Issues in the interpretation of associations of PCBs and IQ

The literature concerning the relationship between polychlorinated biphenyl (PCB) exposure and Intelligence (IQ) is not entirely consistent. Two studies showed inverse associations between PCBs and IQ in cohorts of children whose mothers consumed Great Lakes fish contaminated with PCBs and other organochlorines (Jacobson & Jacobson 1996; Stewart et al. 2008). Another study from the general US population, where women were exposed to background levels of PCBs, showed no association between PCBs and IQ (Gray et al. 2005). The current report examines two potential sources of inconsistency across studies: 1) confounding with non-PCB organochlorines [Hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and Mirex]; and 2) the presence of negative confounding (i.e., suppressor variables). The former could confound PCBs and lead to spurious associations (Type I errors), while the latter could suppress PCB associations and obscure true associations (Type II errors). These issues were explored through the analysis of associations between placental levels of organochlorines and IQ in children at 9 and 11 years of age in the Oswego study. Neither DDE nor mirex was related to lower IQ at either age; PCBs predicted lower IQ at both ages; and hexachlorobenzene (HCB) appeared as a significant predictor of IQ at the 11-year assessment. However, analysis of the IQ data set as a whole showed that both PCBs and HCB predicted lower IQ in a generally independent fashion. There was, however, overlap in the variance in some cases, and the pattern of findings between the two was remarkably similar. These results may provide some evidence for the potential involvement of non-PCB organochlorines in the Oswego study. To explore negative confounding, we analyzed the relationships between PCB exposure and demographic variables as well as the unadjusted and adjusted relationships between PCB and IQ. Results revealed that placental PCB levels were associated with older mothers who were more educated and came from higher socioeconomic strata. Due to this fact, unadjusted relationships between PCBs and IQ appeared null or slightly positive. After control for confounders, several significant negative associations between PCBs and IQ were revealed. These data might suggest that inadequate control for confounders in PCB studies, where negative confounding is present, may bias results toward the null (Type II error) rather than spurious associations (Type I error). This pattern of confounding with PCB exposure in the Oswego study also has implications for the assessment of risk. The most highly exposed children came from families with somewhat higher socioeconomic status, and tended to score in the average to above-average range, well above IQ scores that are considered “at risk.” Further, such children were exposed prenatally to PCBs through maternal consumption of PCB-contaminated Great Lakes fish in the early 1990s, when PCB levels were higher than today.

► PCBs predicted lower IQ at 9 and 11 years, HCB predicted lower IQ at the 11 years.
► PCBs and HCB predicted a similar pattern of outcomes.
► Placental PCB were related to older, more educated mothers with higher SES.
► Associations after confounder control may have implications for risk assessments.