-KNOPIK This re-revised new investigator R01 seeks funding to investigate the effects of prenatal tobacco exposure on offspring attention problems and associated learning and cognitive deficits. Maternal smoking during pregnancy (MSDP) is a major health concern associated with higher rates of a variety of poor child outcomes, including attention deficit hyperactivity disorder (ADHD), conduct disorder, impaired learning and memory, lowered IQ, and cognitive dysfunction. ADHD and many of these childhood outcomes are clinically significant conditions with clear public health implications and also are, in turn, substantial predictors of adolescent drug use problems. However, the evidence suggesting causal effects of MSDP for these childhood outcomes is muddied in the existing literature due to the frequent inability to separate these prenatal tobacco exposure effects from other confounding environmental and genetic factors. Specifically, the vast majority of prior studies provide only limited control for the fact that prenatal exposures may be correlated with parental behaviors that could also act as important risk factors that are in turn transmitted to their offspring. Failure to control for such (possibly heritable) confounding factors may account for a large part of the suggested associations between MSDP and offspring outcomes, resulting in biased effect sizes. Therefore, this application proposes to collect interview and comprehensive neuropsychological lab-based data from 400 families with at least 2 Missouri-born children (aged 8-15 at the time of testing), where the mother smoked during one pregnancy but not during a another pregnancy by the same father (thus, with offspring who are full sibling pairs discordant for prenatal tobacco exposure). This within-mother, between-pregnancy contrast provides the best possible methodologic control for confounding factors, such as heritable and sociodemographic characteristics of the mother that predict increased probability of MSDP, as well as other differences between mothers who do and do not smoke during pregnancy (and their partners). Such confounding factors, if not controlled for, might otherwise artifactually create, or alternatively mask, an association between MSDP and child outcomes (of particular interest for this proposal: memory, executive function, language/reading, and ADHD). Such a design will therefore provide opportunities to accurately determine effect sizes while also allowing us to develop a cohort which, in the future, could be followed longitudinally through periods of increased externalizing symptoms and substance use initiation.

Public Health Relevance

In two or three sentences, describe the relevance of this research to public health. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. Maternal smoking during pregnancy (MSDP) is a major public health concern with nearly half of all women who smoke continuing to do so throughout their pregnancies. As a result, more than half a million infants per year are prenatally exposed to maternal smoking. This genetically informed study on effects of prenatal exposure considers the potential confounding effects of differences between women who smoke and don't smoke during pregnancy. Findings could provide yet one more incentive for pregnant women to overcome tobacco dependence and quit, but findings can also guide treatment providers to think more comprehensively about smoking during pregnancy and the potential correlates of said behavior.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-HOP-T (04))
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Boyce, Cheryl A
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Rhode Island Hospital
United States
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Micalizzi, Lauren; Knopik, Valerie S (2018) Maternal smoking during pregnancy and offspring executive function: What do we know and what are the next steps? Dev Psychopathol 30:1333-1354
Knopik, Valerie S; Marceau, Kristine; Bidwell, L Cinnamon et al. (2018) Prenatal substance exposure and offspring development: Does DNA methylation play a role? Neurotoxicol Teratol :
Micalizzi, Lauren; Marceau, Kristine; Brick, Leslie A et al. (2018) Inhibitory control in siblings discordant for exposure to maternal smoking during pregnancy. Dev Psychol 54:199-208
Marceau, Kristine; Cinnamon Bidwell, L; Karoly, Hollis C et al. (2018) Within-Family Effects of Smoking during Pregnancy on ADHD: the Importance of Phenotype. J Abnorm Child Psychol 46:685-699
Bidwell, L Cinnamon; Marceau, Kristine; Brick, Leslie A et al. (2017) Prenatal Exposure Effects on Early Adolescent Substance Use: Preliminary Evidence From a Genetically Informed Bayesian Approach. J Stud Alcohol Drugs 78:789-794
Waldron, Mary; Bucholz, Kathleen K; Lian, Min et al. (2017) Single Motherhood, Alcohol Dependence, and Smoking During Pregnancy: A Propensity Score Analysis. J Stud Alcohol Drugs 78:745-753
Palmer, Rohan H C; Beevers, Christopher G; McGeary, John E et al. (2017) A Preliminary Study of Genetic Variation in the Dopaminergic and Serotonergic Systems and Genome-wide Additive Genetic Effects on Depression Severity and Treatment Response. Clin Psychol Sci 5:158-165
Knopik, Valerie S; Marceau, Kristine; Palmer, Rohan H C et al. (2016) Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters. Behav Genet 46:353-64
Marceau, Kristine; Palmer, Rohan H C; Neiderhiser, Jenae M et al. (2016) Passive rGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight. Behav Genet 46:365-77
Palmer, Rohan H C; Bidwell, L Cinnamon; Heath, Andrew C et al. (2016) Effects of Maternal Smoking during Pregnancy on Offspring Externalizing Problems: Contextual Effects in a Sample of Female Twins. Behav Genet 46:403-15

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