Over the past few decades the field of fetal therapy has experienced several paradigm shifts. While initially targeted at life threatening conditions, over time fetal interventions have expanded in scope to now include a number of procedures directed at life-limiting congenital anomalies. As early as 1982 Harrison et al. proposed criteria for fetal therapy which included the importance of having an accurate diagnosis, a known natural history, prior animal model research, and no effective post-natal therapy.1,2 Contemporary fetal interventions now aim to prevent or mitigate the damage attributed to congenital diseases/anomalies by correcting or ablating aspects of the condition prior to birth with the assumption that earlier intervention isolates the fetal tissues from the potential noxious effects of exposure to amniotic fluid or ongoing trauma. Recent advances in prenatal genetic diagnosis, high-resolution ultrasonography, ultra-fast magnetic resonance imaging (MRI) and minimally invasive fetoscopy enable the treatment of a number of structural, functional and metabolic conditions such as: spina bifida, gastroschisis, congenital diaphragmatic hernia, twin-to-twin transfusion (TTTS) syndrome, lysosomal storage disorders, and fetal sickle cell disease and thalassemias, to name a few.

Clinical trials are the cornerstone of evidence for translating innovations into safe and effective prenatal interventions. These studies aim to address unique characteristics of prenatal intervention: consideration for both maternal and fetal safety, small heterogenous population, as well as, the need for long-term longitudinal follow up through infancy and childhood.3 Overall, clinical trials in fetal intervention not only enhance evidence-based practice, but also enhance the understanding of fetal physiology, intrauterine development and maturation, maternal physiology and immunology. Here we review key clinical trials in fetal intervention with a focus on the impact these trials have had on expanding our knowledge and advancing the field. Continued evolution of clinical trials will lead to the next generation of fetal interventions; ameliorative and curative therapies.