Perinatal Nicotine and Auditory Evoked Potentials in Early Infancy

描述（由申请人提供）：由母亲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、语言和一般智力的缺陷有关。在子宫内和生命早期暴露于环境烟草烟雾（ETS）也与儿童和青少年时期的神经认知缺陷、行为障碍和较低的智商有关。人类大脑在子宫内和生命的第一年经历了大量的生长、分化和成熟，使其特别容易受到神经毒性的损害。尼古丁是一种有充分证据证明的神经致畸物，通过胎盘和血脑屏障与尼古丁乙酰胆碱受体结合，尼古丁乙酰胆碱受体广泛参与胎儿和婴儿神经回路的生长、连接和功能发育。因此，PNE或ETS可能对神经化学、神经回路和行为发育有长期影响。吸烟母亲的母乳或不吸烟母亲与吸烟者生活在一起的母乳中的尼古丁暴露，也可能在早期大脑发育期间增加尼古丁暴露。对这些多种来源的婴儿尼古丁水平的量化研究很少，而对尼古丁与早期大脑和神经认知功能的关系的研究更少。方法：我们建议在有或没有围生期尼古丁暴露的婴儿中使用听觉事件相关电位（ERP）来研究神经畸变的生物学标记，这些标记可能预示着未来的神经认知缺陷。我们将检查三组婴儿的感觉和高阶听觉认知加工：50名母亲吸烟（PNE）的婴儿，50名母亲不吸烟与吸烟者生活（ETS）的婴儿，以及50名无烟家庭（CTL）的婴儿。我们将测量母体头发、尿液、过期空气和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评估与年龄相适应的发展，重点关注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的大脑有害影响的神经表型，以便为这一重要的高危人群提供早期干预措施。我们计划使用获得的发现来支持更详细的纵向研究的申请。

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.