PROSPECTIVE, LONGITUDINAL ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY

Methodological issues in the design of prospective, longitudinal studi es of developmental neurotoxicity in humans are reviewed. A comprehens ive assessment of potential confounding influences is important in the se studies because inadequate assessment of confounders can threaten t he validity of causal inferences drawn from the data. Potential confou nders typically include demographic background variables, alcohol and smoking during pregnancy, the quality of parental stimulation, the chi ld's age at test, and the examiner. Exposure to other substances is as sessed where significant exposure is expected in the target population . in most studies, control variables even weakly related to outcome ar e included in all multivariate statistical analyses, and a toxic effec t is inferred only if the effect of exposure is significant after cont rolling for the potential confounders. Once a neurotoxic effect has be en identified, suspected mediating variables may be added to the analy sis to examine underlying processes or mechanisms through which the ex posure may impact on developmental outcome. Individual differences in vulnerability may be examined in terms of either an additive compensat ory model or a synergistic ''risk and resilience'' approach. Failure t o detect real effects (Type II error) is of particular concern in thes e studies because public policy considerations make it likely that neg ative findings will be interpreted to mean that the exposure is safe. Important sources of Type II error include inadequate representation o f highly exposed individuals, overcontrol for confounders, and inappro priate correction for multiple comparisons. Given the high cost and co mplexity of prospective, longitudinal investigations, cross-sectional pilot studies focusing on highly exposed individuals can be valuable f or the initial identification of salient domains of impairment.