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

项目摘要 在美国，每年有超过25，000例妊娠发生胎儿死亡，在全世界的妊娠中有超过250万例发生胎儿死亡- 宽某些母-胎-胎盘异常可能有很高的胎儿死亡风险。尽管取得了进展， 胎儿监护与超声波和心脏分娩，减少胎儿死亡率落后于 在过去的十年里几乎没有下降。这表明胎儿监护的类型 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） 和连续心率（HR）监测用于每个重症监护病房或急诊室; 然而，对于胎儿，ECG信号几乎完全绝缘并且不可接近。因此，间接 使用超声心动图/多普勒获得心律的评估，但回波/多普勒不具有 评估心跳间HR变异性的精度，根本无法评估心脏复极。在本研究中， 我们将评估五种高危情况（胎儿主要先天性心脏病、胎儿水肿（免疫缺陷）、 和非免疫）、单绒毛膜双胎妊娠、终止胎儿死亡的既往妊娠和腹裂） 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，已进行了几个 几十年来，最近获得FDA批准，可以记录所有年龄段的心脏信号，包括胎儿。 257年在威斯康星州-麦迪逊大学生物磁学实验室获得了规范性数据 健康的胎儿，由共同研究员罗纳德T。Wakai博士超过550例严重的胎儿心律失常， 至今评价。胎儿MCG已被证明在胎儿长QT综合征中识别风险标志物的价值 猝死，如尖端扭转型室性心动过速（VT）、T波交替、二度AV 到目前为止，fMCG尚未系统地应用于不适合的疾病， 与可识别的心律失常相关，因为无症状传导和复极缺陷的影响 被低估了在这项研究中，我们假设胎儿心跳间心率变异性 异常和电生理异常，存在于五个高风险的母亲-胎儿-胎盘 与胎儿死亡有关的病症。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。我们在健康正常受试者中的初步发现显示， 复极异常高达5%，其中一些是可修改的，一旦承认。我们将研究200 转诊时（约20-25周GA）和妊娠后期32-37岁时5年以上的妊娠患者 周GA，以确定是否出现特定的异常率，节律和传导模式， 描述的条件，这将使高风险产科医生更好地预测胎儿死亡的风险， 未来

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.