Effects of Prenatal Opiates on Infant Brain and Neurobehavioral Development

产前阿片类药物对婴儿大脑和神经行为发育的影响

• 批准号: 10619361
• 负责人: Wei Gao
• 金额: $ 8.4万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10619361
• 关键词: Attention; Behavioral; Biological; Birth; Brain; Childhood; Cognition; Cognitive; Complement; Data; Development; Drug Exposure; Environment; Environmental Risk Factor; Exposure to; Gender; Glean; Goals; Graduate Degree; Grant; Growth; Health; Human; Impairment; Infant; Infant Development; Informal Social Control; Knowledge; Life; Longitudinal Studies; Measures; Mediating; Mothers; Neonatal; Opioid; Outcome; Pharmaceutical Preparations; Postpartum Period; Pregnancy; Public Health; Reporting; Research; Risk; Testing; Time; Woman; Work; base; cognitive ability; critical period; experience; fetal; fetal drug exposure; fetal opioid exposure; illicit opioid; indexing; infancy; infant outcome; innovation; machine learning method; maternal outcome; neurobehavior; neurobehavioral; novel; opioid epidemic; opioid exposure; opioid use; opioid use in pregnancy; parent grant; postnatal; prenatal; prenatal exposure; prescription opioid; relating to nervous system; response; training opportunity

ABSTRACT Opioid use during pregnancy has increased dramatically in the past decade, and may pose significant health challenges for the rapidly growing number of exposed infants born to mothers using illicit and/or prescribed opioids. Prenatal opioid exposure (OE) is inconsistently related to impaired neurobehavior, attention, and cognition in infancy and childhood, suggesting persistent, potentially life-long, consequences. This fetal exposure occurs during a time of extraordinary brain growth and organization, making it a critical period of vulnerability to environmental insult. However, little is known about the effects of OE on early human brain development that may contribute to reported deficits. The objectives of this proposal are to quantify the effects of OE on the development of infant brain functional connectivity in postnatal months 1-12, to determine associations with neurobehavioral and cognitive outcomes, and to examine how gender, other prenatal drug exposures, and postnatal environmental factors moderate these effects. Our central hypothesis is that fetal brain development and organization are altered by OE; deficits in developing connections and networks mediate the negative effects of OE on simultaneously developing neurobehavior and early cognition; gender, other drugs and postnatal environment interact with OE to influence growth trajectories of rapidly developing connections and networks that subserve emerging abilities. This hypothesis is based on the study team’s substantial research experience with mother-infant dyads with prenatal opioid and other drug exposures (Jones, Grewen), and on strong preliminary data showing normative development of functional networks from birth to 2 years (Gao), disruptions in neonatal functional connectivity due to prenatal opioids and other drugs (Grewen, Gao), and on associations between functional connections and behavioral effects (Grewen, Gao). The rationale for the proposed research is that longitudinal study will quantify direct and interactive effects of initial neural insult, infant gender and postnatal environment on developing functional connections. The hypotheses will be tested with 3 Specific Aims: 1) Quantify the extent to which OE impairs developing functional connections at 2 weeks and again at 12 months; 2) Determine the extent to which the effects of OE on neurobehavior, attention, self-regulation and cognition are related to developmental trajectories of functional connections; 3) Determine how infant gender, other prenatal drug exposures, and a Cumulative Environmental Risk Index moderate the effects of OE on developing connectivity. This approach is innovative because it will employ hypothesis-driven analyses as well as novel, exploratory data-driven and machine learning methods to quantify direct and interactive effects of OE and other drug exposures on functional circuitry. The proposed research is significant because rates of prenatal OE and NAS have increased 5-fold since 2000, in parallel with the opioid epidemic, and because knowledge gleaned has potential to identify factors that may protect or further harm growing functional networks underlying nascent cognitive abilities in this at-risk group.

摘要 在过去的十年中，怀孕期间使用阿片类药物的人数急剧增加， 使用非法和（或）处方药物的母亲所生婴儿数量迅速增加所面临的挑战 阿片类药物产前阿片类药物暴露（OE）与神经行为、注意力和 婴儿期和儿童期的认知，这表明持续的，可能终身的后果。这个胎儿 暴露发生在非凡的大脑生长和组织的时间，使其成为一个关键时期， 易受环境伤害。然而，关于OE对早期人类大脑的影响知之甚少 可能导致报告赤字的发展。本提案的目的是量化影响 OE对出生后1-12个月婴儿大脑功能连接发育的影响，以确定 与神经行为和认知结果的关系，并检查性别，其他产前药物 暴露和产后环境因素缓和了这些影响。我们的核心假设是胎儿 大脑发育和组织被OE改变;发展连接和网络的缺陷 介导OE对同时发育的神经行为和早期认知的负面影响;性别， 其他药物和产后环境与OE相互作用，影响快速发育的 连接和网络有助于新兴能力。这一假设是基于研究小组的 产前暴露于阿片类药物和其他药物的母婴配对的大量研究经验 （Jones，Grewen），并根据强有力的初步数据显示， 出生至2岁（Gao），产前阿片类药物和其他药物导致新生儿功能连接中断 （Grewen，Gao），以及功能连接和行为效应之间的关联（Grewen，Gao）。 拟议研究的基本原理是，纵向研究将量化的直接和相互作用的影响， 初始神经损伤、婴儿性别和出生后环境对发育功能连接的影响。的 将通过3个具体目标对假设进行检验：1）量化运行经验损害发展的程度 2周时和12个月时的功能连接; 2）确定OE的影响程度 在神经行为、注意、自我调节和认知方面， 3）确定婴儿性别、其他产前药物暴露和累积环境因素 风险指数缓和运行经验对发展连通性的影响。这种方法是创新的，因为它将 采用假设驱动的分析以及新颖的探索性数据驱动和机器学习方法， 量化OE和其他药物暴露对功能电路的直接和交互影响。拟议 研究是重要的，因为产前OE和NAS的发生率自2000年以来增加了5倍，与此同时， 阿片类药物流行病，因为收集的知识有可能确定可能保护或 进一步损害这一高危人群中新生认知能力的功能网络。