PROJECT SUMMARY / ABSTRACT The placenta is a vital fetal organ that serves to oxygenate, nourish, and remove waste from fetal blood in utero. Robust maternal perfusion is essential for this function and requires high capacitance, slow blood flow to the placenta. Maternal-placental perfusion can be temporarily compromised by uterine contractions, which occur throughout pregnancy, also known as Braxton Hicks contractions. Healthy fetuses with normally developed placentas have enough placental reserve capacity that Braxton Hicks contractions and minor vascular pathology do not significantly affect necessary placental oxygen transport. However, in dysfunctional placentas with poor reserve (as in some placentas associated with intrauterine growth restriction-IUGR) these events may lead to hypoxic stress. There is a lack of information and quantitative data regarding the effect of antepartum uterine activity (Braxton Hicks contractions) in human pregnancies and whether these findings may help to characterize placental reserve and function and inform development of future tests to identify fetuses at risk for adverse outcomes during delivery mediated by placental dysfunction. New methods to assess uteroplacental function in humans and the impact of contractions on fetal respiratory exchange across pregnancy in pregnancies with normally growing and IUGR fetuses are needed. Here, we will characterize Braxton Hicks contractions across gestation, analyze spatiotemporal changes in placental oxygenation during these contractions and monitor the effect of these placental oxygenation changes on fetal movement and organ oxygenation via MRI. Our hypothesis is that the change in placental flow during Braxton Hicks contractions may have a larger impact on placental oxygen transport for IUGR fetuses compared to normally growing ones. If successful we will have identified placental and fetal MR signal changes during contractions as a possible method to understand individual placental reserve. Such understanding may enable the development of novel therapies and the ability to monitor changes in these dynamics is critical to the assessment of the impact of novel therapies. Towards this end, we propose the following specific aims: Aim 1: Characterize Braxton Hicks contractions and the associated change in placental oxygenation across gestation in pregnancies with normally growing and IUGR fetuses. We will characterize placental oxygenation using T2* mapping approach and analyze regional differences in placental T2*. Then we will compare and correlate differences in pregnancies with normally growing and IUGR fetuses. Aim 2: Determine the impact of placental oxygenation change during Braxton Hicks contractions on fetal motion and brain and liver oxygenation in pregnancies with normally growing and IUGR fetuses. We will track fetal motion and characterize fetal brain and liver oxygenation using T2* mapping. Then we will compare and correlate differences in pregnancies with normally growing and IUGR fetuses.

PROJECT NARRATIVE While normally growing fetuses with healthy placentas have enough placental reserve capacity that Braxton Hicks contractions do not significantly affect necessary placental oxygen transport, in dysfunctional placentas with poor reserve these events may lead to hypoxic stress. There is a lack of information regarding the effect of Braxton Hicks contractions in human pregnancies and whether these findings may provide information that will inform development of future tests to identify fetuses at risk for adverse outcomes during delivery mediated by placental dysfunction. We propose to characterize Braxton Hicks contractions across gestation, to analyze spatio-temporal changes in placental oxygenation during these contractions and to monitor the effect of placental oxygenation changes on fetal movement and fetal organ oxygenation via MRI.