Prenatal tobacco exposure: effects on neuropsychological outcomes and ADHD

产前烟草暴露：对神经心理学结果和多动症的影响

• 批准号: 7916831
• 负责人: Valerie S Knopik
• 金额: $ 65.24万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7916831
• 关键词: Accounting; Affect; Age; Alcohol or Other Drugs use; Attention; Attention deficit hyperactivity disorder; Basic Science; Behavior; Birth Records; Blood specimen; Brain region; Characteristics; Child; Childhood; Cognition; Cognitive; Cognitive deficits; Complement; Conduct Disorder; Confidential Information; DNA; Databases; Diagnostic; Enrollment; Environmental Tobacco Smoke; Event; Exposure to; Failure; Family; Fathers; Funding; Future; Genetic; Goals; Health; Health Personnel; Impaired cognition; Incentives; Infant; Interview; Language; Learning; Life; Literature; Low Birth Weight Infant; Masks; Measures; Memory; Missouri; Molecular Genetics; Mothers; Neurocognitive; Newborn Infant; Outcome; Parents; Perinatal; Pregnancy; Pregnant Women; Probability; Psychopathology; Public Health; Reading; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Scheme; School-Age Population; Shipping; Ships; Siblings; Smoke; Smoking; Symptoms; TNFRSF5 gene; Testing; Text; Time; Tobacco Dependence; Woman; Work; adolescent drug use; adolescent substance use; aged; base; clinically significant; cohort; design; early life exposure; executive function; externalizing behavior; fetal tobacco exposure; genetic analysis; interest; maternal cigarette smoking; neuropsychological; offspring; postnatal; prenatal; prenatal exposure; transmission process

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.

描述（由申请人提供）：本重新修订的新研究者R01寻求资助，以调查产前烟草暴露对后代注意力问题和相关学习和认知缺陷的影响。孕妇在怀孕期间吸烟（MSDP）是一个主要的健康问题，与各种不良儿童结局的高发率有关，包括注意缺陷多动障碍（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时期的结果在临床上具有重要意义，具有明确的公共卫生影响，同时也是青少年吸毒问题的重要预测因素。然而，在现有文献中，表明MSDP对这些儿童结局的因果影响的证据是模糊的，因为经常无法将这些产前烟草暴露影响与其他混杂的环境和遗传因素分开。具体来说，绝大多数先前的研究只提供了有限的控制事实，即产前暴露可能与父母的行为有关，而父母的行为也可能是重要的风险因素，进而传染给他们的后代。未能控制这些（可能是遗传的）混杂因素可能是MSDP和后代结果之间的关联的主要原因，从而导致偏倚效应大小。因此，本应用程序建议收集来自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2名密苏里出生的孩子（测试时年龄为8-15岁），其中母亲在一次怀孕期间吸烟，但在同一父亲的另一次怀孕期间没有吸烟（因此，与完全兄弟姐妹的后代在产前烟草暴露方面不一致）。这种母亲内部和怀孕之间的对比为混淆因素提供了最好的方法学控制，例如预测MSDP可能性增加的母亲的遗传和社会人口特征，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。这些混杂因素，如果不加以控制，可能会人为地创造或掩盖MSDP与儿童结果之间的关联（本提案特别感兴趣的是：记忆、执行功能、语言/阅读和ADHD）。因此，这样的设计将为准确确定效应大小提供机会，同时也使我们能够建立一个队列，在未来，可以纵向跟踪外化症状增加和物质使用开始的时期。公共卫生相关性：用两到三句话描述本研究与公共卫生的相关性。如果该应用程序获得资助，则此描述将成为公共信息。因此，不要包含专有/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，所有吸烟妇女中有近一半在整个怀孕期间继续吸烟。因此，每年有50多万婴儿在出生前暴露在母亲吸烟的环境中。这项关于产前吸烟影响的遗传学研究考虑了怀孕期间吸烟和不吸烟妇女之间差异的潜在混淆效应。研究结果可以为孕妇克服烟草依赖和戒烟提供更多的激励，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及其行为的潜在相关性。