HHS STTR RFA-HD-15-019

This Funding Opportunity Announcement (FOA) invites grant applications for research in for the development of safe, real-time, non-invasive (or minimally invasive), in vivo methods to assess the development and function of the human placenta.

The placenta is essential for the maintenance of pregnancy. The prominent function of the placenta is in the transfer of nutrients, gases and waste products between the mother and fetus. It is effectively the lung, gut, and kidney of the fetus. Abnormalities of placental development and function are known to underlie many major pathologies of pregnancy including spontaneous preterm birth, fetal growth restriction, and preeclampsia. Most information on placental biology is obtained studying placental tissue obtained from pathological pregnancies, such as a preterm deliveries occurring predominately in the third trimester, or from term deliveries in which placental development has already crested.  Hence, there is a paucity of information obtained earlier in gestation, a period of time when many of the pregnancy pathologies are believed to have their origins, as well as limited information gleaned throughout gestation from normal pregnancies. The development of real-time, non-invasive (or minimally invasive) methods to assess the development and functionality of the placenta in vivo throughout gestation would serve as valuable research tools enhancing our understanding of placental biology and rooted pathologies. The development of these tools could lead to the identification of markers and predictors of pregnancy outcome, and provide a future foundation for better pregnancy monitoring in the clinical setting.

This FOA is for the development of safe, real-time, non-invasive (or minimally invasive), in vivo methods to assess the placenta to evaluate normal and abnormal development and function. These methods may include imaging or sensor technologies. The objective of this FOA is to push the field beyond existing paradigms, such as in vitro measurement of analytes obtained from maternal blood and/or Doppler velocimetry of the uterine arteries, both of which have been associated with placental function.  Thus, applications for studies solely measuring biomarkers using in vitro methods of placental function will not be considered responsive. Similarly, studies focusing only on uterine artery Doppler waveforms as a measure of placental perfusion would not be considered responsive. Projects that would be responsive to this FOA include novel methods as well as adapting or optimizing current imaging or real-time analyte(s) sensing technologies. In the case of imaging technologies, the development of signaling markers, safe contrasting materials, and/or software enhancement will be deemed responsive. In regard to analyte sensors, multiplexing analyte measurements is preferable. Special consideration will be given to applications that develop methods that are applicable throughout pregnancy, preferably starting in early gestation during the period of trophoblast invasion and remodeling of the uterine spiral arteries, and which also establish reference values. Other areas of interest include, but are not limited to:

• Development of in vivo methods to assess in vivo placental function.
• Development of in vivo methods to assess in vivo placental metabolism.
• Development of in vivo methods to measure placental nutrient transfer.
• Development of in vivo methods to measure in vivo placental microvascular blood flow.
• Development of in vivo methods to measure placental structural development.
• Development of in vivo methods for the measurement of placental perfusion.
• Development of in vivo methods for the measurement of placental function in complicated pregnancies and patterns of progression to disease states.
• Development of in vivo methods for the spatial and temporal regional mapping of placental function and association with placental histopathology in normal and pathologic states.
• Development of in vivo methods for the measurement of placental response to environmental stressors (e.g. oxygen levels, tobacco exposure, maternal exercise, psychological stress).

Human studies are preferable, but animal studies are acceptable to evaluate proof of concept and the safety of methods that are directly applicable for future translational studies in the human.