Person:

Valeri, Linda

Background: Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neural tube defect (myelomeningocele) among a highly exposed population in rural Bangladesh. Methods: We performed a case–control study that recruited physician-confirmed cases from community health clinics served by Dhaka Community Hospital in Bangladesh, as well as local health facilities that treat children with myelomeningocele. Controls were selected from pregnancy registries in the same areas. Maternal arsenic exposure was estimated from drinking water samples taken from wells used during the first trimester of pregnancy. Periconceptional folic acid use was ascertained by self-report, and maternal folate status was further assessed by plasma folate levels measured at the time of the study visit. Results: Fifty-seven cases of myelomeningocele were identified along with 55 controls. A significant interaction was observed between drinking water inorganic arsenic and periconceptional folic acid use. As drinking water inorganic arsenic concentrations increased from 1 to 25 μg/L, the estimated protective effect of folic acid use declined (OR 0.22 to 1.03), and was not protective at higher concentrations of arsenic. No main effect of arsenic exposure on myelomeningocele risk was identified. Conclusions: Our study found a significant interaction between drinking water inorganic arsenic concentration from wells used during the first trimester of pregnancy and reported intake of periconceptional folic acid supplements. Results suggest that environmental arsenic exposure reduces the effectiveness of folic acid supplementation in preventing myelomeningocele.

Household air pollution (HAP) and chronic HIV infection are each associated with significant respiratory morbidity. Little is known about relationships between HAP and respiratory symptoms among people living with HIV. The objective of this study was to investigate the relationship between cooking fuel type and chronic respiratory symptoms in study participants from the Uganda AIDS Rural Treatment Outcomes Study. Study participants were enrolled at the time of antiretroviral therapy initiation and seen quarterly from 2005 to 2014 for health-focused questionnaires, CD4 count and HIV viral load. We used multivariable logistic regression and generalised estimating equations, with each study visit as a unit of observation, to investigate relationships between cooking fuel type and chronic respiratory symptoms. We observed an association between cooking with firewood (versus charcoal) and chronic cough among HIV-infected females in rural Uganda (adjusted OR 1.41, 95% CI 1.00–1.99; p=0.047). We did not observe an association between cooking fuel type and respiratory symptoms among males (adjusted OR 0.88, 95% CI 0.47–1.63; p=0.658). Associations between cooking fuel and chronic cough in this HIV-infected cohort may be influenced by sex-based roles in meal preparation. This study raises important questions about relationships between household air pollution, HIV infection and respiratory morbidity.

Background: The people of Bangladesh are currently exposed to high concentrations of arsenic and manganese in drinking water, as well as elevated lead in many regions. The objective of this study was to investigate associations between environmental exposure to these contaminants and neurodevelopmental outcomes among Bangladeshi children. Methods: We evaluated data from 524 children, members of an ongoing prospective birth cohort established to study the effects of prenatal and early childhood arsenic exposure in the Sirajdikhan and Pabna Districts of Bangladesh. Water was collected from the family’s primary drinking source during the first trimester of pregnancy and at ages 1, 12 and 20–40 months. At age 20–40 months, blood lead was measured and neurodevelopmental outcomes were assessed using a translated, culturally-adapted version of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Results: Median blood lead concentrations were higher in Sirajdikhan than Pabna (7.6 vs. <LODμg/dL, p <0.0001) and water arsenic concentrations were lower (1.5 vs 25.7 μg/L, p <0.0001). Increased blood lead was associated with decreased cognitive scores in Sirajdikhan (β = −0.17, SE = 0.09, p = 0.05), whereas increased water arsenic was associated with decreased cognitive scores in Pabna (β = −0.06, SE = 0.03, p = 0.05). Water manganese was associated with fine motor scores in an inverse-U relationship in Pabna. Conclusion: Where blood lead levels are high, lead is associated with decreased cognitive scores on the BSID-III, and effects of other metals are not detected. In the setting of lower lead levels, the adverse effects of arsenic and manganese on neurodevelopment are observed. Electronic supplementary material The online version of this article (doi:10.1186/s12940-016-0127-y) contains supplementary material, which is available to authorized users.

Background: Lead toxicity is of particular public health concern given its near ubiquitous distribution in nature and established neurotoxicant properties. Similar in its ubiquity and ability to inhibit neurodevelopment, early childhood stunting affects an estimated 34 % of children under 5 in low- and middle-income countries. Both lead and stunting have been shown to be associated with decreased neurodevelopment, although the relationship between these childhood burdens is underexplored. The association between lead exposure and stunting has been previously established, yet limited data are available on susceptibility windows. Methods: Whole blood lead samples were collected from rural Bangladeshi children at delivery (umbilical cord blood) and at age 20–40 months (fingerstick blood). Stunting was determined using the Child Growth Standards developed from the World Health Organization Multicentre Growth Reference Study. Children with height for age < -2 z-scores below the median of the WHO Child Growth Standards were classified as stunted in all analyses. Results: Median (IQR) umbilical cord and fingerstick blood lead levels were 3.1 (1.6–6.3) μg/dl and 4.2 (1.7–7.6) μg/dl, respectively. In adjusted multivariable regression models, the odds of stunting at 20–40 months increased by 1.12 per μg/dl increase in blood lead level (OR = 1.12, 95 % CI: 1.02–1.22). No association was found between cord blood lead level and risk of stunting (OR = 0.97, 95 % CI: 0.94–1.00). Conclusions: There is a significant association between stunting and concurrent lead exposure at age 20–40 months. This association is slightly attenuated after controlling for study clinic site. Additional research including more precise timing of lead exposure during these critical 20–40 months is needed. Electronic supplementary material The online version of this article (doi:10.1186/s12940-016-0190-4) contains supplementary material, which is available to authorized users.

Background: Exposure to chemical mixtures is recognized as the real-life scenario in all populations, needing new statistical methods that can assess their complex effects. Objectives: We aimed to assess the joint effect of in utero exposure to arsenic, manganese, and lead on children’s neurodevelopment. Methods: We employed a novel statistical approach, Bayesian kernel machine regression (BKMR), to study the joint effect of coexposure to arsenic, manganese, and lead on neurodevelopment using an adapted Bayley Scale of Infant and Toddler Development™. Third Edition, in 825 mother–child pairs recruited into a prospective birth cohort from two clinics in the Pabna and Sirajdikhan districts of Bangladesh. Metals were measured in cord blood using inductively coupled plasma-mass spectrometry. Results: Analyses were stratified by clinic due to differences in exposure profiles. In the Pabna district, which displayed high manganese levels [interquartile range (IQR): 4.8, 18μg/dl], we found a statistically significant negative effect of the mixture of arsenic, lead, and manganese on cognitive score when cord blood metals concentrations were all above the 60th percentile (As≥0.7μg/dl, Mn≥6.6μg/dl, Pb≥4.2μg/dl) compared to the median (As=0.5μg/dl, Mn=5.8μg/dl, Pb=3.1μg/dl). Evidence of a nonlinear effect of manganese was found. A change in log manganese from the 25th to the 75th percentile when arsenic and manganese were at the median was associated with a decrease in cognitive score of −0.3 (−0.5, −0.1) standard deviations. Our study suggests that arsenic might be a potentiator of manganese toxicity. Conclusions: Employing a novel statistical method for the study of the health effects of chemical mixtures, we found evidence of neurotoxicity of the mixture, as well as potential synergism between arsenic and manganese. https://doi.org/10.1289/EHP614