Person:

Grandjean, Philippe

A cohort of 1022 consecutive singleton births was generated during 1987–1988 in the Faroe Islands, where increased methylmercury exposure occurs from traditional seafood diets that include pilot whale meat. The prenatal exposure level was determined from mercury analyses of cord blood, cord tissue, and maternal hair. At age 14 years, 878 of 1010 living cohort members underwent detailed neurobehavioral examination. Eighteen participants with neurological disorders were excluded. Blood and hair samples obtained from the participants were analyzed for mercury. The neuropsychological test battery was designed based on the same criteria as applied at the examination at age 7 years. Multiple regression analysis was carried out and included adjustment for confounders. Indicators of prenatal methylmercury exposure were significantly associated with deficits in finger tapping speed, reaction time on a continued performance task, and cued naming. Postnatal methylmercury exposure had no discernible effect. These findings are similar to those obtained at age 7 years, and the relative contribution of mercury exposure to the predictive power of the multiple regression models was also similar. An analysis of the test score difference between results at 7 and 14 years suggested that mercury-associated deficits had not changed between the two examinations. In structural equation model analyses, the neuropsychological tests were separated into five groups; methylmercury exposure was significantly associated with deficits in motor, attention, and verbal tests. These findings are supported by independent assessment of neurophysiological outcomes. The effects on brain function associated with prenatal methylmercury exposure therefore appear to be multi-focal and permanent.

To determine the possible neurotoxic impact of prenatal exposure to polychlorinated biphenyls (PCBs), we analyzed banked cord blood from a Faroese birth cohort for PCBs. The subjects were born in 1986–1987, and 917 cohort members had completed a series of neuropsychological tests at age 7 years. Major PCB congeners (118, 138, 153, and 180), the calculated total PCB concentration, and the PCB exposure estimated in a structural equation model showed weak associations with test deficits, with statistically significant negative associations only with the Boston Naming test. Likewise, neither hexachlorobenzene nor p,p'-dichlorodiphenyldichloroethylene showed clear links to neurobehavioral deficits. Thus, these associations were much weaker than those associated with the cord-blood mercury concentration, and adjustment for mercury substantially attenuated the regression coefficients for PCB exposure. When the outcomes were joined into motor and verbally mediated functions in a structural equation model, the PCB effects remained weak and virtually disappeared after adjustment for methylmercury exposure, while mercury remained statistically significant. Thus, in the presence of elevated methylmercury exposure, PCB neurotoxicity may be difficult to detect, and PCB exposure does not explain the methylmercury neurotoxicity previously reported in this cohort.

In observational studies, the presence of confounding can distort the true association between an exposure and a toxic effect outcome if the confounding variable is not controlled either in the study design or the analysis phase. While confounding is often assumed to occur in the same direction as the toxicant exposure, the relationship between the benefits and risks associated with fish and seafood consumption is a classic example of negative confounding: the exposure to methylmercury occurs from fish and seafood which are also associated with beneficial nutrients, thereby counteracting the signs of mercury toxicity. Mercury and nutrients may affect the same epidemiological outcomes, but most studies addressing one of them have ignored the potential negative confounding by the other. This article reviews the existing evidence of effects of both nutrient and contaminant intakes as predictors of neurodevelopmental and cardiovascular outcomes. Substantial underestimation of the effects of mercury toxicity and fish benefits occurs from the lack of confounder adjustment and imprecision of the exposure parameters. Given this inherent bias in observational studies, regulatory agencies should reconsider current dietary advisories to provide better guidance to consumers in making prudent choices to maintain a nutritious diet with seafood that is low in mercury concentrations. Attention should also be paid to the occurrence of negative confounding in other connections.

The extent to which postnatal methylmercury exposure contributes to neurobehavioral delays is uncertain. Confounding may occur because the child's dietary exposure likely correlates with the mother's. This conundrum was examined in the Faroese birth cohort 1 born in 1986–1987. Exposure parameters included mercury concentrations in maternal hair at parturition, cord blood, and child blood and hair at the age-7 clinical examination (N = 923). In regression analyses, the child's current blood-mercury at age 7 (N = 694) showed only weak associations with the neuropsychological test variables, but visuospatial memory revealed a significant negative association. Mutual adjustment caused decreases of the apparent effect of the prenatal exposure. However, such adjustment may lead to underestimations due to the presence of correlated, error-prone exposure variables. In structural equation models, all methylmercury exposure parameters were instead entered into a latent exposure variable that reflected the total methylmercury load. This latent exposure showed significant associations with neurodevelopmental deficits, with prenatal exposure providing the main information. However, postnatal methylmercury exposure appeared to contribute to neurotoxic effects, in particular in regard to visuospatial processing and memory. Thus, addition in the regression analysis of exposure information obtained at a different point in time was not informative and should be avoided. Further studies with better information on exposure profiles are needed to characterize the effects of postnatal methylmercury exposure.

Prenatal exposure to mercury has been associated with adverse effects on child neurodevelopment. The present study aims to determine the extent to which methylmercury-associated cognitive deficits persist into adult age. In a Faroese birth cohort originally formed in 1986–1987 (N=1,022), prenatal methylmercury exposure was assessed in terms of the mercury concentration in cord blood and maternal hair. Clinical examinations of 847 cohort members at age 22 years were carried out in 2008–2009 using a panel of neuropsychological tests that reflected major functional domains. Subjects with neurological and psychiatric diagnoses were excluded from the data analysis, thus leaving 814 subjects. Multiple regression analysis included covariates previously identified for adjustment. Deficits in Boston Naming Test and other tests of verbal performance were significantly associated with the cord-blood mercury concentration. Deficits were also present in all other tests applied, although most were not statistically significant. Structural equation models were developed to ascertain the possible differences in vulnerability of specific functional domains and the overall association with general intelligence. In models for individual domains, all of them showed negative associations, with crystallized intelligence being highly significant. A hierarchical model for general intelligence based on all domains again showed a highly significant negative association with the exposure, with an approximate deficit that corresponds to about 2.2 IQ points at a 10-fold increased prenatal methylmercury exposure. Thus, although the cognitive deficits observed were smaller than at examinations at younger ages, maternal seafood diets were associated with adverse effects in this birth cohort at age 22 years. The deficits affected major domains of brain functions as well as general intelligence. Thus, prenatal exposure to this marine contaminant appears to cause permanent adverse effects on cognition.