HEART RATE AND BLOOD FLOW VELOCITY VARIABILITY IN HUMAN EMBRYO AND FETUS

围产期发病率和死亡率仍然是一个大的公共卫生问题， 在美国，每1000例妊娠中有8到10例死亡 和欧洲 妊娠高血压综合征的发生率为10%， 怀孕。 子宫胎盘功能不全可能导致宫内 生长迟缓和胎儿低氧血症-由异常胎心鉴定 心率和心血管流速模式。 虽然这些 并发症只在怀孕后期才明显， 妊娠高血压综合征和胎儿宫内发育迟缓开始 胎盘螺旋动脉滋养层异常浸润 发生在怀孕10到18周之间 及早识别 一个受影响的胎儿将允许密集的观察和潜在的 治疗，从而减少胎儿病理的后果。 在 目前，还没有准确的技术来识别早期胎儿 心血管病理血流动力学状态。 长期目标：发展 胎儿心血管健康的非侵入性测量， 鉴定胎儿心血管功能障碍， 允许潜在的治疗干预。 我们假设： 有特定的心率频率和血流速度振幅 在10到18周内， 人类胚胎-胎儿。 胎儿心率与动静脉血流速度幅值 变异性与胎儿心血管功能直接相关， 滋养层细胞侵入的关键转变。 这些曲线的变化是衡量心血管功能障碍的一个指标 与不良结局直接相关。 我们研究人类胎儿， 10至18周妊娠使用多普勒超声技术的血液 来自经阴道和/或经腹部的速度分布测量 探头：母体子宫动脉，胎儿脐动脉，下行 主动脉和静脉导管。 胎儿年龄由胎儿的顶臀决定 长度或双顶径。 数字信号处理用于 定义频率和振幅变化以及波形分析。 统计相关性由灵敏度、特异性、 阳性和阴性预测值和多元Logistic回归。 具体目标包括： 开发一种自动算法来分析动脉和静脉多普勒 频率和振幅变化的速度波形。 定义横截面中的正常频率和振幅变异性 研究了300例妊娠10至18周的人类胎儿。 胎儿动脉和静脉频率和振幅变异性相关 在一项200人队列纵向研究中， 胎儿 意义：这项研究对于我们理解早期的 人体心血管系统，因为没有措施， 发育中的胚胎或胎儿定义正常或异常的心血管 功能不到20周。 有一个明确的和目前的需要， 一种早期准确的测量方法，可以识别出处于危险中的胎儿， 仔细监测和早期干预。 及早识别 受影响的胎儿导致及时干预， 疾病，改善胎儿结局和降低医疗保健成本。

Perinatal morbidity and mortality remain a large public health problem, accounting for 8 to 10 deaths per 1000 pregnancies in the United States and Europe. Pregnancy induced hypertension occurs i 10% of all pregnancies. Uteroplacental insufficiency likely results in intrauterine growth retardation and fetal hypoxemia-identified by abnormal feta heart rate and cardiovascular flow velocity patterns. While these complications are apparent only late in pregnancy, the pathogenesis of pregnancy induced hypertension and intrauterine growth retardation begins with abnormal trophoblast invasion of the spiral arteries of the placenta that occurs between 10 and 18 weeks gestation. Early identification of an affected fetus would permit intensive observation and potential treatment, thereby reducing the consequences of fetal pathology. At present, there are no accurate techniques to identify early fetal cardiovascular pathologic hemodynamic states. Long term aim: Develop a non-invasive measure of fetal cardiovascular well being that allows early identification of the fetus with cardiovascular dysfunction and thereby permit potential therapeutic intervention. We hypothesize: There are specific heart rate frequency and blood velocity amplitude variabilities that indicate cardiovascular health in the 10 to 18 week human embryo-fetus. Fetal heart rate and arterial and venous flow velocity amplitude variability correlate directly with fetal cardiovascular function during the critical transition of trophoblast invasion. Variation from these profiles is a measure of cardiovascular dysfunction that correlate directly wit poor outcome. We study the human fetus at 10 to 18 weeks gestation using Doppler ultrasound techniques of blood velocity profile measurements from a trans-vaginal and/or trans abdominal probe of: maternal uterine artery, fetal umbilical artery, descending aorta and ductus venosus. Fetal age is determined by fetal crown-rump length or biparietal diameter. Digital signal processing is used to define frequency and amplitude variability and wave form analysis. Statistical correlation is determined by sensitivity, specificity, positive and negative predictive value and multiple logistic regression. The specific aims include: Develop an automated algorithm to analyze arterial and venous Doppler velocity waveforms for frequency and amplitude variability. Define normal frequency and amplitude variability in a cross sectional study of 300 human fetuses from 10 to 18 weeks gestation. Correlate fetal arterial and venous frequency and amplitude variability wit fetal outcome in a longitudinal study in a cohort of 200 human fetuses. Significance: This study is essential to our understanding of the early human cardiovascular system because there are no measures of the developing embryo or fetus define normal or abnormal cardiovascular function at less than 20 weeks. There is a clear and present need for an early accurate measure that identifies the fetus at risk and allow for careful monitoring and early intervention. Early identification of the affected fetus leads to timely intervention reducing the burden of disease, improving fetal outcome and reducing health care cost.