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Background: Vulnerability of the central nervous system to mercury exposure is increased during early development. The aim of this study is to evaluate the association between prenatal exposure to mercury and child neuropsychological development in high-fish-intake areas in Spain.Methods: Study subjects were 1362 children, participants in the INMA (Environment and Childhood) birth cohort study. Cord blood total mercury (CB-Hg) and cord polyunsaturated fatty acids (PUFA) concentrations were analysed in samples collected between 2004 and 2008. Child neuropsychological development was assessed at age 4-5 years by the McCarthy Scales of Children's Abilities (MSCA). Socio-demographic, lifestyle and dietary information was obtained by questionnaires administered during pregnancy and childhood.Results: The geometric mean of CB-Hg was 8.8 µg/L [95% confidence interval (CI) 8.4, 9.2]. A doubling in CB-Hg was associated with higher scores in most of the MSCA scales ( β =1.29; 95% CI 0.28, 2.31 for the general cognitive scale). The association between CB-Hg and the scores obtained on the scales was inverse among children whose mothers consumed fewer than three weekly servings of fish during the first trimester of pregnancy, although confidence intervals did not exclude the null ( β =-1.20; 95% CI -2.62, 0.22 for the perceptive-manipulative scale and β =-3.06; 95% CI -6.37, 0.24 for the general cognitive scale). An inverse association between CB-Hg and the scores on the motor scale was also suggested for children with an n-6/n-3 PUFA ratio above the median ( β =-0.23; 95% CI -0.87, 0.40, interaction p -value=0.03).Conclusion: The relationship between CB-Hg concentrations and child neuropsychological development was influenced by maternal nutritional factors, such as fish consumption and the PUFA status. [ABSTRACT FROM AUTHOR]