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: 7528650
• 负责人: Valerie S Knopik
• 金额: $ 61.78万
• 依托单位: BROWN UNIVERSITY
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7528650
• 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; Condition; Confidential Information; DNA; Databases; Depth; Diagnostic; Disease; 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; Rate; Reading; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Scheme; School-Age Population; Shipping; Ships; Siblings; Smoke; Smoking; Standards of Weights and Measures; Symptoms; TNFRSF5 gene; Testing; Text; Thinking; Time; Tobacco Dependence; Woman; Work; adolescent drug use; adolescent substance use; aged; base; clinically significant; cohort; design; executive function; externalizing behavior; fetal tobacco exposure; genetic analysis; interest; maternal cigarette smoking; neuropsychological; postnatal; prenatal; prenatal exposure; size; 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）：经过重新修订的新研究者 R01 寻求资金来调查产前烟草暴露对后代注意力问题以及相关学习和认知缺陷的影响。母亲在怀孕期间吸烟（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。 ADHD 和许多此类儿童结局是临床上重要的疾病，具有明显的公共卫生影响，反过来也是青少年吸毒问题的重要预测因素。然而，由于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，表明 MSDP 对这些儿童结局的因果影响的证据在现有文献中并不明确。具体而言，绝大多数先前的研究仅对以下事实提供有限的控制：产前暴露可能与父母的行为相关，而父母的行为也可能成为重要的风险因素，进而传递给后代。未能控制此类（可能是遗传的）混杂因素可能是 MSDP 与后代结果之间建议的关联的很大一部分原因，从而导致效应大小出现偏差。因此，本申请建议从 400 个至少有 2 个密苏里州出生的孩子（测试时年龄为 8-15 岁）的 400 个家庭收集访谈和综合神经心理学实验室数据，其中母亲在一次怀孕期间吸烟，但在同一个父亲的另一次怀孕期间不吸烟（因此，后代是完全兄弟姐妹，在产前烟草暴露方面不一致）。这种母亲内部、怀孕期间的对比为混杂因素提供了最佳的方法控制，例如预测 MSDP 可能性增加的母亲的遗传和社会人口学特征，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，可能会人为地创建或掩盖 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，这样的设计将提供准确确定效应大小的机会，同时也使我们能够开发一个队列，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：用两到三个句子描述本研究与公共卫生的相关性。如果申请获得资助，该描述将按原样成为公共信息。因此，请勿包含专有/机密信息。母亲怀孕期间吸烟 (MSDP) 是一个主要的公共卫生问题，近一半的女性在怀孕期间继续吸烟。因此，每年有超过 50 万婴儿在产前接触母亲吸烟。这项关于产前暴露影响的遗传学研究考虑了怀孕期间吸烟和不吸烟女性之间差异的潜在混杂影响。研究结果可能为孕妇克服烟草依赖和戒烟提供更多动力，但研究结果也可以指导治疗提供者更全面地思考怀孕期间吸烟以及上述行为的潜在相关性。