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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要美国每年有超过 25,000 例妊娠发生胎儿死亡，全世界有超过 250 例妊娠发生胎儿死亡。宽的。某些母体-胎儿-胎盘异常可能具有很高的胎儿死亡风险。尽管取得了进展通过超声和胎心监护进行胎儿监测，胎儿死亡率的下降落后于新生儿，并且在过去十年中几乎没有下降。这表明所使用的胎儿监测类型可能没有评估正确的死亡率指标。在所有其他年龄组中，心电图 (ECG) 每个重症监护病房或紧急情况下都使用连续心率 (HR) 监测；然而，对于胎儿来说，心电图信号几乎是完全绝缘的，无法接触到。其结果是，间接心律的评估是通过超声心动图/多普勒获得的，但回波/多普勒没有评估逐次心率变异性的精确度，并且根本无法评估心脏复极。在这项研究中，我们将评估五种高危病症（胎儿主要先天性心脏病、胎儿水肿（免疫性疾病）和非免疫）、单绒毛膜双胎妊娠、先前妊娠导致胎儿死亡和腹裂）使用胎儿心磁图 (fMCG) 检测伴随心脏的自然磁信号电信号。这是一种新的、安全的、非侵入性的记录技术，已经在多个领域进行了应用。几十年来，最近获得 FDA 批准用于记录所有年龄段的心脏信号，包括胎儿的心脏信号。规范数据已于 257 年在威斯康星大学麦迪逊生物磁实验室获得共同研究员 Ronald T. Wakai 博士的健康胎儿研究。超过 550 例严重胎儿心律失常迄今为止评估。胎儿 MCG 已被证明在胎儿长 QT 综合征识别风险标记方面具有无价的价值猝死，如尖端扭转型室性心动过速 (VT)、T 波交替、二度 AV 阻滞，且 QTc>590 ms。迄今为止，fMCG 尚未系统地应用于非由于无声传导和复极缺陷的影响，与可识别的心律失常相关一直被低估。在这项资助中，我们假设逐次胎心率变异性异常和电生理异常，存在于五种高危母体-胎儿-胎盘中与胎儿死亡相关的情况。我们将确定哪些电生理异常先于胎儿死亡或不良妊娠结局。我们对健康正常受试者的初步研究结果表明复极异常率高达 5%，其中一些一旦识别出来是可以改变的。我们将学习200 转诊时（GA 约 20-25 周）以及妊娠后期 32-37 岁期间超过 5 年的怀孕患者 GA 周以确定是否出现特定的异常率、节律和传导模式描述病情特征，使高危产科医生能够更好地预测胎儿死亡的风险未来。