Search

Chronic arsenic exposure is known to affect the immune system. We aimed to evaluate the association between arsenic exposure and immune cell profile in 15 years old adolescents (n=389) in rural Bangladesh, with chronic exposure to groundwater arsenic. Single blood and urine were collected. Urinary arsenic (U-As) concentration was measured using atomic absorption spectrometry. Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry. Non-linear association was found between U-As (median, 24.9 µg/L) and immune cells with a cut-off at U-As 20 µg/L. U-As (<20 µg/L) were significantly associated with increases in CD8 + T (21 %), na ï ve CD8 + T (42 %) and early B cells (40 %), and classical monocytes (55 %), but reduction in CD3 + T cells (37 % ) and intermediate-monocytes (56 %). U-As (>20 µg/L) were associated with a 3 % reduction in memory B cells. Arsenic exposure was associated with altered immune cell profile in adolescents likely rendering them vulnerable to adverse health effects in later life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is growing interest in understanding the contribution of environmental toxicant exposure in early life to development of cardiometabolic diseases (CMD) in adulthood. We aimed to assess associations of early life exposure to arsenic and cadmium with biomarkers of CMD in children in rural Bangladesh. From a longitudinal mother-child cohort in Matlab, Bangladesh, we followed up 540 pairs. Exposure to arsenic (U-As) and cadmium (U-Cd) was assessed by concentrations in urine from mothers at gestational week 8 (GW8) and children at ages 4.5 and 9 years. Blood pressure and anthropometric indices were measured at 4.5 and 9 years. Metabolic markers (lipids, glucose, hemoglobin A1c, adipokines, estimated glomerular filtration rate (eGFR) were determined in plasma/blood of 9 years old children. In linear regression models, adjusted for child sex, age, height-for-age z score (HAZ), BMI-for-age z score (BAZ), socioeconomic status (SES) and maternal education, each doubling of maternal and early childhood U-Cd was associated with 0.73 and 0.82 mmHg increase in systolic blood pressure (SBP) respectively. Both early and concurrent childhood U-Cd was associated with diastolic (D)BP (β = 0.80 at 4.5 years; β = 0.75 at 9 years). Each doubling of U-Cd at 9 years was associated with decrements of 4.98 mg/dL of total cholesterol (TC), 1.75 mg/dL high-density lipoprotein (HDL), 3.85 mg/dL low-density lipoprotein (LDL), 0.43 mg/dL glucose and 4.29 units eGFR. Each doubling of maternal U-Cd was associated with a decrement of 1.23 mg/dL HDL. Both maternal and childhood U-As were associated with decrement in TC and HDL. Multiple comparisons were checked with family-wise error rate Bonferroni-type-approach. The negative associations of arsenic and cadmium with biomarkers of CMD in preadolescent children indicated influence of both metal(loid)s on fat and carbohydrate metabolism, while cadmium additionally influenced kidney function and BP. Thus, fewer outcomes were associated with U-As compared to U-Cd at preadolescence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Early-life arsenic exposure has been associated with reduced cell-mediated immunity, but little is known about its effects on humoral immunity., Objective: We evaluated whether prenatal and childhood arsenic exposure was associated with humoral immune function in school-aged children., Methods: Children born in a prospective mother–child cohort in rural Bangladesh were immunized with measles, mumps, and rubella (MMR) vaccines at 9 years of age (n=525). Arsenic exposure was assessed in urine (U-As), from mothers during pregnancy and their children at 4.5 and 9 years of age. Total IgG (tIgG), tIgE, tIgA, and MMR-specific IgG concentrations were measured in plasma using immunoassays., Results: Arsenic exposure was positively associated with child tIgG and tIgE, but not tIgA. The association with tIgG was mainly apparent in boys ( p for interaction=0.055), in whom each doubling of maternal U-As was related to an increase in tIgG by 28 mg/dL. The associations of U-As at 9 years with tIgG and tIgE were evident in underweight children ( p for interaction <0.032). Childhood arsenic exposure tended to impair mumps-specific vaccine response, although the evaluation was complicated by high preimmunization titers. Postimmunization mumps–specific IgG titers tended to decrease with increasing U-As at 4.5 and 9 years of age [regression coefficient (β)=−0.16; 95% confidence interval (CI): −0.33, 0.01; p=0.064 and β=−0.12; 95% CI: −0.27, −0.029; p=0.113, respectively) in 25% children with the lowest preexisting mumps-specific IgG titers., Conclusions: Arsenic exposure increased tIgG and tIgE in plasma, and tended to decrease mumps-specific IgG in children at 9 years of age. https://doi.org/10.1289/EHP318.

Exposure to arsenic has been associated with increased risk of reduced lung function in adults, but the adverse impacts in early life are unclear. We aim to examine whether prenatal and childhood arsenic exposure is associated with reduced lung function and increased airway inflammation in school-aged children. Children born in the MINIMat cohort in rural Bangladesh were evaluated at 9years of age (n=540). Arsenic exposure was assessed in urine (U-As) that was collected from mothers during early pregnancy and their children aged 4.5 and 9years. In the 9-year-old children, lung function was assessed using spirometry and airway inflammation was assessed by the NIOX MINO system. C-reactive protein (CRP) and Clara cell secretory protein (CC16) concentrations were measured in plasma by immunoassays. The U-As concentrations in 9-year-old children were lower (median 53μg/l) compared to their mothers (median 76μg/l). Maternal U-As (log 2 transformed) was inversely associated with forced vital capacity (FVC) and forced expiratory volume at 1s (FEV1) (β=-12; 95% CI: -22, -1.5; p=0.031 and β=-12; 95% CI: -22, -1.9; p=0.023, respectively) in all children, and the associations were stronger in boys and among children with adequate height and weight, as well as among those whose mothers had higher percentages of methylarsonic acid (MMA) and lower percentages of dimethylarsinic acid (DMA). U-As (log 2 transformed) at 4.5 and 9years was positively associated with fractional exhaled nitric oxide (FE NO ) concentrations in boys (β=0.89; 95% CI: 0.13, 1.66; p=0.022 and β=0.88; 95% CI: 0.16, 1.61; p=0.017, respectively) but not in girls. Increased CC16 concentrations were associated with higher lung function indices. In conclusion, our findings suggest that prenatal arsenic exposure is related to impaired lung function, while childhood exposure may increase airway inflammation, particularly in boys., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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 children's 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 children's 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Prenatal arsenic exposure has been associated with reduced thymic index and increased morbidity in infants, indicating arsenic-related impaired immune function. We aimed at elucidating potential effects of pre- and postnatal arsenic exposure on cell-mediated immune function in pre-school aged children. Children born in a prospective mother-child cohort in rural Bangladesh were followed up at 4.5 years of age (n = 577). Arsenic exposure was assessed by concentrations of arsenic metabolites (U-As) in child urine and maternal urine during pregnancy, using high-performance liquid chromatography online with inductively coupled plasma mass spectrometry. For assessment of delayed type hypersensitivity response, an intradermal injection of purified protein derivative (PPD) was given to Bacillus Calmette-Guerin vaccinated children. The diameter (mm) of induration was measured after 48-72 h. Plasma concentrations of 27 cytokines were analyzed by a multiplex cytokine assay. Children's concurrent, but not prenatal, arsenic exposure was associated with a weaker response to the injected PPD. The risk ratio (RR) of not responding to PPD (induration <5 mm) was 1.37 (95% confidence interval (CI): 1.07, 1.74) in children in the highest quartile of U-As (range 126-1228 μg/l), compared with the lowest (range 12-34 μg/l). The p for trend across the quartiles was 0.003. The association was stronger in undernourished children. Children's U-As in tertiles was inversely associated with two out of 27 cytokines only, i.e., IL-2 and TNF-α, both Th1 cytokines (in the highest tertile, regression coefficients (95% CI): -1.57 (-2.56, -0.57) and -4.53 (-8.62, -0.42), respectively), but not with Th2 cytokines. These associations were particularly strong in children with recent infections. In conclusion, elevated childhood arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to reduced concentrations of Th1 cytokines., (© The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Exposure to inorganic arsenic (As) through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations., Methodology/findings: Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites (U-As). Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B-ALP), intact parathyroid hormone (iPTH), and phosphate (PO4) were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 µg/L) was significantly inversely associated with concurrent plasma IGF-1 (β=-0.27; 95% confidence interval: -0.50, -0.0042) at 4.5 years. The effect was more obvious in girls (β=-0.29; -0.59, 0.021) than in boys, and particularly in girls with adequate height (β=-0.491; -0.97, -0.02) or weight (β=-0.47; 0.97, 0.01). Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO4 in stunted boys (β=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA, arsenic metabolite) (median split at 9.7%), a much stronger inverse association between U-As and IGF-1 in the girls (β=-0.41; -0.77, -0.03) was obtained above the median split., Conclusion: The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.

Background: Chronic exposure to toxic metals such as arsenic and cadmium has been implicated in the development of kidney and cardiovascular diseases but few studies have directly measured exposure during inutero and early child development., Methods: We investigated the impact of exposure to arsenic (mainly in drinking water) and cadmium (mainly in rice) during pregnancy on blood pressure and kidney function at 4.5 years of age in rural Bangladesh. The effect of arsenic exposure in infancy was also assessed., Results: Within a cohort of 1887 children recruited into the MINIMat study, exposure to arsenic (maternal urinary arsenic, U-As), but not cadmium, during in utero development was associated with a minimal increase in blood pressure at 4.5 years. Each 1 mg/l increase in pregnancy U-As was associated with 3.69 mmHg (95% CI: 0.74, 6.63; P: 0.01) increase in child systolic and a 2.91 mmHg (95% CI: 0.41, 5.42; P: 0.02) increase in child diastolic blood pressure. Similarly, a 1 mg/l increase in child U-As at 18 months of age was associated with a 8.25 mmHg (95% CI: 1.37, 15.1; P: 0.02) increase in systolic blood pressure at 4.5 years. There was also a marginal inverse association between infancy U-As and glomerular filtration rate at 4.5 years (-33.4 ml/min/1.72 m(2); 95% CI: -70.2, 3.34; P: 0.08). No association was observed between early arsenic or cadmium exposure and kidney volume at 4.5 years assessed by ultrasound., Conclusions: These modest effect sizes provide some evidence that arsenic exposure in early life has long-term consequences for blood pressure and maybe kidney function.

Prenatal exposures to arsenic (As) and cadmium (Cd) have been associated with decreased size at birth. We here studied associations of prenatal As and Cd exposures with multiple fetal size parameters measured by ultrasound in gestational week (GW) 14 and 30 in a population-based mother-child cohort in rural Bangladesh. We measured As (n=1929) and Cd (n=1616) in urine during pregnancy. In the longitudinal evaluation of combined exposure, urinary Cd (UCd) showed an inverted U-shaped association (turning-point 1.5 μg Cd/L) with all fetal size parameters, while UAs showed no significant association. Cross-sectional analyses indicated that associations with UCd were somewhat stronger in early gestation. Stratification indicated stronger associations between UCd and fetal size in girls than in boys, and in poorer than in richer families, while UAs was weakly associated with fetal size in boys. In conclusion, particularly Cd, but also As, appeared to influence fetal development in a sex-dependent manner., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Prenatal arsenic exposure is associated with increased infant morbidity and reduced thymus size, indicating arsenic-related developmental immunotoxicity. We aimed to evaluate effects of prenatal arsenic exposure on thymic function at birth and related mechanisms of action. In a Bangladeshi cohort, arsenic was measured in urine (U-As, gestational week (GW) 8 and 30) and blood (B-As, GW14) in 130 women. Child thymic index was measured by sonography at birth and thymic function by signal-joint T-cell receptor-rearrangement excision circles (sjTRECs) in cord blood mononuclear cells (CBMC). In a subsample (n = 44), sjTRECs content in isolated CD4(+) and CD8(+) T cells, expression of oxidative-stress defense and apoptosis-related genes in CBMC, arsenic concentrations (urine, placenta, and cord blood), and oxidative stress markers in placenta and cord blood were measured. In multivariable-adjusted regression, ln U-As (GW8) was inversely associated with ln sjTRECs in CBMC (B = -0.25; 95% confidence interval [CI] -0.48 to -0.01). Using multivariable-adjusted spline regression, ln U-As (GW30) and ln B-As (GW14) were inversely associated with ln sjTRECs in CBMC (B = -0.53; 95% CI -0.93 to -0.13 and B = -1.27; 95% CI -1.89 to -0.66, respectively) below spline knots at U-As 150 µg/l and B-As 6 µg/kg. Similar inverse associations were observed in separated CD4(+) and CD8(+) T cells. Arsenic was positively associated with 8-hydroxy-2'-deoxyguanosine in cord blood (B = 0.097; 95% CI 0.05 to 0.13), which was inversely associated with sjTRECs in CD4(+) and CD8(+) T cells. In conclusion, prenatal arsenic exposure was associated with reduced thymic function, possibly via induction of oxidative stress and apoptosis, suggesting subsequent immunosuppression in childhood.

Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n=140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.