Prenatal tobacco exposure: effects on neuropsychological outcomes and ADHD

描述(由申请人提供)：这个重新修订的新调查员R01寻求资金，以调查产前烟草暴露对后代注意力问题以及相关的学习和认知缺陷的影响。孕妇孕期吸烟(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有关，包括注意力缺陷多动障碍(ADHD)、品行障碍、学习和记忆受损、智商下降和认知功能障碍。ADHD和其中许多儿童结局是具有明显公共卫生影响的临床重大疾病，反过来也是青少年药物使用问题的重要预测因素。然而，现有文献中表明MSDP对这些儿童结局的因果影响的证据是混乱的，因为经常无法将这些产前烟草暴露的影响与其他混杂的环境和遗传因素分开。具体地说，绝大多数先前的研究只提供了有限的控制，因为产前暴露可能与父母的行为相关，而父母的行为也可能是重要的风险因素，继而传递给他们的后代。未能控制这种(可能可遗传的)混杂因素可能是MSDP和后代结局之间存在关联的很大一部分原因，从而导致有偏见的效应大小。因此，该应用程序建议收集400个家庭的访谈和综合神经心理学实验室数据，这些家庭至少有两个密苏里州出生的孩子(测试时年龄为8-15岁)，其中母亲在一次怀孕期间吸烟，但不在同一父亲另一次怀孕期间吸烟(因此，子女是不符合产前烟草暴露的完全兄弟姐妹对)。这种母亲内部、怀孕之间的对比为混杂因素提供了最好的方法学控制，例如母亲的遗传和社会人口学特征预测MSDP的可能性增加，以及怀孕期间吸烟和不吸烟的母亲(及其伴侣)之间的其他差异。这些混杂的因素，如果不加以控制，可能会人为地创造或掩盖MSDP和儿童结果之间的联系(这一提议特别感兴趣的是：记忆、执行功能、语言/阅读和ADHD)。因此，这样的设计将提供机会来准确确定效果大小，同时也允许我们制定一个队列，在未来可能会在外化症状增加和开始使用药物的时期纵向跟踪。公共卫生相关性：用两三句话描述这项研究与公共卫生的相关性。如果申请得到资助，这一描述将成为公开信息。因此，不包括专有/机密信息。孕妇在怀孕期间吸烟是一个主要的公共卫生问题，近一半吸烟的妇女在整个怀孕期间继续吸烟。因此，每年有50多万婴儿产前暴露在母亲吸烟的环境中。这项关于产前暴露影响的基因研究考虑了怀孕期间吸烟和不吸烟的女性之间差异的潜在混杂影响。研究结果可能会为孕妇克服烟草依赖和戒烟提供另一种激励，但研究结果也可以指导治疗提供者更全面地考虑怀孕期间吸烟以及上述行为的潜在相关性。

DESCRIPTION (provided by applicant): 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 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.