Prospective, longitudinal assessment of developmental neurotoxicity

Environ Health Perspect. 1996 Apr;104 Suppl 2(Suppl 2):275-83. doi: 10.1289/ehp.96104s2275.


Methodological issues in the design of prospective, longitudinal studies of developmental neurotoxicity in humans are reviewed. A comprehensive assessment of potential confounding influences is important in these studies because inadequate assessment of confounders can threaten the validity of causal inferences drawn from the data. Potential confounders typically include demographic background variables, alcohol and smoking during pregnancy, the quality of parental stimulation, the child's age at test, and the examiner. Exposure to other substances is assessed where significant exposure is expected in the target population. In most studies, control variables even weakly related to outcome are included in all multivariate statistical analyses, and a toxic effect is inferred only if the effect of exposure is significant after controlling for the potential confounders. Once a neurotoxic effect has been identified, suspected mediating variables may be added to the analysis to examine underlying processes or mechanisms through which the exposure may impact on developmental outcome. Individual differences in vulnerability may be examined in terms of either an additive compensatory model or a synergistic "risk and resilience" approach. Failure to detect real effects (Type II error) is of particular concern in these studies because public policy considerations make it likely that negative findings will be interpreted to mean that the exposure is safe. Important sources of Type II error include inadequate representation of highly exposed individuals, overcontrol for confounders, and inappropriate correction for multiple comparisons. Given the high cost and complexity of prospective, longitudinal investigations, cross-sectional pilot studies focusing on highly exposed individuals can be valuable for the initial identification of salient domains of impairment.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Confounding Factors, Epidemiologic
  • Data Interpretation, Statistical
  • Embryonic and Fetal Development / drug effects
  • Female
  • Humans
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / epidemiology
  • Neurotoxins / adverse effects*
  • Pregnancy
  • Prospective Studies
  • Research Design
  • Risk Assessment


  • Neurotoxins