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BACKGROUND: Several metals act as endocrine disruptors, but there are few large longitudinal studies about associations with puberty onset. OBJECTIVES: We evaluated whether early life cadmium, lead, and arsenic exposure was associated with timing of menarche. METHODS: In a mother–child cohort in rural Bangladesh (푛=935), the exposure was assessed by concentrations in maternal erythrocytes in early pregnancy and in girls’ urine at 5 and 10 years of age using inductively coupled plasma mass spectrometry. The girls were interviewed twice, at average ages 13.3 [standard deviation (SD)=0.43] and 13.8 (SD=0.43) y, and the date of menarche, if present, was recorded. Associations were assessed using Kaplan–Meier analysis and multivariable-adjusted Cox regression. RESULTS: In total, 77% of the girls (푛=717) had reached menarche by the second follow-up. The median age of menarche among all girls was 13.0 y (25th–75th percentiles: 12.4–13.7 y). At 10 years of age, median urinary cadmium was 0.25 μg/L (5th–95th percentiles: 0.087–0.72 μg/L), lead 1.6 μg/L (0.70–4.2 μg/L), and arsenic 54 μg/L (19–395 μg/L). Given the same age, girls in the highest quartile of urinary cadmium at 5 and 10 years of age had a lower rate of menarche than girls in the lowest quartile, with an adjusted hazard ratio of (HR) 0.80 (95% CI: 0.62, 1.01) at 5 years of age, and 0.77 (95% CI: 0.60, 0.98) at 10 years of age. This implies that girls in the highest cadmium exposure quartile during childhood had a higher age at menarche. Comparing girls in the highest to the lowest quartile of urinary lead at 10 years of age, the former had a higher rate of menarche [adjusted HR=1.23 (95% CI: 0.97, 1.56)], implying lower age at menarche, whereas there was no association with urinary lead at 5 years of age. Girls born to mothers in the highest quartile of erythrocyte arsenic during pregnancy were less likely to have attained menarche than girls born to mothers in the lowest quartile [adjusted HR= 0.79 (95% CI: 0.62, 0.99)]. No association was found with girls’ urinary arsenic exposure. DISCUSSION: Long-term childhood cadmium exposure was associated with later menarche, whereas the associations with child lead exposure were inconclusive. Maternal exposure to arsenic, but not cadmium or lead, was associated with later menarche. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported associations between prenatal arsenic exposure and increased risk of infant mortality. An increase in infectious diseases has been proposed as the underlying cause of these associations, but there is no epidemiologic research to support the hypothesis. Objective: We evaluated the association between arsenic exposure in pregnancy and morbidity during infancy. Methods: This prospective population-based cohort study included 1,552 live-born infants of women enrolled during 2002-2004 in Matlab, Bangladesh. Arsenic exposure was assessed by the concentrations of metabolites of inorganic arsenic in maternal urine samples collected at gestational weeks 8 and 30. Information on symptoms of lower respiratory tract infection (LRTI) and diarrhea in infants was collected by 7-day recalls at monthly home visits. Results: In total, 115,850 person-days of observation were contributed by the infants during a 12-month follow-up period. The estimated risk of LRTI and severe LRTI increased by 69% [adjusted relative risk (RR) = 1.69; 95% confidence interval (CI), 1.36-2.09)] and 54% (RR = 1.54; 95% CI, 1.21-1.97), respectively, for infants of mothers with urinary arsenic concentrations in the highest quintile (average of arsenic concentrations measured in early and late gestation, 262-977 μg/L) relative to those with exposure in the lowest quintile (< 39 μg/L). The corresponding figure for diarrhea was 20% (RR = 1.20; 95% CI, 1.01-1.43). Conclusions: Arsenic exposure during pregnancy was associated with increased morbidity in infectious diseases during infancy. Taken together with the previous evidence of adverse effects on health, the findings strongly emphasize the need to reduce arsenic exposure via drinking water. [ABSTRACT FROM AUTHOR]

Background: We recently reported that the main reason for the documented higher prevalence of arsenic-related skin lesions among men than among women is the result of less efficient arsenic metabolism. Objective: Because smoking has been associated with less efficient arsenic methylation, we aimed to elucidate interactions between tobacco use and arsenic metabolism for the risk of developing skin lesions. Methods: We used a population-based case-referent study that showed increased risk for skin lesions in relation to chronic arsenic exposure via drinking water in Bangladesh and randomly selected 526 of the referents (random sample of inhabitants > 4 years old; 47% male) and all 504 cases (54% male) with arsenic-related skin lesions to measure arsenic metabolites [methylarsonic acid (MA) and dimethylarsinic acid (DMA)] in urine using high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICPMS). Results: The odds ratio for skin lesions was almost three times higher in the highest tertile of urinary %MA than in the lowest tertile. Men who smoked cigarettes and bidis (locally produced cigarettes; 33% of referents, 58% of cases) had a significantly higher risk for skin lesions than did nonsmoking men; this association decreased slightly after accounting for arsenic metabolism. Only two women smoked, but women who chewed tobacco (21% of referents, 43% of cases) had a considerably higher risk of skin lesions than did women who did not use tobacco. The odds ratio (OR) for women who chewed tobacco and who had ⩽ 7.9 %MA was 3.8 [95% confidence interval (CI), 1.4-10] compared with women in the same MA tertile who did not use tobacco. In the highest tertile of %MA or %inorganic arsenic (iAs), women who chewed tobacco had ORs of 7.3 and 7.5, respectively, compared with women in the lowest tertiles who did not use tobacco. Conclusion: The increased risk of arsenic-related skin lesions in male smokers compared with nonsmokers appears to be partly explained by impaired arsenic methylation, while there seemed to be an excess risk due to interaction between chewing tobacco and arsenic metabolism in women. [ABSTRACT FROM AUTHOR]

BACKGROUND: The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear. OBJECTIVES: In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water. METHODS: We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry. RESULTS: The median concentration of As in urine was 97 μg/L (range, 5-1,216 μg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation. CONCLUSIONS: In spite of the high As exposure and prevalent malnutrition, overall As methylation in women in early pregnancy was remarkably efficient. The As exposure level had the greatest impact on As methylation among the studied factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this population-based case-referent study in Matlab, Bangladesh, was to assess the susceptibility to arsenic-induced skin lesions by age and sex, in a population drinking water from As-contaminated tube wells. METHODS: Identification of As-related skin lesions was carried out in three steps: a) screening of the entire population > 4 years of age (n = 166,934) by trained field teams; b) diagnosis of suspected As-related cases by physicians; and c) confirmation by experts based on physicians' records and photographs. A total of 504 cases with skin lesions were confirmed. We randomly selected 2,201 referents from the Matlab health and demographic surveillance system; 1,955 were eligible, and 1,830 (94%) were available for participation in the study. Individual history of As exposure was based on information obtained during interviews and included all drinking-water sources used since 1970 and concentrations of As (assessed by atomic absorption spectrophotometry) in all the tube wells used. RESULTS: Cases had been exposed to As more than referents (average exposure since 1970: male cases, 200 µg/L; female cases, 211 µg/L; male referents, 143 µg/L; female referents, 155 µg/L). We found a dose-response relationship for both sexes (p < 0.001) and increased risk with increasing socioeconomic status. Males had a higher risk of obtaining skin lesions than females (odds ratio 10.9 vs. 5.78) in the highest average exposure quintile (p = 0.005). Start of As exposure (cumulative exposure) before 1 year of age was not associated with higher risk of obtaining skin lesions compared to start of As exposure later in life. CONCLUSIONS: The results demonstrate that males are more susceptible than females to develop skin lesions when exposed to As in water from tube wells. [ABSTRACT FROM AUTHOR]

Background: Several metals act as endocrine disruptors, but there are few large longitudinal studies about associations with puberty onset., Objectives: We evaluated whether early life cadmium, lead, and arsenic exposure was associated with timing of menarche., Methods: In a mother-child cohort in rural Bangladesh ( n = 935 ), the exposure was assessed by concentrations in maternal erythrocytes in early pregnancy and in girls' urine at 5 and 10 years of age using inductively coupled plasma mass spectrometry. The girls were interviewed twice, at average ages 13.3 [standard deviation ( SD ) = 0.43 ] and 13.8 ( SD = 0.43 ) y, and the date of menarche, if present, was recorded. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox regression., Results: In total, 77% of the girls ( n = 717 ) had reached menarche by the second follow-up. The median age of menarche among all girls was 13.0 y (25th-75th percentiles: 12.4-13.7 y). At 10 years of age, median urinary cadmium was 0.25 μ g / L (5th-95th percentiles: 0.087 - 0.72 μ g / L ), lead 1.6 μ g / L ( 0.70 - 4.2 μ g / L ), and arsenic 54 μ g / L ( 19 - 395 μ g / L ). Given the same age, girls in the highest quartile of urinary cadmium at 5 and 10 years of age had a lower rate of menarche than girls in the lowest quartile, with an adjusted hazard ratio of (HR) 0.80 (95% CI: 0.62, 1.01) at 5 years of age, and 0.77 (95% CI: 0.60, 0.98) at 10 years of age. This implies that girls in the highest cadmium exposure quartile during childhood had a higher age at menarche. Comparing girls in the highest to the lowest quartile of urinary lead at 10 years of age, the former had a higher rate of menarche [adjusted HR = 1.23 (95% CI: 0.97, 1.56)], implying lower age at menarche, whereas there was no association with urinary lead at 5 years of age. Girls born to mothers in the highest quartile of erythrocyte arsenic during pregnancy were less likely to have attained menarche than girls born to mothers in the lowest quartile [adjusted HR = 0.79 (95% CI: 0.62, 0.99)]. No association was found with girls' urinary arsenic exposure., Discussion: Long-term childhood cadmium exposure was associated with later menarche, whereas the associations with child lead exposure were inconclusive. Maternal exposure to arsenic, but not cadmium or lead, was associated with later menarche. https://doi.org/10.1289/EHP11121.