In the primary analysis that included 48 models we found no adverse association between exposure using either surfaces or occlusal point scores and 46 endpoints. There was an adverse association between amalgam points and the W-J Letter Word score. Prenatal Hg0
exposure using our secondary metric, the occlusal point score, showed a significant slope of -0.16 (p = 0.04) in males indicating an adverse association. This finding was present only using the UEL and was present in two models [without (data not shown) and with () adjustment for prenatal and recent postnatal MeHg exposure]. There were no other adverse associations between any of the 4 dental amalgam scores and the 6 endpoints either without or with adjustment for MeHg. The UEL carries a higher degree of uncertainty than the LEL since it is derived by including ‘possible’ restorations. Considering we fit 48 primary models, the presence of two adverse associations could be a chance finding and does not imply that prenatal exposure to Hg0
from dental amalgams results in neurobehavioral consequences. Accumulation of Hg in the fetal brain attributable to maternal inhalation of Hg0
is reported to be significantly less than in the maternal brain.48
This is likely due to ‘first pass’ oxidation of Hg0
in the fetal liver to divalent mercury (Hg++
), which does not cross the blood-brain barrier as well as Hg0.49
However, several studies have found that males are more susceptible to the toxic effects of mercury than females.50,51,52
The two adverse findings in males are therefore intriguing and warrant further prospective investigation.
We found several significant interactions with sex, both using our primary surface metric () and our secondary occlusal points metric (). Most of the significant interactions were with the UEL metric. As the number of prenatal occlusal points increased, females performed significantly better on the GCI (with both LEL and UEL), the PLS Total Score (with the UEL), and the W-J Applied Problems Score (with the UEL), in covariate-adjusted models, with and without adjustment for pre and postnatal MeHg. We know of no scientific reason to believe that maternal amalgam might improve neurodevelopmental outcomes in either sex. Dental care is free in Seychelles and access to services should be equivalent. However, higher SES mothers may place a greater value on regular dental care and optimally utilize restorative services. Although higher SES might favorably influence outcomes, it would not explain the apparent disparity between males and females. The findings could also be spurious.
A compelling reason for examining this cohort of children was to explore whether the risk of adverse neurodevelopmental outcomes was accentuated by co-exposure to MeHg and Hg0
. Children in this cohort were exposed prenatally and postnatally to elevated levels of MeHg. Consumption of fish is the primary protein source for inhabitants of the island nation of Seychelles. Mothers in this study reported eating approximately 12 fish meals per week during pregnancy.21
This high level of fish consumption resulted in a mean prenatal MeHg (hair THg) exposure of 6.7 ppm. The children also consumed fish and their recent postnatal MeHg exposure was 6.4 ppm on average. In comparison, the 1999-2000 U.S. NHANES study found a mean exposure (hair THg) of 0.47 ppm in females of child bearing age (16-49 years of age) and postnatal exposure of 0.22 ppm in children aged 1-5 years.53
Compared to the US NHANES, the Seychelles mean prenatal MeHg exposure was 14 times higher and the postnatal exposure was 29 times higher. Our models of prenatal and recent postnatal MeHg exposure in this study ( and ) confirm the absence of any detectable adverse influence of prenatal and recent postnatal MeHg exposures, as reported in our earlier analyses of the entire cohort.21
To our knowledge, this is the first study to comprehensively examine the risk of prenatal Hg0 exposure from maternal amalgams. The study's strengths include a large, well-defined cohort, sensitive neurodevelopmental assessments, and the presumption that if adverse effects were present, they may be more readily detectable in subjects with other forms of mercury exposure. Moreover, we utilized two different metrics as biomarkers of Hg0 exposure from amalgam restorations and did find significant associations between covariates known to influence child development and endpoints. This suggests there was sufficient power to detect associations if they were present.
The most significant limitation of this study was its retrospective design. We determined the maternal amalgam status during gestation by examining the mothers 10 years after delivery and then reviewing their past dental records to complete the picture. Although dental records in Seychelles were very good, we adjusted for this uncertainty by utilizing two measures of exposure. The LEL and the UEL represent the most likely ‘minimum’ and ‘maximum’ respective numbers of amalgams present in the mother during pregnancy. The true exposure level presumably lies ‘bracketed’ between these levels. It is most likely closer to the LEL, which represents amalgams with documented presence. Consequently, some amalgam exposures could have been misclassified. In addition, there may have been covariates that were important that were not measured.
We do not consider results of this retrospective study to be definitive and are currently studying developmental outcomes in another cohort of children in which maternal amalgam status during gestation was recorded prospectively.