Interpreting epidemiologic studies of developmental neurotoxicity: conceptual and analytic issues

This paper discusses issues pertaining to the validity, precision, and interpretation of epidemiologic studies of neurotoxicity. With regard to validity, the critical issues pertain to the appropriate strategy for confounder adjustment, particularly when confounders are complex, multi-faceted constructs, and to the need for greater clarity and transparency in articulating the causal relationships implicit in the analytic approach applied. With regard to precision, the critical issue is a need to identify the contributors to the substantial variability observed in the effect estimates that describe dose-response and dose-effect relationships. In addition to methodological sources, such as imprecision in estimating dose at the critical organ site(s), true inter-individual differences in susceptibility to a neurotoxicant could also contribute to the variability. Variability might be reduced by taking full account of factors such as co-exposures or health co-morbidities, genetic polymorphisms, and the social ecology of exposure. With regard to interpretation, we need to do a better job as a field conveying to risk assessors and others the ecological significance of the types of performance deficits observed following neurotoxicant exposure, emphasizing the distinction between individual and population risk. A final issue discussed is the need to define standards for the conduct, analysis, and reporting of epidemiologic studies of neurotoxicity, similar to those developed for other fields.