In the US, approximately 13 million people are exposed to drinking water that exceeds the US standard . Although the current EPA standard for As in drinking water is 10 μg/L , at least one state (New Jersey) has enacted a standard of 5 μg/L .
Adjusting for HOME scores, for maternal education and IQ, for school district, and for the number of other children in the home (Model 2), children exposed to WAs ≥ 5 μg/L from household wells (compared to WAs < 5 μg/L) showed significant reductions in Full Scale, Working Memory, Perceptual Reasoning and Verbal Comprehension scores. Categories of WAs exposure at levels higher than 5 μg/L did not differ significantly among themselves in their contributions to IQ score reductions. However, the small sample size may have hindered finding associations.
In Bangladesh, with similarly aged children, drinking from wells with more widely ranging WAs concentrations (0.1-790 μg/L), and using an earlier test version (WISC-III), we found negative associations between WAs and Performance scales that persisted upon adjustment for sociodemographic contributors , and observed similar results in Bangladeshi 6-year olds for Performance scores on the WPPSI-III . More recently, we reported negative associations between As measured in blood and WISC-IV Working Memory; with adjustment for blood Mn, and for other contributors, this association remained marginally significant at p < 0.09 . In re-standardization leading to the WISC-IV, certain WISC-III Performance subtests were re-organized into Working Memory, Processing Speed and Perceptual Reasoning domains (and other subtests revised, added or eliminated). The Digit Span subtest is common to both WISC-IV Working Memory and WISC-III Performance Scale. Collectively, our work in Bangladesh and in Maine suggests that aspects of Performance intelligence, particularly Perceptual Reasoning and Working Memory, are impacted by exposure to As in drinking water.
Among older adults , with adjustment for age, gender, education and ethnicity, WAs (mean WAs = 6.3 μg/L) was associated with a wide range of cognitive skills, including processing speed, executive function, and memory. Moreover, animal studies have shown a dose-dependent accumulation of As in many parts of the brain [31, 32] that play important roles in human cognition and memory. In As-exposed rodents, morphological and neurochemical changes have been noted in the hippocampus, along with expectable learning and memory deficits [33, 34].
Comparisons with findings from Bangladesh
Cross-cultural accommodations in the measurement of intelligence in our earlier work prompted the present US replication. Our findings of adverse impact in a US sample, particularly in Performance-related functioning, gives confidence to the generalizability of findings from our work in Bangladesh, where we also observed a steep drop in intelligence scores in the very low range of WAs concentrations (see Figure one in our earlier work ).
Because there is no currently standardized test of child intelligence for use in Bangladesh, in earlier work we adapted widely-used instruments. Most particularly, we used weighted sums of items, rather than more commonly used IQ scores. Moreover, we dropped certain items from our battery because of differences in experience that were practically universal for our study children; as examples, rural Bangladeshi children are unfamiliar with Christopher Columbus (Information subscale). Most subtests were unchanged (e.g., Digit Span, Block Design); alterations affected three or fewer items or else the entire subtest was eliminated. While these changes were minimal, they added some measure of uncertainty.
Children in Bangladesh and in the US also differ in regularity of school attendance, health and nutritional status. Stunting has consequences for later intellectual function and school progress . Almost 30% of children included in our Bangladesh studies would have been characterized as stunted . The negative association between WAs and Performance intelligence in the Bangladesh sample persisted, even with adjustment for stunting .
Differences in the distributions of WAs between the present US sample and our earlier work with Bangladeshi children likely explain some points of contrast between present and earlier findings. In much of Asia, WAs levels range far higher than in the US. The differences across samples in exposure characteristics may have affected our ability to detect effects at all points across the exposure/outcome curve. We lacked high-end exposures in the Maine sample, and we had far fewer low-end exposures in Bangladesh. For example in our initial Bangladesh studies of 6- and 10-year old children, mean WAs levels were, respectively, 120.1 and 116.6 μg/L. To illustrate further, approximately 70% of the present sample were exposed to WAs < 10 μg/L, compared to 30% among our Bangladeshi 10-year-olds . Differences are also substantial when we consider WAs < 5 μg/L (52% in Maine, 25% in Bangladesh), or WAs >20 μg/L (12% in Maine, 67% in Bangladesh). At the far lower levels reported here (mean WAs = 9.9 μg/L), we still detected an adverse association attributable to WAs for Index and FSIQ scores. Conceivably, a US sample with children exposed at the higher levels seen in Bangladesh might detect continued adverse associations at those levels.
Magnitude of associations
With adjustment for other contributors, WAs ≥ 5 μg/L was associated with reductions of 4.5-6.5 points in FSIQ and in most Index scores. The magnitudes of these associations are similar to those observed with modest increases in blood lead, an established risk factor for diminished IQ. An increase in blood lead from 2.4 to 10 μg/dl or from 10 to 20 μg/dL is associated with estimated decrements of 3.9 and 1.9 IQ points, respectively . Household use of the pesticide chlorpyrifos has been associated with a decline in FSIQ and Working Memory of 1.4 and 2.8 points, respectively, for each standard deviation of cord blood levels . Among 7-year olds, prenatal (but not postnatal) exposure to organophosphate pesticides was associated with a loss of 7 FSIQ points, comparing highest to lowest quartile, as well as with all Index Scores .
Overall, the variance explained in predicting component indices of the WISC-IV was slightly smaller, relative to what we have noted in our work in Bangladesh (where R2 is generally in the range of 20%-30%), most likely a consequence of the lower and narrow range of exposures examined here.
NAs as a biomarker of exposure
The significant correlation between NAs and home WAs levels suggests that household well WAs contributes to the body burden of As. On the other hand, NAs was not significantly associated with changes in IQ scores. This lack of a significant association might reflect that only 248 participating children provided nails, and that the range of NAs concentrations was narrow, so that we had less power to detect a small effect size. Alternatively, NAs may reflect exposure less accurately in children than in adults, due to the rapid growth of other organ systems in children that may alter the relative distribution of As across tissues.
Although we were able to characterize levels of As exposure in home drinking water, we did not collect information on quantity of water consumed. At the time of our study, public water sources, such as schools, were required to evaluate drinking water and to maintain WAs levels < 10 μg/L. Compared to circumstances in many other parts of the world, where children’s consumption can be directly linked to use of wells at home and/or at school, US children access water through a wide range of processed sources (bottled water, soft drinks), complicating consumption estimates. Scheduling home visits across our largely rural communities at times convenient for staff and families proved challenging, and resulted in children occasionally not being present during the home visit; defining these children as “Missing” on HOME allowed their retention in analyses, but we were unable to characterize the quality of the home environment for 29 families. Finally, in this cross-sectional study, we were unable to characterize WAs exposure retrospectively across the lifespan. We measured current well characteristics, and length of residence, but few children had resided in the present home for their entire lives. And while using “entire life residence” as a more stringent exclusion criterion would have better characterized exposure during period(s) of peak brain development, lack of residential mobility may be a marker for other social features not considered here. As we note, when we restricted analysis to the 215 children with 5 years of continuous residence, results were essentially unchanged.
Do new analytic approaches need to be considered?
Since the 1980’s , the field of developmental neurotoxicology has relied upon descriptive models that adjust for other possible contributors to child intelligence, such as maternal intelligence and education. The underlying assumption in that approach is that these known predictors of child intelligence are not associated with exposure. In older studies, and in developing nations, this assumption likely remains reasonable. However, with growing public awareness of the hazards associated with certain environmental exposures, contemporary studies in developed nations need to be aware that maternal characteristics may influence exposure levels; for example, more educated mothers may be more likely to avoid exposure. Our observations have implications for the design of future studies of highly publicized potentially toxic exposures. We suggest that future studies collect data related to parental knowledge of exposure patterns and health risks of these agents. Such data can be used in deciding which parental factors to include in statistical models.