Fetal Electrophysiologic Abnormalities in High-risk Pregnancies Associated with Fetal Demise

高危妊娠中胎儿电生理异常与胎儿死亡相关

• 批准号: 9906264
• 负责人: Janette F Strasburger
• 金额: $ 61.17万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906264
• 关键词: 37 weeks gestation; Affect; Age; Arrhythmia; Cardiac; Cardiotocography; Cessation of life; Chromosome abnormality; Clinic; Clinical Trials; Congenital Heart Defects; Data; Data Set; Decision Making; Defect; Detection; Diagnosis; Diagnostic; Diagnostic Sensitivity; Discipline of obstetrics; Disease; Doctor of Philosophy; Doppler Echocardiography; Electrocardiogram; Electrophysiology (science); FDA approved; Fetal Death; Fetal Diseases; Fetal Heart Rate; Fetal Monitoring; Fetal Mortality Statistics; Fetal Tissues; Fetus; Frequencies; Future; Gastroschisis; Genetic; Gestational Age; Grant; Heart Abnormalities; High-Risk Pregnancy; Hydrops Fetalis; Immune; Infant; Intensive Care Units; Ions; Laboratories; Laboratory Diagnosis; Lead; Life; Long QT Syndrome; Magnetism; Maternal-fetal medicine; Measurement; Measures; Observational Study; Patients; Pattern; Placenta Diseases; Play; Predisposition; Pregnancy; Pregnancy Outcome; Premature Birth; Prematurity of fetus; Property; Research Personnel; Resources; Risk; Risk Marker; Role; Sensitivity and Specificity; Signal Transduction; Small for Gestational Age Infant; Sudden Death; Sudden infant death syndrome; Techniques; Time; Tissues; Torsades de Pointes; Twin Multiple Birth; Ultrasonography; United States; Universities; Ventricular Tachycardia; Visit; Wisconsin; Woman; adverse pregnancy outcome; age group; analog; base; biomagnetism; congenital heart disorder; emergency settings; fetal; fetal diagnosis; heart rate monitor; heart rate variability; heart rhythm; high risk; in utero; innovation; maternal risk; medical specialties; mortality; neonatal death; neonate; non-invasive monitor; novel; postnatal; pregnant; prenatal; prevent; prospective; recruit; time interval; transmission process

PROJECT SUMMARY Fetal demise occurs in over 25,000 pregnancies annually in the US and over 2.5 million in pregnancies world- wide. Certain maternal-fetal-placental abnormalities can have a high risk of fetal demise. Despite advances in fetal surveillance with ultrasound and cardiotocography, the reduction in fetal mortality lags behind that of the neonate and has shown little decline in the past decade. This suggests that the type of fetal monitoring used may not be assessing the correct indicators of mortality. In all other age groups, electrocardiographic (ECG) and continuous heart rate (HR) monitoring are used in every intensive care unit or emergency setting; however, for the fetus, the ECG signal is nearly completely insulated and inaccessible. As the result, indirect assessment of cardiac rhythm is obtained using echocardio-graphy/Doppler, but echo/Doppler does not have the precision to assess beat-to-beat HR variability and cannot assess cardiac repolarization at all. In this study, we will evaluate five high risk conditions (major congenital heart disease in the fetus, fetal hydrops (immune and non-immune), monochorionic twin pregnancy, prior pregnancy ending in fetal demise, and gastroschisis) using Fetal Magnetocardiography (fMCG)which detects the natural magnetic signals accompanying the cardiac electrical signal. It is a new, safe, and non-invasive recording technique that has been performed for several decades, and has recently gained FDA approval for recording cardiac signals at all ages, including in the fetus. Normative data has been obtained at the University of Wisconsin - Madison Biomagnetism Laboratory in 257 healthy fetuses by co-investigator Ronald T. Wakai, PhD. Over 550 serious fetal arrhythmias have been evaluated to date. Fetal MCG has proven invaluable in fetal Long QT Syndrome in identifying markers for risk of sudden death such as Torsades de Pointes Ventricular Tachycardia (VT), T wave alternans, 2nd degree AV block, and QTc>590 ms. To date, fMCG has not been systematically applied to diseases that are not associated with recognizable arrhythmias because the impact of silent conduction and repolarization defects has been underappreciated. In this grant, we hypothesize that beat-to-beat fetal heart rate variability abnormalities and electrophysiologic abnormalities, are present in five high risk maternal-fetal-placental conditions associated with fetal demise. We will determine which electrophysiologic abnormalities precede fetal demise or adverse pregnancy outcome. Our preliminary findings in healthy normal subjects show repolarization abnormalities in up to 5%, and some of these are modifiable once recognized. We will study 200 pregnant patients over a 5 year period both at referral (~20-25 weeks GA) and later in pregnancy at 32-37 weeks GA to determine whether specific abnormal rate, rhythm and conduction patterns emerge that characterize the condition which will allow the high risk obstetrician to better predict risk of fetal demise in the future.

项目摘要 胎儿死亡每年在美国每年25,000多次怀孕，怀孕超过250万怀孕 - 宽的。某些母亲 - 善良的异常异常可能会有胎儿灭亡的高风险。尽管进步 超声检查和心脏图的胎儿监视，胎儿死亡率降低了。 在过去的十年中，新生儿几乎没有下降。这表明使用的胎儿监测类型 可能无法评估死亡率的正确指标。在所有其他年龄组中，心电图（ECG） 在每个重症监护病房或紧急情况下都使用持续的心率（HR）监测； 但是，对于胎儿而言，ECG信号几乎完全绝缘且无法访问。结果，间接 使用echocardio-graphy/Doppler获得心律的评估，但Echo/Doppler没有 评估Beat to-Beat HR变异性并根本无法评估心脏复极化的精度。在这项研究中， 我们将评估五种高风险状况（胎儿的主要先天性心脏病，胎儿水力（免疫） 和非免疫性），单chorionic双胞胎妊娠，胎儿死亡的妊娠和胃造成的） 使用胎儿心动图（FMCG）检测伴随心脏的天然磁信号 电信号。这是一种新的，安全且无创的录音技术，已针对多个 几十年来，最近在包括胎儿在内的所有年龄段记录心脏信号的记录中获得了FDA批准。 在威斯康星大学 - 麦迪逊生物磁学实验室已获得规范性数据257 共同入选者Ronald T. Wakai博士的健康胎儿。超过550个严重的胎儿心律不齐 迄今为止评估。胎儿MCG在识别风险标记方面已证明胎儿长QT综合征无价 突然死亡，例如Torsades de Pointes心室心动过速（VT），T波替代品，第二度AV 块，QTC> 590 ms。迄今为止，FMCG尚未系统地应用于没有的疾病 与可识别的心律不齐相关，因为无声传导和重极化缺陷的影响 被低估了。在这笔赠款中，我们假设跳动胎儿心率变异性 异常和电生理异常存在于五个高风险母亲置换率中 与胎儿灭亡有关的条件。我们将确定哪种电生理异常先于胎儿 丧生或不良怀孕结果。我们在健康正常受试者中的初步发现显示 重度化异常最高可达5％，其中一些是可修改的，一旦识别。我们将研究200 孕妇在转诊（〜20-25周GA）和怀孕期间在32-37的孕妇患者 几周GA确定特定异常率，节奏和传导模式是否出现 表征将允许高风险产科医生更好地预测胎儿死亡风险的状况 未来。