Prenatal and postnatal environmental tobacco smoke (ETS) exposure have been associated with a range of adverse cognitive and neurobehavioral outcomes in children, including higher rates of Attention-Deficit / Hyperactivity Disorder (ADHD). However, our understanding of both the developmental timing of ETS-induced effects on cognitive outcomes, as well as the possible mechanisms underlying such effects is limited. This study will take advantage of a perinatal birth cohort that has obtained prospectively collected data from the first trimester through infancy inclusive of surveys regarding smoking history, data from medical records, maternal blood at the first trimester, and cord blood and buccal cells at delivery. Preliminary data indicates prenatal exposure and cord blood DNA methylation are related to externalizing behavioral problems at one year. The proposed study will conduct detailed assessments of childhood cognitive, neurobehavioral function, and ADHD symptoms among a subcohort of children (n=400) at ages 3-5 years and two-years later at 5-7 years. Using maternal blood specimens collected during the first trimester, cord blood at birth, and blood specimens from the children at the first postnatal assessments we will characterize cotinine levels. DNA methylation for select regulatory control regions for genes that have been associated with ADHD symptoms or similar neurodevelopmental phenotypes will be characterized from the child's cord blood and their peripheral blood collected at 3-5 and 5-7 years of age. We hypothesize that prenatal and postnatal exposure to ETS will be associated with cognitive deficits in executive functioning, that DNA methylation will be associated with deficits, and that the association between ETS and cognitive and neurobehavioral outcomes will be partially mediated by DNA methylation. The study will be the first of its kind to help disentangle the associations between ETS and childhood cognitive outcomes by exploring potential epigenetic factors that may help explain these associations. Because DNA methylation is malleable, the findings may inform novel methods for improving cognitive deficits resulting from ETS.

Public Health Relevance

This study combines biological and behavioral data to 1) clarify the relationship between environmental tobacco smoke exposure and childhood neurodevelopmental phenotypes like attention deficit and hyperactivity disorder, and 2) assess the extent to which potentially reversible epigenetic factors contribute to this association. Results may lead to new early interventions to ensure optimal neurodevelopment.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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Duke University
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