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

项目总结 在美国，每年有超过2.5万名孕妇发生胎儿死亡，全球超过250万名孕妇-- 很宽。某些母亲-胎儿-胎盘异常可能有很高的胎儿死亡风险。尽管取得了进展，但 通过超声和心电监护进行胎儿监测，胎儿死亡率的下降滞后于 新生儿，在过去十年中几乎没有下降。这表明使用的胎儿监护类型 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) 并在每个重症监护室或急诊室使用持续心率(HR)监测； 然而，对于胎儿来说，心电信号几乎完全绝缘，无法接触到。因此，间接的 心率的评估是通过超声心动图/多普勒获得的，但回声/多普勒没有 评估心率变异性的准确性，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情况(胎儿严重先天性心脏病、胎儿积水(免疫 和非免疫性)，单绒毛膜双胎妊娠，先前怀孕以胎儿死亡为结局，以及腹裂) 使用胎儿磁心图(FMCG)检测伴随心脏的自然磁信号 电信号。它是一种新的、安全的、非侵入性的记录技术，已经进行了几次 几十年，最近获得了FDA的批准，可以记录所有年龄的心脏信号，包括胎儿。 威斯康星大学麦迪逊分校生物磁学实验室于257年获得了规范数据 共同研究人员Ronald T.Wakai博士的健康胎儿。已有超过550例严重的胎儿心律失常 评估到目前为止。胎儿心磁图在胎儿长QT间期综合征中识别危险标志物的价值 猝死，如尖端扭转室性心动过速、T波交替、二度房室 BLOCK和QTC&GT；590毫秒。到目前为止，快速消费品还没有系统地应用于非 与可识别的心律失常有关，因为静默传导和复极缺陷的影响 被低估了。在这项资助中，我们假设胎儿心率变异性为 5例高危母胎胎盘均存在异常和电生理异常 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。我们在健康的正常受试者中的初步发现表明 复极异常高达5%，其中一些一旦被识别就可以修改。我们将研究200 转诊时(GA约20-25周)和怀孕后期(32-37周)超过5年的孕妇 每周GA以确定是否出现特定的异常率、节律和传导模式 描述将使高危产科医生更好地预测胎儿死亡风险的条件 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.