Whereas dysglycemia among adolescents without overweight/obesity was reported in an urban hospital in Bangladesh during 2001–2002, rural epidemiological studies using fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) identified only type 1 and type 2 diabetes, with increased BMI reported as a risk factor. Thus, we aimed to determine the prevalence of dysglycemia and its association with body mass index-for-age z-score (BAZ) among adolescents in rural Bangladesh during a rapid nutritional transition. A population-based cross-sectional study was conducted from December 2017 to March 2018 in the Matlab Health and Demographic Surveillance System of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) using a random sampling technique to recruit adolescents aged 10–19 years. A total of 291 adolescents underwent anthropometry and measurement of FPG and glycated hemoglobin (HbA1c). OGTT was performed on those with elevated FPG, elevated HbA1c, and/or positive postprandial glycosuria. Dysglycemia was defined according to the American Diabetes Association criteria of diabetes and prediabetes. Comparisons between adolescents with and without dysglycemia were performed using the Student’s t-test and the Mann–Whitney U test. Crude and adjusted odds ratios (cORs, aORs) for dysglycemia were calculated. Dysglycemia was detected in 43 of 291 adolescents(14.8

Background:The causal mechanisms by which socioeconomic status (SES) affects blood pressure (BP) in low- and middle-income countries (LMICs) remain poorly understood. We examined the effects of SES on BP, and the extent to which disparities in metal mixture exposures mediate these effects among rural Bangladeshi adults. Methods:This study included 5923 participants from the Bangladesh Vitamin E and Selenium Trial (BEST), a prospective cohort followed for six years with repeated BP assessments at baseline and three biennial follow-ups. Baseline exposures included SES indicators: education and agricultural land ownership (socioeconomic position, SEP), and metal mixtures: blood arsenic, lead, selenium, and urinary arsenic. We applied the parametric and mediational g-formula, along with generalized weighted quantile sum regression, to estimate total, direct, and indirect effects of SES on BP outcomes and conduct causal mediation analysis with four-way decomposition. Results:Higher education increased BP, whereas SEP decreased the elevation of BP. Both higher education and SEP lowered metal exposures. Metal mixtures mediated the effects of SES on BP. For example, higher education increased systolic blood pressure (SBP) by 3.53 mmHg (95% CI: 2.23, 4.82), while the pure natural indirect effect showed a protective pathway of -0.44 mmHg (95% CI: -0.62, -0.27) through reduced metals. For SEP, nearly 42% of its protective effect on SBP was mediated by lower metal exposures. Conclusions:Socioeconomic differentials in BP outcomes in rural Bangladesh are partly explained by inequalities in metal mixture exposures. Reducing metal exposures may mitigate SES-related disparities in BP measures in LMICS.

Background: Epidemiological studies have indicated that anti-Ascaris IgE enhances asthma and allergies under specific conditions although the association between them is still controversial. The association of anti-Ascaris IgE with increased asthma symptoms among children from a general population with a mild to moderate Ascaris infection prevalence was investigated. Methods: A total of 126 children aged 5 years with wheezing during the previous year and 110 children who did not have wheezing were selected randomly from the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Serum levels of total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anti-cockroach IgEs were tested, and their risks for wheezing were analyzed. The wheezing children were then classified by hierarchical cluster analysis to investigate the contribution of anti-Ascaris IgE to wheezing. Results: The anti-Ascaris IgE levels in wheezing and never-wheezing children were 1.07 and 0.65 UA/mL, and it contributed to 11% of wheezing in children. Anti-Ascaris IgE was significantly associated with wheezing (odds ratio [OR] per loge increment: 1.37 [95% CI: 1.01–1.87], p = 0.046). The ORs, which were adjusted for sex, parental asthma, pneumonia history, helminth infections, Haemophilus influenzae type B combination vaccination, antibiotic use during infancy, and total and specific IgE levels, increased even when only children with more specific symptoms of asthma were included in the analysis. Namely, the ORs for wheezing with sleep disturbance, four or more attacks, and wheezing with speech difficulties during the previous 1 year were OR = 1.44/loge increment [95% CI: 1.01–2.07], OR = 1.90/loge increment [95% CI: 1.11–3.25], and OR = 1.78/loge increment [95% CI: 1.01–3.14], respectively. Conclusions: The anti-Ascaris IgE levels in wheezing and never-wheezing children in the current study significantly decreased concurrently with Ascaris infection prevalence compared with their corresponding values in 2001. The contribution of anti-Ascaris IgE to wheezing also dropped from 26% in 2001 to 11% in the current study. Despite significant decreases in the levels and the seroprevalence and its contribution to wheezing, anti-Ascaris IgE remained significantly associated with increased risk of wheezing. Anti-Ascaris IgE significantly increased the risk of wheezing in a general population with a mild to moderate Ascaris infection prevalence, suggesting robustness as a risk factor and a possible dose-response relationship.

Background: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970’s, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease.Methods: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%).Results: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3–4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group.Conclusions: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

Chronic arsenic (As) exposure is a major environmental threat to human health affecting >100 million people worldwide. Low blood selenium (Se) increases the risk of As-induced health problems. Our aim was to reduce As toxicity through a naturally Se-rich lentil diet. In a randomized, double-blind, placebo-control trial in Bangladesh, 405 participants chronically exposed to As were enrolled. The intervention arm (Se-group) consumed Se-rich lentils (55 μg Se/day); the control arm received lentils of similar nutrient profile except with low Se (1.5 μg Se/day). Anthropometric measurements, blood, urine and stool samples, were taken at baseline, 3 and 6 months; hair at baseline and 6 months after intervention. Morbidity data were collected fortnightly. Measurements included total As in all biological samples, As metabolites in urine, and total Se in blood and urine. Intervention with Se-rich lentils resulted in higher urinary As excretion (p = 0.001); increased body mass index (p ≤ 0.01), and lower incidence of asthma (p = 0.05) and allergy (p = 0.02) compared to the control group. The Se-group demonstrated increased excretion of urinary As metabolite, dimethylarsinic acid (DMA) at 6 months compared to control group (p = 0.008). Consuming Se-rich lentils can increase As excretion and improve the health indicators in the presence of continued As exposure.

AbstractIntroductionEpidemiological research on the prevalence of asthma and helminthic infections in various countries has led to the hypothesis that helminthic infections protect against asthma by suppressing the host's immune response. This study was conducted to elucidate whether decreased Ascaris infection following a national deworming program was associated with increased recurrent wheezing among rural Bangladeshi children and to test their anti‐inflammatory immunity.MethodsThis nested case‐control study was conducted from December 2015 to October 2016 in the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Of the 1800 5–year old children randomly selected for the study, informed consent was obtained from the guardians of 1658 children. Data were collected using a semistructured questionnaire adopted from the International Study of Asthma and Allergies in Childhood and blood samples for the analysis of regulatory T (Treg) cell immune responses and the balance between Th1 and Th2 immunity in Ascaris infections.ResultsA total of 145 children were found to have wheezing, yielding a prevalence rate of 8.7%, which was significantly lower than the rate found in 2001 (16.2%, P < .001); Ascaris infection also decreased from 2001 to 2016. The 127 wheezing children who agreed to participate further were compared to 114 randomly selected never‐wheezing children. Wheezing had a significant positive association with antibiotic use, history of pneumonia, parents’ history of asthma, and Ascaris infection; children with Ascaris infection were twice as likely to have wheezing (adjusted odds ratio = 2.31, P = .053). Flow cytometry found no significant differences in the rates of Th1, Th2, and CD4 +CD25 +CD127low cells by the wheezing group.ConclusionsAscaris infection had a positive rather than a negative association with wheezing and the rates of wheezing and Ascaris infections both decreased from 2001 to 2016. These findings undermines the hypothesis that such infections provide protection against asthma.

Available evidence is limited on the association between weather factors and childhood pneumonia, especially in developing countries. This study examined the effects of weather variability on childhood pneumonia after the introduction of pneumococcal conjugate vaccines (PCV) intervention in rural Bangladesh. Data on pneumonia cases and weather variables (temperature and relative humidity) between the 1st January 2012 and the 31st December 2016 were collected from Matlab Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, and Bangladesh Meteorological Department, respectively. Time series cross-correlation functions were applied to identify the time lags of the effect of each weather factor on pneumonia. Generalized linear regression model with Poisson link was used to quantify the association between weather factors and childhood pneumonia after adjustment of PCV intervention. The annual incidence rate of pneumonia reduced from 5691/100,000 to 2000/100,000 after PCV intervention. Generalized linear regression model suggested that temperature had a negative association with childhood pneumonia (relative risk, 0.985; 95% confidence interval (CI), 0.974–0.997), and PCV intervention was a protective factor with the relative risk estimate of 0.489 (95% CI, 0.435–0.551). However, no substantial association was found with relative humidity. PCV intervention appeared protective against childhood pneumonia, and temperature might be associated with this disease in children. Our findings may help inform public health policy, including the potential of development of early warning systems based on weather factors and PCV for the control and prevention of pneumonia in lower middle-income country like Bangladesh.

Pneumonia is the leading cause of mortality and morbidity in developing countries, particularly for children and elderly. The main objective of this review paper is to review the epidemiological evidence about the effects of sociodemographic and climatic variability on pneumonia and other lower respiratory tract infections. A detailed literature search was conducted in PubMed and Scopus following PRISMA guidelines. The articles, which considered the effect of only climatic or both climatic and sociodemographic factors on pneumonia and other lower respiratory tract infections, included in this review. A total thirty-four relevant articles were reviewed. Of 34 studies, only 14 articles (41%) examined the joint effects of sociodemographic and climate factors on pneumonia and other lower respiratory infections while most of them (59%) assessed climate factors separately. Among these fourteen, only three articles (8.8%) considered detailed sociodemographic factors. All of the reviewed articles suggested different degrees of positive or negative relationship of temperature with pneumonia or other lower respiratory tract infections. Fifteen (44%) articles suggested an association with relative humidity and 13 (38%) with rainfall. Only 3 articles (8.8%) found a relationship with wind speed. Three articles (8.8%) considered other risk factors such as particulate matter 2.5 (PM 2.5 ) and particulate matter 10 (PM 10 ). One study among the reviewed articles used spatial analysis methods but this study did not examine the joint effects. Among the reviewed articles, 18 (53%) articles used different time series models, one article (3%) used spatiotemporal time series model, 8 (23%) studies used other models and rest 7 (21%) studies used simple descriptive analysis. A total of 18 studies (53%) were conducted in Asia, most of them in China. There were 6 studies (17%) in Europe and 8 studies (23%) in America (South, North and Central). In Africa and Oceania, only one study was found for each region. The joint effect of climate and sociodemographic factors on pneumonia and other lower respiratory tract infections remain to be determined and further research is highly recommended for future prevention of this important and common disease.

Objectives The objective of this study was to estimate the magnitude and determinants of inadequate weight gain in the third-trimester among rural women in Matlab, Bangladesh. Methods The study analyzed data on weight gain in the third trimester in 1,883 pregnant women in Matlab, Bangladesh. All these women were admitted to Matlab hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) for childbirth during 2012–2014, and they had singleton live births at term. Data were retrieved from the electronic databases of Matlab Health and Demographic Surveillance System and Matlab hospital. A multivariable logistic regression for inadequate weight gain in the third trimester (≤4 kg) was built with sociodemographic, environmental and maternal factors as predictors. Results One thousand and twenty-six (54%) pregnant women had inadequate weight gain in the third trimester. In the multivariable model, short stature turned out to be the most robust risk factor for inadequate weight gain in the third trimester (OR = 2.5; 95% CI 1.8, 3.5 for short compared to tall women). Pre-third-trimester BMI was inversely associated with insufficient weight gain (OR = 0.96; 95% CI 0.93, 0.99 for 1 unit increase in BMI). Other risk factors for inadequate weight gain in the third trimester were advanced age (OR = 1.9; 95% CI 1.2, 3.1 for ≥35 years compared to ≤19 years), parity (OR = 1.5; 95% CI 1.2, 1.9 for multipara compared to nulliparous women), low socioeconomic status (OR = 1.7; 95% CI 1.2, 2.3 for women in the lowest compared to women in the highest wealth quintile), low level of education (OR = 1.6; 95% CI 1.2, 2.1 for ≤5 years compared to ≥10 years of education), belonging to the Hindu religious community (OR = 1.8; 95% CI 1.3, 2.5), consuming arsenic-contaminated water (OR = 1.4; 95% CI 1.1, 1.9), and conceiving during monsoon or dry season compared to summer (OR = 1.4; 95% CI 1.1, 1.8). Conclusions Among rural Bangladeshi women in Matlab, third-trimester weight gain was in general poor. Maternal characteristics such as short stature, low BMI, advanced age, parity, low level of education and socioeconomic status, being Hindu, intake of arsenic contaminated water, and conceiving during monsoon or dry season were the risk factors for inadequate weight gain in the third trimester. Special attention should be given during prenatal care to women with the risk factors identified in this study.

BACKGROUND:Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established.OBJECTIVES:We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh.METHODS:Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality.RESULTS:We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure.CONCLUSIONS:Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age.

1511 Background: Selenium and vitamin E supplementation previously have shown some evidence of a beneficial effect in the secondary prevention of non-melanoma skin cancer (NMSC). More than 100 million people worldwide are at increased risk of NMSC and other cancers due to arsenic exposure from drinking water and diet – a risk that persists for several decades even after the exposure has terminated. Here, we report on the design, methods and main results of the Bangladesh Vitamin E and Selenium Trial (BEST) – a population-based chemoprevention study conducted among 7,000 adults with visible arsenic toxicity. Methods: BEST is a 2 × 2 full factorial, double-blind, randomized placebo controlled trial of 7,000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 μg daily) for the prevention of NMSC incidence. Results: Excellent compliance was maintained through the course of the trial, based on data from pill counts, self-reported compliance, and bioadherence. Among participants on treatment through the end of the 6-year intervention period, > 85% were adherent to at least 80% of study supplements. More than 500 new NMSC cases were ascertained using a three-tiered biopsy protocol. No significant beneficial effects were observed on NMSC incidence during the study period for selenium or vitamin E. Among more than 500 observed deaths (including 182 cancer-related deaths), there were also no significant treatment effects on total mortality, cancer-related mortality or arsenical cancer-related mortality. Conclusions: This large population-based trial does not support any beneficial effect of vitamin E or selenium supplementation for the primary prevention of NMSC or mortality in an arsenic-exposed population. With the rapidly increasing burden of preventable cancers in low- and middle-income countries, efficient and feasible chemoprevention study designs and approaches, such as employed in Bangladesh, may prove impactful in conceiving large scale cancer chemoprevention trials in low-resource settings. Clinical trial information: NCT00392561.

Background: Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water.Methods: We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1799 individuals. Association between arsenic exposure and a qPCR-based telomere length measure was assessed among 167 individuals.Results: Urinary arsenic was possitively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P < 0.00035, Bonferroni-corrected threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction =0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02).Discussion: Our findings suggest that arsenic's carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes. (C) 2014 Elsevier Inc. All rights reserved.

There is increasing concern regarding adverse effects of prenatal arsenic exposure on the neurodevelopment of children. We analyzed mortality data for children, who were born to 11,414 pregnant women between 2002 and 2004, with an average age of 5 years of follow-up. Individual drinking-water arsenic exposure during pregnancy was calculated using tubewell water arsenic concentration between last menstrual period and date of birth. There were 84 drowning deaths registered, with cause of death ascertained using verbal autopsy (International Classification of Diseases, 10th revision, codes X65–X70). The prenatal water arsenic exposure distribution was tertiled, and the risk of drowning mortality was estimated by Cox proportional hazard models, adjusted for potential confounders. We observed a significant association between prenatal arsenic exposure and drowning in children aged 1–5 years in the highest exposure tertile (HR=1.74, 95% CI: 1.03–2.94). This study showed that in utero arsenic exposure might be associated with excess mortality among children aged 1–5 years due to drowning.

Background Arsenic in drinking water causes increased coronary artery disease (CAD) and death from CAD, but its association with stroke is not known. Methods Prospective cohort study with arsenic exposure measured in well water at baseline. 61074 men and women aged 18 years or older on January 2003 were enrolled in 2003. The cohort was actively followed for an average of 7 years (421,754 person-years) through December 2010. Based on arsenic concentration the population was categorized in three groups and stroke mortality HR was compared to the referent. The risk of stroke mortality Hazard Ratio (HR) and 95% Confidence Interval was calculated in relation to arsenic exposure was estimated by Cox proportional hazard models with adjustment for potential confounders. Results A total of 1033 people died from stroke during the follow-up period, accounting for 23% of the total deaths. Multivariable adjusted HRs (95% confidence interval) for stroke for well water arsenic concentrations <10, 10-49, and ≥50 μg/L were 1.0 (reference), 1.20 (0.92 to 1.57), and 1.35 (1.04 to 1.75) respectively (P trend =0.00058). For men, multivariable adjusted HRs (95%) for well water arsenic concentrations <10, 10-49, and ≥50 μg/L were 1.0 (reference), 1.12 (0.78 to 1.60), and 1.07 (0.75 to 1.51) respectively (P trend =0.45) and for women 1.0 (reference),1.31 (0.87 to 1.98), and 1.72 (1.15 to 2.57) respectively (P trend =0.00004). Conclusion The result suggests that arsenic exposure was associated with increased stroke mortality risk in this population, and was more significant in women compared to men.

BACKGROUND:Chronic arsenic exposure through drinking water is a public health problem affecting millions of people worldwide, including at least 30 million in Bangladesh. We prospectively investigated the associations of arsenic exposure and arsenical skin lesion status with lung disease mortality in Bangladeshi adults.METHODS:Data were collected from a population-based sample of 26,043 adults, with an average of 8.5 years of follow-up (220,157 total person-years). There were 156 nonmalignant lung disease deaths and 90 lung cancer deaths ascertained through October 2013. We used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for lung disease mortality.RESULTS:Creatinine-adjusted urinary total arsenic was associated with nonmalignant lung disease mortality, with persons in the highest tertile of exposure having a 75% increased risk for mortality (95% CI = 1.15-2.66) compared with those in the lowest tertile of exposure. Persons with arsenical skin lesions were at increased risk of lung cancer mortality (hazard ratio = 4.53 [95% CI = 2.82-7.29]) compared with those without skin lesions.CONCLUSIONS:This prospective investigation of lung disease mortality, using individual-level arsenic measures and skin lesion status, confirms a deleterious effect of ingested arsenic on mortality from lung disease. Further investigations should evaluate effects on the incidence of specific lung diseases, more fully characterize dose-response, and evaluate screening and biomedical interventions to prevent premature death among arsenic-exposed populations, particularly among those who may be most susceptible to arsenic toxicity.

Background: Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh.Methods: We compared menopausal age in two groups of women - with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies-participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women.Results: Women with arsenic skin lesions were 1.5 years younger (p < 0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p < 0.001) for respondents with arsenic skin lesions.Conclusions: The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

Background Arsenic in drinking water was associated with increased risk of all-cause, cancer, and cardiovascular death in adults. However, the extent to which exposure is related to all-cause and deaths from cancer and cardiovascular condition in young age is unknown. Therefore, we prospectively assessed whether long-term and recent arsenic exposures are associated with all-cause and cancer and cardiovascular mortalities in Bangladeshi childhood population. Methods and Findings We assembled a cohort of 58406 children aged 5–18 years from the Health and Demographic Surveillance System of icddrb in Bangladesh and followed during 2003–2010. There were 185 non-accidental deaths registered in-about 0.4 million person-years of observation. We calculated hazard ratios for cause-specific death in relation to exposure at baseline (µg/L), time-weighted lifetime average (µg/L) and cumulative concentration (µg-years/L). After adjusting covariates, hazard ratios (HRs) for all-cause childhood deaths comparing lifetime average exposure 10–50.0, 50.1–150.0, 150.1–300.0 and ≥300.1µg/L were 1.37 (95% confidence interval [CI], 0.74–2.57), 1.44 (95% CI, 0.88–2.38), 1.22 (95% CI, 0.75–1.98) and 1.88 (95% CI, 1.14–3.10) respectively. Significant increased risk was also observed for baseline (P for trend = 0.023) and cumulative exposure categories (P for trend = 0.036). Girls had higher mortality risk compared to boys (HR for girls 1.79, 1.21, 1.64, 2.31; HR for boys 0.52, 0.53, 1.14, 0.99) in relation to baseline exposure. For all cancers and cardiovascular deaths combined, multivariable adjusted HRs amounted to 1.53 (95% CI 0.51–4.57); 1.29 (95% CI 0.43–3.87); 2.18 (95%CI 1.15–4.16) for 10.0–50.0, 50.1–150.0, and ≥150.1, comparing lowest exposure as reference (P for trend = 0.009). Adolescents had higher mortality risk compared to children (HRs = 1.53, 95% CI 1.03–2.28 vs. HRs = 1.30, 95% CI 0.78–2.17). Conclusions Arsenic exposure was associated with substantial increased risk of deaths at young age from all-cause, and cancers and cardiovascular conditions. Girls and adolescents (12–18 years) had higher risk compared to boys and child.