From the womb to the classroom: Linking perinatal micronutrients and toxicants to neural and behavioral development in utero and in childhood

从子宫到教室：将围产期微量营养素和有毒物质与子宫内和儿童期的神经和行为发育联系起来

• 批准号: 10247799
• 负责人: Christine Austin
• 金额: $ 50.55万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-26 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10247799
• 关键词: Address; Affect; Age; Area; Arsenic; Attention; Attention deficit hyperactivity disorder; Behavioral; Belief; Biological; Biological Assay; Biological Markers; Birth; Brain; Buffers; Cadmium; Chemicals; Child; Childhood; Copper; Data; Data Collection; Development; Dorsal; Elements; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Event; Exposure to; Family; Fetus; Functional Magnetic Resonance Imaging; Health; High Prevalence; Human; Knowledge; Lead; Link; Lithium; Magnesium; Magnetic Resonance Imaging; Manganese; Measurement; Measures; Methodology; Micronutrients; Modeling; Mothers; Nutrient; Nutritional; Nutritional status; Outcome; Parent-Child Relations; Parents; Participant; Pathway interactions; Performance; Perinatal; Personal Satisfaction; Pregnancy; Problem behavior; Property; Readiness; Research; Rest; Risk; Schools; Second Pregnancy Trimester; Signal Transduction; Statistical Models; Sum; System; Techniques; Technology; Testing; Third Pregnancy Trimester; Time; Tin; Tooth structure; Toxicant exposure; Uterus; Variant; Weight; Work; Zinc; base; cognitive control; cohort; connectome; deciduous tooth; early childhood; executive function; externalizing behavior; fetal; follow-up; human fetal brain; in utero; indexing; innovation; insight; interest; micronutrient deficiency; neural circuit; neural network; neurobehavioral; neurobehavioral disorder; neurodevelopment; neuroimaging; novel; offspring; postnatal; prenatal; prenatal exposure; preventive intervention; protective factors; psychologic; psychosocial; public health relevance; relating to nervous system; sex; toxicant

PROJECT SUMMARY Maternal toxicant exposure and nutritional status during pregnancy contribute to the emergence of attention deficit hyperactivity disorder (ADHD) and serious externalizing behavioral problems. A prevailing belief is that toxicants and fetal micronutrient deficiencies disrupt fetal brain development, with subsequent long-term implications for offspring health and development. However, evidence that prenatal toxicant exposure and micronutrient imbalances influence fetal neural systems in humans is lacking, as is evidence that changes in the fetal brain precede nutrient- and toxicant-related developmental concerns of childhood. Filling these gaps in knowledge is critical, given the high prevalence of prenatal toxicant exposure worldwide and evidence that events during gestation influence long-range health and well-being. The central objective of this proposal is to examine development of human neural networks in utero, and to link variation in prenatal brain development to prenatal toxicant and nutrient levels (measured in the fetus) and to child outcomes. This will be done in a way that is sensitive both to chemical mixture effects and to time-variant exposure across the course of gestation, which are both likely to have specific neurodevelopmental consequences. We will pair advances in fetal resting-state functional connectivity (RSFC) MRI with innovations in tooth-biomarker assays to rigorously investigate associations between prenatal chemical/micronutrient exposures and human fetal neural connectome development, and will determine how exposome and connectome development in utero relate to child neurobehavioral development. Data collection in a Detroit-based pregnancy cohort was initiated more than 7 years ago, beginning with fetal brain RSFC MRI. Children have been followed over time, with assessments at birth, 7 months, age 3 and age 5, and have begun to naturally shed their deciduous teeth. The primary aims of this project are to (i) identify fetal brain connectome abnormalities associated with prenatal toxicant exposure and micronutrient imbalance, and identify key windows of gestational vulnerability; (ii) evaluate prenatal exposures and fetal neural connectivity as longitudinal predictors of executive function, externalizing problems and school readiness at age 5; and (iii) isolate protective factors in the postnatal environment that promote resilient outcomes in children with prenatal micronutrient deficiency and toxicant exposure. We will thus be able to meaningfully evaluate whether and how prenatal nutrient availability and toxic exposure events affect functional neurocircuitry of the developing fetal brain, and the longer-term neurobehavioral consequences of those associations. Such work would constitute a substantial advance in our understanding of both the longitudinal effects of micronutrient and toxicant exposures in the prenatal period and the origins of child neurobehavioral disorders.

项目概要 孕期母亲有毒物暴露和营养状况引起关注 缺陷多动障碍（ADHD）和严重的外化行为问题。一个普遍的信念是 有毒物质和胎儿微量营养素缺乏会扰乱胎儿大脑发育，从而导致长期 对后代健康和发展的影响。然而，有证据表明产前有毒物暴露和 微量营养素失衡对人类胎儿神经系统的影响尚缺乏，也缺乏证据表明微量营养素失衡的变化 胎儿大脑的发育先于儿童时期与营养和毒物相关的发育问题。填补这些空白 鉴于全世界产前有毒物暴露的发生率很高，而且有证据表明，了解这一知识至关重要 妊娠期间的事件会影响长期的健康和福祉。该提案的中心目标是 检查子宫内人类神经网络的发育，并将产前大脑发育的变化与 产前有毒物和营养物水平（在胎儿中测量）以及对儿童结局的影响。这将以某种方式完成 对化学混合物效应和妊娠过程中随时间变化的暴露都很敏感， 这两者都可能产生特定的神经发育后果。我们将配对胎儿的进步 静息态功能连接 (RSFC) MRI 与牙齿生物标志物检测方面的创新，可严格检测 研究产前化学品/微量营养素暴露与人类胎儿神经之间的关联 连接组发育，并将确定子宫内暴露组和连接组发育如何与 儿童神经行为发育。开始在底特律的妊娠队列中收集数据 7年前，开始进行胎儿脑部RSFC MRI检查。随着时间的推移，儿童受到跟踪， 在出生、7个月、3岁和5岁时进行评估，并开始自然脱落乳牙。这 该项目的主要目标是 (i) 识别与产前相关的胎儿脑连接组异常 有毒物暴露和微量营养素失衡，并确定妊娠脆弱性的关键窗口； (二) 评估产前暴露和胎儿神经连接作为执行功能的纵向预测因子， 5岁时外化问题和入学准备； (iii) 隔离产后的保护因素 促进产前微量营养素缺乏和有毒物质儿童恢复健康的环境 接触。因此，我们将能够有意义地评估产前营养素的可用性是否以及如何 有毒物质暴露事件会影响发育中胎儿大脑的功能神经回路，以及长期影响 这些关联的神经行为后果。此类工作将构成我们的重大进步 了解产前微量营养素和有毒物质暴露的纵向影响 以及儿童神经行为障碍的起源。