May 19 2010

Pesticides and ADHD

A recent article published in the journal Pediatrics links exposure to certain types of organophosphate pesticides with ADHD.  This is a reasonable study and the results should be taken seriously, but as always they need to be put into context – something most media outlets are failing to do.

First – the study itself – here are the methods:

Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1139 children, who were representative of the general US population. A structured interview with a parent was used to ascertain ADHD diagnostic status, on the basis of slightly modified criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.

They looked at the results of spot urine tests (a one time urine sample) for six different organophosphate metabolites, and found that two of them correlated with a statistically significant higher chance of  meeting criteria for ADHD.

One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher urinary dialkyl phosphate concentrations, especially dimethyl alkylphosphate (DMAP) concentrations, were more likely to be diagnosed as having ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio of 1.55 (95% confidence interval: 1.14–2.10), with adjustment for gender, age, race/ethnicity, poverty/income ratio, fasting duration, and urinary creatinine concentration. For the most-commonly detected DMAP metabolite, dimethyl thiophosphate, children with levels higher than the median of detectable concentrations had twice the odds of ADHD (adjusted odds ratio: 1.93 [95% confidence interval: 1.23–3.02]), compared with children with undetectable levels.

There are solid results, but it should be noted that the lower end of the confidence interval (1.14 and 1.23) are only slightly greater than one, which represents only a small increase in risk. But they are statistically significant.

To put this into perspective, however, this is a correlational study only and cannot be used to conclude cause and effect. It may be possible, for example, that children with ADHD engage in behaviors that expose them to more organophosphates.

Other weaknesses acknowledged by the authors include the fact that exposure was determined by a single spot urine test – which may not reflect long term exposure. Organophosphates are generally cleared by the urine in 3-6 days.

I also noted that the prevalence of ADHD in this study, 12%, is about twice the 4-7% found by other studies. This could reflect a hidden bias in the data collection methods.

Regarding plausibility, a possible link between organophosphates and ADHD is a mixed bag. There is basic science plausibility in that organophosphates do have neurotoxicity, and specifically inhibit acetylcholine function which is involved in memory and attention.

On the other hand, toxicity is also related to dose, so the real question is are the doses detected above or below toxic levels. The EPA insists they are below safe levels, but critics contend that chronic low levels of exposure have not been adequately studied. Of course – you can always make this claim when the data does not show toxicity.

For epidemiological studies, where correlation alone can be concluded, in order to infer cause and effect we would want to see multiple different lines of epidemiological evidence. For example – are there differences in ADHD incidence in different regions and countries depending on organophosphate exposure, or over time. It has been noted that the EPA has decreased organophosphate use in the last five years but we have not seen a corresponding decrease in ADHD diagnoses.

Conclusion

This study is sufficiently rigorous that it should be taken seriously – which means that it should lead to further research.  Specifically, prospective studies including longitudinal sampling of urine for organophosphate metabolites should be done. There are also many follow up epidemiological studies that can be done, as I mentioned above, specifically looking for correlations between exposure and ADHD. Eventually we should be able to triangulate to a reliable answer.

Meanwhile – how should we respond? We often have to make decisions in medicine and public health with imperfect data, and the precautionary principle is a reasonable guide. So even though considerable doubt remains as to what, exactly, the relationship is between organophosphate exposure and ADHD, we may want to reduce exposure in the meantime just to be on the safe side.

The EPA, at least in this country, has the job of reviewing the data and suggesting policy for safe use and levels of exposure. They have been decreasing levels of organophosphate exposure recently, and perhaps will want to continue this trend.

For consumers, two options have been proposed (other than just doing nothing and waiting for more research) – assuming you want to minimize your exposure to pesticides in general. The first is simply to wash your fruits and vegetables thoroughly. This does significantly reduce (but not eliminate) pesticide exposure. If you want to go the extra step, you can wash them with a small amount of dish washing detergent. Some have suggested using vinegar and hydrogen peroxide followed by a thorough rinse, but I have not seen data to show that this is superior.

The other method is to buy organic produce, and many people do for this reason. However, this option is controversial for several reasons. First, organic produce is more expensive – it’s certainly cheaper to just wash your produce. Also, organic farming  often uses organic pesticides, and we should not assume that they are any safer. And there may be unintended consequences from massive shifting to organic farming – such as the ability to produce enough food with these methods, and higher costs may reduce consumption of fruits and vegetables, which could have more adverse health consequence than the alleged benefits of reducing pesticides.

I know that the organic farming controversy is a complex topic, and I am not trying to cover it in any detailed or thorough manner today – perhaps for another time (i.e. I don’t have time to get dragged into a long discussion about this in the comments). I am simply bringing up the points that people consider. If you want to buy organic to reduce pesticide exposure, that is reasonable and I am not criticizing that option – just pointing out that this is a complex and still controversial topic.

Like much good research, this study raises more questions than it answers. I think this does justify further research. It is unfortunate, however, that much of the press coverage is treating this study as if it is definitive. The link between pesticides and ADHD is now in the public consciousness, whether or not future research will show the link to be real or causative.

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