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Daniel A. Axelrad,¹ David C. Bellinger,^2,3 Louise M. Ryan,⁴ and Tracey J. Woodruff^5*

¹U.S. Environmental Protection Agency, Office of Policy, Economics, and Innovation, Washington, DC, USA; ²Department of Neurology, Harvard Medical School and Children's Hospital Boston, and ³Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; ⁴Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA; ⁵U.S. Environmental Protection Agency, Office of Policy, Economics and Innovation, San Francisco, California, USA

Abstract
Background: Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure.

Objectives: We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ) , using a Bayesian hierarchical model to integrate data from three epidemiologic studies.

Methods: Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability.

Results: We find a central estimate of –0.18 IQ points (95% confidence interval, –0.378 to –0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from –0.13 to –0.25.

Conclusions: IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.

Key words: Bayesian hierarchical model, benefits, dose–response model, epidemiology, IQ, mercury, neurodevelopmental effects, noncancer risk assessment, prenatal exposure. Environ Health Perspect 115:609–615 (2007) . doi:10.1289/ehp.9303 available via http://dx.doi.org/ [Online 11 January 2007]

Address correspondence to D. Axelrad, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave. NW (1809T) , Washington, DC 20460 USA. Telephone: (202) 566-2304. Fax: (202) 566-2336. E-mail: axelrad.daniel@epa.gov

*Current address: University of California, San Francisco.

Supplemental Material is available online at http://www.ehponline.org/docs/2007/9303/suppl.pdf

We appreciate the additional analysis of the Faroe Islands data provided by E. Budtz-Jorgensen and P. Grandjean, and the comments on an earlier version of this work provided by J. Bailar III, T. Burke, D. Dunson, and J. Jacobson.

L.M.R.'s work was supported by U.S. EPA contract 4W-1280-NAEX and National Institute of Environmental Health Sciences grant ES000002. The views expressed in this article are those of the authors and do not necessarily reflect those of the U.S. EPA.

The authors declare they have no competing financial interests.

Received 28 April 2006 ; accepted 11 January 2007.

Correction

In the Abstract, the sections "Primary analysis" and "Discussion," and Table 5, the 95% CI for estimate of childhood IQ was –0.387 to –0.012 in the original manuscript published online. It has been corrected here.