking water (up to 210 microg/L), we found remarkably high concentrations of lithium (highest 1000 microg/L), cesium (320 microg/L), rubidium (47 microg/L), and boron (5950 microg/L). Similarly elevated concentrations of arsenic, lithium, cesium, and boron were found in urine of the studied women (N=198): village median values ranged from 26 to 266 microg/L of arsenic, 340 to 4550 microg/L of lithium, 34 to 531 microg/L of cesium, and 2980 to 16,560 microg/L of boron. There is an apparent risk of toxic effects of long-term exposure to several of the elements, and studies on associations with adverse human health effects are warranted, particularly considering the combined, life-long exposure. Because of the observed wide range of concentrations, all water sources used for drinking water should be screened for a large number of elements; obviously, this applies to all drinking water sources globally.

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.

Environmental Exposure to Metals and Children's Growth to Age 5 Years: A Prospective Cohort Study

In this prospective cohort study, based on 1,505 mother-infant pairs in rural Bangladesh, we evaluated the associations between early-life exposure to arsenic, cadmium, and lead, assessed via concentrations in maternal and child urine, and childrens weights and heights up to age 5 years, during the period 2001–2009. Concurrent and prenatal exposures were evaluated using linear regression analysis, while longitudinal exposure was assessed using mixed-effects linear regression. An inverse association was found between childrens weight and height, age-adjusted z scores, and growth velocity at age 5 years and concurrent exposure to cadmium and arsenic. In the longitudinal analysis, multivariable-adjusted attributable differences in childrens weight at age 5 years were −0.33 kg (95% confidence interval (CI): −0.60, −0.06) for high (≥95th percentile) arsenic exposure and −0.57 kg (95% CI: −0.88, −0.26) for high cadmium exposure, in comparison with children with the lowest exposure (≤5th percentile). Multivariable-adjusted attributable differences in height were −0.50 cm (95% CI: −1.20, 0.21) for high arsenic exposure and −1.6 cm (95% CI: −2.4, −0.77) for high cadmium exposure. The associations were apparent primarily among girls. The negative effects on childrens growth at age 5 years attributable to arsenic and cadmium were of similar magnitude to the difference between girls and boys in terms of weight (−0.67 kg, 95% CI: −0.82, −0.53) and height (−1.3 cm, 95% CI: −1.7, −0.89).

Metals and trace element concentrations in breast milk of first time healthy mothers: a biological monitoring study

BackgroundBreast milk is the best source of nutrition for the newborn infant. However, since all infants cannot be breast-fed, there is a need for background data for setting adequate daily intakes. Previously, concentration data on major essential elements and some toxic elements in breast milk, based on different analytical techniques, have been published. There is no recent study on a large number of metals and trace elements in breast milk, using a sensitive analytical method for determination of low element concentrations.MethodsBreast milk concentrations of 32 metals and elements in early lactation (days 14-21) were determined in a random sample of first time Swedish mothers (n = 60) using inductively coupled plasma mass spectrometry (ICPMS).ResultsThere were small inter-individual concentration variations in the macroelements Ca, K, Mg, P and S, and striking similarities across studies and over time, supporting a tight regulation of these elements in breast milk. Large inter-individual and over time differences were detected for Na concentrations, which may reflect an increase in salt consumption in Swedish women. Large inter-individual differences were also detected for the microelements Co, Cr, Mn and Mo, and the toxic metals As, Cd, Pb, Sb and V. Arsenic and B were positively correlated with fish consumption, indicating influence of maternal intake on breast milk concentrations. Observed differences in breast milk element concentrations across studies and over time could be attributed to the timing of sampling and a general decline over time of lactation (Cu, Fe, Mo, Zn), a possible lack of regulation of certain elements in breast milk (As, B, Co, Mn, Se) and time trends in environmental exposure (Pb), or in some cases to differences in analytical performance (Cr, Fe).ConclusionsThis study provides reliable updated information on a number of metals and elements in breast milk, of which some have not previously been reported.

Gender and age differences in mixed metal exposure and urinary excretion

BACKGROUND Little is known about the variation in exposure to toxic metals by age and gender and other potential modifying factors. We evaluated age and gender differences by measurements of metal/element concentrations in urine in a rural population in Matlab, Bangladesh, in three age groups: 8-12 (N=238), 14-15 (N=107) and 30-88 (N=710) years of age, living in an area with no point sources of metal exposure but where elevated water arsenic concentrations are prevalent. RESULTS We found marked differences in urine concentrations of metals and trace elements by gender, age, tobacco use, socioeconomic and nutritional status. Besides a clearly elevated urinary arsenic concentration in all age groups (medians 63-85 μg As/L), and despite the low degree of contamination from industries and traffic, the urine concentrations of toxic metals such as cadmium and lead were clearly elevated, especially in children (median 0.31 μg Cd/L and 2.9 μg Pb/L, respectively). In general, women had higher urinary concentrations of toxic metals, especially Cd (median 0.81 μg/L) compared to men (0.66 μg/L) and U (median 10 ng/L in women, compared to 6.4 ng/L in men), while men had higher urinary concentrations of the basic and essential elements Ca (69 mg/L in men, 30-50 years, compared to 52 mg/L in women), Mg (58 mg/L in men compared to 50 mg/L in women), Zn (182 μg/L in men compared to 117 μg/L in women) and Se (9.9 μg/L in men compared to 8.7 μg/L in women). Manganese was consistently higher in females than in males in all age groups, suggesting a biological difference between females and males in Mn metabolism. Increasing socioeconomic status decreased the toxic metal exposure significantly in children and especially in men. Poor iron status was detected in 17% of children, adolescents and women, but only in 6% of men. Also zinc deficiency was more prevalent in females than in males. CONCLUSIONS Women and children seemed to be more at risk for toxic metal exposure than men and at the same time more vulnerable to micronutrient deficiency. Higher concentrations of the toxic metals in urine in women are likely to reflect an increased gastrointestinal absorption of these metals at micronutrient deficiency, such as low body iron stores and Zn deficiency. Higher urinary concentrations of the essential elements in men likely reflect a better nutritional status. There is a need for information on exposure, lifestyle and socioeconomic factors, stratified by gender and age, for the purpose of conducting balanced risk assessment and management that considers such differences.

Persistent Exposure to Arsenic via Drinking Water in Rural Bangladesh Despite Major Mitigation Efforts

OBJECTIVES Elevated arsenic levels in tube-well water in Bangladesh have prompted extensive mitigation projects. We evaluated the effectiveness of long-term mitigation efforts by longitudinally measuring arsenic exposure in pregnant women and their children, the most susceptible population groups. METHODS The study was nested in a population-based nutrition intervention in Matlab, Bangladesh. Mother-child pairs (n = 1951) were followed from 2001 to 2003, beginning in early gestation and continuing to 5 years postpartum. We measured arsenic concentrations in urine (U-As) of the 5-year-old children by using high-performance liquid chromatography online with hydride generation and inductively coupled plasma mass spectrometry and compared them with earlier childhood U-As and maternal U-As during pregnancy. RESULTS Children had elevated U-As at 5 years old (median = 51 μg/L, 5th-95th percentiles = 16-355 μg/L), and U-As distribution was similar to that observed in the mothers during gestation. Childrens U-As at 5 years old significantly correlated with their U-As at 1.5 years old and to maternal U-As during early and late gestation. CONCLUSIONS Despite major mitigation efforts, arsenic exposure remains highly elevated in rural Bangladesh. Further mitigation strategies are required and must be rigorously evaluated for long-term efficacy.

Impaired arsenic metabolism in children during weaning.

BACKGROUND Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. AIM To elucidate the development of arsenic metabolism in early childhood. METHODS We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, a rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. RESULTS Arsenic concentrations in child urine (median 34 microg/L, range 2.4-940 microg/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, which has been associated with increased risk of health effects. CONCLUSION The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.