MATERNAL HYPERGLYCEMIA--EFFECT ON NEONATAL CARDIOVASCULAR SYSTEM

母体高血糖——对新生儿心血管系统的影响

• 批准号: 3842600
• 负责人: ROBERT N. WOLFSON
• 金额: --
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3842600
• 关键词: cardiac output; embryo /fetus; female; gestational age; glucose metabolism; human subject; hyperglycemia; hypertrophic myocardiopathy; newborn human (0-6 weeks); placental transfer; pregnancy circulation; ultrasonography; ultrasound blood flow measurement; umbilical cord

Maternal hyperglycemia in diabetes mellitus is associated with fetal morbidity and mortality and hypertrophic cardiomyopathy in the newborn with varying degrees of cardiorespiratory distress. In the fetal sheep there is evidence that hyperglycemia by itself may alter cardiac performance and umbilical circulation. We propose to investigate in the human if there are specific, end- organ effects of maternal hyperglycemia on umbilical circulation in the fetus and on cardiovascular anatomy and performance in the fetus and infant. We will use state-of-the-art technology including high-resolution, two-dimensional realtime ultrasound imaging, M-mode echocardiography and Doppler ultrasound to gain non-invasive access to the fetal cardiovascular system. We will use an interdisciplinary approach to document umbilical vein mean flow, umbilical artery impedance to blood flow and a series of intracardiac variables that describe right and left ventricular anatomy and performance in the fetus and infant. We will first examine the normal late gestation pregnancy flow effects of maternal hyperglycemia alone upon umbilical blood flow. We will investigate if an acute sustained maternal hyperglycemia produced by the glucose-clamp technique results in decreased umbilical vein flow. We will examine if there is s corresponding increase in impedance to blood flow in the umbilical artery suggesting control of flow in the microvasculature of the placenta. We will next examine serially in the late second trimester and third trimester of pregnancy the effects of chronic, intermittent maternal hyperglycemia (gestational diabetes) on umbilical vein flow and umbilical artery impedance to flow and correlate any alterations with the quality of maternal glycemic control. We will also correlate prenatal and postnatal findings of hypertrophic cardiomyopathy to extend this diagnosis into the prenatal period and correlate the quality of glycemic control with the degree of hypertrophy and other measures of cardiac performance. We believe that such acute studies in the prenatal period and serial studies in the prenatal and postnatal period may lead to an understanding of the pre-morbid events in the human fetal cardiovascular system that may progress or regress with varying quality of glycemic control and thus explain some of the metabolic alterations of physiologic events that lead to fetal and infant morbidity and mortality in diabetic pregnancies.

糖尿病母亲的高血糖与以下因素有关： 胎儿发病率和死亡率以及肥厚型心肌病 新生儿有不同程度的心肺窘迫。 在胎羊中，有证据表明高血糖本身 可能会改变心脏功能和脐带循环。 我们 提议在人类身上进行调查是否存在特定的、最终的 孕妇高血糖对脐循环的器官影响 对胎儿以及心血管解剖和表现的影响 胎儿和婴儿。 我们将使用最先进的技术 包括高分辨率、二维实时超声 成像、M 型超声心动图和多普勒超声来获得 无创地进入胎儿心血管系统。 我们将 使用跨学科方法记录脐静脉平均值 血流、脐动脉对血流的阻抗等一系列 描述右心室和左心室的心内变量 胎儿和婴儿的解剖结构和表现。 我们首先会 检查正常妊娠晚期妊娠人流的影响 母亲高血糖仅影响脐血流量。 我们将 调查母亲是否发生急性持续高血糖 通过葡萄糖钳技术导致脐静脉减少 流动。 我们将检查是否有相应的增加 脐动脉血流阻抗提示控制 胎盘微脉管系统中的血流。 我们接下来 在妊娠中期末和妊娠晚期进行连续检查 妊娠期慢性、间歇性产妇的影响 高血糖（妊娠糖尿病）对脐静脉血流的影响 脐动脉血流阻抗并与任何变化相关 与母亲血糖控制的质量。 我们还将 关联肥厚的产前和产后发现 心肌病将诊断延伸至产前时期 并将血糖控制的质量与血糖控制的程度相关联 肥厚和心脏功能的其他测量。 我们相信 产前时期的此类急性研究和系列研究 在产前和产后期间可能会导致理解 人类胎儿心血管系统的病前事件 可能会随着血糖质量的不同而进展或退化 控制，从而解释一些代谢变化 导致胎儿和婴儿发病的生理事件以及 糖尿病妊娠的死亡率。