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)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LKB-K (P0))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
United States
Zip Code
King, Katherine E; Kane, Jennifer B; Scarbrough, Peter et al. (2016) Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example. Biodemography Soc Biol 62:87-104
Fuemmeler, Bernard F; Wang, Lin; Iversen, Edwin S et al. (2016) Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort. Child Obes 12:210-8
Slotkin, Theodore A; Stadler, Ashley; Skavicus, Samantha et al. (2016) Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine. Brain Res Bull 122:71-5
Fuemmeler, Bernard F; Lee, Chien-Ti; Soubry, Adelheid et al. (2016) DNA Methylation of Regulatory Regions of Imprinted Genes at Birth and Its Relation to Infant Temperament. Genet Epigenet 8:59-67
Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer et al. (2016) Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes. Toxicology 372:42-51
Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer et al. (2015) Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Toxicol Sci 147:178-89
Murphy, Susan K; Erginer, Erin; Huang, Zhiqing et al. (2015) Genotype-Epigenotype Interaction at the IGF2 DMR. Genes (Basel) 6:777-89
Levin, Edward D (2015) Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery. Neurotoxicol Teratol 52:88-92
Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer et al. (2015) Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors. Toxicology 333:63-75
Nye, Monica D; Hoyo, Cathrine; Murphy, Susan K (2015) In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST. Toxicol In Vitro 29:544-50

Showing the most recent 10 out of 17 publications