Renal Anhydramnios Fetal Therapy (RAFT) Trial

总结 本提案的目的是评估一种新的胎儿胰岛素输注方法--连续输注的安全性、可行性和有效性。 妊娠早期肾性羊水过少（EPRA）。EPRA发生在2000例妊娠中的1例以上， 每年影响美国1500个家庭。EPRA以前被认为是普遍致命的，因为它 相关的肺发育不全和新生儿呼吸衰竭。最近，来自案件的初步数据 有报道表明，连续静脉输注治疗与短期产后 EPRA胎儿的存活率，在新生儿期具有良好的呼吸功能。此外，长期 在少数病例中观察到存活，这主要是由于新生儿透析的进步和安全透析的出现。 幼儿活体肾移植用于EPRA管理的系列注射液已被 在临床实践中实施，但没有系统的和前瞻性的研究评估这种治疗， 发生了。因此，缺乏关于母体/胎儿安全性、可行性和 这种干预的短期和长期临床结果。研究胎儿肾性羊水过少的建议 治疗（RAFT）包括一项多中心、非随机前瞻性试验，以解决以下特定问题 目的：（1）探讨EPRA系列注射液对母儿的安全性和可行性 (2)观察RAFT的近期疗效;（3）观察RAFT对急性心肌梗死的远期疗效。 生存和生活质量。一个由8个先进的胎儿中心组成的联盟将在一个机构下运作。 审查委员会与一个协议，有严格的纳入和排除标准。每个中心都被选中了 基于在先进的胎儿治疗和新生儿透析方面的长期经验和专业知识。该试点还将 通过在治疗过程中捕获放射学和羊水生物标志物来阐明RAFT的机制。 此外，它将允许第一次前瞻性分析的子宫内自然历史的EPRA，通过严格的 跟踪那些不终止EPRA妊娠但不希望接受连续静脉输注的患者。 RAFT试验不仅有可能提高我们对连续输注药物对 EPRA中的肺生长以及其他损害肺功能的胎儿疾病。此外，serial EPRA妊娠中的羊水灌注和羊水生物标志物的连续采集沿着评估 放射性生物标志物的研究可能为正常肺部发育的机制提供新的线索。最 重要的是，这项试验将提供重要的数据，以帮助家庭作出决定，胎儿治疗， 受EPRA影响的胎儿，使所有儿童从出生起就获得健康的目标逐步取得进展。

Summary The goal of this proposal is to evaluate the safety, feasibility and efficacy of serial amnioinfusions, a novel fetal therapy for early pregnancy renal anhydramios (EPRA). EPRA occurs in more than 1 in 2000 pregnancies and affects 1500 families in the U.S annually. EPRA has previously been considered universally fatal due to its associated pulmonary hypoplasia and neonatal respiratory failure. More recently, preliminary data from case reports have demonstrated an association between serial amnioinfusion therapy and short-term postnatal survival in EPRA fetuses, with excellent respiratory function in the neonatal period. Furthermore, long-term survival has been observed in a few cases, largely due to advances in neonatal dialysis and the advent of safe living donor kidney transplantation in toddlers. Serial amnioinfusions for the management of EPRA have been implemented in clinical practice, but no systematic and prospective study evaluating this treatment has occurred. Therefore, there is a lack of generalizable knowledge about the maternal/fetal safety, feasibility and short- and long-term clinical outcomes of this intervention. This proposal to study Renal Anhydramnios Fetal Therapy (RAFT) consists of a multi-center, non-randomized prospective trial to address the following specific aims: (1) To determine the maternal and fetal safety and feasibility of serial amnioinfusions for EPRA (2) To examine the short-term efficacy of RAFT and (3) To determine the long-term efficacy of RAFT on survival and quality of life. A consortium of 8 advanced fetal centers will operate under a single institutional review board with one protocol that has strict inclusion and exclusion criteria. Each center has been selected based on long experience and expertise in advanced fetal therapy and neonatal dialysis. This pilot trial will also seek to elucidate the mechanism of RAFT by capturing radiologic and amniotic fluid biomarkers during therapy. Furthermore, it will permit the first prospective analysis of the in utero natural history of EPRA by rigorously tracking patients who do not terminate their EPRA pregnancy but do not wish to undergo serial amnioinfusions. The RAFT trial not only has the potential to improve our understanding of the effect of serial amnioinfusions on lung growth in EPRA but also on other fetal diseases that impair lung function. Furthermore, serial amnioinfusions in EPRA pregnancies and serial acquisition of amniotic fluid biomarkers along with assessment of radiologic biomarkers may shed new light on the mechanisms of normal lung development. Most importantly, this trial will provide crucial data to assist families in making decisions about fetal therapy for fetuses affected by EPRA, making incremental progress toward the goal of health from birth for all children.