A Randomized Controlled Trial to Improve Mother-Infant Synchrony Among Women with Childhood Adversity

一项改善童年逆境妇女母婴同步性的随机对照试验

基本信息

批准号：
10368157
负责人：
ALEECA F BELL
金额：
$ 56.97万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-30 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10368157
关键词：
Adult Adverse event Affect Age-Months Auditory Behavior Behavior Therapy Behavioral Biological Markers Birth Blood Brain Cause of Death Child Code Cognitive deficits Complex Consumption Control Groups Cost Savings Cues DNA Methylation Development Disease Distress Education Empathy Endocrine system Epigenetic Process Exhibits Eye Frequencies Functional disorder Gene Expression Gene Proteins Health Home Hormones Household Human Immune system Infant Infant Behavior Infant Care Infant Development Intervention Knowledge Late pregnancy Learning Life Link Liquid substance Massage Maternal Behavior Measures Messenger RNA Methods Methylation Modeling Molecular Molecular Profiling Mothers Nervous system structure Neuropeptides Outcome Oxytocin Oxytocin Receptor Pathway interactions Pattern Peptides Peripheral Physiological Pilot Projects Plasma Population Premature Infant Process Psychopathology Public Health Randomized Randomized Controlled Trials Receptor Gene Research Design Risk Risk Factors Rodent Role Saliva Science Site Social Adjustment Social Behavior Speech System Tactile Testing Time Touch sensation Treatment Efficacy Visual Woman Work abuse neglect alertness attentional control base behavior measurement biological systems childhood adversity clinical research site clinical trial implementation economic cost efficacy evaluation efficacy testing epigenetic regulation experience gaze group intervention health disparity health economics high risk population improved infant outcome innovation intervention cost intervention effect maternal outcome member multisensory postnatal prevent psychosocial receptor relating to nervous system social social engagement socioeconomics stress reactivity success translational potential visual-vestibular

项目摘要

Childhood adversity (e.g., abuse, neglect, or household dysfunction), is a common experience significantly contributing to the leading causes of death and increased US economic health burdens. Childhood adversity causes long-term alterations on the nervous, endocrine, and immune systems well into adulthood, including dampening of the neuropeptide oxytocin (OXT). A healthy OXT system facilitates responsive social engagement and promotes maternal-infant (M-I) synchrony (reciprocal gaze, affect speech, and touch). Optimal M-I synchrony fuels early brain development and prevents low empathy, disruptive behavior, poor social adaptation, cognitive deficits, and psychopathology in children. We posit that mothers with childhood adversity will have more difficulty with M-I synchrony, due in part to a dampened OXT system, and will benefit from interventions that improve responsive, nurturing, engagement by epigenetic regulation of the OXT system. Most interventions are costly, complex, and time-consuming. We aim to fill this gap by testing whether a simple early behavioral intervention (ATVV) will improve OXT system function and M-I synchrony in mothers with childhood adversity. The ATVV (Auditory, Tactile, Visual, Vestibular) is a 15-minute behavioral intervention consisting of infant- directed speech, moderate touch massage, eye to eye gaze, and horizontal rocking. We extend the known success of ATVV with preterm infants to full-term infants. We will compare M-I synchrony at 3 postnatal months in 250 first-time mothers (and their full-term infants) randomized to apply ATVV daily from birth to 3 months (n = 125) or receive infant care education in an attention control group (n = 125). We apply a rigorous measure of M-I synchrony that micro-codes video-recorded M-I behavior quantifying shared gaze, affect, speech, and touch. Coding requires only 3-minutes of interaction and is valid when infants can reliably interact starting by 3 months of age. We will also assess ATVV's effect on maternal and infant peripheral OXT level, a known biomarker of M-I synchrony. OXT levels relate to quality of M-I synchrony, yet we extend this knowledge to identify an epigenetic role of the oxytocin receptor gene (OXTR). We will analyze maternal plasma for OXTR methylation, OXTR gene expression, OXTR protein, and oxytocin peptide in late pregnancy, and at 1, 2, and 3 postnatal months (along with infant saliva OXT). In summary, aims are to 1) determine effects of daily ATVV, compared with an attention control group, from birth to 3 postnatal months on behavioral and physiologic measures of M-I synchrony in mothers with childhood adversity, and 2) for the first time identify molecular mechanisms in the OXT system underlying M-I synchrony in maternal plasma. Regression based methods (including covariates) will assess ATVV effects on M-I synchrony and OXT measures, and identify relations among M-I synchrony and oxytocin measures. Clustering methods will be used to discover molecular profiles. An early behavioral intervention that successfully promotes M-I synchrony in vulnerable women through epigenetic regulation of the OXT system can then be tested in a multi-site clinical implementation trial with other high-risk groups.

童年时期的逆境（例如虐待、忽视或家庭功能障碍）是一种常见的经历，造成死亡的主要原因并增加了美国的经济健康负担。童年逆境导致成年后神经、内分泌和免疫系统的长期改变，包括抑制神经肽催产素（OXT）。健康的 OXT 系统有助于响应式社交参与促进母婴 (M-I) 同步（相互凝视、情感言语和触摸）。最佳M-I 同步性促进早期大脑发育，防止同理心低下、破坏性行为、社交适应不良、认知缺陷和儿童的精神病理学。我们假设，童年经历过逆境的母亲将会 M-I 同步变得更加困难，部分原因是 OXT 系统受到抑制，并且将从干预中受益通过 OXT 系统的表观遗传调控来提高反应能力、培养能力和参与度。大多数干预措施成本高昂、复杂且耗时。我们的目标是通过测试简单的早期行为是否可以填补这一空白。干预 (ATVV) 将改善童年逆境母亲的 OXT 系统功能和 M-I 同步性。 ATVV（听觉、触觉、视觉、前庭）是一项 15 分钟的行为干预，包括婴儿定向讲话、适度的触摸按摩、目光对视、水平摇摆。我们扩展已知的 ATVV 在早产儿到足月儿中的成功。我们将在产后 3 个月比较 M-I 同步性 250 名首次当妈妈（及其足月婴儿）随机从出生到 3 个月每天应用 ATVV（n = 125）或在注意力对照组中接受婴儿护理教育（n = 125）。我们采取严格的措施 M-I 同步对视频记录的 M-I 行为进行微编码，量化共享的凝视、情感、言语和触摸。编码仅需要 3 分钟的互动，并且当婴儿在 3 个月大时能够可靠地互动时才有效的年龄。我们还将评估 ATVV 对母婴外周 OXT 水平的影响，OXT 是一种已知的生物标志物 M-I 同步。 OXT 水平与 M-I 同步的质量相关，但我们扩展了这一知识来识别催产素受体基因（OXTR）的表观遗传作用。我们将分析母体血浆的 OXTR 甲基化，妊娠晚期以及产后 1、2、3 时的 OXTR 基因表达、OXTR 蛋白和催产素肽个月（连同婴儿唾液 OXT）。总之，目标是 1) 确定每日 ATVV 的效果，并进行比较与注意力对照组一起，从出生到产后 3 个月进行 M-I 的行为和生理测量母亲与童年逆境的同步性，2）首次确定了童年逆境的分子机制 OXT 系统是母体血浆中 M-I 同步的基础。基于回归的方法（包括协变量）将评估 ATVV 对 M-I 同步和 OXT 测量的影响，并确定 M-I 同步和 OXT 测量之间的关系催产素措施。聚类方法将用于发现分子谱。早期的行为通过表观遗传调控成功促进弱势女性 M-I 同步的干预措施然后可以在与其他高危人群的多地点临床实施试验中对 OXT 系统进行测试。