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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

基本信息

批准号：
10436297
负责人：
Wei Gao
金额：
$ 67.29万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/10436297
关键词：
Alcohols Amygdaloid structure Animals Anterior Area Arousal Attention Attention deficit hyperactivity disorder Behavior Behavioral Biological Biological Markers Birth Brain Brain Stem Buprenorphine Calcarine Sulcus Characteristics Child Childhood Cocaine Cognition Cognitive Data Development Dorsal Drug Exposure Emotional Emotions Environment Environmental Risk Factor Exposure to Face Female Fetal alcohol effects Gender Glean Growth Health Human Impairment Impulsivity Infant Infant Development Informal Social Control Insula of Reil Knowledge Language Lateral Life Light Link Longitudinal Studies Magnetic Resonance Imaging Marijuana Medial Mediating Methadone Mission Mothers Motor National Institute of Drug Abuse Neonatal Neonatal Abstinence Syndrome Nicotine Opiate Addiction Opioid Opioid agonist Outcome Perinatal Pharmaceutical Preparations Physiological Postpartum Period Prefrontal Cortex Pregnancy Pregnant Women Public Health Reporting Research Rest Rewards Risk Second Pregnancy Trimester Structure System Temperament Testing Thalamic structure Time Ventral Tegmental Area Visual Visual Cortex Visual attention Vulnerable Populations Woman Work base brain behavior brain dysfunction cingulate cortex cognitive ability critical period drug of abuse emotion regulation executive function experience fetal fetal drug exposure fetal opioid exposure illicit opioid imaging modality in utero indexing infancy innovation intraparietal sulcus joint attention machine learning method male medication-assisted treatment motor control neonate neurobehavior neurobehavioral neuroimaging novel offspring opioid epidemic opioid exposure opioid use opioid use in pregnancy postnatal prenatal prenatal exposure prescription opioid relating to nervous system resilience response sex social standard of care visual control visual motor white matter

项目摘要

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.

抽象的在过去十年中，怀孕期间阿片类药物的使用急剧增加，并可能对健康造成重大影响使用非法和/或处方药物的母亲所生的暴露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、注意力和神经行为受损的关系不一致。婴儿期和儿童期的认知，表明持续的、可能终生的后果。这个胎儿暴露发生在大脑异常生长和组织的时期，使其成为一个关键时期容易受到环境侵害。然而，人们对 OE 对早期人类大脑的影响知之甚少。可能导致所报告赤字的发展。该提案的目标是量化影响 OE 对出生后 1-12 个月婴儿大脑功能连接发展的影响，以确定与神经行为和认知结果的关联，并检查性别、其他产前药物如何影响暴露和产后环境因素会减轻这些影响。我们的中心假设是胎儿 OE 会改变大脑的发育和组织；发展联系和网络方面的缺陷调节 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，影响快速发育的生长轨迹促进新兴能力的联系和网络。这个假设是基于研究小组的对产前阿片类药物和其他药物暴露的母婴二人组有丰富的研究经验（Jones，Grewen），以及显示功能网络规范发展的强有力的初步数据出生至 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直接和交互影响初始神经损伤、婴儿性别和产后环境对发展功能连接的影响。这假设将通过 3 个具体目标进行检验： 1) 量化 OE 损害发育的程度 2周时和12个月时再次进行功能连接； 2) 确定 OE 的影响程度在神经行为方面，注意力、自我调节和认知与功能的发展轨迹有关连接； 3) 确定婴儿性别、其他产前药物暴露和累积环境风险指数调节 OE 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。拟议的这项研究意义重大，因为自 2000 年以来，产前 OE 和 NAS 的发生率增加了 5 倍，同时阿片类药物流行病，并且因为收集到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不断增长的功能网络。