The conundrum of unmeasured confounding: Comment on: "Can some of the detrimental neurodevelopmental effects attributed to lead be due to pesticides? by Brian Gulson".

The problem described by Dr. Brian Gulson - confounding by unmeasured exposures to pesticides - is only the most recent in a series of potential confounders cited to explain the observed effect of lead on children's intellectual abilities or behavioral problems. Despite the persistent problem of unmeasured confounders, there are several lines of evidence implicating lead as a toxicant at blood lead levels <10 microg/dL. First, in striking contrast with pesticides, there is considerable evidence from numerous studies linking low-level lead exposure with cognitive deficits and behavioral problems, even after controlling for a variety of potential confounders. Second, the consistency of evidence from diverse cohorts and distinct, if not always directly measured potential confounders - enhances our confidence that the lead effect observed at blood lead levels <10 microg/dL is not attributable to unmeasured confounders. Third, in our reanalysis of the Rochester Lead Study, the inclusion of parent-reported mouthing behaviors and breastfeeding status did not attenuate the effect of lead exposure on children's intellectual function. Finally, although we can never entirely dismiss unmeasured confounding in observational studies, we can rely on experimental studies of lead-exposed animals to confirm that lead is a toxicant. Thus, while we must remain vigilant for unmeasured or poorly measured confounders, it is crucial to balance the endless search for confounders with the evidence of toxicity and the need to take action to protect public health. The alternative, to perpetually permit children to be exposed to lead and other emerging toxicants, is both absurd and unacceptable.