Effects of Placental Transfusion on Early Brain Development

描述(申请人提供)：美国目前的产科做法是，婴儿出生时立即夹住脐带。当立即发生夹闭时，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含铁的红细胞，以满足婴儿出生后4至6个月的铁需求。研究表明，延迟夹住脐带可以增加早期铁的储存，而不会导致不良后果。早期的铁充足对长期的神经健康至关重要。婴儿期缺铁会对认知、运动、社会情绪和行为发育产生不利影响。人类和动物的研究表明，婴儿早期铁储存不足对发育中的大脑有不可逆转的负面影响，即使在铁水平通过补充铁恢复后，铁缺乏仍然存在。铁是髓鞘形成的重要组成部分，而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，在大脑的不同区域之间建立和保持有效的沟通。髓鞘异常是各种儿童发育障碍的基础，包括自闭症等疾病。差距在于，由于延迟夹住脐带而增加的铁储存对儿童早期髓鞘形成和神经发育的影响尚不清楚。我们的假设是，胎盘输注通过以下方式影响髓鞘形成和幼儿发育：1)胎盘输注导致出生时血液容量(BV)和红细胞体积(RCV)增加；2)RCV增加导致体内早期铁存储更多可用铁；3)体内铁存储增加，为最佳髓鞘形成提供必要的铁供应；4)最佳髓鞘形成结果i改善发育和认知能力。我们建议对128名婴儿进行随机对照纵向试验(出生到24个月)，以衡量胎盘输注对发育中大脑结构和功能的影响。我们将使用一种非侵入性神经成像技术来测量随着时间的推移髓鞘的获取，并将发现与铁的储存和发育结果相关联。入选的妇女将在出生时随机分为立即夹脐带组或延迟夹脐带组。我们将在4个月和10个月时评估婴儿的铁充足和髓鞘沉积，并在4、10和24个月时评估发育结果。本研究将为脑发育相关的脐带夹闭时机的选择提供科学依据。这项研究的创新之处在于延缓脊髓夹闭的简单性，并结合使用了一种新的MRI方法，可以定量测定髓鞘沉积。这种临床实践中的低技术改变有可能减少铁缺乏。 并改善发展成果。如果延迟夹紧绳索显示出对最佳发展的保护作用，改变做法将转化为大量节省成本，提高对整个社会有益的终身生产率。

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.