Effects of Placental Transfusion on Early Brain Development

描述（由申请人提供）：美国目前的产科实践是在婴儿出生时立即夹住脐带。当立即夹紧发生时，20%至40%的胎儿-胎盘血容量留在胎盘中。这种血液含有足够的富铁红细胞，以满足婴儿在生命的前4至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备，而不会导致不良后果。早期的铁充足对于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对发育中的大脑具有不可逆转的负面影响，即使通过补充铁恢复铁水平后，赤字仍持续存在。铁是髓鞘形成的重要组成部分，这对正常的大脑发育和功能至关重要。髓鞘形成在生命的第一年达到顶峰，建立并保持大脑离散区域之间的有效沟通。髓鞘形成异常是各种儿童发育障碍的基础，包括自闭症等疾病。 差距是延迟的脊髓钳夹导致的铁储备增加对早期儿童髓鞘形成和神经发育的影响尚不清楚。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）和红细胞体积（RCV）增加; 2）RCV增加导致早期体内铁储存更多可用铁; 3）增加体内铁储存为最佳髓鞘形成提供必需的铁供应; 4）最佳的髓鞘形成结果改善了发育和认知表现。我们提出了一个随机对照纵向（出生到24个月）试验的128名婴儿，以衡量胎盘输血对发育中的大脑的结构和功能的影响。我们将使用一种非侵入性神经影像学技术来测量髓磷脂随时间的获得，并将结果与铁储存和发育结果相关联。入组的妇女将在出生时随机分配到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鞘沉积，并在4个月、10个月和24个月时评估发育结果。这项研究将有助于为大脑发育相关的脐带夹持时机建立科学依据。这项研究的创新之处在于延迟脊髓夹闭的简单性，并结合使用一种新的MRI方法，可以量化髓鞘沉积。这种临床实践中的低技术变化有可能减少铁缺乏症 改善发展成果。如果延迟的脐带夹紧证明了对最佳发展的保护作用，那么改变实践将转化为大量的成本节约，从而提高整个社会的终身生产力。 公共卫生相关性：美国目前的产科实践是在婴儿出生时立即夹紧婴儿的脐带，每年影响超过400万婴儿。短暂延迟脊髓夹闭导致婴儿铁储存增加，婴儿有可能预防早期铁缺乏，并由于更好的髓鞘形成而导致神经发育结果改善。如果延迟的脐带夹紧证明了对最佳发展的保护作用，那么改变实践将转化为大量的成本节约，从而提高整个社会的终身生产力。

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. PUBLIC HEALTH RELEVANCE: The current obstetrical practice at birth in the United States is that the umbilical cord of the infant is clamped immediately affecting over 4 million infants annually. A brief delay in cord clamping results in increased iron stores for the infant who has the potential to prevent early iron deficiency and result in improved neurodevelopmental outcomes due to better myelination. 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.