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.