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Requiring Attention: Pesticides and ADHD
Abstract & Commentary
By Russell H. Greenfield, MD, Editor
Source: Bouchard MF, et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics 2010;125:e1270-1277.
Synopsis: Using NHANES data from 2000 to 2004, researchers collected and analyzed information on urinary organophosphate pesticide metabolite levels and children with a diagnosis of ADHD, as well as ADHD subtypes. They found that children with higher levels of pesticide residue in their urine were more likely to have a diagnosis of ADHD. One of the distinctive aspects of this study is that it focused not on high-risk populations, but on the U.S. population in general and, thus, common degrees of pesticide exposure, most probably through food. The results, however compelling, do not in and of themselves indicate causality.
The investigators' purpose was to examine the relationship between urinary concentrations of dialkyl phosphate (DAP) metabolites of organophosphate pesticides and attention deficit/hyperactivity disorder (ADHD) in children 8-15 years of age. Cross-sectional data from the 2000-2004 National Health and Nutrition Examination Survey (NHANES) were available for 1,139 children (during this specific NHANES time frame, ADHD was assessed in children aged 8-15). Participating children were assumed to be representative of the general U.S. population because NHANES is a population-based health survey of non-institutionalized U.S. residents. Participants completed household surveys, and blood and spot urine samples were collected during physical examinations at mobile centers. Urinary DAP metabolite levels were measured for a random sub-sample. A structured diagnostic interview (DISC-IV, which helps identify subtypes of ADHD) with a parent or caretaker by phone was used 2-3 weeks following the physical examination to ascertain ADHD diagnostic status on the basis of modified DSM-IV criteria. The investigators also conducted analyses in which a diagnosis of ADHD was defined as either meeting DISC-IV diagnostic criteria for ADHD or a child having regularly taken medications for ADHD during the previous year. Urine samples were frozen, stored, and sent to the Centers for Disease Control and Prevention's (CDC's) National Center for Environmental Health where testing for 6 urinary DAP metabolites, resulting from the degradation of a variety of organophosphates, was performed (3 dimethyl alkylphosphate molecules [DMAP, such as malathion] and 3 diethyl alkylphosphate [DEAP, such as chlorpyrifos] molecules were measured). Individual urinary DAP metabolite levels were below the analytical limits of detection for many of the subjects, so additional analyses on the metabolite with the highest detection frequency (dimethyl triphosphate) were performed. Analyses accounted for the impact of potentially confounding variables such as gender, race/ethnicity, self-reported family income, blood lead concentrations, and maternal age at birth.
A total of 119 children met diagnostic criteria for ADHD, this corresponding to a population prevalence of 12.1% (the inclusion of children taking ADHD medications raised the total number of ADHD cases to 148). Subtype prevalence estimates were 7.6% for inattentive subtype, 1.5% for hyperactive/impulsive subtype, and 3.0% for combined ADHD subtype.
Almost all children (93.8%) had ≥ 1 detectable DAP metabolite. The odds of meeting DISC-IV criteria for ADHD increased with increasing urinary concentrations of total DAP metabolites. For the most commonly detected DMAP metabolite, dimethyl thiophosphate, which was identified in 64.3% of children, those with levels higher than the median detectable concentrations had twice the odds of ADHD (adjusted odds ratio [AOR], 1.93; 95% confidence interval [CI], 1.23-3.02) compared with children with undetectable levels. Adjustment for covariates attenuated the estimates but they remained statistically significant. When children taking ADHD medications were included, higher effect estimates were obtained for DMAPs (AOR, 1.72; 95% CI, 1.31-2.28). Associations between DMAP levels and ADHD were similar for girls and boys.
The researchers closed by summarizing their findings: Children with higher urinary levels of organophosphate metabolites, reflecting levels of exposure common among U.S. children, are more likely to meet the diagnostic criteria for ADHD. They called for prospective studies to determine whether the association between organophosphate exposure, especially from but not limited to specific food consumption, and ADHD might be causal.
A growing number of studies have raised the specter of environmental toxin exposure playing a significant role in the development of specific diseases, including cancer and Parkinson's disease. With regard to behavioral issues in children and specific exposure to organophosphate pesticides, prior investigations have focused mainly on populations known to have exposure levels higher than the general population. Results of such studies largely showed that childhood exposure to organophosphates was associated with negative impacts on neurobehavioral development, including poor cognition. The current paper is perhaps the first to consider the risk of "average" organophosphate exposure.
Children seem to be at high risk from organophosphate toxicity because the developing brain is more susceptible to neurotoxicants, the dose of pesticides per body weight is likely to be larger, and children have reduced expression of detoxifying enzymes.
The study can be dinged for using but a single spot urine test to determine level of organophosphate exposure, but the authors point out that since organophosphates are cleared from the body within 6 days, the relatively consistent presence of metabolites in the subjects' urine implies continued exposure, suggesting that exposure is likely coming from the diet so long as that diet has been consistent. The EPA considers food, drinking water, and residential pesticide use significant potential sources of exposure. Residential pesticide use is common, but the major source of exposure to pesticides for infants and children is through the diet, according to the National Academy of Sciences. For example, the 2008 U.S. Pesticide Residue Program Report indicates that malathion was detectable in 28% of frozen blueberry samples, 25% of strawberry samples, and 19% of celery samples. The study authors quote data suggesting that disruptions in cholinergic signaling may occur with ADHD (organophosphates inhibit acetylcholinesterase). Organophosphates are among the most commonly used pesticides.
Considering that the President's Cancer Panel recently released information tying various environmental chemicals to an increased risk of cancer, and that articles on toxic hazards have been appearing in lay publications like Time magazine and The New Yorker, practitioners can expect questions about environmental health hazards from their patients to increase and concern a widening array of topics. In particular, the topic of pervasive developmental disorders in children is an understandably emotional one, perhaps made even more so by the results of studies like the one addressed here that suggests pesticide exposure may contribute to developmental disorders.
Practitioners are often left in the unenviable position of explaining that "We don't know why ADHD occurs" now made all the more so because if these data pan out we may indeed understand a potential contributing factor to the development of ADHD but have little in our arsenal to recommend either for prevention or treatment. Recommend strictly organic foods? That knocks out most of the population due to issues of either access or expense. Perhaps what data like these provide practitioners is added motivation to act as a cohesive unit concerned with public health and demand greater regulation of the food industry. Until such time we may all be at risk.