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: 10405539
• 负责人: Christine Austin
• 金额: $ 50.77万
• 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/10405539
• 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.

项目摘要 怀孕期间母亲的毒物暴露和营养状况有助于引起人们的注意 赤字多动障碍（ADHD）和严重的外在行为问题。一个普遍的信念是 有毒物质和胎儿微量营养素缺陷破坏了胎儿脑发育，随后长期长期 对后代健康和发展的影响。但是，有证据表明产前毒物的暴露和 缺乏微量营养素的失衡会影响人类的胎儿神经系统，这证明了变化的变化 胎儿大脑先于童年的营养和毒物相关的发育问题。填补这些空白 鉴于全球产前毒物的暴露率很高，在知识中至关重要，并且证明了证据表明 妊娠期间的事件会影响长期健康和福祉。该提议的核心目的是 检查子宫内人类神经网络的发展，并将产前大脑发育的变化联系起来 产前毒物和养分水平（以胎儿为例）和儿童结局。这将以某种方式完成 这对化学混合物效应和妊娠过程中的时间变化都很敏感， 它们都可能具有特定的神经发育后果。我们将配对胎儿的进步 静止状态功能连通性（RSFC）MRI，具有牙齿折痕测定中的创新 研究产前化学/微量营养素暴露与人类胎儿神经之间的关联 连接组的开发，并将确定子宫内的杂物体和连接组的发展与 儿童神经行为发展。在基于底特律的怀孕队列中收集数据更多 比7年前，从胎儿脑RSFC MRI开始。随着时间的流逝，孩子们随着时间的流逝 出生时，7个月，3岁和5岁时的评估，并且已经开始自然脱落凹凸不平的牙齿。这 该项目的主要目的是（i）确定与产前相关的胎儿脑连接异常 有毒的暴露和微量营养素失衡，并确定妊娠脆弱性的关键窗口； （ii） 评估产前暴露和胎儿神经连通性，作为执行功能的纵向预测指标， 5岁时将问题和学校准备就绪； （iii）产后分离的保护因子 促进产前微量营养素缺乏和有毒物质儿童中有弹性结果的环境 接触。因此，我们将能够有意义地评估产前营养的可用性以及如何 有毒暴露事件会影响发育中胎儿大脑的功能性神经记录，并长期 这些关联的神经行为后果。这种工作将在我们的 了解在产前时期微量营养素和毒性暴露的纵向作用 以及儿童神经行为疾病的起源。