Perinatal Nicotine and Auditory Evoked Potentials in Early Infancy

围产期尼古丁和婴儿早期听觉诱发电位

• 批准号: 8243958
• 负责人: Karen M Grewen
• 金额: $ 22.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8243958
• 关键词: Achievement; Adolescence; Age; Age-Months; Air; Asthma; Attention; Attention Deficit Disorder; Auditory; Auditory Evoked Potentials; Behavior; Behavior Disorders; Behavioral; Binding; Biological Markers; Biological Markers; Birth; Blood - brain barrier anatomy; Brain; Breast Feeding; Carbon Monoxide; Child; Childhood; Cigarette; Cognitive; Communication; Control Groups; Cotinine; Data; Defect; Detection; Development; Developmental Process; Differentiation and Growth; Disease; Early treatment; Electroencephalography; Environment; Environmental Tobacco Smoke; Event-Related Potentials; Exposure to; Future; Goals; Growth; Hair; Health; Health Benefit; Home environment; Human; Human Milk; Impulsivity; Infant; Intelligence; Language; Life; Link; Longitudinal Studies; Low Birth Weight Infant; Measures; Medical Records; Memory; Methods; Mothers; Neurocognitive; Neurocognitive Deficit; Nicotine; Nicotinic Receptors; Outcome; Parents; Performance; Perinatal; Populations at Risk; Postpartum Period; Pregnancy; Pregnant Women; Process; Productivity; Psychotropic Drugs; Public Health; Quality of life; Risk; Risk Factors; Sampling; Sensory; Sensory Process; Short-Term Memory; Sleep; Smoke; Smoker; Smoking; Source; Substance abuse problem; Sudden infant death syndrome; Surveys; TNFRSF5 gene; Techniques; Teratogens; Testing; Third Pregnancy Trimester; Time; Toddler; United States; Urine; Visit; Visual; Visuospatial; activity marker; adverse outcome; brain behavior; cost; critical period; early childhood; fetal; fetal tobacco exposure; in utero; infancy; instrument; maternal cigarette smoking; myelination; neural circuit; neurochemistry; neurotoxic; non-smoking; postnatal; prenatal; prenatal exposure; relating to nervous system; response; sensory gating; skills; tool; urinary

DESCRIPTION (provided by applicant): Prenatal nicotine exposure (PNE) caused by maternal cigarette-smoking is linked to defects in auditory and visual sensory processing, behavior, memory, language, and generalized intelligence. Exposure to environmental tobacco smoke (ETS), in utero and early life is also related to neurocognitive deficits, behavioral disorders, and lower IQ measured in childhood and adolescence. The human brain undergoes massive growth, differentiation and maturation in utero and the first year of life, making it especially vulnerable to neurotoxic insult. Nicotine, a well-documented neural teratogen, crosses the placental and blood brain barriers to bind to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity and function of developing fetal and infant neural circuits. Thus PNE or ETS may have long term impact on neurochemical, neural circuitry, and behavioral development. Nicotine exposure from breast milk of smoking mothers or from breast milk of non-smoking mothers living with a smoker, may also contribute added nicotine exposure during early brain development. Quantification of infant nicotine levels from these multiple sources has been done in few studies, and fewer still have studied nicotine in association with very early brain and neurocognitive function. Methods: We propose to use auditory event-related potentials (ERP) in young infants with and without perinatal nicotine exposure, to study biological markers of neural aberration that may herald future neurocognitive deficits. We will examine sensory and higher order auditory cognitive processing in 3 groups of infants: 50 infants of mothers who smoke (PNE), 50 infants of non-smoking mothers living with a smoker (ETS), and 50 infants from smoke-free homes (CTL). We will measure biomarkers of nicotine exposure in maternal hair, urine and expired air, and in infant urine. We will use well- validated tools to estimate age-appropriate development focusing on items dependent upon auditory processing. A long term goal is to identify and refine a neurophenotype of nicotine's detrimental effects on the developing brain, in order to inform early interventions in this important at-risk population. We plan to use acquired findings to support an application for more detailed, longitudinal study. PUBLIC HEALTH RELEVANCE: Cigarette-smoke in the home during pregnancy and early life are risk factors for poor performance on memory, language, attention and IQ tests later in childhood. In addition to all the other well known health risks of smoking, the hidden costs of nicotine-induced damage to early brain development may be particularly burdensome, starting before birth and lasting a lifetime. We propose to study brain activity in sleeping 4-month old infants, using state-of-the-art electrophysiological (EEG) techniques to compare the effects of maternal cigarette-smoking and second-hand smoke to smoke-free environments. We will measure nicotine exposure during pregnancy using a small sample of mothers' hair, and nicotine exposure during early postpartum with by-products of nicotine in urine from infants and mothers. We will relate both to levels of brain activity and markers of neurocognitive development at measured at 4 and 12 months of age. To the extent that nicotine imposes damage to developing neural circuits, the effects on productivity, achievement and quality of life will be borne by the most vulnerable 'involuntary smokers.' Greater understanding of the early effects of nicotine on neural substrates of cognitive development will, therefore, provide public health benefit.

描述（由申请人提供）：母体吸烟引起的产前尼古丁暴露（PNE）与听觉和视觉感觉处理、行为、记忆、语言和广义智力缺陷有关。在子宫内和早年接触环境烟草烟雾（ETS）也与儿童和青少年时期测量的神经认知缺陷、行为障碍以及智商较低有关。人类大脑在子宫内和生命的第一年经历大规模的生长，分化和成熟，使其特别容易受到神经毒性的伤害。尼古丁是一种有据可查的神经致畸剂，可穿过胎盘和血脑屏障与烟碱乙酰胆碱受体结合，烟碱乙酰胆碱受体广泛参与发育中的胎儿和婴儿神经回路的生长、连接和功能。因此，PNE或ETS可能对神经化学，神经回路和行为发育产生长期影响。吸烟母亲或与吸烟者一起生活的非吸烟母亲的母乳中的尼古丁暴露也可能导致早期大脑发育期间的尼古丁暴露增加。在少数几项研究中，对这些多种来源的婴儿尼古丁水平进行了定量分析，研究尼古丁与极早期大脑和神经认知功能相关性的研究更少。研究方法：我们建议使用听觉事件相关电位（ERP）在年轻的婴儿与围产期尼古丁暴露，研究生物标志物的神经畸变，可能预示着未来的神经认知缺陷。我们将研究3组婴儿的感觉和高阶听觉认知处理：50名吸烟母亲的婴儿（PNE），50名与吸烟者生活在一起的非吸烟母亲的婴儿（ETS），以及50名来自无烟家庭的婴儿（CTL）。我们将测量母亲头发、尿液和呼出气体以及婴儿尿液中尼古丁暴露的生物标志物。我们将使用经过验证的工具来估计与年龄相适应的发展，重点是依赖于听觉处理的项目。长期目标是确定和完善尼古丁对发育中大脑的有害影响的神经表型，以便为这一重要的高危人群的早期干预提供信息。我们计划使用获得的发现来支持更详细的纵向研究的应用。 公共卫生相关性：怀孕期间和早年在家中吸烟是儿童后期记忆力、语言、注意力和智商测试表现不佳的危险因素。除了所有其他众所周知的吸烟健康风险外，尼古丁对早期大脑发育造成的损害的隐藏成本可能特别沉重，从出生前开始并持续一生。我们建议研究睡眠中的4个月大的婴儿的大脑活动，使用最先进的电生理（EEG）技术来比较母亲吸烟和二手烟对无烟环境的影响。我们将使用母亲头发的小样本测量怀孕期间的尼古丁暴露，并使用婴儿和母亲尿液中的尼古丁副产物测量产后早期的尼古丁暴露。我们将与大脑活动水平和神经认知发展的标志物在4个月和12个月的年龄测量。就尼古丁对发育中的神经回路造成损害而言，对生产力、成就和生活质量的影响将由最脆弱的"非自愿吸烟者“承担。“因此，更好地了解尼古丁对认知发展神经基质的早期影响将为公众健康带来好处。