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)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
United States
Zip Code
Tindula, Gwen; Murphy, Susan K; Grenier, Carole et al. (2018) DNA methylation of imprinted genes in Mexican-American newborn children with prenatal phthalate exposure. Epigenomics 10:1011-1026
House, John S; Mendez, Michelle; Maguire, Rachel L et al. (2018) Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes. Front Cell Dev Biol 6:107
Gonzalez-Nahm, Sarah; Mendez, Michelle A; Benjamin-Neelon, Sara E et al. (2018) DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years. Clin Epigenetics 10:90
Gao, Lu; Liu, Xiaochen; Millstein, Joshua et al. (2018) Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes. Clin Epigenetics 10:98
Schechter, Julia C; Fuemmeler, Bernard F; Hoyo, Cathrine et al. (2018) Impact of Smoking Ban on Passive Smoke Exposure in Pregnant Non-Smokers in the Southeastern United States. Int J Environ Res Public Health 15:
Cauley, Marty; Hall, Brandon J; Abreu-Villaça, Yael et al. (2018) Critical developmental periods for effects of low-level tobacco smoke exposure on behavioral performance. Neurotoxicology 68:81-87
Hall, Brandon J; Abreu-Villaça, Yael; Cauley, Marty et al. (2017) The ventral hippocampal muscarinic cholinergic system plays a key role in sexual dimorphisms of spatial working memory in rats. Neuropharmacology 117:106-113
Hoffman, Kate; Butt, Craig M; Webster, Thomas F et al. (2017) Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States. Environ Sci Technol Lett 4:112-118
Breton, Carrie V; Marsit, Carmen J; Faustman, Elaine et al. (2017) Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environ Health Perspect 125:511-526
Slotkin, Theodore A; Stadler, Ashley; Skavicus, Samantha et al. (2017) Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure? Toxicol Sci 155:75-84

Showing the most recent 10 out of 31 publications