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

童年的逆境(例如，虐待、忽视或家庭功能障碍)是一种非常常见的经历 导致死亡的主要原因和增加美国经济健康负担的因素。童年逆境 导致神经、内分泌和免疫系统在成年后的长期变化，包括 抑制神经肽催产素(OXT)。健康的OXT系统促进了响应的社会参与 并促进母婴(M-I)同步(相互凝视、影响言语和触摸)。最优M-I 同步性促进了大脑的早期发育，防止了同理心不足、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，有童年逆境的母亲会有 M-I同步的更多困难，部分原因是OXT系统受阻，并将受益于干预 通过对OXT系统的表观遗传调控来改善反应、培育和参与。大多数干预措施 都是昂贵、复杂和耗时的。我们的目标是通过测试简单的早期行为是否能填补这一空白 干预(ATVV)将改善有童年逆境的母亲的OXT系统功能和M-I同步性。 ATVV(听觉、触觉、视觉、前庭)是一种15分钟的行为干预，由婴儿- 定向演讲，适度触摸按摩，眼神对视，水平摇摆。我们扩展了已知的 早产儿至足月儿ATVV成功。我们将比较出生后3个月的M-I同步性 在250名首次怀孕的母亲(及其足月婴儿)中，随机从出生到3个月每天应用ATVV(n= 或在注意对照组(n=125)中接受婴儿护理教育。我们采取了严格的措施 M-I同步微代码视频记录的M-I行为，量化共享的凝视、情感、言语和触摸。 编码只需要3分钟的交互，当婴儿从3个月开始可以可靠地交互时，编码是有效的 年纪大了。我们还将评估ATVV对母婴外周血OXT水平的影响，这是一种已知的 我-我同步。OXT水平与M-I同步的质量有关，但我们将这一知识扩展到识别 催产素受体基因的表观遗传学作用。我们将分析母体血浆中的OXTR甲基化， 妊娠晚期、出生后1、2、3天OXTR基因表达、OXTR蛋白和催产素多肽 几个月(连同婴儿唾液牛)。总而言之，目的是1)确定每日ATVV的效果，比较 注意对照组从出生到出生后3个月对M-I的行为和生理测量 母亲与童年逆境的同步性，以及2)首次确定了儿童逆境中的分子机制 母体血浆中潜在M-I同步性的OXT系统。基于回归的方法(包括协变量) 将评估ATVV对M-I同步性和OXT度量的影响，并确定M-I同步性和OXT度量之间的关系 催产素测量。聚类法将被用于发现分子图谱。早期行为 通过表观遗传调控成功促进脆弱女性M-I同步性的干预 然后，OXT系统可以在与其他高风险组进行的多点临床实施试验中进行测试。

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.