Project 2 - Consequences of As and Mn Exposure on Children

Joseph Graziano PhD, Principal Investigator (PI)
Investigating health effects from exposure to arsenic and manganese in water: conception to adolescence

This project builds upon our discovery that exposure to arsenic (As) and manganese (Mn) in drinking water has adverse effects on intelligence in children.  The research under project 2 now focuses on the consequences of As and Mn exposure on respiratory and neuropsychological functions in 780 adolescents in Bangladesh. 

We successfully launched this new study in 2012, and recruitment has continued to go well since then.  To date over 355 participants have been enrolled.  Each study participant visits our field clinic twice, one week apart.  At the first visit we perform standard pulmonary function tests by spirometry, and also collect exhaled breath condensate (over a ten minute period) for the measurement of pH and 8-isoprostane levels.  Low pH and elevated 8-isoprostane are indicators of pulmonary inflammation.  At the second visit, we assess child IQ and also administer seven subtests of the CANTAB, a computerized assessment of brain/neuropsychological functioning.

Basically, this study first asks whether the As-induced respiratory disease observed in adults also manifests itself in adolescents, and what are possible physiologic mechanisms?  Second, to what extent do associations between WAs and both lung function and brain function reflect the effects of exposure in utero and in infancy, periods of dramatic development for these systems? Third, are WAs and WMn associated with specific domains of cognitive function in addition to overall intelligence?

The study draws on an existing sample of 780 adolescents (15-17 years old) whose mothers are participants in the HEALS Study (Project #1).  Based on mothers' well As, measured five times from 2000 until the present, we were able to define four groups of adolescents with varying levels and patterns of exposure to As.  Defined on the basis of WAs levels, four groups include adolescents with exposures that are: Group 1) consistently low (mean WAs = 3 ppb); Group 2) consistently moderate (mean WAs = 26 ppb); Group 3) consistently high (mean WAs = 146 ppb); and Group 4) high from conception through roughly age one (mean WAs = 201 ppb) but much lower thereafter (mean WAs =13 ppb).  Within each group, there is wide variation in WMn concentrations.   Three specific aims target As exposure and pulmonary function (FEV1 and FVC) as well as biomarkers of lung dysfunction in exhaled breath condensate.

Three additional aims expand our earlier work on As, Mn and neuropsychologic outcomes by considering components of Executive Function (planning, sustained attention, working memory) that have been mapped to brain regions thought to be affected by exposure to these elements. Components of Executive Function will be measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized and well validated set of tests; intelligence will also be assessed.  We are examining adolescents, an understudied age group, because certain components of Executive Function and lung development do not mature until this age; studies with younger children would miss these health effects.

Collectively, the work conducted in this project has contributed to the growing body of knowledge concerning the adverse health effects of both As and Mn on children’s health.  We believe that knowledge of these adverse health effects on children will increase the rate at which families will alter their behavior – both in the United States and abroad – to test their wells and pursue remediation when necessary.

Project/Core Lead

Joseph Graziano PhD, Principal Investigator (PI)

Project/Core Scientists

Co-Investigator (Co-I)
Co-Investigator (Co-I)
Co-Investigator (Co-I)
Associate Research Scientist
Associate Research Scientist
Co-Investigator (Co-I)
Co-Investigator (Co-I)

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