Regression trees form a potentially useful alternative to continuous linear regression models. The goodness of fit for five out of six endpoints, as measured by the R-squared, in this reanalysis is much higher than those of the linear regression analysis in previous studies of the same data. In addition, the covariate effects are simpler to describe as cluster effects. The main advantage of the regression tree approach is that it allows us to explore non-homogeneous exposure effects in different clusters. As expected, there were some clusters with small sample sizes. However, the design of the Seychelles study focuses on overall population effect and may not be powered to identify subtle effects at either end of the developmental spectrum.

The regression tree based on the FSIQ was consistent with child development theory and further confirms that a child's development can be improved by providing a more stimulating home environment and better family support. Although our main study was designed to examine prenatal exposure, we included a measure of the postnatal exposure, since fish consumption and consequently MeHg exposure is continuous in this society. We found one of the five endpoints we examined, the CTRS, had an adverse association with postnatal exposure. This association may be fortuitous, but its interpretation is not clear and more extensive postnatal analyses are currently in progress.

For prenatal mercury exposure, this tree-structured reanalysis with a common linear effect of exposure (Model (1)) confirms the results reported earlier (

Myers et al., 2003). The models for both the CTRS and the Grooved Pegboard (non-dominant hand) have higher R-squared values and the same association with prenatal exposure. In addition, B-O test scores improved significantly with increasing MeHg exposure in the reanalysis. For every 10ppm increase in exposure, the B-O mean score improved by 1.3 points. MeHg in the B-O test score had a positive coefficient in the linear analysis (coefficient estimate 0.093), but did not reach significance in the linear analysis (p=0.10). When allowing separate prenatal exposure effects for different subgroups (Model (2)), B-O test scores improved significantly with increasing MeHg exposure for cluster 5, a group of 53.35% of the children who had average developmental stimulation. When outliers were removed, CTRS test scores improved significantly with increasing MeHg for cluster 5 and Grooved Pegboard—dominant hand scores declined significantly with increasing MeHg for cluster 2. The Groove Pegboard – dominant hand was not significant in the linear analysis. Cluster 2 had 7.28% of the children and had a mean IQ of 71.9 (range 53-87). This association indicated that with every 10 ppm increase of exposure, the child needed on average an additional 13.4 seconds to complete the task (95% confidence interval [2.3, 24.4]).

In summary, this reanalysis using the regression tree approach supports the findings from the primary linear regression analysis (

Myers et al., 2003). We continue to find no consistent evidence for effects from prenatal MeHg through fish consumption at the exposure levels present in the Seychelles Child Development cohort. However, the current results do raise an interesting point that goes beyond previous analyses: the exposure/outcome relationship may not be homogeneous across all individuals. Using the regression tree methods, some associations appeared that were not present using other analysis methods. The B-O and CTRS showed improvement as MeHg exposure increased for children with average stimulating environments. In addition there was a decline in Grooved Pegboard test—dominant hand scores with increasing MeHg that appeared in children with lower scores on the HOME indicating they had a less stimulating home environment. These findings suggest that the effects of prenatal MeHg exposure from maternal fish consumption during pregnancy are complex and may not be homogeneous between children with different backgrounds and developmental environments. Further study is needed to see if these associations are consistent and related to mercury exposure.