Effects of Placental Transfusion on Early Brain Development

描述（由申请人提供）：目前在美国出生时的产科实践是立即夹住婴儿的脐带。当立即夹紧时，20%至40%的胎胎盘血容量留在胎盘中。这种血液含有足够的富含铁的红细胞，以满足婴儿生命最初4到6个月的铁需求。延迟脐带夹紧已被证明可以增加早期铁储存而不会导致不良后果。早期铁的充足对长期的神经系统健康至关重要。婴儿期缺铁会对认知、运动、社会情感和行为发育产生不利影响。人类和动物研究表明，婴儿早期铁储备不足会对发育中的大脑产生不可逆转的负面影响，即使通过补充铁恢复了铁水平，这种缺陷仍会持续存在。铁是髓鞘形成的重要组成部分，髓鞘形成对大脑的正常发育和功能至关重要。髓鞘形成在生命的第一年达到顶峰，它在大脑的离散区域之间建立并保持有效的沟通。异常髓鞘形成是多种儿童发育障碍的基础，包括自闭症等疾病。目前尚不清楚延迟脐带夹紧导致的铁储存增加对儿童早期髓鞘形成和神经发育的影响。我们的假设是胎盘输血通过以下方式影响髓鞘形成和儿童早期发育：1)胎盘输血导致出生时血容量（BV）和红细胞容量（RCV）增加；2)增加的RCV导致更多的铁可用于早期体内铁储存；3)体内铁储量的增加为髓鞘形成提供必需的铁供应；4)最佳髓鞘生成结果：改善了发育和认知能力。我们建议对128名婴儿进行随机对照纵向（出生至24个月）试验，以测量胎盘输血对发育中的大脑结构和功能的影响。我们将使用非侵入性神经成像技术来测量髓磷脂随时间的获取，并将研究结果与铁储存和发育结果联系起来。入选的妇女将在出生时随机分为立即脐带夹紧组或延迟脐带夹紧组。我们将在4个月和10个月时评估婴儿的铁充足性和髓磷脂沉积，并评估4、10和24个月时的发育结果。本研究将有助于建立一个科学的脐带夹紧时机，参考大脑发育。这项研究的创新之处在于延迟脐带夹紧的简单性，并结合使用一种新的MRI方法，可以量化髓磷脂沉积。在临床实践中，这种低技术含量的改变有可能减少缺铁

DESCRIPTION (provided by applicant): The current obstetrical practice at birth in the United States is that the umbilical cord of the infant is clamped immediately. When immediate clamping occurs, 20 to 40% of the fetal-placental blood volume is left behind in the placenta. This blood contains enough iron-rich red blood cells to meet the infant's iron needs for the first 4 to 6 months of life. Delaying cord clamping has been shown to increase early iron stores without contributing to adverse outcomes. Early iron sufficiency is essential for long term neurologic health. Iron deficiency in infancy adversely affects cognitive, motor, socio-emotional, and behavioral development. Human and animal studies have shown that inadequate iron stores in early infancy have an irreversible negative impact on the developing brain with deficits persisting even after iron levels have been restored by iron supplementation. Iron is an essential component of myelination which is critical for normal brain development and function. Myelination, which peaks during the first year of life, establishes and maintains efficient communication between the discrete regions of the brain. Abnormal myelination underlies a variety of childhood developmental disorders including conditions such as autism. The gap is that the effect of increased iron stores from delayed cord clamping on myelination and neurodevelopment during early childhood is unknown. Our hypothesis is that placental transfusion affects myelination and early childhood development in the following ways: 1) placental transfusions lead to increased blood volume (BV) and red cell volume (RCV) at birth; 2) increased RCV results in more available iron for early body iron stores; 3) increased body iron stores provide essential iron supply for optimal myelination; 4) optimal myelination results i improved developmental and cognitive performance. We propose a randomized controlled longitudinal (birth to 24 months) trial of 128 infants to measure the effect of placental transfusin on the structure and function of the developing brain. We will use a non-invasive neuroimaging technique to measure myelin acquisition over time and to correlate the findings with iron stores and developmental outcomes. Enrolled women will be randomized at birth to the immediate cord clamping group or the delayed cord clamping group. We will assess infants for iron sufficiency and myelin deposition at 4 and 10 months and evaluate developmental outcomes at 4, 10, and 24 months. This study will help to establish a scientific basis for the timing of cord clamping with reference to brain development. The innovation of this study is in the simplicity of delaying cord clamping combined with the use of a new method of MRI that can quantify myelin deposition. This low-tech change in a clinical practice has the potential to reduce iron deficiency and improve developmental outcomes. If delayed cord clamping demonstrates protective effects for optimal development, changing practice will translate into a large cost savings improving lifetime productivity beneficial to society as a whole.