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

童年的不幸（例如，虐待、忽视或家庭功能障碍）是一种常见的经历， 导致死亡的主要原因，并增加了美国的经济健康负担。童年逆境 导致神经，内分泌和免疫系统的长期改变，直到成年，包括 抑制神经肽催产素（OXT）。一个健康的OXT系统有助于响应社会参与 并促进母婴（M-I）同步（相互凝视，情感语言和触摸）。最优M-I 同步促进早期大脑发育，防止低同情心，破坏性行为，不良的社会适应， 认知缺陷和儿童精神病理学。我们认为，童年不幸的母亲 M-I同步更困难，部分原因是OXT系统受到抑制，并将受益于干预 通过OXT系统的表观遗传调节来改善反应性、培育性和参与性。大多数干预措施 是昂贵的、复杂的和耗时的。我们的目标是填补这一空白，通过测试是否一个简单的早期行为 干预（ATVV）将改善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，包括婴儿- 有针对性的讲话，适度的触摸按摩，眼睛对眼睛的凝视，和水平摇摆。我们将已知的 早产儿至足月儿ATVV的成功。我们将在出生后3个月比较M-I同步性 在250名首次分娩的母亲（及其足月婴儿）中，从出生到3个月（n = 10）， 125)或在注意力控制组中接受婴儿护理教育（n = 125）。我们采取了严格的措施， 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。 编码只需要3分钟的互动，当婴儿从3个月开始就能可靠地互动时，编码是有效的。 年龄。我们还将评估ATVV对母体和婴儿外周OXT水平的影响，OXT水平是一种已知的 M-I同步。OXT水平与M-I同步的质量有关，但我们扩展了这一知识，以确定 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， 妊娠晚期和产后1、2和3时OXTR基因表达、OXTR蛋白和催产素肽 个月（沿着婴儿唾液OXT）。总之，目的是1）确定每日ATVV的效果， 与注意力控制组比较，从出生到出生后3个月进行M-I的行为和生理测量 母亲与儿童逆境的同步性，以及2）首次确定了儿童逆境中的分子机制。 母体血浆中M-I同步的基础OXT系统。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之间的关系。 催产素测量。聚类方法将用于发现分子谱。早期行为 干预，成功地促进M-I同步在脆弱的妇女通过表观遗传调节的 然后，OXT系统可以在多中心临床实施试验中与其他高危人群一起进行测试。

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.