Prenatal tobacco exposure: effects on neuropsychological outcomes and ADHD

摘要-KNOPIK 这项重新修订的新研究R 01寻求资金，以调查产前烟草暴露对 后代注意力问题和相关的学习和认知缺陷。母亲吸烟期间 妊娠（MSDP）是一个主要的健康问题，与各种不良儿童结局的发生率较高相关， 包括注意力缺陷多动障碍（ADHD）、行为障碍、学习和记忆受损， 智商降低和认知功能障碍多动症和许多这些儿童的结果是临床意义 这些条件具有明显的公共卫生影响，反过来也是青少年吸毒的重要预测因素 使用问题。然而，表明MSDP对这些儿童结局的因果影响的证据是 由于经常无法区分这些产前烟草暴露， 其他混杂的环境和遗传因素的影响。特别是，绝大多数的前 研究仅提供了有限的控制，因为产前暴露可能与父母的 这些行为也可能成为重要的风险因素，进而传递给后代。未能 对这些（可能是遗传的）混杂因素的控制可能占建议的很大一部分。 MSDP和后代结果之间的关联，导致偏倚效应量。因此本 应用程序建议从400名患者中收集访谈和综合神经心理学实验室数据。 至少有2个密苏里州出生的孩子（测试时年龄为8-15岁）的家庭，母亲吸烟 在一次怀孕期间，但不是在同一个父亲的另一次怀孕期间（因此， 兄弟姐妹对产前烟草暴露不一致）。这种母亲内部，怀孕之间的对比 为混杂因素提供了最佳的方法学控制，如遗传和 母亲的社会人口学特征预测MSDP的可能性增加，以及其他 怀孕期间吸烟和不吸烟的母亲（及其伴侣）之间的差异。等 混杂因素，如果不加以控制，可能会人为地产生或掩盖， MSDP与儿童结局之间的关联（本提案特别关注：记忆、执行 功能、语言/阅读和ADHD）。因此，这种设计将提供机会， 确定效应量，同时也使我们能够开发一个队列，在未来， 纵向通过增加的外部化症状和物质使用开始的时期。

ABSTRACT-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.