Habibul Ahsan

Water Manganese Exposure and Children's Intellectual Function in Araihazar, Bangladesh

Exposure to manganese via inhalation has long been known to elicit neurotoxicity in adults, but little is known about possible consequences of exposure via drinking water. In this study, we report results of a cross-sectional investigation of intellectual function in 142 10-year-old children in Araihazar, Bangladesh, who had been consuming tube-well water with an average concentration of 793 μg Mn/L and 3 μg arsenic/L. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children’s intellectual function was assessed on tests drawn from the Wechsler Intelligence Scale for Children, version III, by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead, As, Mn, and hemoglobin concentrations. After adjustment for sociodemographic covariates, water Mn was associated with reduced Full-Scale, Performance, and Verbal raw scores, in a dose–response fashion; the low level of As in water had no effect. In the United States, roughly 6% of domestic household wells have Mn concentrations that exceed 300 μg Mn/L, the current U.S. Environmental Protection Agency lifetime health advisory level. We conclude that in both Bangladesh and the United States, some children are at risk for Mn-induced neurotoxicity.

Association between Body-Mass Index and Risk of Death in More Than 1 Million Asians

BACKGROUND Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

The Broad Scope of Health Effects from Chronic Arsenic Exposure: Update on a Worldwide Public Health Problem

Background: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. Objectives: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. Methods: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. Discussion: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. Conclusions: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.

Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study

BACKGROUND Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. METHODS In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. FINDINGS 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. INTERPRETATION Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. FUNDING US National Institutes of Health.

Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study

Objective To evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association. Design Prospective cohort study with arsenic exposure measured in drinking water from wells and urine. Setting General population in Araihazar, Bangladesh. Participants 11 746 men and women who provided urine samples in 2000 and were followed up for an average of 6.6 years. Main outcome measure Death from cardiovascular disease. Results 198 people died from diseases of circulatory system, accounting for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100 000 person years in people drinking water containing <12.0 µg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with ≥12.0 µg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease; the hazard ratios in increasing quarters of arsenic concentration in well water (0.1-12.0, 12.1-62.0, 62.1-148.0, and 148.1-864.0 µg/L) were 1.00 (reference), 1.22 (0.65 to 2.32), 1.35 (0.71 to 2.57), and 1.92 (1.07 to 3.43) (P=0.0019 for trend), respectively, after adjustment for potential confounders including age, sex, smoking status, educational attainment, body mass index (BMI), and changes in urinary arsenic concentration since baseline. Similar associations were observed when baseline total urinary arsenic was used as the exposure variable and for mortality from ischaemic heart disease specifically. The data indicate a significant synergistic interaction between arsenic exposure and cigarette smoking in mortality from ischaemic heart disease and other heart disease. In particular, the hazard ratio for the joint effect of a moderate level of arsenic exposure (middle third of well arsenic concentration 25.3-114.0 µg/L, mean 63.5 µg/L) and cigarette smoking on mortality from heart disease was greater than the sum of the hazard ratios associated with their individual effect (relative excess risk for interaction 1.56, 0.05 to 3.14; P=0.010). Conclusions Exposure to arsenic in drinking water is adversely associated with mortality from heart disease, especially among smokers.

Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh.

Background We recently reported results of a cross-sectional investigation of intellectual function in 10-year-olds in Bangladesh, who had been exposed to arsenic from drinking water in their home wells. Objectives We present results of a similar investigation of 301 randomly selected 6-year-olds whose parents participated in our ongoing prospective study of the health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Methods Water As and manganese concentrations of tube wells at each home were obtained by surveying all study region wells. Children and mothers were first visited at home, where the quality of home stimulation was measured, and then seen in our field clinic, where children received a medical examination wherein weight, height, and head circumference were assessed. We assessed children’s intellectual function using subtests drawn from the Wechsler Preschool and Primary Scale of Intelligence, version III, by summing weighted items across domains to create Verbal, Performance, Processing Speed, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and were asked to provide blood samples for blood lead measurements. Results Exposure to As from drinking water was associated with reduced intellectual function before and after adjusting for water Mn, for blood lead levels, and for sociodemographic features known to contribute to intellectual function. With covariate adjustment, water As remained significantly negatively associated with both Performance and Processing Speed raw scores; associations were less strong than in our previously studied 10-year-olds. Conclusion This second cross-sectional study of As exposure expands our concerns about As neurotoxicity to a younger age group.

Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer

AbstractObjective: The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case–control study. Methods: Cases were aged 30–79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview. Results: History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4–3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2–9.3). Ever having used H2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5–1.5). The odds ratio was 1.3 (95% CI 0.6–2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8–5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H2 blockers or antacids was associated with risk of the other three tumor types. Conclusions: Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H2blockers or antacids.

Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh.

Chronic exposure to arsenic is occurring throughout South and East Asia due to groundwater contamination of well water. Variability in susceptibility to arsenic toxicity may be related to nutritional status. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism, a biochemical pathway that is dependent on folate. The majority of one-carbon metabolism methylation reactions are devoted to biosynthesis of creatine, the precursor of creatinine. Our objectives of this cross-sectional study were to characterize the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. Water arsenic, urinary arsenic, urinary creatinine, plasma folate, cobalamin, and homocysteine were assessed in 1,650 adults; urinary arsenic metabolites were analyzed for a subset of 300 individuals. The percentage of DMA in urine was positively associated with plasma folate (r = 0.14, p = 0.02) and negatively associated with total homocysteine (tHcys; r = −0.14, p = 0.01). Conversely, percent MMA was negatively associated with folate (r = −0.12, p = 0.04) and positively associated with tHcys (r = 0.21, p = 0.0002); percent inorganic arsenic (InAs) was negatively associated with folate (r = −0.12, p = 0.03). Urinary creatinine was positively correlated with percent DMA (r = 0.40 for males, p < 0.0001; 0.25 for females, p = 0.001), and with percent InAs (r = −0.45 for males, p < 0.0001; −0.20 for females, p = 0.01). Collectively, these data suggest that folate, tHcys, and other factors involved in one-carbon metabolism influence arsenic methylation. This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high.

Health Effects of Arsenic Longitudinal Study (HEALS): Description of a multidisciplinary epidemiologic investigation

Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes, including premalignant and malignant skin tumors, total mortality, pregnancy outcomes, and childrens cognitive development. In this paper, we provide descriptions of the study methods including study design, study population, data collection, response rates, and exposure and outcome assessments. We also present characteristics of the study participants including the distribution of exposure and the prevalence of skin lesion at baseline recruitment. A total of 11,746 married men and women between 18 and 75 years of age participated in the study at baseline (a response rate of 98%) and completed a full questionnaire interview that included a food frequency questionnaire, with a response rate of 98%. Among the 98% of the participants who completed the clinical evaluation, over 90% provided blood samples and spot urine samples. Higher educational status, male gender, and presence of premalignant skin lesions were associated with an increased likelihood of providing blood and urine samples. Older participants were less likely to donate a blood sample. About one-third of the participants consumed water from a well with As concentration in each of three groups: >100 μg/l, 25–100 μg/l, and <25 μg/l. Average urinary As concentrations were 140 and 136 μg/l for males and females, respectively. HEALS has several unique features, including a prospective study design, comprehensive assessments of both past and future changes in As exposure at the individual level, a large repository of biological samples, and a full dose range of As exposures in the study population. HEALS is a valuable resource for examining novel research questions on the health effects of As exposure.

Promotion of well-switching to mitigate the current arsenic crisis in Bangladesh

OBJECTIVE To survey tube wells and households in Araihazar upazila, Bangladesh, to set the stage for a long-term epidemiological study of the consequences of chronic arsenic exposure. METHODS Water samples and household data were collected over a period of 4 months in 2000 from 4997 contiguous tube wells serving a population of 55000, the position of each well being determined to within +/- 30 m using Global Positioning System receivers. Arsenic concentrations were determined by graphite-furnace atomic-absorption spectrometry. In addition, groundwater samples collected every 2 weeks for an entire year from six tube wells were analysed for arsenic by high-resolution inductively coupled plasma-mass spectrometry. FINDINGS Half of the wells surveyed in Araihazar had been installed in the previous 5 years; 94% were privately owned. Only about 48% of the surveyed wells supplied water with an arsenic content below 50 micro g/l, the current Bangladesh standard for drinking-water. Similar to other regions of Bangladesh and West Bengal, India, the distribution of arsenic in Araihazar is spatially highly variable (range: 5-860 micro g/l) and therefore difficult to predict. Because of this variability, however, close to 90% of the inhabitants live within 100 m of a safe well. Monitoring of six tube wells currently meeting the 50 micro g/l standard showed no indication of a seasonal cycle in arsenic concentrations coupled to the hydrological cycle. This suggests that well-switching is a viable option in Araihazar, at least for the short term. CONCLUSIONS Well-switching should be more systematically encouraged in Araihazar and many other parts of Bangladesh and West Bengal, India. Social barriers to well-switching need to be better understood and, if possible, overcome.