The prenatal MeHg exposures of the participants of the 14-year examinations () were similar to those of the cohort as a whole [13
]. Exposure levels at age 14 years averaged about one-fifth of those experienced prenatally, although exposures at age 7 years were slightly higher [26
Results of mercury analyses for 860 members of a Faroese birth cohort examined at age 14 years
shows associations with potential confounders. Continuous variables were trichotomized for the purpose of this table only. The expected pattern of associations reflects dietary habits and local differences in availability of whale meat during 1986–1987. Accordingly, participants from fishing villages had higher prenatal exposures than those living in towns or in Denmark. Participants tested in Denmark or in the Danish language had lower exposure. Lower exposure was also associated with a higher maternal Raven score. Adolescents from smaller primary schools had higher exposure, as had participants examined in the afternoon, at an older age, and those living with both parents.
Geometric averages and interquartile ranges (25th–75th percentiles) for cord-blood mercury concentrations (μg/l) in relation to potential predictors of neurobehavioral performance
The neuropsychological test results were generally within expected limits, based on Scandinavian and similar norms for this age range (). However, the Faroese adolescents performed above expectation given available norms for Block Designs, with a marked ceiling effect during the first year of examinations. Adding the three last designs from the adult version (WAIS-R) corrected for this imperfection in resolution at the high end, but was available for less than half of the participants.
Raw scores for neurobehavioral function tests administered at age 14 years.
All multiple regression analyses were based on complete cases (). Thus, the number of participants included depended upon the choice of exposure biomarker and confounders. Higher prenatal MeHg exposure was associated with lower finger tapping scores, increased reaction time, and lower cued naming scores; the cord-blood mercury concentration was a significant predictor of outcomes of all three types. The maternal hair mercury concentration showed significant or near-significant associations with deficits only on the three conditions of finger tapping, and the two measures of reaction time. The cord tissue mercury concentration showed no clear relation to finger tapping and reaction time results, but was associated with deficits on the naming and verbal learning results. One surprising find was that higher MeHg exposure was associated with better scores on WMS-III Spatial Span.
Test score change in percent of test score standard deviation associated with doubling in exposure, as indicated by multiple regression analysis with adjustment for covariates.a
The estimated mercury effects remained virtually unchanged after adjustment for the extended set of confounders, except that, in this reduced data set, the p-value for the effect on the cued naming score was slightly above a 5% significance level. Some outcomes were transformed to obtain normally distributed residuals, but this change barely affected the mercury effects. therefore shows the effect on the untransformed variables. The logarithmic transformation of the exposure variables assume a linear effect of each doubling of the exposure. The appropriateness of this assumption was confirmed in non-parametric models ( and ).
Fig. 2 Association between prenatal methylmercury exposure and the average reaction time (ms) on the NES2 Continuous Performance Test administered to 859 participants from a Faroese birth cohort at age 14 years. Each line at the bottom represents one observation (more ...)
Fig. 3 Association between prenatal methylmercury exposure and the total correct score on the Boston Naming Test after cues administered to 859 participants from a Faroese birth cohort at age 14 years. Each line at the bottom represents one observation at the (more ...)
In contrast to the prenatal exposure variables, markers of postnatal exposures were generally only weakly related to cognitive test scores at 14 years, with many coefficients suggesting effects in the direction opposite to expectation. Only one significant association was seen, i.e., for the hair mercury concentration at age 14 years on the NES2 finger tapping score on the preferred hand (effect, −5.18; p = 0.019). This effect appeared less clear when corrected for the full set of confounders (effect, −3.18; p = 0.17) and decreased further when adjusted for the prenatal exposure level (effect, −2.74; p = 0.26). On the other hand, prenatal effects changed only slightly after adjustments for postnatal exposure markers. However, due to limited power in a regression model with both prenatal and postnatal exposure variables, the p-values generally increased slightly. Thus, the p values for the three outcomes significantly associated with the cord blood mercury concentration without adjustment for postnatal exposure increased to levels ranging from 0.061 (CPT reaction time) to 0.11 (finger tapping), after adjustment for postnatal exposure. On the other hand, the Copying test (5 most difficult designs) now showed a significant p-value of 0.03 for the effect of prenatal exposure effects after adjustment for postnatal exposure.
Likewise, PCB exposure, although only available for half of the subjects, showed only weak associations with the outcomes, none of them reaching statistical significance. The p values for the three outcomes showing significant deficits associated with the cord blood mercury concentration () varied from 0.15 (CPT reaction time) to 0.98 (finger tapping with both hands).
In general, a high percentage of the outcome variation could not be explained in the regression models and most covariate associations were weaker than at age 7 years [18
]. Age was not a general predictor of test performance at this developmental stage and within the limited age range covered, and was only weakly related to scores on verbal abstraction, attention, and manual motor speed tasks. Sex was a stronger predictor of test performance, where boys performed faster on tasks assessing manual motor speed, while girls earned higher scores on most other tasks. No sex difference was seen in vocabulary, nonverbal abstraction, and visuospatial memory. The maternal Raven score was again an important predictor for most outcomes. Residence in towns was positively associated with naming ability and, to some degree, with other abilities. Computer experience was associated with better performance on the continuous performance tasks and finger tapping. However, the full complement of predictors explained only about 10% of the total variation (). Although prenatal MeHg exposure seemed a less important predictor of neuropsychological performance at age 14 than at age 7 years, this risk factor appeared to represent about the same proportion of the total variance explained by the regression model at the two occasions.
Percent of variance explained by the multiple regression models for the outcome variables that showed statistically significant negative associations with cord blood mercury exposure at 14 years of age.a
Assuming that prenatal MeHg neurotoxicity causes permanent changes, the mercury-associated effects observed at age 14 years could represent the deficits previously observed at age 7 years, as modified by learning and maturation. An analysis was therefore conducted based on outcomes available from both examinations and with a significant mercury effect at age 7 or 14 years (). For most outcomes, prenatal MeHg exposure showed only weak effects on the test score difference. The sign of the coefficients generally suggested that highly exposed participants may have been able to compensate in part for deficits seen at age 7 years. However, this effect was weak and only statistically significant for one of the CVLT scores. For two finger tapping scores (non-preferred hand and both hands), this analysis indicated that, between ages 7 and 14 years, highly exposed participants had fallen even further behind those less exposed, but again this tendency was not statistically significant. A supplementary analysis of the relative difference in test scores yielded similar results, but these models provided a poorer fit to the data.
Effect (beta) of 10-fold increase in the prenatal MeHg exposure on the change in scores of neuropsychological tests first applied at age 7 years and repeated at 14 years, after adjustment for covariates.
To take into account multiple statistical testing, exposure imprecision and missing data, we then applied structural equation models. The crude, initial models fitted the data poorly, but after adjustment for local dependence and differential item functioning, models with an acceptable fit were obtained for all five test groups (). The strongest mercury effect was found in regard to the motor and attention groupings. The effect for the verbal grouping is close to being significant at the 5% level, while the effect on spatial and memory groups is far from significant.
Mercury effects on five groups of neurobehavioral tests estimated in structural equation analysis with covariate adjustment with and without maternal fish intake during pregnancy.
Maternal fish intake during pregnancy was then added to the structural equation models (). Although fish intake appeared to exert a weak beneficial effect, it was not statistically significant. Inclusion of this adjustment changed the mercury coefficients in the direction anticipated.
Significant mercury effects corresponded to a decrease corresponding to 6.5–8.5% of the standard deviation for each doubling in the exposure (). These results are in accordance with the strongest regression coefficients in . For motor function, a doubling of the true MeHg exposure corresponded to 1.3 fewer taps on NES2 finger tapping with the preferred hand. As a result, at age 14 years, this effect is slightly stronger than at 7 years. Other effects were about the same or less. In the regression analysis, a strong positive mercury effect had been obtained for Spatial Span, and this tendency led to poorer fit of the structural equation for attention. A better fitting model with a stronger effect would be obtained by excluding this score, but this possibility was not further pursued.
As expected, local dependence were observed for the two naming scores, the four CVLT scores, the NES2 continuous performance scores, and the two Copying scores. Likewise, differential item functioning occurred for some outcomes, mostly because test scores depended on sex. Allowance for these factors improved the fit of the models, but affected the mercury coefficients only minimally. For the spatial outcomes the final model did not fit data as well as the unrestricted model and the results should be cautiously interpreted.