Francheska M Merced-Nieves1, John Chelonis2, Ivan Pantic3, Lourdes Schnass3, Martha M Téllez-Rojo4, Joseph M Braun5, Merle G Paule2, Rosalind J Wright6, Robert O Wright6, Paul Curtin7. 1. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: francheska.merced-nieves@mssm.edu. 2. Division of Neurotoxicology, National Center for Toxicological Research, FDA, Jefferson, AR, USA. 3. Division of Community Interventions Research, National Institute of Perinatology, Mexico City, Mexico. 4. Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico. 5. Department of Epidemiology, Brown University, Providence, RI, USA. 6. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: Associations between lead (Pb) and neurodevelopment have been studied widely in the context of global measures of cognitive function, such as IQ. Operant test batteries consist of behavioral tasks that can be used to target discrete cognitive and behavioral mechanisms, which contribute to global cognitive faculties. OBJECTIVES: The goals of this study were to identify Pb-associated deficits in cognitive development and determine the underlying mechanisms involved, utilizing an operant test battery. We evaluated effect modification by child sex. METHODS: This study utilized data from a prospective cohort in Mexico City. We included 549 participants aged 6-to-7 years with complete data on prenatal blood Pb measurements, Operant Test Battery (OTB) tasks, and demographic covariates. General linear models were used to examine the association of Pb levels at each prenatal timepoint and OTB performance. Effect modification by child sex was evaluated using 2-way interaction terms. RESULTS: In three of the operant tasks, we observed that higher late-pregnancy blood Pb concentrations were associated with greater response latencies. In the temporal processing task, we observed that higher late-pregnancy Pb exposure was associated with worse overall task performance. Further, in two operant tasks, the effects of Pb were dependent on the sex of the child, such that the effects of Pb were more pronounced in females in the condition position responding task, but stronger in males in the temporal processing task. CONCLUSIONS: Our results suggest that prenatal Pb concentrations yield broad dysregulation of executive functions, which can be attributed to dysregulation of temporal processing. In addition, we observed sex differences in two operant tasks suggesting that some Pb effects on neurocognitive function may be sexually dimorphic.
BACKGROUND: Associations between lead (Pb) and neurodevelopment have been studied widely in the context of global measures of cognitive function, such as IQ. Operant test batteries consist of behavioral tasks that can be used to target discrete cognitive and behavioral mechanisms, which contribute to global cognitive faculties. OBJECTIVES: The goals of this study were to identify Pb-associated deficits in cognitive development and determine the underlying mechanisms involved, utilizing an operant test battery. We evaluated effect modification by child sex. METHODS: This study utilized data from a prospective cohort in Mexico City. We included 549 participants aged 6-to-7 years with complete data on prenatal blood Pb measurements, Operant Test Battery (OTB) tasks, and demographic covariates. General linear models were used to examine the association of Pb levels at each prenatal timepoint and OTB performance. Effect modification by child sex was evaluated using 2-way interaction terms. RESULTS: In three of the operant tasks, we observed that higher late-pregnancy blood Pb concentrations were associated with greater response latencies. In the temporal processing task, we observed that higher late-pregnancy Pb exposure was associated with worse overall task performance. Further, in two operant tasks, the effects of Pb were dependent on the sex of the child, such that the effects of Pb were more pronounced in females in the condition position responding task, but stronger in males in the temporal processing task. CONCLUSIONS: Our results suggest that prenatal Pb concentrations yield broad dysregulation of executive functions, which can be attributed to dysregulation of temporal processing. In addition, we observed sex differences in two operant tasks suggesting that some Pb effects on neurocognitive function may be sexually dimorphic.
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