Neuroendocrine Mechanisms of Developmental Massage Therapy in Preterm Infants

描述（由申请人提供）：本研究的目的是确定发育性按摩治疗（DMT）对早产儿（<37周妊娠）的神经内分泌机制。早产儿因疾病和/或日常护理而感到压力。压力的直接负面影响包括循环皮质醇、心跳和呼吸频率增加以及低氧血症，长期影响包括出生后生长不良、免疫系统抑制和学习能力受损。因此，生理稳定性对早产儿的健康至关重要。生理稳定性依赖于自主神经系统（ANS）的交感神经（SNS）和副交感神经（PNS）分支以及内分泌系统的下丘脑-垂体-肾上腺（HPA）轴。PNS发生在妊娠后期（~37 ~ 38周），年龄较小的婴儿（<36周）往往有一个压倒性的SNS，导致生理不稳定和持续的应激反应。“触摸”或按摩疗法与早产儿皮质醇水平降低和体重增加有关。需要设计良好的随机对照临床试验来评估按摩治疗早产儿的生理和神经内分泌机制：1)进一步了解出生后的生长发育，2)最终促进按摩治疗与传统医疗保健的结合。我们计划研究ANS和HPA轴在早产儿中的相互关系，以评估发育按摩疗法（DMT）如何调节生理稳定性和促进出生后生长。该建议的中心假设是，DMT与皮质醇产生减少、PNS张力和胰岛素样生长因子1 （IGF-1）表达增加的状态有关，从而改善早产儿的出生后生长。在验证这一假设的过程中，我们希望确定发育性按摩治疗改善PNS张力和IGF-1表达的机制。我们的假设将通过以下具体目标进行检验：#1)我们将确定在DMT之前，期间和之后通过心率变异性测量的ANS平衡；#2)我们将比较DM前后ANS平衡与HPA反应的关系；3)我们将评估接受DMT的早产儿的生长发育（生长激素和IGF-1）轴反应。本研究的目的是确定发育性按摩治疗（DMT）在早产儿（<37周妊娠）中的神经内分泌机制。公共卫生相关性：早产儿因疾病和/或常规护理而经历压力。压力的直接负面影响包括循环皮质醇、心跳和呼吸频率增加以及低氧血症，长期影响包括出生后生长不良、免疫系统抑制和学习能力受损。因此，生理稳定性对早产儿的健康至关重要。生理稳定性依赖于自主神经系统（ANS）的交感神经（SNS）和副交感神经（PNS）分支以及内分泌系统的下丘脑-垂体-肾上腺（HPA）轴。PNS发生在妊娠后期（~37 ~ 38周），年龄较小的婴儿（<36周）往往有一个压倒性的SNS，导致生理不稳定和持续的应激反应。按摩疗法与降低皮质醇水平和改善早产儿体重增加有关。需要设计良好的随机对照临床试验来评估按摩治疗早产儿的生理和神经内分泌机制：1)进一步了解出生后的生长发育，2)最终促进按摩治疗与传统医疗保健的结合。我们计划研究ANS和HPA轴在早产儿中的相互关系，以评估发育按摩疗法（DMT）如何调节生理稳定性和促进出生后生长。该建议的中心假设是，DMT与皮质醇产生减少、PNS张力和胰岛素样生长因子1 （IGF-1）表达增加的状态有关，从而改善早产儿的出生后生长。在验证这一假设的过程中，我们希望确定发育按摩疗法改善PNS张力、IGF-1活性和出生后生长的机制。我们的假设将通过以下具体目标进行检验：#1)我们将确定在DMT之前，期间和之后通过心率变异性测量的ANS平衡；#2)我们将比较DM前后ANS平衡与HPA反应的关系；3)我们将评估接受DMT的早产儿的生长发育（生长激素和IGF-1）轴反应。这些类型的临床试验将指导按摩治疗神经内分泌机制的基础研究，并导致：1)增强生理稳定性和产后生长的策略；2)早产儿ANS/HPA成熟及其失调的新机制见解。

DESCRIPTION (provided by applicant): The purpose of this study is to identify neuroendocrine mechanisms of developmental massage therapy (DMT) in preterm infants (<37 weeks gestation). Preterm infants experience stress due to illness and/or routine care. Immediate adverse effects of stress include increases in circulating cortisol, heart and respiratory rates, and hypoxemia and long-term effects include poor postnatal growth, suppression of the immune system, and impaired learning. Thus, the physiological stability is crucial to the preterm infant's well-being. Physiologic stability is dependent upon the sympathetic (SNS) and parasympathetic (PNS) branches of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis of the endocrine system. PNS develops later in gestation (~37-38 weeks) and younger infants (<36 weeks) tend to have an overriding SNS which leads to physiological instability and a sustained stress response. `Touch' or massage therapy is associated with decreased cortisol levels and improved weight gain in premature infants. Well-designed, randomized controlled clinical trials to evaluate the physiological and neuroendocrine mechanisms of massage therapy in premature infants are needed to: 1) further our understanding of postnatal growth and development and 2) ultimately promote the integration of a massage therapy with conventional medical care. We plan to study the interrelationship of the ANS and HPA axis in premature infants to assess how developmental massage therapy (DMT) modulates physiologic stability and promote postnatal growth. The central hypothesis of this proposal is that DMT is associated with a state of decreased cortisol production and increased PNS tone and insulin-like growth factor 1 (IGF-1) expression leading to improved postnatal growth in premature infants. In the process of testing this hypothesis, we expect to determine the mechanisms by which developmental massage therapy improves PNS tone and IGF-1 expression. Our hypothesis will be tested by the following specific aims: #1) We will determine ANS balance, measured by heart rate variability, before, during, and after DMT; #2) We will compare the relationships between ANS balance and HPA response before and after DM; and #3) We will evaluate somatotrophic (growth hormone and IGF-1) axis response in premature infants who receive DMT. The purpose of this study is to identify neuroendocrine mechanisms of developmental massage therapy (DMT) in preterm infants (<37 weeks gestation). PUBLIC HEALTH RELEVANCE: Preterm infants experience stress due to illness and/or routine care. Immediate adverse effects of stress include increases in circulating cortisol, heart and respiratory rates, and hypoxemia and long-term effects include poor postnatal growth, suppression of the immune system, and impaired learning. Thus, the physiological stability is crucial to the preterm infant's well-being. Physiologic stability is dependent upon the sympathetic (SNS) and parasympathetic (PNS) branches of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis of the endocrine system. PNS develops later in gestation (~37-38 weeks) and younger infants (<36 weeks) tend to have an overriding SNS which leads to physiological instability and a sustained stress response. Massage therapy is associated with decreased cortisol levels and improved weight gain in premature infants. Well-designed, randomized controlled clinical trials to evaluate the physiological and neuroendocrine mechanisms of massage therapy in premature infants are needed to: 1) further our understanding of postnatal growth and development and 2) ultimately promote the integration of a massage therapy with conventional medical care. We plan to study the interrelationship of the ANS and HPA axis in premature infants to assess how developmental massage therapy (DMT) modulates physiologic stability and promote postnatal growth. The central hypothesis of this proposal is that DMT is associated with a state of decreased cortisol production and increased PNS tone and insulin-like growth factor 1 (IGF-1) expression leading to improved postnatal growth in premature infants. In the process of testing this hypothesis, we expect to determine the mechanisms by which developmental massage therapy improves PNS tone, IGF-1 activity, and postnatal growth. Our hypothesis will be tested by the following specific aims: #1) We will determine ANS balance, measured by heart rate variability, before, during, and after DMT; #2) We will compare the relationships between ANS balance and HPA response before and after DM; and #3) We will evaluate somatotrophic (growth hormone and IGF-1) axis response in premature infants who receive DMT. These types of clinical trials will then direct basic research studies of neuroendocrine mechanisms of massage therapy and lead to: 1) strategies to enhance physiologic stability and postnatal growth and 2) new mechanistic insights about ANS/HPA maturation and its dysregulation in premature infants.