ENRICH-2: Stress-Reactivity and Self-Regulation in Infants with Prenatal Alcohol Exposure

ENRICH-2：产前酒精暴露婴儿的应激反应和自我调节

基本信息

批准号：
10480757
负责人：
Ludmila Nicole Bakhireva
金额：
$ 65.2万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480757
关键词：
Address Adrenal Glands Affect Age-Months Alcohols Area Arousal Autonomic nervous system Behavioral Biological Biological Markers Brain Caregivers Child Child Health Classification Clinical Clinical Data Collection Corticotropin-Releasing Hormone Cortisone DSM-V Data Development Diagnostic Disease Early Intervention Electrophysiology (science)Environment Enzymes Ethanol Evaluation Exposure to Face Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fetal alcohol effects Funding Glucocorticoid Receptor Goals Grant Guidelines Health Human Hydrocortisone Hypothalamic structure Impairment Infant Infant Health Informal Social Control Infrastructure Interview Knowledge Life Literature Longevity Measures Mediating Mediator of activation protein NR3C1 gene National Institute on Alcohol Abuse and Alcoholism Nervous System Physiology Neurodevelopmental Disorder Neurosecretory Systems New Mexico Newborn Infant Outcome Paper Peer Review Physiological Pituitary Gland Procedures Prospective cohort Prospective cohort study Public Health Publishing Recovery Regulation Reporting Research Secondary to Services Severities Specimen Stress Techniques Testing Time Umbilical Cord Blood Umbilical cord structure Update behavior measurement clinical care cognitive function cohort convict disability fetal fetal diagnosis fetal programming heart rate variability hypothalamic-pituitary-adrenal axis indexing infancy infant outcome innovation interest negative affect neurodevelopment neuroimaging novel novel strategies overexpression postnatal pre-clinical prenatal stress prospective recruit response stress reactivity stressor

项目摘要

SUMMARY/ABSTRACT The new clinical guidelines for diagnosing Fetal Alcohol Spectrum Disorders (FASD) list self-regulation as one of the key behavioral deficits in children affected by prenatal alcohol exposure (PAE). There is a fundamental gap in knowledge about the underlying mechanisms, spectrum, and severity of such deficits early in life and the best analytical approaches to identify them. In addition, the effect of prenatal stress and postnatal environment on PAE-induced alterations is poorly understood. In this renewal application of the Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH) study, we seek continuous support for our established recruitment/retention pipeline, and propose new highly innovative studies of stress reactivity/regulation in infants with PAE. The long-term goal is to identify indices of atypical brain development following PAE as early as possible to enable early interventions. The objective of this application is to continue our focus on moderate PAE and to evaluate PAE effects on infant stress reactivity/regulation and the mechanisms underpinning altered hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) functioning. We will evaluate the relationship between PAE (exposure of interest), prenatal stress (moderator), biological measures of HPA axis (mediators), and physiological and behavioral measures of stress reactivity/regulation in infants (outcomes). The rationale for this proposal is driven by the conviction that HPA and ANS dysregulation leading to altered stress reactivity/regulation in children with PAE might be the basis for some of the key PAE-induced behavioral deficits, and increased vulnerability to secondary disabilities. The central hypothesis is that PAE will be associated with heightened infant stress reactivity and poorer self-regulation (beyond the effect of prenatal stress) through fetal programming of the HPA axis. This hypothesis has been formulated on the basis of preclinical data at UNM and clinical data from the current funding cycle of ENRICH-1 and will be tested by pursuing three specific aims, which evaluate the contributing effects of PAE on 1) Programming of the fetal HPA axis, assessed as expression of key placental and umbilical cord markers of HPA axis; 2) Infant physiological reactivity (heart rate variability [HRV]) dynamic changes during basal-stressor-recovery periods assessed in the newborn period and at 6-months of age; 3) Infant behavioral reactivity and regulation assessed in the newborn period and at 6-months of age. The comprehensive multi-systemic approach employed in this study is highly innovative and has not previously been used. Innovation is further driven by our focus on moderate PAE and ability to assess the trajectory of impaired stress reactivity/regulation (newborn, 6-months evaluations) in a large prospective cohort study. This research is significant because it involves comprehensive repeated-measures assessment of neuroendocrine, electrophysiological, and behavioral indices of impaired stress reactivity/regulation, which will lead to refinement of analytical techniques for accurate identification of PAE deficits in infancy before higher-order behavioral deficits manifest.

摘要/摘要诊断胎儿酒精谱系障碍 (FASD) 的新临床指南将自我调节列为其中之一受产前酒精暴露（PAE）影响的儿童的主要行为缺陷。有一个基本的对生命早期此类缺陷的根本机制、范围和严重程度的了解存在差距，识别它们的最佳分析方法。此外，产前应激和产后应激的影响环境对 PAE 引起的改变的影响尚不清楚。在乙醇的更新应用中，神经发育、婴儿和儿童健康 (ENRICH) 研究，我们寻求持续支持我们已建立的招募/保留管道，并提出新的高度创新的应激反应/调节研究患有 PAE 的婴儿。长期目标是尽早确定 PAE 后非典型大脑发育的指标尽可能进行早期干预。此应用程序的目的是继续我们对中等程度的关注 PAE 并评估 PAE 对婴儿应激反应/调节的影响及其支撑机制改变下丘脑-垂体-肾上腺（HPA）轴和自主神经系统（ANS）功能。我们将评估 PAE（感兴趣暴露）、产前应激（调节因子）、生物测量之间的关系 HPA 轴（介质）的变化，以及婴儿应激反应/调节的生理和行为测量（结果）。该提案的基本原理是坚信 HPA 和 ANS 失调会导致 PAE 儿童应激反应/调节的改变可能是 PAE 引起的一些关键疾病的基础行为缺陷，并增加继发性残疾的可能性。中心假设是 PAE 将与婴儿应激反应性增强和自我调节能力较差有关（超出产前的影响）压力）通过胎儿的 HPA 轴编程。这一假设是在以下基础上提出的： UNM 的临床前数据和 ENRICH-1 当前资助周期的临床数据，并将由追求三个具体目标，评估 PAE 对 1) 胎儿编程的影响 HPA 轴，根据 HPA 轴关键胎盘和脐带标志物的表达进行评估； 2) 婴儿基础压力源恢复期间的生理反应性（心率变异性 [HRV]）动态变化在新生儿期和 6 个月大时进行评估； 3）婴儿行为反应和调节在新生儿期和 6 个月大时进行评估。综合性多系统方法本研究中采用的方法具有高度创新性，以前从未使用过。创新的进一步驱动力是我们关注适度的 PAE 以及评估应激反应/调节受损轨迹的能力（新生儿，6 个月评估）在一项大型前瞻性队列研究中。这项研究意义重大，因为它涉及神经内分泌、电生理学和神经内分泌的综合重复测量评估应激反应/调节受损的行为指数，这将导致分析技术的完善在高阶行为缺陷出现之前准确识别婴儿期的 PAE 缺陷。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Early developmental trajectory of children with prenatal alcohol and opioid exposure.

产前酒精和阿片类药物暴露儿童的早期发育轨迹。

DOI：
发表时间：
2022-08-10
期刊：
影响因子：
3.6
作者：
Lowe, Jean R;DiDomenico, Jared;Stephen, Julia M;Roberts, Melissa H;Rodriguez, Dominique E;Bakhireva, Ludmila N
通讯作者：
Bakhireva, Ludmila N

Growing potential and remaining uncertainties in assessing prenatal alcohol exposure in dry blood spots.

评估干血斑产前酒精暴露的潜力不断增加，但仍存在不确定性。

DOI：
发表时间：
2020
期刊：
影响因子：
3.6
作者：
Bakhireva; Ludmila N
通讯作者：
Ludmila N

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

产前酒精暴露对围产期结局的剂量反应效应。

DOI：
发表时间：
2024-04
期刊：
影响因子：
0
作者：
Bakhireva, Ludmila N;Ma, Xingya;Wiesel, Alexandria;Wohrer, Fiona E;DiDomenico, Jared;Jacobson, Sandra W;Roberts, Melissa H
通讯作者：
Roberts, Melissa H

Self-regulation and emotional reactivity in infants with prenatal exposure to opioids and alcohol.

产前接触阿片类药物和酒精的婴儿的自我调节和情绪反应。

DOI：
发表时间：
2020-09
期刊：
影响因子：
2.5
作者：
Beauchamp, Kathryn G;Lowe, Jean;Schrader, Ronald M;Shrestha, Shikhar;Aragón, Crystal;Moss, Natalia;Stephen, Julia M;Bakhireva, Ludmila N
通讯作者：
Bakhireva, Ludmila N

Potentially modifiable risk and protective factors affecting mental and emotional wellness in pregnancy.

影响怀孕期间精神和情绪健康的潜在可改变风险和保护因素。